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XV th<br />
NH City Hotel and Tower<br />
Bolivar 160
International Society of Ocular Oncology Committee<br />
President<br />
Jacob Pe’er, MD<br />
Hadassah, Israel<br />
Secretary<br />
Tero Kivela, MD<br />
Helsinki, Finland<br />
Chaiperson Membership<br />
Michael Giblin, MD<br />
Sydney, Australia<br />
Chairperson-Research<br />
William Harbour, MD<br />
St. Louis, USA<br />
Chairperson-<strong>Program</strong><br />
Martine Jager, MD, PhD<br />
Leiden, the Netherlands<br />
Executive Secretary<br />
Sandra Dailey<br />
Philadelphia, USA<br />
Local Organizing Committee<br />
2<br />
Vice-President<br />
Bertil Damato, FRCS<br />
Liverpool, UK<br />
Treasurer<br />
Timothy Murray, MD<br />
Miami, USA<br />
Chairperson-ByLaws<br />
John Hungerford, FRCS<br />
London, UK<br />
Chairperson-Nominated<br />
Committee<br />
Jerry A. Shields, MD<br />
Philadelphia, USA<br />
Chairperson-Website<br />
Shahar Frenkel, MD, PhD<br />
Jerusalem, Israel<br />
Chair: J. Oscar Croxatto, MD<br />
Miguel Materin, MD<br />
Arturo Irarrazaval, MD<br />
David Pelayes, MD<br />
Guillermo Chantada, MD<br />
Marcelo Zas, MD<br />
Adriana Fandiño, MD<br />
EmilianoBecerra, MD<br />
Ignacio Zeolite, MD<br />
Carolina Gentile, MD
List of Congress Meetings of the International Society of Ocular<br />
Oncology<br />
I<br />
II<br />
III<br />
IV<br />
V<br />
VI<br />
VII<br />
VIII<br />
IX<br />
X<br />
XI<br />
XII<br />
XIII<br />
XIV<br />
XV<br />
1977 Cambridge (England)<br />
1981 Schwerin (former East Germany)<br />
1984 Nylon (Switzerland)<br />
1987 Zusdel/Moskow (Russia)<br />
1989 Essen (Germany)<br />
1992 New York (USA)<br />
1994 Florence (Italy)<br />
1997 Jerusalem (Israel)<br />
1999 Philadelphia (USA)<br />
2001 Amsterdam (The Netherlands)<br />
2003 Hyderabad (India)<br />
2005 Whistler (Canada)<br />
2007 Siena (Italy)<br />
2009 Cambridge (England)<br />
2011 Buenos Aires (Argentina)<br />
3
Patronage<br />
Agencia Nacional de Promoción Científica y Tecnológica<br />
4
Table of Contents<br />
Welcome address<br />
Keynote Lectures<br />
The Stallard Lecture<br />
General Information<br />
Buenos Aires MAP<br />
<strong>Program</strong> Overview<br />
Research Day<br />
Presentations<br />
Abstracts<br />
Retinoblastoma<br />
Presentations<br />
Abstracts<br />
Posters<br />
Poster Abstracts<br />
Eyelid, Conjuntiva, Orbit and Other Intraocular Tumors<br />
Presentations<br />
Rapid Fire Cases<br />
Posters<br />
Abstracts<br />
Rapid Fire Abstracts<br />
Poster Abstracts<br />
Uveal Melanoma<br />
Presentations<br />
Posters<br />
Abstracts<br />
Posters Abstracts<br />
Index (First Authors)<br />
5<br />
7<br />
8<br />
9<br />
10<br />
12<br />
13<br />
15<br />
18<br />
29<br />
35<br />
32<br />
48<br />
61<br />
62<br />
65<br />
67<br />
75<br />
83<br />
91<br />
94<br />
96<br />
108<br />
118
Dear Friends,<br />
Welcome Address<br />
ISOO Committee<br />
Welcome to the 15th meeting of the International Congress of Ocular Oncology, the fifth one as the official congress of the<br />
International Society of Ocular Oncology. Our Society has made progress in working as an organization in recent years, and for the<br />
first time the preparations for our biennial meeting including membership and registration payments and submission of abstracts<br />
were done through the new website of our Society.<br />
Our Society continues to grow, and we have members from many countries throughout the world. This is the first time<br />
that the International Ocular Oncology meeting is being held in Latin America. This fact reflects our goal to expose our specialty to<br />
all parts of the world.<br />
I welcome all those from Latin American countries who have an interest in ocular oncology to join us in our meeting and to<br />
join our Society.<br />
The basic research day, which started as an annex at our meeting in Amsterdam in 2001, has become an integral part of<br />
our general meeting. I’m happy that basic researchers are interested in participating in our meetings, which have become more and<br />
more scientific.<br />
I wish to thank the local organizing committee, headed by J. Oscar Croxatto, who worked so hard to take care of all the<br />
logistics of our meeting, and for planning the social program. I want to thank Martine Jager, head of the program committee, for all<br />
her efforts in planning the scientific program and to Bill Harbour for organizing the research day. I would also like to thank Bertil<br />
Damato, vice president, and Tero Kivela, secretary of the ISOO for their advice, and a special thanks to Shahar Frenkel for his hard<br />
work in establishing and running our new website.<br />
I wish all of you interesting scientific sessions and enjoyable social functions. Please take this opportunity of the congress<br />
being held in the beautiful City of Buenos Aires to meet friends, learn from each other, and plan collaborations for future clinical and<br />
basic studies in our so very special field of ocular oncology.<br />
Jacob Pe’er, M.D.<br />
President<br />
International Society of Ocular Oncology<br />
Dear Members and Guests,<br />
Local Committee<br />
In representation of the Local Organizing Committee, I would first of all like to offer you our warmest personal greetings<br />
and welcome you to Buenos Aires, Argentina. We are both proud and excited to host the XV Biannual Meeting of the International<br />
Society of Ocular Oncology.<br />
We express our gratitude to all scientists, ophthalmologists and oncologists from all over the world traveling to South<br />
America, and the support of all members of ISOO for having selected Buenos Aires to host this biennial meeting. Especially, we<br />
would like to thank Dr. Jacob Pe’er, President of ISOO for his enthusiasm and continuous guidance, Dr. William Harbour for the<br />
organization of an exciting research day, Dr. Jerry Shields and his fervor on “rapid-fire cases”, Dr. Martine Jager for putting together<br />
the whole program, and none the less, Dr. Shahar Frenkel, who did a strenuous work in the arrangement and maintenance of the<br />
web page, and gathering all registrations and submitted abstracts.<br />
Scientific sessions contain a compressed range of topics on ocular oncology, including four keynote lectures, The Stallard Medal<br />
Lecture, 122 paper presentations, 85 posters, and 35 brief case reports. The expectations of the meeting are high. New diagnostic<br />
tools, advances therapies and results of creative and in deep molecular biology research in tumors of the eye and ocular adnexa will<br />
evolve in better therapies and prognosis.<br />
We would like to take this opportunity to thank all those who have contributed to make this event possible. We express<br />
our sincere wish that the exchange of ideas and opinions at the conference will benefit scientists, physicians and patients.<br />
With our warmest regards,<br />
Juan Oscar Croxatto, MD<br />
Chair<br />
Local Organizing Committee.<br />
7
Keynote Lectures<br />
Lymphoma of the ocular adnexa<br />
Steffen Heegaard, MD<br />
Professor of Ophthalmology, University of Copenhagen, Denmark.<br />
Steffen has worked mostly with characterising ocular adnexal lymphoma clinically, pathologically and genetically.<br />
The latest results regarding lacrimal gland lymphoma will be presented in the key note lecture. Also the results of<br />
the latest treatment modalities will be given.<br />
Intraocular melanoma and their metastatic pattern have been described and the invasion pattern into the optic<br />
nerve head has been characterised along with the description of so called neurophilic intraocular melanomas. Also<br />
Melanoma Associated Spongioform Scleropathy has been characterised by the different metalloproteinases and<br />
the possible correlation to extraocular extension of malignant melanoma.<br />
Clinical implications of GNAQ and GNA11 mutations in Uveal Melanoma<br />
Emine Kilic, MD, PhD<br />
Ophthalmology Erasmus MC Rotterdam.<br />
Dr Emine Kilic (Ocular Oncologist and Vitreoretinal surgeon) holds a position as a staff member in the Ophthalmology<br />
department of the Erasmus MC University Hospital, Rotterdam in the Netherlands. She completed her PhD on<br />
genetics of uveal melanoma at the Clinical Genetics and Ophthalmology departments of the Erasmus University<br />
and did her residency in Ophthalmology in the Erasmus MC. She has a special interest in the genetics of Uveal<br />
Melanoma and is a senior researcher in the Rotterdam Ocular Melanoma Studygroup (ROMS). ROMS research<br />
has focussed on the cytogenetic and molecular genetic evaluation of genetic changes in Uveal Melanoma, in<br />
particular on aberrations of chromosomes 1, 3, 6 and 8 and expression profiling of a well-selected subpopulation<br />
of genetically well-characterized tumours. With the availability of newer and more specific techniques for studying<br />
Uveal Melanoma these are further explored and applied for this group of patients. Besides this she is involved in the<br />
study on etiologic factors that may be important in the pathogenesis of Uveal Melanoma and their role in tumour<br />
progression and metastasis.<br />
Insights From Sequencing the Melanoma Exome<br />
Ruth Halaban, PhD<br />
Department of Dermatology, Yale University School of Medicine,<br />
New Haven, CT, USA<br />
Ruth Halaban, a Senior Research Scientist/Professor at Yale University School of Medicine, is an established<br />
scientist in the field of pigmentation and melanoma research. Her main scientific contributions are growth factors/<br />
receptors regulating the proliferation and differentiation of normal melanocytes, aberrant autonomous growth<br />
of melanoma cells, molecular biology of melanocyte specific genes, mechanisms of malignant transformation,<br />
epigenetic regulation, signal transduction and drug responses. More recently, she and her colleagues sequenced<br />
~100 melanoma exomes. The results of this effort are now being investigated in the context of melanocyte<br />
transformation, oncogenes/tumor suppressor genes and melanoma cell heterogeneity. Her prominence in the field<br />
of melanocyte and melanoma biology is reflected by her authoring over 121 publications in peer-reviewed journals,<br />
including 19 solicited reviews, and her receipt of numerous awards, such as the 2009 Lifetime Achievement Award<br />
in melanoma research granted by the Society of Melanoma Research and this year Myron Gordon medal by the<br />
Inrerbational Federation of Pigment Cell Societies.<br />
8
Intravitreal injection in retinoblastoma revisited: from prohibition<br />
to conditional indications<br />
Francis Munier, MD<br />
Head of Retinoblastoma and Oculogenetic Units, Jules Gonin Eye<br />
Hospital, Lausanne, Switzerland.<br />
Prof. Francis Munier studied at the University of Lausanne Medical School in Switzerland. On top of clinical<br />
training at Jules Gonin Eye Hospital and Division of medical Genetics in Lausanne, he received additional training<br />
in Pediatric Ophthalmology and Ocular Oncology at Childrens Hospital Los Angeles, University of Southern<br />
California in USA. Professor Munier is board certified in both Ophthalmology and Medical Genetics. He is presently<br />
head of the the Retinoblastoma Unit and the Oculogenetic Unit at Jules Gonin Eye Hospital. In addition Prof.<br />
Munier is an associated researcher at the Institut de Recherche en Ophtalmologie (IRO) in Sion, Switzerland.<br />
The Stallard Medal<br />
Anterior Segment Surgery of Intraocular Tumors<br />
Enrique S. Malbran, MD<br />
Director, Clínica Oftalmológica Malbran, Buenos Aires, Argentina.<br />
Dr. Enrique S. Malbran is one of the most prestigious surgical and clinical ophthalmologists with a wide area<br />
of expertise. He founded and is currently President of the Fundación Oftalmológica Jorge Malbran. He holds a<br />
chair at the National Academy of Medicine of Buenos Aires, and is a member of the Academia Ophthalmologica<br />
Internationalis, Concilium Ophtalmologicum Universale, among many other national and international societies.<br />
He delivered numerous named lectures including the 28th Edward Jackson Memorial Lecture in 1971, and received<br />
many distinctions and awards around the world. The themes of his original contributions, to mention a few, comprise<br />
corneal surgery, cataract surgery, vitreoretinal surgery, and surgery of intraocular tumors.<br />
9
The venue for the Biannual Meeting of the International Society of<br />
Ocular Oncology (ISOO) is the nH City Hotel & Tower, Bolivar 160/120<br />
Ciudad Autónoma de Buenos Aires.<br />
The intended audience for the Biannual Meeting ISOO 2011 of ocular<br />
oncology program are ophthalmologists, medical oncologists, pediatric<br />
oncologists, radiation oncologists, radiation physicists, radiologists,<br />
pathologists, pharmacologists, molecular biologists, and geneticists<br />
who are engaged in the diagnosis and treatment of tumors of eye and<br />
ocular adnexa.<br />
The objective of the International Society of Ocular Oncology and the<br />
Biennial Meeting ISOO 2011 is to provide opportunities for the free<br />
expression and interchange of ideas and information for educational<br />
purposes. Neither the ISOO nor the Local Committee of the meeting<br />
accepts responsibility for any opinions, positions, or statements<br />
contained or expressed in such material and such opinion, positions or<br />
statements are not necessary those of the ISOO or the Local Committee<br />
of the meeting.<br />
LANGUAGE<br />
English is the official language of the meeting. Translation will not be<br />
provided.<br />
ATTENDEE REGISTRATION<br />
Attendees which did not register in advance may register on-site. The<br />
On-site Registration Area will be staffed from Monday to Thursday,<br />
November 14, from 7:30 am to 4:00 pm.<br />
Forms of Payment<br />
Forms of payment that will be accepted will be cash and credit cards<br />
in Argentine pesos and US dollars. Forms of payment that cannot be<br />
accepted are personal checks, traveler’s checks, or other cash currencies<br />
that are not Argentine pesos or US dollars.<br />
On-site Registration Fees (US Dollars)<br />
Active Member US$ 935<br />
Associate/ Non- member US$ 1035<br />
Welcome Cocktail (only companions) U$S 50<br />
Tango Show & Dinner (per person) U$S 175<br />
Gala Dinner (per person) U$S 150<br />
The registration fee is for all scientific events. There are no additional<br />
course fees. .<br />
Badges and Replacement of Lost Badges<br />
Your badge is your pass to enter the exhibit areas, scientific sessions<br />
and social events. Please wear it at all times. Replacement of badges is<br />
available at the On-site Registration Area. There is a $50 replacement<br />
fee for lost badges. Badges are not transferable and cannot be lent to<br />
anyone for any purpose during the Biennial Meeting ISOO 2011. Altered<br />
badges (including attaching business cards) will be confiscated by<br />
security guards.<br />
Children<br />
Children ages 17 and under receive a complimentary registration and<br />
may enter the Exhibit Area only if accompanied by a registered adult.<br />
Registration for children in this category must be done at the On- Site<br />
Registration Area in the foyer of the Gaudi Room of the nH City & Tower<br />
Hotel.<br />
Proof of Attendance Certificate<br />
Attendees of the Biennial Meeting ISOO 2011 have to ask for a certificate<br />
of attendance in the registration area.<br />
General Information<br />
10<br />
SCIENTIFIC SESSIONS<br />
SPEAKER READY ROOM<br />
Gaudi Room<br />
To assist program participants with their audiovisual needs, the Speaker<br />
Ready Box Room within the Gaudi Room, is staffed from Monday to<br />
Thursday, November 14-17. Scientific session presenters must submit<br />
their Power Point presentations to this room at least three working<br />
hours before their presentations. Early morning presenters should<br />
submit their material before 4:00 pm on the preceding day. PowerPoint<br />
presentations may be previewed in this room, and videotapes may be<br />
cued to the section to be shown.<br />
Buenos Aires: A brief historical profile<br />
The Argentine Republic is the most extensive country in the Spanishspeaking<br />
world, in the extreme south of Latin America, and constitutes a<br />
vast triangle situated in the Andes mountain range. The actual Argentine<br />
territory was colonized by Spain at the beginning of the 16th century.<br />
In 1810, as a result of the Napoleonic occupation of the Kingdom of<br />
Spain, Buenos Aires started the patriotic independence on the 9th of<br />
July 1816.<br />
The name Argentina comes from the Latin “Argentum” which means<br />
silver in the sense of “Country of Silver.” The origin of this term dates<br />
back to the arrival of the first conquistadors to the Rio de la Plata. The<br />
men who were shipwrecked in the expedition of Juan Diaz de Solís,<br />
the discoverers of this river “the sweet sea,” were to meet with the<br />
indigenous inhabitants who presented them with silver objects. These<br />
items were taken to Spain until 1524, along with tales of a fabulous<br />
mountain rich in the metal, the land of silver. From that moment, they<br />
called the Solís River “Rio de la Plata” or the Silver River. In 1820,<br />
President decreed that the government adopted the name “Argentine<br />
Republic.”<br />
Buenos Aires and its surroundings<br />
The city of Buenos Aires is situated on the banks of Rio de la Plata.<br />
This immense estuary, the widest in the world, gives this metropolis a<br />
vision of the infinite. Buenos Aires offers the visitor an attractive cultural<br />
pluralism, from the eclectic nature of its architecture to the varied ethnic<br />
nature of its inhabitants or the wealth of its gastronomy.<br />
The cultural heritage includes the Colon Theatre, a historical national<br />
monument, and one of the great concert halls in the entire world. It<br />
also includes theatres such as the Coliseum, Cervantes, General San<br />
Martín and President Alvear; also impressive are the cultural centers in<br />
Recoleta, Ricardo Rojas and Jorge Luis Borges. Moreover, there are 80<br />
museums, more than a hundred art galleries, hundreds of bookshops,<br />
24 libraries and a Planetarium.<br />
There are also a number of antiques shops, elegant shopping centers<br />
and a great number of boutiques catering to sophisticated tastes.<br />
Nightlife is particularly varied, especially in the city center where there<br />
are the most important nightclubs, discotheques, cafes and places to<br />
dance tango or to enjoy folkloric music.<br />
Parks, squares, avenues and districts of many different kinds, each with<br />
a distinct idiosyncrasy, extend from the center to the south, the north<br />
and the west: the areas of San Telmo, la Boca, Palermo or Belgrano,<br />
Lezama Park, Puerto Madero, Plaza San Martin, Plaza Lavalle, Plaza del<br />
Congreso, Recoleta, the avenues of Mayo, 9 de Julio, Santa Fe, Alvear<br />
or pedestrian street Florida and many other places which give to the<br />
cosmopolitan capital of Argentina, in its different manifestations, a soul<br />
that is different and unmistakable. As Borges said, “a silent magic which<br />
bewitches almost completely all those who come to visit her.”
Climate<br />
In November, the weather of Buenos Aires is generally pleasant,<br />
with sunny days and nights still fresh. The average temperature is<br />
20.3°C/68.5 F.<br />
Clothing<br />
Since it is spring in Buenos Aires, bring appropriate clothing, especially<br />
for going out at night. All varieties of attire are used in Buenos Aires,<br />
from casual attire to gala attire.<br />
Currency<br />
The Argentine currency is the peso. However, American dollars are also<br />
accepted in the majority of shops and restaurants for conveniences.<br />
American dollars and traveler’s cheques can be exchanged at banks<br />
and hotels at the daily exchange rate.<br />
Tipping<br />
10% to 15% of the bill is considered a reasonable tip for good<br />
service. In Argentina, the tip is almost never included in the check.<br />
Always pay the tip in cash separately from the check; for example,<br />
when paying the check with credit card, do not include the tip in<br />
the total amount.<br />
Electricity<br />
The electric current is 220 volts AC. For travelers coming from countries<br />
where 110 volts AC/60 cycles is common, be sure to protect your<br />
equipment from damage.<br />
Bank and Money Exchange<br />
Cash machines are located in several locations. You can always<br />
exchange money at the front desk of your Hotel.<br />
11<br />
Drinking Water<br />
It is always wiser to drink bottled water, although most hotels and<br />
establishments have purified water.<br />
Public Transportation<br />
Buenos Aires boasts of an extensive public transportation system of<br />
buses and a metro system. Please inquire at the front desk of your Hotel<br />
for detailed tourist information.<br />
Taxis & Airport Transportation<br />
Taxis from the Ezeiza International Airport to downtown coasts<br />
approximately between 40 US dollars (130 pesos). When traveling about<br />
the city ask for a taxi in the lobby of your hotel. Do not accept rides from<br />
unmarked taxis.<br />
SOCIAL EVENTS<br />
Opening Ceremony & Cocktail<br />
Tango Show & Dinner<br />
Gala Dinner,<br />
SAFETY TIPS<br />
ALWAYS remove your badge when leaving your Hotel.<br />
RIDE rather than walk, especially at night.<br />
AVOID unlighted driveways and other shadowed places.<br />
WALK with another person when sightseeing or shopping, especially at night.<br />
ASK at the front desk or the concierge desk about the neighborhood<br />
around your hotel.<br />
BE WARY of strangers. Never accompany a stranger anywhere.<br />
REMAIN ALERT at all time.<br />
DON´T TAKE unmarked taxis or accept a ride from anyone you don’t know.<br />
DON´T WALK through dark, unattended parking lots or other desert area.
Buenos Aires Downtown MAP<br />
12<br />
Venue
Monday, November 14<br />
Tuesday, November 15 Wednesday, November 16 Thursday, November 17<br />
RESEARCH DAY<br />
RETINOBLASTOMA EYELID, CONJUNCTIVA & ORBIT UVEAL MELANOMA<br />
8:30 hs Papers Poster Presentations (Rbp 100- Poster Presentations (ECOp Poster Presentations (Ump<br />
120)<br />
101-111)<br />
101-113)<br />
9:00 hs Papers<br />
9:20 hs Papers<br />
9:30 hs Papers<br />
10:10 hs Break<br />
10:20 hs Break Break<br />
10:40 hs Keynote Lecture<br />
10:50 hs Emine Kilic, MD PhD Papers Stallard Lecture<br />
11:00 hs Break Prof. Enrique S. Malbran<br />
11:05 hs Papers<br />
11:20 hs Papers Papers<br />
12:00 hs Keynote Lecture Poster Presentations (Ump<br />
114-126)<br />
<strong>Program</strong> Overview<br />
12:25 hs Ruth Halaban, MD PhD Keynote Lecture<br />
12:30 hs Lunch Francis L. Munier, MD Lunch<br />
12:45 hs Poster Presentations (OTp 101-<br />
110)<br />
12:50 hs Lunch<br />
13:15 hs Lunch<br />
14:00 hs Panel Discussion Papers<br />
13<br />
14:10 hs Poster Presentations (Rbp 121-<br />
138)<br />
14:15 hs Keynote Lecture<br />
Steffen Heegard, MD<br />
14:35 hs Rapid Fire Cases<br />
14:45 hs Papers<br />
14:50 hs Papers<br />
15:40 hs Break<br />
15:45 hs Break<br />
16:00 hs Break<br />
16:10 hs Papers<br />
16:15 hs Papers<br />
16:20 hs Papers<br />
17:00 hs Discussion<br />
17:20 hs Business Meeting<br />
17:30 hs<br />
17:35 hs<br />
18:20 hs
MORNING<br />
8.30-10.10 Papers<br />
(Moderators: D. Wilson, H. Grossniklaus)<br />
1836 RES 1<br />
GENE EXPRESSION DIFFERENCES BETWEEN<br />
MONOSOMY 3 AND DISOMY 3 UVEAL MELANOMA<br />
Arun D. Singh, Nakul Singh, Gurkan Bebek, Charis Eng, Raymond Tubbs,<br />
Yogen Saunthararajah, Pierre Triozzi<br />
2242 RES 2<br />
CORRELATION BETWEEN GEP AND OTHER<br />
PROGNOSTIC FACTORS FOR METASTATIC DEATH IN<br />
205 PATIENTS WITH POSTERIOR UVEAL MELANOMA<br />
EVALUATED BY FNAB<br />
Zélia M. Corrêa, James J. Augsburger, J. William Harbour<br />
2227 RES 3<br />
MOLECULAR GENETICS MUTATION PROFILES OF<br />
UVEAL MELANOMA METASTASES ASSOCIATED WITH<br />
SURVIVAL<br />
Colleen M. Cebulla, Benjamin N. Christopher, Vishal Verma, Dominic<br />
Buzzacco, Thomas Olencki, Frederick H. Davidorf, Mohamed H. Abdel-<br />
Rahman<br />
2226 RES 4<br />
NOTCH SIGNALING PROMOTES UVEAL MELANOMA<br />
GROWTH<br />
Charles Eberhart, Katayoon Ebrahimi, Karisa Schreck, Eli Bar, J. William<br />
Harbour James Handa, Shannath Merbs, Laura Asnaghi<br />
1624 RES 5<br />
IN VIVO CONTRAST-ENHANCED HIGH-FREQUENCY<br />
ULTRASONOGRAPHY OF UVEAL MELANOMA<br />
IN ANIMAL MODELS: IMAGING FEATURES AND<br />
HISTOPATHOLOGIC CORRELATIONS<br />
Hans E. Grossniklaus, Qing Zhang, Hua Yang, Shin J. Kang, Yanggan<br />
Wang, Tonya Coulthard<br />
21 RES 6<br />
HISTOPATHOLOGICAL AND DOSIMETRIC FINDINGS<br />
IN A PORCINE MODEL OF OCULAR RADIATION INJURY<br />
FROM IODINE-125 PLAQUE BRACHYTHERAPY<br />
Scott C. N. Oliver, Victor Hsu, Lucy Bollinger, Moyed Miften, Laurie Gaspar,<br />
Philip Boyer<br />
2347 RES 7<br />
USE OF A MICROCATHETER TO OBTAIN BIOPSIES<br />
FROM UVEAL MELANOMA<br />
David J. Wilson, William J. Harbour<br />
RESEARCH DAY<br />
Monday November 14, 2011<br />
15<br />
148 RES 8<br />
EVALUATION OF HISTONE H3K4 METHYLATION BY<br />
IMMUNOHISTO-CHEMISTRY AND RELATIONSHIP TO<br />
AGGRESSIVE UVEAL MELANOMA<br />
L. Schoenfield, M. Turell, P. Carver, R. Tubbs, A. Singh, Y.<br />
Saunthararajah<br />
42 RES 9<br />
ROLE OF THE CHEMOKINE RECEPTOR CXCR4 IN<br />
THE DEVELOPMENT AND PROGRESSION OF UVEAL<br />
MELANOMA<br />
Shahar Frenkel, Ariela Miller, Amnon Peled, Jacob Pe’er<br />
1703 RES 10<br />
EXPRESSION OF MACROPHAGE-ATTRACTION<br />
MOLECULES IN UVEAL MELANOMA: INDUCTION BY<br />
HYPOXIA?<br />
I.H.G. Bronkhorst, M. Versluis, G.P.M. Luyten, P.A. van der Velden, M.J.<br />
Jager<br />
10.10-10.40 BREAK<br />
10.40-11.05<br />
Keynote Lecture: Dr. Emine Kilic<br />
CLINICAL IMPLICATIONS OF GNAQ AND GNA11<br />
MUTATIONS IN UVEAL MELANOMA<br />
11.05-12.00 Papers<br />
(Moderators M. Materin, Z. Correa)<br />
525 RES 11<br />
ONCOGENE MUTATION PROFILING IN OCULAR<br />
MELANOMA<br />
Ivana K. Kim, Laura MacConaill, Emanuele Palescandolo, Shan Lu, Joo-<br />
Eun Lee, Scott Adams, Margaret M. DeAngelis, Paul Van Hummelen,<br />
Anthony Daniels, Levi Garraway, J. William Harbour, Evangelos S.<br />
Gragoudas<br />
1958 RES 12<br />
DETECTION OF GNAQ/GNA11 MUTATIONS IN<br />
CIRCULATING CELL-FREE DNA AS A BIOMARKER OF<br />
UVEAL MELANOMA<br />
Jordan Madic, Bénédicte Trouiller, David Gentien, Maud Milder,<br />
Stéphanie Saada, Franck Assayag, Fariba Nemati, Didier Decaudin,<br />
Laurence Desjardins, Sophie Piperno-Neumann, Olivier Lantz, Marc-<br />
Henri Stern
2109 RES 13<br />
GNAQ/11 MUTANT DEPENDENT UVEAL MELANOMA -<br />
SENSITIVITY TO MEK AND PI3K INHIBITION<br />
Scott E. Woodman, Xiaoxing Yu, Jahan Khalili, Chandrani Chattopadhyay,<br />
Michelle Williams, Nancy Poindexter, Martine J. Jager, Elizabeth Grimm,<br />
Dan Gombos, Bita Esmaeli<br />
149 RES 14<br />
INACTIVATING MUTATIONS IN BAP1 IN METASTASIZ-<br />
ING CLASS 2 UVEAL MELANOMAS<br />
J. William Harbour, Michael D. Onken, Lori A. Worley, Anne M. Bowcock,<br />
Eli Roberson<br />
1944 RES 15<br />
A RECURRENT DELETION OF THE BAP1 LOCUS IN<br />
OCULAR MELANOMA<br />
Suresh C. Jhanwar, Yuqiang Fang, Lu Wang, Klaus Busam, David H.<br />
Abramson<br />
1843 RES 16<br />
BAP 1 MUTATION IN TWO FAMILIES WITH UVEAL<br />
MELANOMA<br />
Miguel A. Materin, Camila Simoes, Ruth Halaban, J. William Harbour<br />
12.00-12.30<br />
Keynote Lecture: Dr. Ruth Halaban<br />
INSIGHTS FROM SEQUENCING THE MELANOMA EXOME<br />
12.30-14.00 LUNCH<br />
AFTERNOON<br />
14.00-14.45 Panel discussion Uveal Melanoma<br />
(Moderator J.W. Harbour)<br />
14.45-15.45 Papers<br />
(Moderator D. Abramson)<br />
103 RES 17<br />
IDENTIFICATION OF MOLECULAR SUBGROUPS OF<br />
RETINOBLASTOMA<br />
M. Parulekar, G. Kapatai, M.A. Brundler, A. Peet, M. Wilson, H. Jenkinson,<br />
C. McConville<br />
1820 RES 18<br />
A NEW DISEASE: RETINOBLASTOMA WITH NO<br />
DETECTABLE RB1 MUTATIONS DRIVEN BY MYCN<br />
AMPLIFICATION<br />
Brenda L. Gallie, D.E. Rushlow, S. Yee, J.Y. Kennett, P. Boutros, N.L.<br />
Prigoda-Lee, W. Halliday, S. Pajovic, C. Spencer, B.L. Thériault, H.<br />
Dimaras, A. Raizis, C. Houdayer, W.L. Lam, T. Corson, D. Lohmann<br />
RESEARCH DAY<br />
<strong>Program</strong><br />
16<br />
39 RES 19<br />
TARGETING THE P-53 PATHWAY IN RETINOBLAS-<br />
TOMA PRECLINICAL MODELS WITH SUBCONJUNC-<br />
TIVAL NUTLIN-3A<br />
Rachel C. Brennan, Sara Federico, Cori Bradley, Jiakun Zhang, Jacqueline<br />
Flores-Otero, Matthew Wilson, Clinton Stewart, Fangyi Zhu, Kip Guy,<br />
Michael A. Dyer<br />
1656 RES 20<br />
RB DEPLETION SELECTIVELY INDUCES PROLIFERATION<br />
OF CONE-PRECURSOR LIKE CELLS<br />
David Cobrinik, Xiaoliang L. Xu, Suresh C. Jhanwar, and David H.<br />
Abramson<br />
615 RES 21<br />
TRB2 AND SKP2 IN THE RETINOBLASTOMA PATHWAY<br />
Xiaoliang L. Xu, Renbing Jia, Nengyi Zhou, Xianqun Fan, David H.<br />
Abramson, David Cobrinik and Suresh C. Jhanwar<br />
1515 RES 22<br />
NESTED RT-PCR DETERMINATION OF GD2<br />
SYNTHASE AS A MARKER FOR MINIMAL DISEASE IN<br />
RETINOBLASTOMA IN THE CEREBRO-SPINAL FLUID<br />
(CSF).<br />
Viviana Laurent, Claudia Sampor, Jorge Rossi, Mariano Gabri, Maria T.G.<br />
de Davila, Daniel Alonso, Guillermo Chantada<br />
15.45-16.15 BREAK<br />
16.15-17.00 Papers (moderators R. Hurwitz, G.<br />
Chantada)<br />
1824 RES 23<br />
SUPER-SELECTIVE INTRA-OPHTHALMIC ARTERY<br />
CHEMOTHERAPY: RETINAL ENDOTHELIAL TOXICITY<br />
IN PRE-CLINICAL MODELS<br />
Matthew W. Wilson, J. Scott Williams, John S. Jackson, Fan Wang, Clinton<br />
F. Stewart, Timothy D. Mandrell, Barrett G. Haik, Jena J. Steinle<br />
2107 RES 24<br />
EMBRYONIC RETINAL TUMORS IN TRANSGENIC MICE<br />
CONTAIN CD133+ TUMOR-INITIATING CELLS<br />
Richard L. Hurwitz , Lalita Wadhwa, Wesley Bond, Laszlo Perlaky, Paul<br />
Overbeek, Mary Y. Hurwitz, Patricia Chévez-Barrios<br />
2333 RES 25<br />
TREATMENT OF LHBETATAG RETINOBLASTOMA<br />
TUMORS WITH ANGIOGENIC AND GLYCOLYTIC<br />
INHIBITORS AVOIDS CHEMOTHERAPY<br />
Samuel K. Houston, Timothy G. Murray, Yolanda Pina, Christina Decatur
50 RES 26<br />
USING THE GLYCOLYTIC INHIBITOR 2-FLUORODEOXY-<br />
D-GLUCOSE, A NOVEL APPROACH TO TARGET THE<br />
CHEMORESISTANT CELL POPULATION IN LHBETATAG<br />
RETINAL TUMORS<br />
Yolanda Piña, Christina L. Decatur, Samuel Houston, Timothy G. Murray,<br />
Ludimila Cavalcante, and Theodore Lampidis<br />
2140 Res 27<br />
MTOR TARGETING IN COMBINATION WITH<br />
CHEMOTHERAPY: UPSTREAM REGULATION<br />
OF ANAEROBIC GLYCOLYSIS TO TARGET THE<br />
CHEMORESISTANT CELL POPULATION IN RB<br />
Timothy G. Murray, Yolanda Piña, Christina L. Decatur, Samuel Houston,<br />
Ludimila Cavalcante, and Theodore Lampidis<br />
17.00-17.30 Discussion<br />
(moderator B. Gallie)<br />
RESEARCH DAY<br />
<strong>Program</strong><br />
17
1836 RES 1<br />
GENE EXPRESSION DIFFERENCES BETWEEN MONO-<br />
SOMY 3 AND DISOMY 3 UVEAL MELANOMA<br />
Arun D Singh, Nakul Singh, Gurkan Bebek, Charis Eng, Raymond<br />
Tubbs, Yogen Saunthararajah, Pierre Triozzi. Cole Eye Institute, Human<br />
Genomics Institute, Taussig Cancer Center, Cleveland Clinic Foundation<br />
(singha@ccf.org)<br />
Purpose. Presence of monosomy 3 in uveal melanoma has been<br />
associated with metastatic disease. We aim to characterize the gene<br />
expression differences between disomy 3 and monosomy 3 uveal<br />
melanoma tumor samples.<br />
Methods. The gene expression profile of 24,357 genes from 57 uveal<br />
melanomas tumor samples were measured (Illumina HumanRef8-<br />
Version 3). Copy number status was assessed by SNP microarray<br />
(Illumina 660W V1) and FISH. 38 samples were found to have monosomy<br />
3 or uniparental disomy and 19 samples were disomic. Raw gene<br />
expression data was transformed by variance stabilizing and robust<br />
spline normalized. Finally, gene expression differences were calculated<br />
using the LIMMA package in R.<br />
Results. In total, 622 genes were found to be differentially expressed;<br />
with 43 overexpressed genes (2 fold) and 49 under expressed genes<br />
(2 fold) in monosomy 3 tumors. When enriched for gene ontology<br />
(GO) annotations, GO 0048856 [anatomical structural development]<br />
and GO 0042273 [ribosomal large subunit biogenesis] were found<br />
to be statistically significantly overrepresented. PTP4A3 and ENPP2<br />
[autotaxin] have been previously implicated in uveal melanoma, lending<br />
credibility to list.<br />
Conclusions. Analysis of most differentially expressed genes indicates<br />
that several pathways are involved in pathogenesis of metastatic uveal<br />
melanoma, suggesting heterogeneous nature of the tumor. Furthermore<br />
the list of differentially expressed genes provides potential therapeutic targets.<br />
Financial disclosure. None<br />
2242 RES 2<br />
CORRELATION BETWEEN GEP AND OTHER<br />
PROGNOSTIC FACTORS FOR METASTATIC<br />
DEATH IN 205 PATIENTS WITH POSTERIOR<br />
UVEAL MELANOMA EVALUATED BY FNAB<br />
Zélia M. Corrêa, MD, PhD, James J. Augsburger, MD, J. William Harbour<br />
MD (correazm@uc.edu)<br />
Department of Ophthalmology, University of Cincinnati College of<br />
Medicine, Cincinnati, Ohio, USA<br />
Department of Ophthalmology, Washington University School of<br />
Medicine, St. Louis, Missouri, USA<br />
Purpose. Determine the relationships between gene expression profile<br />
(GEP) class, cytologic diagnosis, and size of melanocytic uveal tumors<br />
sampled by FNAB, and comment on the overall survival of patients.<br />
Methods. 205 patients with a primary posterior uveal melanoma<br />
underwent prognostic FNAB as part of a collaborative multicenter<br />
prospective study. In each case, at least 2 aspirates were obtained and<br />
submitted for both cytopathologic and GEP. Relationships between GEP,<br />
cytopathologic classification, tumor size, and intraocular tumor location<br />
were studied by cross tabulation analysis. Survival was computed<br />
using the Kaplan-Meier method. Significance of differences between<br />
RESEARCH DAY<br />
Abstracts<br />
18<br />
subugroups was evaluated using the logrank test.<br />
Results. 75% of patients 55 years of age or younger had a GEP class 1<br />
tumor. This proportion decreased with older age. Patients with smaller<br />
tumors (LBD ≤ 10mm) had a higher percentage of class 1 tumors (79.2%)<br />
compared to those with larger tumors (LBD > 15 mm) (48.6%). 75%<br />
of purely choroidal tumors were GEP class 1 while more than 50% of<br />
ciliary body tumors were GEP class 2. The relationship between GEP<br />
class 1 and low-grade cytology was present but did not reach statistical<br />
significance. FNAB specimen was insufficient for cytodiagnosis in 43<br />
cases (20.1%), and for GEP in only one case (0.5%). Currently, 189 of<br />
205 patients are alive without metastasis (92.2%). Cumulative actuarial<br />
survival based on deaths from metastatic uveal melanoma in the entire<br />
group was 79.7% at three years. Three-year cumulative actuarial survival<br />
was 95.7% in the GEP Class 1 subgroup versus 59.6% in the GEP Class 2<br />
subgroup (p = 0.007, logrank test).<br />
Conclusions. GEP was both (1) substantially more robust discriminator<br />
between surviving patients and those dying of uveal melanoma<br />
metastasis than any other evaluated variable and (2) much more likely<br />
to yield a definitive prognostic classification than cytopathology.<br />
Financial disclosure. NEI grant EY02687, NCI grant R01CA125970, Kling Family Foundation,Tumori<br />
Foundation, Barnes-Jewish Hosp Foundation, Horncrest Foundation, Research to Prevent<br />
Blindness, Quest for Vision Fund-U Cincinnati<br />
2227 RES 3<br />
MOLECULAR GENETICS MUTATION PROFILES OF<br />
UVEAL MELANOMA METASTASES ASSOCIATED WITH<br />
SURVIVAL<br />
Colleen M. Cebulla1, Benjamin N. Christopher1, Vishal Verma1, Dominic<br />
Buzzacco1, Thomas Olencki3, Frederick H. Davidorf1, Mohamed H.<br />
Abdel-Rahman1,2 (colleen.cebulla@osumc.edu)<br />
1. Department of Ophthalmology; 2. Division of Human Genetics,<br />
Department of Internal Medicine; 3. Medical Oncology <strong>Program</strong>, The<br />
Ohio State University, Columbus, OH<br />
Purpose. To investigate the molecular genetics status of uveal melanoma<br />
(UM) metastases and correlate it with disease progression.<br />
Methods. IRB approval was obtained. Twelve pathologically confirmed<br />
UM metastases from 11 patients were included. Molecular genetic<br />
alterations in chromosomes 3, 8q, 6p, and 1p, and the BAP1 gene region<br />
were investigated by microsatellite genotyping. Mutations in codons 183<br />
and 209 of GNAQ and GNA11 genes were studied by restrictive fragment<br />
length polymorphism (RFLP).<br />
Results. Patients with monosomy 3 tumours (4/11) died rapidly with<br />
metastatic disease (mean survival = 5 months, range 1-8 months).<br />
In contrast, patients with disomy or partial chromosome 3 tumour<br />
alterations showed significantly slower metastatic disease progression<br />
(mean survival = 69 months, range 40- 123 months, p=0.003).<br />
Alterations in chromosomal arms 1p (5/10), 6p (6/10), and 8q (9/11),<br />
BAP1 LOH (8/11), and mutations in either GNAQ or GNA11 (8/11) were<br />
not differentially associated with survival. Prominent mononuclear<br />
inflammatory infiltrate was observed in tumours from patients with<br />
slowly progressive disease.<br />
Conclusions. In UM metastases, monosomy 3 is associated with highly<br />
aggressive, rapidly progressive disease while disomy or partial change<br />
of 3 and prominent mononuclear inflammatory infiltrate in the tumour is<br />
associated with better prognosis. These findings should be considered<br />
when designing clinical trials testing effectiveness of various therapies<br />
of metastatic UM.<br />
Financial disclosure. None
2226 RES 4<br />
NOTCH SIGNALING PROMOTES UVEAL MELANOMA<br />
GROWTH<br />
Eberhart Charles, Ebrahimi Katayoon, Schreck Karisa, Bar Eli, Harbour J,<br />
William Handa, James, Merbs Shannath, Asnaghi Laura (ceberha@jhmi.edu)<br />
Departments of Pathology, Ophthalmology and Oncology, Johns Hopkins<br />
University, School of Medicine, Baltimore, MD, USA<br />
Department of Ophthalmology & Visual Sciences, Washington University<br />
School of Medicine, St. Louis, MO, USA<br />
Purpose. To determine if uveal melanoma requires Notch activity for<br />
growth and metastasis.<br />
Methods. Expression of Notch pathway members was characterized<br />
in primary tumor samples and in cell lines using Western blots, real<br />
time RT PCR and gene expression arrays. Notch inhibition was achieved<br />
using small molecule inhibitors and shRNA constructs targeting multiple<br />
pathway members. Notch signaling was induced with constitutively active<br />
truncated receptors. Growth, invasion and clonogenicity were measured<br />
in vitro using standard assays, and in vivo xenografts were examined<br />
histopathologically.<br />
Results. Notch receptors, ligands and targets were expressed in all five cell<br />
lines examined, and in 30 primary uveal melanoma samples. Interestingly,<br />
the three lines with high levels of baseline pathway activity (OCM1, OCM3,<br />
OCM8) had their growth reduced by pharmacologic Notch blockade using<br />
the gamma-secretase inhibitor (GSI) MRK003. In contrast, two uveal<br />
melanoma lines (Mel285, Mel290) with very low expression of Notch<br />
targets were insensitive to the GSI. Constitutively active forms of Notch1<br />
and Notch2 promoted growth of uveal melanoma cultures and were able<br />
to rescue the inhibitory effects of GSI. MRK003 treatment also inhibited<br />
anchorage-independent clonogenic growth and cell invasion, and reduced<br />
phosphorylation levels of Akt and Erk1/2. Suppression of canonical Notch<br />
activity using shRNA targeting Notch2 or CBF1 was also able to reduce<br />
tumor growth and invasion. Notch signaling was required to maintain<br />
Twist1 expression in uveal melanoma cells, and Twist1 knockdown using<br />
shRNA reduced invasion. Finally, intraocular xenograft growth was<br />
significantly reduced by GSI treatment.<br />
Conclusions. Our findings suggest that Notch plays an important role in<br />
inducing proliferation and invasion in uveal melanoma, and that inhibiting<br />
this pathway may be effective in preventing tumor growth and metastasis.<br />
Financial disclosure. None<br />
1624 RES 5<br />
IN VIVO CONTRAST-ENHANCED HIGH-FREQUEN-<br />
CY ULTRASONOGRAPHY OF UVEAL MELANOMA<br />
IN ANIMAL MODELS: IMAGING FEATURES AND<br />
HISTOPATHOLOGIC CORRELATIONS<br />
Hans E. Grossniklaus1, Qing Zhang1, Hua Yang1, Shin J Kang1, Yanggan<br />
Wang1, Tonya Coulthard2 (ophtheg@emory.edu)<br />
1. Emory University School of Medicine, Atlanta, Georgia<br />
2. Visual Sonics, Toronto, Canada<br />
Purpose. To evaluate the utility of in vivo imaging of a mouse model<br />
of uveal melanoma utilizing high-frequency contrast-enhanced<br />
ultrasound (HF-CE-US) with 2- or 3-dimensional modes, and to correlate<br />
the sonographic findings with histopathologic characteristics.<br />
Methods. Fourteen 12-week-old C57BL6 mice were inoculated into<br />
RESEARCH DAY<br />
Abstracts<br />
19<br />
their right eyes with aliquots of 5X105/2.5µL of B16LS9 melanoma<br />
cells, and randomly assigned into 2 groups. At 7 days post inoculation,<br />
tumor-bearing eyes in group 1 (n = 8) were imaged using high<br />
frequency ultrasound with microbubble contrast agent to determine<br />
the 2-dimensional tumor size and relative blood volume; eyes in<br />
group 2 (n = 6) were imaged by 3-dimensional mode ultrasound with<br />
microbubble enhancement, and the tumor volume was determined.<br />
Histologic tumor burden was quantified in enucleated tumor-bearing<br />
eyes by Image J software, and microvascular density was determined<br />
by counting vWF-positive vascular channels. The 2D or 3D in vivo<br />
imaging were evaluated and compared with histopathologic findings.<br />
A rabbit model of ocular melanoma was also evaluated.<br />
Results. Utilizing high frequency ultrasound with microbubble contrast<br />
agent in the mouse model, melanomas were visualized as relatively<br />
hyperechoic regions in the images. The intraobserver variability was<br />
9.65 ± 7.89% and the coefficient of variation for multiple measurements<br />
was 7.33 ± 5.71%. The correlation coefficient of sonographic volume or<br />
size and histologic area was 0.71 (P = 0.11) and 0.79 (P = 0.32). The<br />
relative blood volume within the tumor demonstrated sonographically<br />
with the contrast agent correlated signficantly with histologic tumor<br />
vascularity (r = 0.83, P < 0.001). Intraturmor vasularization/blood<br />
volume was also demonstrated in the rabbit model.<br />
Conclusions. There is a positive linear correlation between in vivo<br />
sonographic tumor volume/size and histologic tumor size in our mouse<br />
ocular melanoma model. Contrast-enhanced intensity corresponds with<br />
microvascular density and blood volume in the model. High frequency<br />
ultrasound with microbubble contrast enhancement is a real-time,<br />
non-invasive and reliable method for in vivo evaluation of experimental<br />
intraocular melanoma tumor area and relative blood volume.<br />
Financial disclosure. Visual Sonices (TC)<br />
21 RES 6<br />
HISTOPATHOLOGICAL AND DOSIMETRIC FINDINGS<br />
IN A PORCINE MODEL OF OCULAR RADIATION INJURY<br />
FROM IODINE-125 PLAQUE BRACHYTHERAPY<br />
Scott C. N. Oliver, MD, Victor Hsu, BA, Lucy Bollinger, Moyed Miften,<br />
PhD, Laurie Gaspar, MD, Philip Boyer, MD (scott.oliver@ucdenver.edu)<br />
Departments of Ophthalmology, Radiation Oncology and Pathology,<br />
University of Colorado School of Medicine<br />
Purpose. An animal model for acute radiation injury to the eye does<br />
not exist. This study sought to describe the histopathological and<br />
dosimetric findings in a porcine model of ocular radiation injury<br />
from Iodine-125 (I-125) plaque brachytherapy.<br />
Methods. The eyes from six pigs were irradiated with a high<br />
dose of I-125 radiation (125-140 Gy), with progressively<br />
lengthening survival durations of 1 to 11 weeks. Intraoperative<br />
thermoluminescent dosimetry was compared to theoretical dose<br />
calculations at five points along the globe. Sectioned eyes were<br />
analyzed to determined histopathologic markers of acute radiation<br />
injury.<br />
Results. High-dose plaque brachytherapy in a porcine model was<br />
technically feasible and well tolerated. Dosimetric measurements<br />
demonstrated unacceptable variability and reproducibility when<br />
oriented in a radial direction due to difficulty in positioning the<br />
detectors on the posterior half of the globe. Equatorial orientation<br />
of the dosimeters resulted in reliable measurements in close<br />
agreement with theoretical dose calculations. Histopathological<br />
evidence of acute radiation injury to the eye was detectable as
early as 2 weeks post irradiation, as evidenced by outer nuclear<br />
layer (ONL) thinning, choroidal beading and thinning, and<br />
derangement of retinal pigment epithelium (RPE) granules with<br />
loss of RPE cells.<br />
Conclusions. The porcine eye is a viable model for acute radiation<br />
injury from I-125 plaque brachytherapy, with anatomical and size<br />
similarity to the human eye. External dosimetry was validated<br />
using an equatorial orientation of the detectors. For the first<br />
time, histopathological markers of acute radiation injury were<br />
identified, including ONL thinning of the retina, choroidal beading,<br />
and RPE loss.<br />
Financial disclosure. None<br />
2347 RES 7<br />
USE OF A MICROCATHETER TO OBTAIN BIOPSIES<br />
FROM UVEAL MELANOMA<br />
David J. Wilson1, MD; William Harbour2, MD (wilsonda@ohsu.edu)<br />
1. Casey Eye Institute, Oregon Health and Science University<br />
2. Barnes Eye Institute, Washington University<br />
Purpose. To determine if a flexible microcatheter can be used to<br />
obtain diagnostic material from uveal melanomas.<br />
Methods. Following enucleation of two eyes with the clinical diagnosis<br />
of choroidal melanoma, a flexible microcatheter (iScience) was<br />
introduced into the supraciliary space. The catheter was advanced<br />
posteriorly into the suprachoroidal space, with the progress of<br />
the catheter monitored by direct observation of the blinking light<br />
emitting diode at the tip of the catheter. When the catheter tip was<br />
at the location of the uveal melanoma, cells were harvested from the<br />
tumor using a specially designed trocar. Cells were analyzed using<br />
routine cytology and gene expression profiling.<br />
Results. Satisfactory material for cytologic diagnosis and gene<br />
expression profiling was obtained for both eyes.<br />
Conclusions. With further refinement, a flexible microcatheter might<br />
permit sampling of posterior uveal melanomas to obtain clinically<br />
useful information.<br />
Financial disclosure. None<br />
148 RES 8<br />
EVALUATION OF HISTONE H3K4 METHYLATION BY<br />
IMMUNOHISTOCHEMISTRY AND RELATIONSHIP TO<br />
AGGRESSIVE UVEAL MELANOMA<br />
L. Schoenfield1, M. Turell2, P. Carver1, R. Tubbs1, A. Singh2, Y.<br />
Saunthararajah3 (schoenl@ccf.org)<br />
Cleveland Clinic<br />
1. Pathology and Lab Medicine Institute<br />
2. Cole Eye Institute<br />
3. Taussig Cancer Institute<br />
Purpose. Aberrant histone modification patterns measured at the<br />
level of single nuclei have been predictive of cancer recurrence and<br />
poorer survival in multiple cancers. Similar evaluations have not been<br />
performed in primary uveal melanoma (UM). Such evaluation could be<br />
translationally useful, since unlike genetic alterations in UM, epigenetic<br />
alterations might be reversible with chromatin-relaxing drugs.<br />
RESEARCH DAY<br />
Abstracts<br />
20<br />
Methods. 23 cases of enucleated globes for UM from 2004-11 were<br />
examined by immunohistochemistry for H3K4Me1 using a red chromagen<br />
and compared to patient outcome as well as chromosome 3 or 3p26<br />
status by FISH. Cases were interpreted as negative if at least 10% of the<br />
nuclei had no staining.<br />
Results. At the time of this study, 8 patients were DOD, 1 was alive with<br />
metastasis, 2 were dead without evidence of metastasis and 12 were alive<br />
without metastasis. Of the 13 negative cases, which would presumably<br />
indicate a poorer outcome, 7 were dead of disease, 1 was dead without<br />
metastasis (normal chromosome 3), and 5 were alive without metastasis<br />
(all 5 with monosomy 3 or 3p26del). Of the 10 positive cases, 7 were<br />
alive without metastasis, 1 alive with metastasis, 1 DOD, and 1 dead<br />
without metastasis. When compared to monosomy 3 status alone, 10/13<br />
negative cases and 4/10 positive cases had monosomy 3.<br />
Conclusions. In this small study of 23 cases, lower global levels of<br />
H3K4Me1 were significantly associated with death with metastases<br />
(Chi-test p=0.02), suggesting an important role for therapeutically<br />
targetable epigenetic alterations in UM pathogenesis.<br />
Financial disclosure. None<br />
42 RES 9<br />
ROLE OF THE CHEMOKINE RECEPTOR CXCR4 IN<br />
THE DEVELOPMENT AND PROGRESSION OF UVEAL<br />
MELANOMA<br />
Shahar Frenkel, MD, PhD1, Ariela Miller, MD1, Amnon Peled, PhD2, Jacob<br />
Pe’er, MD1 (shahar.frenkel@gmail.com)<br />
1. Departments of Ophthalmology and 2. Gene Therapy, Hadassah-<br />
Hebrew University Medical Center, Jerusalem, Israel<br />
Purpose. The purpose of this study was to determine the expression<br />
of the CXCR4 chemokine receptor in primary and metastatic Uveal<br />
Melanoma (UM) tissues and in a UM cell line. As well as the effect of<br />
CXCR4 antagonist BKT-140 on two cell lines of UM.<br />
Methods. Immunohistochemistry to detect CXCR4 (monoclonal antihuman<br />
CXCR4, R&D systems, Minneapolis, USA) was performed on 17<br />
eyes of 17 patients with UM, as well as on 9 liver sections of 9 metastatic<br />
UM patients. The tissues were analyzed and graded according to the<br />
intensity of the stain from 0-4 (0- being no staining, and 4- very intense<br />
staining). The primary tumors were examined for tumor cell type,<br />
vasculogenic mimicry patterns, mitotic figures, and tumor size (largest<br />
basal diameter and tumor height). mRNA from OCM1 and C918 cell lines<br />
were examined for the expression of CXCR4 before and after stimulation<br />
with SDF1 (CXCL12), along with expression of SDF1 and VEGF mRNAs.<br />
The expression of cell surface mRNA was examined in both cell lines. The<br />
cell lines were also evaluated for the effect of BKT-140 CXCR4 receptor<br />
agonist after 3hrs, 24hours and 48 hours at 10% Fetal Calf serum (FCS).<br />
Results. CXCR4 expression was observed in both primary and metastatic<br />
uveal melanoma. In the 17 primary tumors 10 (59%) tumors stained grade<br />
3. The mean staining intensity was 2.59. In the metastatic tumor 3/9<br />
(33.3%) liver sections stained grade 4. The mean staining intensity was<br />
2.56. No correlation was found between CXCR4 staining intensity and<br />
any of the histopathologic parameters. SDF1 mRNA was not detected<br />
in OCM1 or C918 cell lines. mRNA levels of CXCR4 did not increase after<br />
stimulation with SDF1, but this stimulation increased the mRNA levels<br />
of VEGF after 24 and 48 hours in the OCM-1 cell line. BKT 140 caused<br />
an increase in the number of dead cells after 3 hours of exposure but<br />
this effect was less after 24 and 48 hours , a decrease in the number of<br />
living cells was less significant in the OCM-1 lines at a dose of 100ug/<br />
ml at 10% FCS after 3, 24 and 48 hours. In the C918 cell line there was
a reduction in the number of living cells especially at 48 hours and an<br />
increase in the percent of dead cells at 10% FCS over 48 hours.<br />
Conclusions. CXCR4 was found to be a relevant molecular pathway in<br />
uveal melanoma as shown in the histopathologic sections from both<br />
primary and metastatic tissues. Preliminary results for the use of the<br />
inhibitor of this pathway, BKT-140, on cell lines show promise that this<br />
inhibitor may have an additive effect in the treatment of UM.<br />
Financial disclosure. Prof. Amnon Peled is the founder and CSO of Biokine Therapeutics Ltd.<br />
The CXCR4 antagonist BKT140 belongs to Biokine Therapeutics.<br />
1703 RES 10<br />
EXPRESSION OF MACROPHAGE-ATTRACTION MOL-<br />
ECULES IN UVEAL MELANOMA: INDUCTION BY HY-<br />
POXIA?<br />
I.H.G. Bronkhorst, M. Versluis, G.P.M. Luyten, P.A. van der Velden, M.J.<br />
Jager (i.h.g.bronkhorst@lumc.nl)<br />
Department of Ophthalmology, Leiden University Medical Center,<br />
Leiden, The Netherlands<br />
Purpose. Hypoxia and inflammation both play a role in cancer. In tumor<br />
cells, hypoxia activates HIF-1α and NF-kB, and these factors may induce<br />
a gene program that recruits leukocytes (through release of chemokines<br />
and cytokines). This study was performed to examine whether hypoxia<br />
induces uveal melanoma cells to release attractants for circulating<br />
monocytes.<br />
Methods. The inflammatory responses of four primary tumors were<br />
studied in an in vitro 24 hour hypoxic culture system using quantitative<br />
real-time PCR for expression of CSF-1, SDF-1,<br />
MCP1 (CCL2), RANTES (CCL5), CCL7, CCL8, and VEGF.<br />
Results. Inflammatory cytokine expression was variable in uveal<br />
melanoma primary cultures. Under hypoxic conditions, we find an<br />
upregulation of VEGF, and CCL7 mRNA, and a decrease of CSF-1 and<br />
MCP1 mRNA. CCL8 was increased in two out of four cultures, and SDF-1<br />
was not altered. CCL5 shows large intervariable differences, but was<br />
only in one culture decreased.<br />
Conclusions. Hypoxia influences inflammatory chemokine expression<br />
in uveal melanoma cells. However, as the genomic levels of these<br />
chemokines may not correlate directly with chemokine production, further<br />
experiments with cell lines are needed. By negatively regulating adaptive<br />
immunity, hypoxia may prevent excessive activation of the immune host<br />
defense, which might otherwise lead to an anti-tumor response.<br />
Financial disclosure. None<br />
525 RES 11<br />
ONCOGENE MUTATION PROFILING IN OCULAR<br />
MELANOMA<br />
Ivana K. Kim1, Laura MacConaill2, Emanuele Palescandolo2, Shan<br />
Lu2, Joo-Eun Lee3, Scott Adams3, Margaret M. DeAngelis3, Paul Van<br />
Hummelen2, Anthony Daniels1, Levi Garraway2, J. William Harbour4,<br />
Evangelos S. Gragoudas1 (ivana_kim@meei.harvard.edu)<br />
1. Massachusetts Eye and Ear Infirmary, Dept of Ophthalmology, Harvard<br />
Medical School<br />
2. Centre for Cancer Genome Discovery, Dana-Farber Cancer Institute,<br />
Dept of Medical Oncology, Harvard Medical School, Boston, MA<br />
3. Ocular Molecular Genetics Institute, Mass Eye and Ear Infirmary,<br />
Harvard Medical School, Boston, MA<br />
RESEARCH DAY<br />
Abstracts<br />
21<br />
4. Department of Ophthalmology and Visual Sciences, Washington<br />
University School of Medicine, St. Louis, MO<br />
Purpose. To perform a systematic screen in uveal melanoma samples for<br />
known oncogenic mutations in order to identify potential therapeutic targets.<br />
Methods. A high-throughput, mass-spectrometry based genotyping<br />
technology (OncoMap) was employed to screen for over 1100 mutations<br />
in 114 known cancer genes. DNA was purified from 146 specimens:<br />
5 uveal melanoma cell lines, 87 fresh frozen (FF) samples of uveal<br />
melanoma tissue, and 54 samples obtained from formalin-fixed,<br />
paraffin-embedded (FFPE) tissue. After whole genome amplification,<br />
adequate DNA was obtained from 128 of these samples for genotyping<br />
with the OncoMap assay.<br />
Results. Forty-two percent (42%) of samples passing all quality control<br />
steps contained candidate mutations. Fifty-five candidate mutations<br />
were found across 27 genes. Overall, only 25% of the mutation calls<br />
were considered conservative based on the confidence of data review.<br />
Validation studies using independent primers and unamplified DNA in<br />
homogenous Mass-Extend (hME) assays confirmed only a few of the<br />
candidate mutations. An FGFR3 mutation was validated in 3 samples<br />
and the BRAF V600E mutation was validated in 3 uveal melanoma cell<br />
lines. Eighty-eight percent of samples had GNAQ or GNA11 mutations.<br />
Conclusions. This study confirmed the high frequency of GNAQ and<br />
GNA11 mutations in uveal melanoma and demonstrated that uveal<br />
melanoma appears to have a relative paucity of oncogenic mutations<br />
seen in other tumour types.<br />
Financial disclosure. None<br />
1958 RES 12<br />
DETECTION OF GNAQ/GNA11 MUTATIONS IN<br />
CIRCULATING CELL-FREE DNA AS A BIOMARKER OF<br />
UVEAL MELANOMA<br />
Jordan Madic1,2, Bénédicte Trouiller1,2, David Gentien1,3, Maud<br />
Milder1,4,5, Stéphanie Saada1,4,, Franck Assayag1,3,6, Fariba<br />
Nemati1,3,6, Didier Decaudin1,3,6, Laurence Desjardins1,7, Sophie<br />
Piperno-Neumann1,8, Olivier Lantz11,4,5,9, Marc-Henri Stern1,2 (jordan.<br />
madic@curie.fr)<br />
1. Institut Curie, Paris; 2. Inserm U830; 3. Département de Recherche<br />
Translationnelle; 4. Département de Biologie des Tumeurs; 5. CIC-BT-<br />
507 Inserm; 6. Laboratoire d’Investigation Préclinique; 7. Département<br />
de Chirurgie; 8. Département d’Oncologie médicale; 9. Inserm U932.<br />
Purpose. Circulating tumor-derived DNA (ctDNA) can be detected<br />
in the plasma of cancer patients. Recently, ctDNA was proposed as a<br />
biomarker to follow tumor burden and monitor treatment efficacy. However,<br />
ctDNA represents a tiny fraction of the normal cell-free circulating DNA, and its<br />
assessment is challenging due to specificity, sensitivity and quantitative issues.<br />
We developed a real-time PCR based on the pyrophosphorolysisactivated<br />
polymerization (bi-PAP) for the quantification of ctDNA in<br />
plasma of patients with uveal melanoma (UM). Bi-PAP can detect known<br />
point mutations independently of large excess of normal DNA. Our assay<br />
targets the activating mutation of codon 626 of GNAQ or GNA11 which<br />
are present in most UM.<br />
Methods. Bi-PAP primer pairs specific for GNAQ 626A>T, GNAQ 626A>C<br />
and GNA11 626A>T have been chosen. Their sensitivity and specificity<br />
were assessed on serial dilutions of tumor DNA in normal DNA.<br />
Results. Each assay could detect a single mutated molecule per reaction,<br />
while 10,000 copies of normal DNA were not detected. In plasma of<br />
mice bearing UM xenografts, ctDNA were proportional to the amount of<br />
circulating human DNA and to the size of the xenograft. Furthermore, in
a retrospective analysis of 19 UM patient sera, 8 were found positive.<br />
Conclusions. In conclusion, bi-PAP represents a promising tool for<br />
the quantification of ctDNA in the blood of UM patients. A prospective<br />
study is on going to confirm the clinical value of ctDNA level in metastatic<br />
UM patients.<br />
Financial disclosure. None<br />
2109 RES 13<br />
GNAQ/11 MUTANT DEPENDENT UVEAL MELANOMA -<br />
SENSITIVITY TO MEK AND PI3K INHIBITION<br />
Scott E. Woodman1A, Xiaoxing Yu1A, Jahan Khalili1A, Chandrani<br />
Chattopadhyay1A, Michelle Williams1B, NancyPoindexter1A , Martine J. Jager2<br />
, Elizabeth Grimm1A, Dan Gombos3, Bita Esmaeli3 (sewmdphd@yahoo.com)<br />
1A. Melanoma Medical Oncology,<br />
1B. Pathology, MD Anderson Cancer Center, Houston, TX;<br />
2. Ophthalmology, Leiden University Med Center, Leiden, The Netherlands;<br />
3. Head & Neck Surgery/Ophthalmology, MD Anderson Cancer Center,<br />
Houston, TX.<br />
Purpose. Metastatic uveal melanoma has a very poor prognosis and<br />
no effective treatment. Activating GNAQ or GNA11 mutations have been<br />
identified in approximately 85% of uveal melanoma tissues. The MEK/<br />
MAPK and PI3K/AKT pathways may mediate GNAQ/11 growth and<br />
survival signaling. The purpose of this study was to test the sensitivity<br />
of uveal melanoma cell lines to combination treatment with clinically<br />
relevant MEK and PI3K small molecule inhibitors.<br />
Methods. The GNAQ/11 mutant (MUT) and wild-type (WT) status of<br />
uveal melanoma cell lines was determined using standard sequencing<br />
approaches. Concentration and time-course western blot experiments<br />
were used to determine the optimal conditions for MEK inhibitor (MEKi)<br />
or PI3K inhibitor (PI3Ki) treatment using GSK1120212 and GSK2126458,<br />
respectively. Cell proliferation assays were performed to determine<br />
the relative sensitivity of MUT vs. WT cells to MEKi and/or PI3Ki. Cell<br />
cycle analysis was performed to determine the relative percentages<br />
of cells in each stage before and after MEKi and/or PI3Ki treatment.<br />
Annexin/Propidium-iodide staining was determined by flow cytometry<br />
to assess the frequency of apoptotic cells before and after MEKi and/<br />
or PI3Ki treatment. Reverse Phase Protein Array was employed to asses<br />
downstream signaling changes that result from MEKi and/or PI3Ki treatment.<br />
Results. Both MEKi and PI3Ki treatment result in early and sustained<br />
loss of MAPK and AKT phosphorylation, respectively, at low nanomolar<br />
concentrations in MUT and WT cells. MEKi and/or PI3Ki treatment<br />
induces more pronounced G1 cell cycle arrest in MUT vs. WT cells.<br />
However, neither MEKi nor PI3Ki treatment alone induces significant<br />
apoptotic cell death in MUT or WT cells. The combination of MEKi +<br />
PI3Ki also fails to induce apoptotic death in WT cells. Conversely,<br />
the combination of MEKi + PI3Ki induces a marked increase (40-60%<br />
of cells) in the subG0 cellular fraction of MUT cells consistent with<br />
apoptotic death at 48 hrs. Annexin V staining is markedly increased<br />
MUT cells after combination treatment. Cell signaling analysis<br />
indicates that combined MEKi + PI3Ki treatment potentiates reduction<br />
in 4EBP1-P, and increases in p27 and cleaved caspase 3 in MUT vs.<br />
WT cells.<br />
Conclusions. These results suggest that uveal melanoma cells with<br />
activating mutations in GNAQ or GNA11 are highly dependent on<br />
the MEK/MAPK and PI3K/AKT pathways for growth and survival.<br />
Combination MEKi + PI3Ki small molecule treatment may be an<br />
effective therapeutic strategy for the majority of metastatic uveal<br />
melanoma patients.<br />
Financial disclosure. GlaxoSmithKline<br />
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22<br />
149 RES 14<br />
INACTIVATING MUTATIONS IN BAP1 IN METASTASIZ-<br />
ING CLASS 2 UVEAL MELANOMAS<br />
J. William Harbour, Michael D. Onken, Lori A. Worley, Anne M. Bowcock,<br />
Eli Roberson (harbour@vision.wustl.edu)<br />
Washington University School of Medicine, St. Louis, Missouri, USA<br />
Purpose. Uveal melanoma (UM), the most common primary cancer<br />
of the eye, has a strong tendency for hematogenous metastasis.<br />
UMs are grouped according to metastatic risk into class 1 (low risk)<br />
and class 2 (high risk) based on gene expression profile. The class<br />
2 signature is usually accompanied by monosomy 3, suggesting that<br />
loss of chromosome 3 unmasks recessive mutations in a metastasis<br />
suppressor gene (or genes) on the remaining copy of chromosome 3.<br />
The purpose of this study was to identify this gene.<br />
Methods. We performed exome capture and massively parallel DNA<br />
sequencing in two class 2 tumors and identified a gene on chromosome<br />
3 containing inactivating mutations in both tumors. Sanger sequencing<br />
of the gene was then performed in additional class 1, class 2 and<br />
metastatic tumors.<br />
Results. Inactivating mutations were identified in BAP1, located at<br />
chromosome 3p21.1, in 26/31 (84%) class 2 tumors 24/28 (86%), 2/3<br />
(67%) liver metastases and in one atypical class 1 tumor that appeared<br />
to be in transition to class 2. No mutations were found in 22 typical<br />
class 1 tumors. The mutation was also present in normal blood DNA in<br />
one case. RNA and protein levels were depleted in tumors harboring<br />
mutations. RNAi mediated depletion of BAP1 in UM cells transformed<br />
them from class 1 to class 2 phenotype.<br />
Conclusions. This gene meets the criteria expected for a putative<br />
metastasis suppressor gene on chromosome 3 in UM. This finding<br />
provides novel opportunities for diagnostic testing and targeted<br />
therapy.<br />
Financial disclosure. Dr. Harbour and Washington University may receive remuneration in the<br />
form of royalties based on a license of related technology by the University to Castle Biosciences,<br />
Inc. This research was not funded by Castle Biosciences, Inc.<br />
1944 RES 15<br />
A RECURRENT DELETION OF THE BAP1 LOCUS IN<br />
OCULAR MELANOMA<br />
Suresh C. Jhanwar1, Yuqiang Fang1, Lu Wang1, Klaus Busam1, David H.<br />
Abramson2 (Jhanwars@mskcc.org)<br />
1. Department of Pathology, 2. Ophthalmic Oncology Service<br />
Memorial Sloan-Kettering Cancer Center, New York, NY, 10065, USA<br />
Purpose. A monosomy of chromosome 3 is one of the most common<br />
cytogenetic abnormalities in ocular melanoma (OM), which may<br />
be predictive of metastasis. Recent studies have shown that BAP1<br />
gene located at 3p21.3 is mutated in approximately 84% of the<br />
metastasizing OM.<br />
Methods. We have performed FISH and SNP microarray analyses on<br />
29 tumors to determine frequency and the nature of abnormalities<br />
for chromosomes 1,3 and 8, in particular BAP1 locus on 3p21.3.<br />
Results. FISH detected monosomy or a relative loss of the<br />
chromosome 3p in 16/29 (55%); low to high level amplification of<br />
MYC was detected in 7/21 (33%) and 14/21 (66%) respectively. The<br />
abnormality of chromosome 1 included relative loss of 1p and gain of<br />
1q in 7/29 (24%) of the cases. SNP arrays, on the other hand detected<br />
hemizygous deletion of BAP1 gene in 18/20 (90%) of the cases, SNP-
array further detected copy number increase of MYC in 16/20 (80%),<br />
whereas, deletion of 1p localized to a minimal region of deletion on<br />
1p36.22 was seen in 13/20(65%) of the cases.<br />
Conclusions. These results suggest that loss of BAP1 is the most<br />
common genetic abnormality in OM, whereas deletion 1p36.22 &<br />
MYC amplification may be secondary events. In addition, combined<br />
use of these two methodologies is powerful to detect biologically<br />
important abnormalities including copy number changes and<br />
uniparental disomy. The clinical implications of these abnormalities,<br />
specifically hemizygous deletion of BAP1 in relation to metastases,<br />
prognosis and response to therapy are currently being examined.<br />
Financial disclosure. None<br />
1843 RES 16<br />
BAP 1 MUTATION IN TWO FAMILIES WITH UVEAL<br />
MELANOMA<br />
Miguel A. Materin1, Camila Simoes1, Ruth Halaban1, William Harbour 2<br />
(miguel.materin@yale.edu)<br />
1. Yale School of Medicine, New Haven, Conncecticut<br />
2. Washington University, St. Louis, Missouri<br />
Purpose. To describe the potential inheritance of BAP 1 mutation in<br />
patients with uveal melanoma.<br />
Methods. Two different families with history of uveal melanoma<br />
were found to have BAP1 mutation. Family 1, patient had choroidal<br />
melanoma, class 2, BAP1 mutation. Maternal grandfather died<br />
from liver metastases from an eye tumor. Patient’’s mother DNA<br />
was positive for BAP1 mutation. Family 2, two brothers with uveal<br />
melanoma had BAP1 mutation.<br />
Results. We are presenting two different families with uveal<br />
melanoma in two different members of the family and BAP1 mutation.<br />
In one of the family, this mutation was found in a family member with<br />
no uveal melanoma present.<br />
Conclusions. We are presenting two different families with uveal<br />
melanoma in two different members of the family and BAP1 mutation.<br />
In one of the family, this mutation was found in a family member with<br />
no uveal melanoma present.<br />
Financial disclosure. Pfizer consultant: Miguel Materin, however, no commercial interest in this<br />
paper.<br />
103 RES 17<br />
IDENTIFICATION OF MOLECULAR SUBGROUPS OF<br />
RETINOBLASTOMA<br />
M. Parulekar, G. Kapatai, M.A. Brundler, A. Peet, M. Wilson, H. Jenkinson,<br />
C. McConville (manojparulekar@aol.com)<br />
School of Cancer Sciences, University of Birmingham, Dept of<br />
Ophthalmology, Oncology & Histopathology, Birmingham Children’’s<br />
Hospital, UK<br />
Purpose. Survival for retinoblastoma patients is excellent, but invasion<br />
into the optic nerve or choroid is relatively frequent, increasing<br />
the potential for extra-ocular metastasis. Little is known about the<br />
molecular events which influence tumour behaviour. The purpose of<br />
our research is to develop a clinically relevant molecular classification<br />
of retinoblastoma and to translate this into 1H-MRS (1H-magnetic<br />
resonance spectroscopy)-detectable markers for the non-invasive<br />
RESEARCH DAY<br />
Abstracts<br />
23<br />
diagnostic assessment of retinoblastomas.<br />
Methods. Gene expression profiling was carried out on 21<br />
retinoblastomas. Principal component analysis (PCA) was used for<br />
classification of molecular sub-groups. Differentially expressed genes<br />
in each subgroup were identified using SAM (Significance Analysis of<br />
Microarrays). In vitro 1H-MRS was carried out to identify metabolite<br />
spectra specific for molecular subgroups.<br />
Results. Molecular analyses identified 3 distinct groups of<br />
retinoblastomas characterized primarily by differing levels of<br />
photoreceptor differentiation. One group showed expression of many<br />
cone-associated genes, a second group expressed markers of rod,<br />
cone and Müller glial cells, while the third showed down-regulation<br />
of these genes.<br />
Conclusions. Photoreceptor differentiation was inversely associated<br />
with adverse histopathological features (choroid and post-laminar<br />
optic nerve invasion), suggesting that loss of differentiation may<br />
be associated with more aggressive tumour behaviour. Recurrent<br />
chromosomal alterations characteristic of retinoblastoma (1q gain, 6p<br />
gain, 16q loss) were almost entirely restricted to less differentiated<br />
retinoblastomas indicating that genes on these chromosomes may<br />
function in differentiation-related pathways and/or in the regulation of<br />
cell cycle exit. Preliminary 1H-MRS results identified several metabolites<br />
(e.g. glutamate/glutamine, taurine) which may have potential as<br />
markers of retinoblastoma subgroups.<br />
Financial disclosure. None<br />
1820 RES 18<br />
A NEW DISEASE: RETINOBLASTOMA WITH NO<br />
DETECTABLE RB1 MUTATIONS DRIVEN BY MYCN<br />
AMPLIFICATION<br />
Brenda L. Gallie, D.E. Rushlow, S. Yee, J.Y. Kennett, P. Boutros, N.L. Prigoda-<br />
Lee, W. Halliday, S. Pajovic, C. Spencer, B..LThériault, H. Dimaras, A. Raizis,<br />
C. Houdayer, W.L. Lam, T. Corson, D. Lohmann (brenda@gallie.ca)<br />
Retinoblastoma Solutions and the Toronto Western Hospital Research<br />
Institute, University Health Network; Department of Molecular<br />
Genetics, University of Toronto; British Columbia Cancer Research<br />
Centre, Vancouver; The Ontario Institute for Cancer Research, Toronto;<br />
Department of Pathology, Hospital for Sick Children, Toronto; Campbell<br />
Family Cancer Research Institute and Ontario Cancer Institute, University<br />
Health Network, Toronto; Departments of Hematology Oncology and<br />
Ophthalmology and Visual Science, Hospital for Sick Children, Toronto;<br />
Department of Molecular Pathology, Canterbury Health Laboratories,<br />
Christchurch, New Zealand; Service de Génétique Oncologique, Institut<br />
Curie and Université Paris Descartes, Paris, France; Eugene and Marilyn<br />
Glick Eye Institute, Department of Ophthalmology; and Department of<br />
Biochemistry and Molecular Biology, Indiana University School of Medicine,<br />
Indianapolis, Indiana; Institut für Humangenetik, Universitätsklinikum<br />
Essen, Germany; Dept. of Ophthalmology and Medical Biophysics, Univ<br />
of Toronto, Canada.<br />
Purpose. Dogma states that all retinoblastoma tumors have lost both<br />
alleles of the RB1 tumor suppressor gene. We can efficiently identify<br />
95% of RB1 mutant alleles. In 2% of tumors we failed to find any mutant<br />
RB1 allele (RB1+/+).<br />
Methods. In the RB1+/+ tumors, we characterized the RB and other<br />
protein expression, the other genomic changes characteristic of primary<br />
retinoblastoma, aCGH, and clinical features. One RB1+/+ cell line was<br />
studied for growth rate in comparison to RB1-/- cell lines.<br />
Results. In 1% of retinoblastoma tumors we discovered high level
amplification of the MYCN oncogene and normal RB1 (RB1+/+MYCNA<br />
tumors). Array CGH showed that the genomic instability characteristic<br />
of RB1-/- retinoblastoma was not present. The children with the<br />
RB1+/+MYCNA tumors presented at very young ages (6 months vs 24<br />
months for non-hereditary retinoblastoma). Distinctive histopathological<br />
features included multiple nucleoli. In vitro the RB1+/+MYCNA cell line<br />
rapidly died when MYCN levels are reduced by shRNA, in comparison to<br />
RB1-/- cell lines with late acquired MYCN amplification that showed only<br />
slowed growth when MYCN was reduced.<br />
Conclusions<br />
Through our clinical analysis of RB1 alleles in more than 1000<br />
retinoblastoma probands, we have discovered a previously unrecognized<br />
disease: retinoblastoma that is not caused by RB1 gene mutations. We<br />
hypothesize that children presenting with unilateral retinoblastoma<br />
filling the eye before 6 months of age, and those with extraocular/<br />
metastatic retinoblastoma before 1 year of age, are likely to have<br />
RB1+/+MYCNA tumors. Despite their rapid growth in very young children,<br />
they may be more responsive to therapy than RB1-/- retinoblastoma,<br />
since they have less genomic instability and therefore less capacity to<br />
achieve drug resistance. Although RB1+/+MYCNA tumors are aggressive<br />
and rapidly growing, targeting MYCN may cure.<br />
Financial disclosure. D Rushlow, N Prigoda are employees of Retinoblastoma Solutions. Brenda<br />
Gallie is the Medical Director and President of Retinoblastoma Solutions.<br />
39 RES 19<br />
TARGETING THE P-53 PATHWAY IN RETINOBLASTOMA<br />
PRECLINICAL MODELS WITH SUBCONJUNCTIVAL<br />
NUTLIN-3A<br />
Rachel C. Brennan 1,2, Sara Federico1,2, Cori Bradley1, Jiakun Zhang1,<br />
Jacqueline Flores-Otero1 , Matthew Wilson3, Clinton Stewart4, Fangyi<br />
Zhu5, Kip Guy5, Michael A. Dyer1,3,6 (rachel.brennan@stjude.org)<br />
1. Department of Developmental Neurobiology, St. Jude Children’s<br />
Research Hospital; 2. Department of Hematology/Oncology, St.<br />
Jude Children’s Research Hospital;3. Department of Ophthalmology,<br />
University of Tennessee Health Sciences Center; 4. Department of<br />
Pharmaceutical Sciences, St. Jude Children’s Research Hospital; 5.<br />
Department of Chemical Biology and Therapeutics, St. Jude Children’s<br />
Research Hospital, Memphis, USA; 6. Howard Hughes Medical Institute<br />
Purpose. Virtually all human retinoblastomas express elevated<br />
levels of MDM4 which silences the p53 pathway, thereby<br />
providing an ideal molecular target for treating children with<br />
advanced stage or refractory disease. A small molecule inhibitor<br />
(nutlin-3a) of MDM2 also binds MDM4, but it does not efficiently<br />
penetrate the blood-ocular barrier. This study tested the efficacy<br />
of subconjunctival nutlin-3a in preclinical models of human<br />
retinoblastoma (RB) and characterized the pharmacokinetics and<br />
toxicity profile.<br />
Methods. We developed an ocular formulation using FDA approved<br />
adjuvants for ocular delivery. We performed pharmacokinetics of<br />
subconjunctival nutlin-3a and compared the vitreal penetration to<br />
that of systemic nutlin-3a. Comprehensive preclinical testing with<br />
nutlin-3a (18 weeks) in two different genetic RB mouse models<br />
and a human orthotopic xenograft were compared to the current<br />
standard of care while monitoring ocular and systemic toxicity.<br />
Results. Subconjunctival delivery of nutlin-3a gave 2,000-20,000<br />
fold increase in intraocular penetration of drug compared to oral<br />
or intravenous dosing. Using subconjunctival nutlin-3a once<br />
every 3 weeks, we observed a dramatic response in our genetic<br />
RESEARCH DAY<br />
Abstracts<br />
24<br />
mouse model of RB with ectopic MDM4 expression. Importantly,<br />
an identical model lacking p53 showed little response, providing<br />
genetic validation of molecular targeting of MDM4 in RB. The<br />
orthotopic xenograft showed a significant improvement in<br />
outcome compared to current standard of care. Few ocular or<br />
systemic toxicities were detected.<br />
Conclusions. Subconjunctivally delivered nutlin-3a is a promising<br />
new molecular targeted therapy for retinoblastoma. Our studies<br />
provide a new standardized approach to evaluate novel agents for<br />
incorporation into future clinical trials for retinoblastoma.<br />
Financial disclosure. This work was supported by grants from the National Institutes of Health<br />
(R01EY018599 and R01EY014867 (MAD) and CA23099 (CFS)); Cancer Center Support CA 21765<br />
from the National Cancer Institute; and grants from the American Cancer Society, the Pew<br />
Charitable Trust, and the American Lebanese Syrian Associated Charities (ALSAC). Dr. Dyer is a<br />
Howard Hughes Medical Institute Early Career Investigator.<br />
1656 RES 20<br />
RB DEPLETION SELECTIVELY INDUCES PROLIFERATION<br />
OF CONE-PRECURSOR LIKE CELLS<br />
David Cobrinik, Xiaoliang L. Xu, Suresh C. Jhanwar, and David H.<br />
Abramson (cobrinid@mskcc.org)<br />
Department of Pediatrics, Department of Pathology, and Ophthalmic<br />
Oncology Service, Memorial Sloan-Kettering Cancer Center, New York,<br />
NY 10021, USA<br />
Purpose. Biallelic inactivation of RB1 is thought to initiate<br />
retinoblastoma tumorigenesis in a specific, yet undefined,<br />
retinal cell type. We previously showed that retinoblastoma<br />
cells prominently express markers of cones but not other cells,<br />
and require factors (TRβ2 and RXRγ) and oncoproteins (N-Myc<br />
and MDM2) that are especially prominent in post-mitotic cone<br />
precursors. These observations are consistent with retinoblastomas<br />
originating either from cone precursors or from cells that adopt<br />
cone precursor circuitry after retinoblastoma inception. Here, we<br />
explore whether cone-related features enable fetal retinal cell<br />
proliferation in response to diminished Rb expression.<br />
Methods. Rb was depleted in gestational week 18-21 retinal cells,<br />
using lentiviral shRNA vectors, either with or without co-depletion<br />
of cone-related factors or oncoproteins. The proliferative status<br />
of cells prior to transduction was evaluated by EdU labeling, and<br />
cellular phenotypes of proliferating cells were evaluated by costaining<br />
for Ki67 and cell type-specific markers.<br />
Results. RB1 knockdown induced proliferation of cells having<br />
properties of cones but not other retinal cell types. Proliferating<br />
cone-like cells lacked EdU, indicating that their forebears were<br />
quiescent prior to Rb depletion. The proliferation of cone-like<br />
cells was suppressed by co-depletion of TRβ2, MDM2, and N-Myc,<br />
suggesting that these factors contribute to the proliferative<br />
response to Rb loss.<br />
Conclusions. Rb depletion provokes proliferation of fetal retinal<br />
cells that have cone precursor properties and dependence<br />
upon cone circuitry similar to retinoblastoma cells. Prospective<br />
isolation of cells that proliferate in response to Rb depletion may<br />
provide insight into the cell type that gives rise to retinoblastoma<br />
tumors.<br />
Financial disclosure. Supported by Perry’s Promise Fund, The Fund for Ophthalmic Knowledge,<br />
Research and Development Funds of the MSKCC Department of Pathology, and NIH<br />
R01CA137124.
615 RES 21<br />
TRB2 AND SKP2 IN THE RETINOBLASTOMA PATH-<br />
WAY<br />
Xiaoliang L. Xu1,4, Renbing Jia1,5, Nengyi Zhou1, Xianqun Fan5, David H.<br />
Abramson2, David Cobrinik ,4 and Suresh C. Jhanwar1 (xux2@mskcc.org)<br />
1. Departments of Pathology; 2. Ophthalmic Oncology Service 3;<br />
Department of Pediatrics<br />
4. Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center,<br />
New York, USA; 5. Department of Ophthalmology, Shanghai Ninth<br />
People’s Hospital, Shanghai Jiaotong University, Shanghai, P. R. China.<br />
Purpose. We previously reported that TRB2 and SKP2 are essential<br />
for retinoblastoma pathogenesis. In this study, we examine how TRB2<br />
regulates SKP2.<br />
Methods. We knocked down (KD) or overexpressed TRB1, TRB2, and<br />
related genes in retinoblastoma and RB1 gene in colon cancer and<br />
neuroblastoma to clarify the TRB and Rb signaling pathway.<br />
Results. TRB2-KD promoted TRB1 activation, Emi1 inactivation, Cdh1<br />
activation, and SKP2 degradation, resulting in S phase arrest. Conversely,<br />
TRB1 KD promoted Emi1 activation, SKP2 stabilization, resulting in G2/M<br />
block. TRB1 activated PP1-CDC25C-CDK1-PLK1 to phosphorylate and<br />
inactivate Emi1, resulting in activation of Cdh1. TRB2 counteracted TRB1<br />
and maintained PP2A mediated Emi1 dephosphorylation and activation.<br />
The TRB knockout promoted, whereas TRB2 KO suppressed anterior<br />
pituitary tumor formation in RB1+/- mice. Phospho-Rb binds to TRB2,<br />
PP2A, and Emi1 to form a nuclear complex, named as S phase promoting<br />
complex (SPC), which is essential for S-phase progression. RB1-KD in<br />
neuroblastoma and colon cancer cells caused TRB1 activation, SPC<br />
dissociation, Emi1 inactivation, Cdh1 activation, and SKP2 degradation,<br />
resulting in S phase arrest.<br />
Conclusions. G1-S and G2-M transitions exhibit a critical balance<br />
regulated by TRB1 and TRB2, in which TRB2 promotes, whereas TRB1<br />
suppresses G1/S transition. Following Rb mutation, TRB1 is activated,<br />
resulting in SPC dissociation, Emi1 inactivation, cdh1 activation, and<br />
SKP2 degradation preventing cell cycle reentry, which is a second<br />
assurance for cell cycle control. Thus, high level TRB2 in cone precursors<br />
counteracts TRB1 by maintaining SPC integrity, disrupting the doubleassurance,<br />
and promoting cell cycle entry in retinoblastoma. The SPC<br />
integrity may be an optimal therapeutic target for retinoblastoma.<br />
Financial disclosure. Research and Development Funds of Department of Pathology, MSKCC.<br />
The Fund for Ophthalmic Knowledge. Gerber Foundation.<br />
1515 RES 22<br />
NESTED RT-PCR DETERMINATION OF GD2 SYNTHASE<br />
AS A MARKER FOR MINIMAL DISEASE IN RETINOBLAS-<br />
TOMA IN THE CEREBRO-SPINAL FLUID (CSF)<br />
Viviana Laurent, Claudia Sampor, Jorge Rossi, Mariano Gabri, Maria TG<br />
de Davila, Daniel Alonso, Guillermo Chantada (gchantada@yahoo.com)<br />
Hospital JP Garrahan, Universidad de Quilmes, Argentina<br />
Purpose. The standard criteria for evaluation of the CSF in retinoblastoma<br />
includes neuro-imaging and cerebrospinal fluid (CSF) cytology. We<br />
hypothesized that RT-PCR-based techniques might increase the yield for<br />
determining minimal dissemination and potentially guide CNS directed<br />
therapy.<br />
Methods. We evaluated the CSF of children with retinoblastoma who<br />
presented IRSS stage 2-4 (n=14) and selected stage 1 with pathology risk<br />
factors (n=8) at diagnosis, at 6 and 12 months and at relapse. Standard<br />
evaluation included cell count and microscopical examination of the<br />
RESEARCH DAY<br />
Abstracts<br />
25<br />
cytoentrifugate. Minimal disease evaluation included immunocytology<br />
for GD2 ganglioside and RT-PCR followed by nested-PCR amplification<br />
of a GD2 synthase mRNA fragment.<br />
Results. Three children underwent treatment for CNS invasion (2 trilateral)<br />
diagnosed by standard evaluation. PCR was negative in both trilateral<br />
cases and it was positive in the remaining case who had a persistent<br />
positivity despite the CSF cytology cleared after chemotherapy. She had<br />
a fatal CNS relapse thereafter. Eleven children with stage 2 to 4a disease<br />
had no CNS involvement at diagnosis by standard evaluation and PCR<br />
was positive in 4 (all of them had massive optic nerve involvement and 1<br />
had also bone marrow metastasis). Two of them had a CNS relapse and<br />
the remaining 2 are in complete remission for 9 and 18 months (followup<br />
PCR is negative) after intensive therapy. CNS relapse occurred in 4<br />
children with negative or not evaluable PCR (CNS mass with normal CSF<br />
in 3). All children with stage 1 had negative CSF evaluation by all techniques<br />
at all times and did not experience CNS relapse.<br />
Conclusions. RT-PCR-based assays for the evaluation of the CSF status<br />
in children with retinoblastoma may improve the sensitivity of standard<br />
techniques by identifying minimal disease.<br />
Financial disclosure. Supported by a grant from the Agencia de Promocion Cientifica y<br />
Tecnologica, Ministerio de Ciencia, Tecnologia e Innovacion Productiva, Argentina, Fund for<br />
Ophthalmic Knowledge, NYC, USA and Fundacion Natali Dafne Flexer, Buenos Aires, Argentina<br />
1824 RES 23<br />
SUPER-SELECTIVE INTRA-OPHTHALMIC ARTERY CHE-<br />
MOTHERAPY: RETINAL ENDOTHELIAL TOXICITY IN<br />
PRE-CLINICAL MODELS<br />
Matthew W. Wilson, MD, FACS1,2,3, J. Scott Williams, MD, PhD4, John S.<br />
Jackson, DVM5, Fan Wang, PhD6, Clinton F. Stewart, PharmD6, Timothy<br />
D. Mandrell, DVM4, Barrett G. Haik, MD, FACS1,2, Jena J. Steinle, PhD1<br />
(mwilson5@uthsc.edu)<br />
University of Tennessee Health Science Center, 1. Hamilton Eye Institute,<br />
Department of Ophthalmology; 4. Department of Radiology and 5.<br />
Department of Comparative Medicine, Memphis, Tennessee, USA<br />
St Jude Children’s Research Hospital, 2. Department of Surgery, Division<br />
of Ophthalmology; 3. Department of Pathology; 6. Department of<br />
Pharmaceutical Sciences, Memphis, Tennessee, USA<br />
Purpose. To report in vitro and in vivo pre-clinical modeling of superselective<br />
intra-ophthalmic artery chemotherapy (SSIOAC).<br />
Methods. Cultured human retinal endothelial cells were exposed to<br />
increasing concentration of melphalan and carboplatin. Post-exposure<br />
cell death, proliferation and migration were measured. Surviving<br />
cells were studied using microarray and ELISA. Six adult male Rhesus<br />
macaques were randomly assigned to treatment with either 5 mg/30 mL<br />
melphalan or 30 mg/30 mL carboplatin. Each animal underwent three<br />
separate SSIOAC procedures at three-week intervals. Digital retinal<br />
images were obtained during each infusion. Intravenous fluorescein<br />
angiography was performed immediately after each procedure.<br />
Results. Highest concentration of melphalan (4mg/ml) and carboplatin<br />
(1mM) caused a 5 fold increase in cell death at 24 hours (p
artery precipitates were seen in 10 (of 18, 56%). Fluorescein angiogram<br />
showed choroidal hypoperfusion (18 of 18, 100%). Histopathology<br />
and electron microscopy showed retinal endothelial sloughing with<br />
leukostasis, birefringent particles and vascular occlusion.<br />
Conclusions. Both in vitro and in vivo models of SSIOAC showed marked<br />
retinal endothelial cell toxicity with resultant vascular occlusion. Our<br />
findings may explain the reported vascular toxicities following SSIOAC<br />
in children.<br />
Financial disclosure. None<br />
2107 RES 24<br />
EMBRYONIC RETINAL TUMORS IN TRANSGENIC MICE<br />
CONTAIN CD133+ TUMOR-INITIATING CELLS<br />
Richard L. Hurwitz1ABC,3 Lalita Wadhwa1,A, Wesley Bond1B, Laszlo<br />
Perlaky1A, Paul Overbeek1, Mary Y. Hurwitz1AC, Patricia Chévez-<br />
Barrios2,3 (rlhurwit@txch.org)<br />
A Texas Children’s Cancer Center<br />
B Translational Biology & Molecular Medicine<br />
C Center for Cell & Gene Therapy<br />
1 Baylor College of Medicine, Houston, TX<br />
2 The Methodist Hospital, Houston, TX<br />
3 Retinoblastoma Center of Houston, Houston, TX<br />
Purpose. Human retinoblastomas caused by Rb1 mutations that result<br />
in functionally defective or absent Rb1 protein originate during the<br />
proliferative phase of retinal development. Similar retinal tumors occur<br />
in mice only when multiple Rb family members are absent. Whether<br />
the tumors originate from proliferating undifferentiated retinal cells or<br />
from terminally differentiated retinal cells remains to be determined.<br />
We tested the hypothesis that a tumor-initiating cell can be isolated from<br />
tumors formed in developing, undifferentiated retinas of transgenic mice.<br />
Methods. A transgenic mouse model of retinoblastoma was developed<br />
by expressing SV40 T-antigen using the early eye development promoter<br />
Pax6. T-antigen, which sequesters all Rb family members and p53, is<br />
expressed in the retina and lens on E10 and tumors are observed by<br />
E12.5, prior to retinal differentiation.<br />
Results. A primary cell line developed from P7 murine tumors expresses<br />
T-antigen, adheres in serum-containing media and forms neurosperes<br />
in supplemented serum-free media. 1.5% of attached cells transferred<br />
to serum-free medium form neurospheres. 0.5% of adherent cells are<br />
CD133+. FACS sorted cells cultured in serum-free medium form 3-fold<br />
more neurospheres in the CD133+ cultures than in the CD133- cultures<br />
(p < 0.001). In vivo, 6/7 mice injected with CD133+ cells and 1/7 mice<br />
injected with CD133- cells form tumors during the 6 month observation<br />
period (p=0.007). These secondary tumors are indistinguishable from<br />
the primary murine tumors.<br />
Conclusions. There exist CD133+ cells within the developing, proliferating<br />
murine retina that can initiate retinal tumors.<br />
Financial disclosure. None<br />
2333 RES 25<br />
TREATMENT OF LHBETATAG RETINOBLASTOMA TU-<br />
MORS WITH ANGIOGENIC AND GLYCOLYTIC INHIBI-<br />
TORS AVOIDS CHEMOTHERAPY<br />
Samuel K. Houston, Timothy G. Murray, Yolanda Pina, Christina Decatur<br />
(shouston@med.miami.edu)<br />
RESEARCH DAY<br />
Abstracts<br />
26<br />
Bascom Palmer Eye Institute, University of Miami Miller School of<br />
Medicine, Miami, Florida, USA<br />
Purpose. The purpose of this study was to evaluate the combination<br />
treatment of angiogenic and glycolytic inhibitors on tumor burden and<br />
hypoxia in advanced LHBETATAG retinoblastoma tumors.<br />
Methods. Thirty advanced LHBETATAG mice (16 weeks of age) were<br />
divided into 5 groups (n=6) and received injections of (a) saline, (b)<br />
anecortave acetate (AA), (c) 2-deoxy-glucose (2-DG), (d) 2-DG 1-day<br />
post-AA treatment), or (e) 2-DG 1-week post-AA treatment. Eyes were<br />
enucleated at 21 weeks and tumor sections were analyzed for tumor<br />
burden and hypoxia.<br />
Results. Combined treatment with 2-DG and AA (2-DG 1-day and 1-week<br />
post-AA) showed significant reduction in tumor burden compared to<br />
saline treated eyes (61% and 56%, respectively) (P < 0.001). There<br />
was not a significant effect of combination treatment when 2-DG was<br />
injected 1-week post-AA when compared to 2-DG alone (P = 0.21).<br />
However, eyes treated with 2-DG 1-day post-AA demonstrated a 23%<br />
reduction in tumor burden compared with 2-DG alone (P = 0.03). In<br />
addition, there was significant reduction in hypoxia with combined<br />
treatment compared to saline controls (P < 0.001), with only 0.24%<br />
and 0.3% hypoxia for 2-DG 1-day post-AA and 1-week post-AA,<br />
respectively.<br />
Conclusions. Combination therapy with angiogenic and glycolytic<br />
inhibitors significantly enhanced tumor control and reduced tumor<br />
hypoxia. There were synergistic effects of these two treatment<br />
modalities that were dependent on treatment timing. Combination<br />
treatment with angiogenic and glycolytic inhibitors avoided<br />
chemotherapy in the treatment of LHBETATAG retinoblastoma tumors<br />
and may potentially serve as adjuvant therapies in the treatment of<br />
children with retinoblastoma.<br />
Financial disclosure. None<br />
50 RES 26<br />
USING THE GLYCOLYTIC INHIBITOR 2-FLUORODEOXY-<br />
D-GLUCOSE, A NOVEL APPROACH TO TARGET THE<br />
CHEMORESISTANT CELL POPULATION IN LHBETATAG<br />
RETINAL TUMORS<br />
Yolanda Piña, Christina L. Decatur, Samuel Houston, Timothy G. Murray,<br />
Ludimila Cavalcante, and Theodore Lampidis. (yoly26@yahoo.com)<br />
Bascom Palmer Eye Institute, University of Miami Miller School of<br />
Medicine, Miami, Florida, USA<br />
Purpose. The aim of the current study is to assess the impact of<br />
2-fluorodeoxy-D-glucose on tumor burden and hypoxia in advanced<br />
LHBETATAG retinal tumors.<br />
Methods. The study protocol was approved by the University of Miami<br />
Institutional Animal Care. 17-week-old (n=54) LHBETATAG transgenic<br />
mice were treated with 2-fluorodeoxy-D-glucose or saline control.<br />
These animals received three different treatments. They were treated:<br />
(1) with one injection and sacrificed at one day post-treatment, (2) with<br />
one injection and sacrificed at one week post-treatment, or (3) twice a<br />
week for three weeks and sacrificed at one day post-last injection. At<br />
the time of enucleation, all eye samples were snap frozen and analyzed<br />
for tumor burden and hypoxia using immunohistochemical techniques.<br />
Average densities of the different groups were statistically analyzed<br />
using ANOVA. Results were considered significant if p≤ 0.05.<br />
Results. There was no apparent toxicity associated with 2-fluorodeoxy-<br />
D-glucose treatment. There was a significant reduction in tumor burden
following treatment with 2-fluorodeoxy-D-glucose at 1 day (86%)<br />
and 3 weeks (63%) post-treatment (p≤0.05). There was no reduction<br />
of tumor burden observed when mice were treated with 1 injection<br />
and eyes harvested at 1 week post-treament (2%, p=0.0640). There<br />
was a significant reduction of hypoxia areas following treatment with<br />
2-fluorodeoxy-D-glucose at 1 day (100%) and 3 weeks (75%) posttreatment<br />
(p≤0.05). There was an increase in hypoxia of 12% following<br />
treatment at 1 week post-injection, but this increase was not statistically<br />
significant.<br />
Conclusions. 2-FDG significantly reduces tumor burden and tumor<br />
hypoxia following a single injection, with continued efficacy following<br />
repeated injections for 3 weeks. 2-FDG treatment is efficacious in<br />
murine retinoblastoma tumors and may enhance tumor control when<br />
combined with other therapies. 2-FDG appears to target hypoxic cells,<br />
a population that has been resistant to chemotherapy and radiation.<br />
Additionally, 2-FDG is commonly used in medical imaging and does not<br />
pose significant toxicities.<br />
Financial disclosure<br />
This work was supported by the American Cancer Society and the<br />
University of Miami Sylvester Comprehensive Cancer Center. NIH center<br />
grant P30EY014801 and by an unrestricted grant to the University of<br />
Miami from Research to Prevent Blindness.<br />
2140 Res 27<br />
MTOR TARGETING IN COMBINATION WITH CHEMO-<br />
THERAPY: UPSTREAM REGULATION OF ANAEROBIC<br />
GLYCOLYSIS TO TARGET THE CHEMORESISTANT CELL<br />
POPULATION IN RB<br />
Timothy G. Murray, Yolanda Piña, Christina L. Decatur, Samuel Houston,<br />
Ludimila Cavalcante, and Theodore Lampidis (tmurray@med.miami.edu)<br />
Bascom Palmer Eye Institute, University of Miami Miller School of<br />
Medicine, Miami, Florida, USA.<br />
Purpose. To assess the efficacy of the combination therapy utilizing<br />
carboplatin chemotherapy and rapamycin mammalian target of<br />
RESEARCH DAY<br />
Abstracts<br />
27<br />
rapamycin (mTOR) inhibitor on tumor burden, hypoxia, and blood<br />
vessels in the LHBETATAG transgenic mouse model of retinoblastoma.<br />
Methods. The study protocol was approved by the University of<br />
Miami Institutional Animal Care and Use Review Board Committee. 12week-old<br />
(n=62) LHBETATAG transgenic mice were treated with the<br />
chemotherapeutic agent carboplatin, the mTOR inhibitor rapamycin, or<br />
both. Animals were treated with subconjunctival injections twice a week<br />
and received treatment for either 1 week or 3 weeks. All animals were<br />
sacrificed at 1 day post-last injection and eyes were enucleated. At the<br />
time of enucleation, all eye samples were snap frozen and analyzed for<br />
tumor burden, hypoxia, new blood vessels, and mature blood vessels<br />
using histopathology and immunohistochemistry. Data were statistically<br />
analyzed using ANOVA.<br />
Results. Mice that received treatment for 1 week had a tumor reduction<br />
of 23.8%, 49.3%, and 60.6% when treated with carboplatin, rapamycin,<br />
and carboplatin + rapamycin, respectively (p
Morning<br />
8.30-9.20 Poster presentations Rbp100-120<br />
(moderators C. Shields, P. Chevez-Barrios)<br />
9.20-10.25 Papers<br />
(moderators A.C. Moll, M.W. Wilson)<br />
152 RB1<br />
GUIDELINES FOR IMAGING OF RETINOBLASTOMA:<br />
DIAGNOSTIC IMAGING STRATEGY AND STANDARD-<br />
IZED MR IMAGING PROTOCOL<br />
P. de Graaf, S. Göricke , F.Rodjan , P. Galluzzi, P. Maeder, J.A. Castelijns,<br />
H.J. Brisse on behalf of the European Retinoblastoma Imaging<br />
Collaboration (ERIC)<br />
1831 RB2<br />
CHEMOTHERAPY FOCAL THERAPY AND BEYOND:<br />
THE IMPORTANCE OF CLINICAL TRIALS & THE ROLE OF<br />
A RETINOBLASTOMA CLINICAL STUDIES CONGLOMER-<br />
ATE.<br />
Helen Dimaras, Ashwin C. Mallipatna, Brenda L. Gallie, Helen S.L. Chan.<br />
1846 RB3<br />
RETINOBLASTOMA: ANALYSIS OF MORTALITY IN UZ-<br />
BEKISTAN<br />
Z. Islamov, F. Islom<br />
1201 RB4<br />
INCIDENCE OF RETINOBLASTOMA IN THE NETHER-<br />
LANDS 1950 - 2010: A SHIFT IN THE PROPORTION OF<br />
HEREDITARY RETINOBLASTOMA.<br />
M.I. Bosscha, L. Razzaq, C.J. Dommering, F.E. van Leeuwen, A.C. Moll<br />
1844 RB5<br />
EARLY DELIVERY OF INFANTS FOR TREATMENT OF<br />
RETINOBLASTOMA DIAGNOSED BY PRENATAL RB1<br />
MUTATION IDENTIFICATION<br />
Brenda L. Gallie, Helen Dimaras, Elise Héon, Joanne Sutherland, Megan<br />
Day, Vikas Khetan, Gardiner Jane, Helen Chan<br />
43 RB6<br />
CLINICAL AND GENETIC FEATURES OF REGRESSED<br />
RETINOBLASTOMA<br />
Manoj Parulekar, Archana Kulkarni, Trevor Cole, Bruce Morland, Helen<br />
Jenkinson, Sarah Turner, John Ainsworth<br />
47 RB7<br />
RETINOBLASTOMA PATIENTS WITH CHROMOSOME<br />
13Q DELETIONS HAVE INCREASED CHEMOTHERAPY-<br />
RELATED TOXICITIES<br />
R.C. Brennan, I. Qaddoumi, C. Billups, C. Odom, T. Douglas, W. Furman, M.W. Wilson<br />
Tuesday November 15, 2011<br />
RETINOBLASTOMA<br />
<strong>Program</strong><br />
29<br />
10.20-10.50 BREAK<br />
10.50-12.25 Papers<br />
(moderators L. Desjardins, L. Teixeira)<br />
358 RB8<br />
TOPOTECAN IS EFFECTIVE IN ADVANCED INTRAOCU-<br />
LAR RETINOBLASTOMA WITH MANAGEABLE TOXIC-<br />
ITY<br />
Ibrahim Qaddoumi, Catherine Billups, Clinton F. Stewart, Jianrong Wu,<br />
Katherine Helton, Mary McCarville, Thomas E. Merchant, Rachel Brennan,<br />
Barrett G. Haik, Carlos Rodriguez-Galindo, Matthew W. Wilson<br />
619 RB9<br />
LACK OF ACUTE TOXICITY FOLLOWING STANDARD<br />
DOSE CARBOPLATIN, ETOPOSIDE AND VINCRISTINE:<br />
RESULTS FROM CHILDREN’S ONCOLOGY GROUP<br />
STUDY ARET-0332<br />
A. Leahey, P. Chevez-Barrios, B. Langholz, A. Javed, V. Khetan, S. Honavar,<br />
R. Eagle, D. Albert J. O’Brien, K. Matthay, A. Meadows, M. Chintagumpala<br />
1615 RB10<br />
CONSERVATIVE TREATMENT OF INTRAOCULAR RETIN-<br />
OBLASTOMA: A PROSPECTIVE PHASE II RANDOMIZED<br />
TRIAL OF NEOADJUVANT CHEMOTHERAPY FOLLOWED<br />
BY LOCAL TREATMENT<br />
Livia Lumbroso-Le Rouic, Isabelle Aerts, David Hajaje, Christine Lévy-<br />
Gabriel, Alexia Savignoni, Nathalie Algret, François Doz, Laurence<br />
Desjardins<br />
24 RB11<br />
OUTCOMES OF 105 EYES WITH INTRAOCULAR RETIN-<br />
OBLASTOMA TREATED WITH SYSTEMIC CHEMOTHER-<br />
APY AND/OR LOCAL THERAPY AS FIRST TREATMENT<br />
Luiz F. Teixeira, Carla R. Donato Macedo, Virginia L. Torres, Camila H.<br />
Hashimoto, Juliana dos Santos Soares, Clelia M. Erwenne<br />
1546 RB12<br />
BRACHYTHERAPY IN THE TREATMENT OF RETINO-<br />
BLASTOMA. EXPERIENCE IN A SPANISH POPULATION<br />
Mónica Asencio-Duran, José Abelairas, José-María Peralta, José-Maria<br />
Fernández-Guardiola, Ernesto Sánchez-jacob,<br />
2130 RB13<br />
RADIOTHERAPY IN COMPLEX TREATMENT OF AD-<br />
VANCED RETINOBLASTOMA IN CHILDREN<br />
Tatiana Ushakova, Igor Glekov, Olga Gopovtzova, Igor Dolgopolov,<br />
Alentina Pavlovskaya, Irina Matveeva, Vladimir Polyakov, Geordge<br />
Mentkevich
1909 Rb14<br />
RESULTS OF PATIENTS WITH UNILATERAL RETINO-<br />
BLASTOMA TREATED WITH INITIAL ENUCLEATION: A<br />
SINGLE INSTITUTION IN BRAZIL<br />
Carla R. Donato Macedo, Luiz F. Teixeira, Camila H Hashimoro, Virginia L.<br />
L Torres, Juliana dos Santos Soares, , Maria T. Seixas, Maria C. Martins,<br />
Clelia M. Erwenne<br />
1940 RB15<br />
PROTON THERAPY FOR RECURRENT LOCALLY AD-<br />
VANCED RETINOBLASTOMA: COMBINED RESULTS<br />
FROM THE RETINOBLASTOMA CENTER OF HOUSTON<br />
& INDIANA UNIVERSITY<br />
D.S. Gombos, A.L. Chang, D.L. Andolino, H.P. Fontanilla, C. Herzog, M.<br />
Chintagumpala, P. Zage, R. Hurwitz, P. Chevez-Barrios, A. Mahajan<br />
1828 RB16<br />
COMPARISON OF HIGH-RISK HISTOPATHOLOGY<br />
BETWEEN UNTREATED AND TREATED EYES OF<br />
PATIENTS WITH RETINOBLASTOMA<br />
M.W. Wilson, R. Brennan, C. Rodriguez-Galindo, C. Billups, B.G. Haik, I.<br />
Qaddoumi<br />
2 Rb17<br />
PATHOLOGY ASSESSMENT IN UNILATERAL RETINO-<br />
BLASTOMA WITH & WITHOUT HISTOPATHOLOGIC<br />
HIGH-RISK FEATURES & THE ROLE OF ADJUVANT<br />
CHEMOTHERAPY: A COG STUDY<br />
P. Chévez-Barrios, R. Eagle, D. Albert, G. Vemuganti, S. Krishnakumar,<br />
B. Langholz, S. Honavar, J. O’Brien, A. Leahey, K. Mattha , A. Meadows,<br />
M. Chintagumpala<br />
12.25-12.50<br />
Keynote Lecture: Dr. Francis L. Munier<br />
CURRENT APPROACHES IN TREATING RETINOBLAS-<br />
TOMA<br />
12.50-14.10 LUNCH<br />
14.10-14.50 Posters presentations Rbp121-138<br />
(Moderators D.H. Abramson, M.A. Reddy)<br />
14.50-16.10 Papers<br />
(moderators J. Hungerford, A. Fandiño)<br />
RETINOBLASTOMA<br />
<strong>Program</strong><br />
30<br />
2123 RB18<br />
LESSONS LEARNED AFTER 5 YEARS (AND 500<br />
INFUSIONS) OF CHEMOSURGERY: PREDICTORS OF<br />
SUCCESS AND FAILURE<br />
David H. Abramson, Brian P. Marr, Scott E. Brodie, Ira J. Dunkel, Y. Sotiria<br />
Palioura, Pierre Gobin<br />
147 RB19<br />
SUPER SELECTIVE OPHTHALMIC ARTERY INFUSION<br />
OF CHEMOTHERAPYFOR INTRAOCULAR RETINO-<br />
BLASTOMA TREATMENT: INITIAL EXPERIENCE IN AR-<br />
GENTINA<br />
Adriana C. Fandiño, Alejandro Ceciliano, Guillermo L. Chantada,<br />
Francisco Villasante, Eduardo Lagomarsino, Julieta Lia Domínguez,<br />
Claudia Sampor, Paula Schaiquevich, José Lipsich, Julio E. Manzitti<br />
2348 RB20<br />
INTRA-ARTERIAL CHEMOTHERAPY FOR RETINOBLAS-<br />
TOMA: EXPOSURES, TUMOR CONTROL, COMPLICA-<br />
TIONS - NEW OBSERVATIONS.<br />
Carol L. Shields., Swathi Kaliki, Sanket U. Shah, Carlos G. Bianciotto,<br />
Jerry A. Shields.<br />
1527 RB21<br />
COMPARATIVE PHARMACOKINETICS OF TOPOTECAN<br />
AND MELPHALAN AFTER INTRA-ARTERIAL ADMINIS-<br />
TRATIONS IN THE SWINE MODEL<br />
Paula Schaiquevich, Emiliano Buitrago, Ana Torbidoni, Alejandro<br />
Ceciliano, Adriana Fandino, Javier Opezzo, Marcelo Asprea, Sergio<br />
Sierre, Flavio Requejo, David H. Abramson, Guillermo F. Bramuglia,<br />
Guillermo L. Chantada.<br />
539 RB22<br />
RELAPSES FOLLOWING INTRA-ARTERIAL CHEMO-<br />
THERAPY WITH MELPHALAN<br />
T. Hadjistilianou, S. De Francesco, S. Bracco, P. Galluzzi, P. Toti, P.<br />
Gennari, A. D’Ambrosio, M. Caini, D. Galimberti, A. Cerase, C. Venturi<br />
2257 RB23<br />
FACTORS INFLUENCING RESPONSE RATE FOLLOWING<br />
INTRA-OPHTHALMIC ARTERY MELPHALAN SALVAGE<br />
THERAPY FOR RELAPSE AFTER PRIMARY TREATMENT<br />
OF RETINOBLASTOMA<br />
John Hungerford, Judith Kingston, Stefan Brew, Ashwin Reddy, Mandeep<br />
Sagoo, Fergus Robertson, Jane Herod<br />
60 RB24<br />
INTRAVITREAL CHEMOTHERAPY WITH MELPHALAN FOR<br />
VITREOUS DISEASE IN ADVANCED RETINOBLASTOMA:<br />
EVIDENCE FOR SAFETY AND EFFICACY<br />
Francis L. Munier, Marie-Claire Gaillard, Aubin Balmer, Susan Houghton,<br />
Maja Beck-Popovic
7 RB25<br />
SELECTIVE INTRA-ARTERIAL CHEMOTHERAPY AS A<br />
TREATMENT FOR INTRAOCULAR RETINOBLASTOMA:<br />
ALTERNATIVES TO DIRECT OPHTHALMIC ARTERY<br />
CANNULATION<br />
Michael A. Klufas, Y. Pierre Gobin, Brian Marr, Scott E. Brodie, Ira J.<br />
Dunkel, David H. Abramson<br />
1448 RB26<br />
INTRA-ARTERIAL CHEMOTHERAPY USING SIMUL-<br />
TANEOUS MULTI AGENT CHEMOTHERAPY, THREE<br />
DRUGS, FOR RESCUE OF EYES WITH INTRAOCULAR<br />
RETINOBLASTOMA.<br />
Brian P. Marr, Y. Pierre Gobin, Scott E. Brodie, Ira J. Dunkel, David H.<br />
Abramson<br />
1550 RB27<br />
OCULAR COMPLICATIONS OF DIRECT INTRA-OPH-<br />
THALMIC ARTERY MELPHALAN TREATMENT FOR RE-<br />
FRACTORY RETINOBLASTOMA<br />
M Ashwin Reddy, Wisam J. Muen, Judith Kingston, John Hungerford,<br />
Fergus Robertson, Stefan Brew, Mandeep Sagoo, Dorothy Thompson<br />
16.00-16.20 BREAK<br />
16.20-17.20 Papers<br />
(moderators T. Murray, T. Hadjistilianou)<br />
438 RB28<br />
LIMITATIONS OF THE INTERNATIONAL CLASSIFICA-<br />
TION IN PREDICTING SUCCESS OF INTRA-ARTERIAL<br />
CHEMOTHERAPY FOR GROUP D/E INTRAOCULAR<br />
RETINOBLASTOMA<br />
Sotiria Palioura, Y. Pierre Gobin, Scott E. Brodie, Brian P. Marr, Ira J.<br />
Dunkel, and David H. Abramson<br />
2330 RB29<br />
INTRA-ARTERIAL MELPHALAN DOSING REGIMENS<br />
FOR THE TREATMENT OF RETINOBLASTOMA<br />
Timothy G. Murray, Samuel K. Houston, Mohammad A. Aziz-Sultan,<br />
Christina E. Fernandes, Christina Decataur, Yolanda Pina<br />
15 RB30<br />
THE GENERAL HEALTH AND PSYCHOSOCIAL FUNCTIONING<br />
OF ADULT SURVIVORS OF RETINOBLASTOMA:PRELIMINARY<br />
RESULTS OF THE RETINOBLASTOMA SURVIVOR STUDY<br />
Ira J. Dunkel, Jennifer S. Ford, Charles A. Sklar, Kevin C. Oeffinger, Joanne F.<br />
Chou, Yuelin Li, Danielle Novetsky Friedman, Mary McCabe, Nancy Kline,<br />
Leslie L. Robison, Ruth A. Kleinerman , Brian P. Marr, David H. Abramson<br />
RETINOBLASTOMA<br />
<strong>Program</strong><br />
31<br />
2323 RB31<br />
LATE MEDICAL OUTCOMES IN SURVIVORS OF EXTRA-<br />
OCULAR RETINOBLASTOMA: THE MEMORIAL SLOAN-<br />
KETTERING CANCER CENTER (MSKCC) EXPERIENCE<br />
D. Novetsky-Friedman, C.A. Sklar, K.C. Oeffinger, N.A. Kernan Y. Khakoo,<br />
B.P. Marr, S.L. Wolden, D.H. Abramson, I.J. Dunkel<br />
1755 RB32<br />
VARIATION OF SECOND CANCER RISK BY FAMILY<br />
HISTORY OF RETINOBLASTOMA AMONG LONG-TERM<br />
SURVIVORS<br />
Ruth A. Kleinerman, Chu-ling Yu, Mark P. Little, Yi Li , David H. Abramson,<br />
Johanna H. Seddon, and Margaret A. Tucker<br />
2039 RB33<br />
A NOVEL, ORAL, NON-INVASIVE METHOD OF DELIV-<br />
ERY FOR THE GLYCOLYTIC INHIBITOR 2-DEOXY-D-<br />
GLUCOSE IN THE TREATMENT OF RETINOBLASTO-<br />
MA.<br />
Christina L. Decatur, Yolanda Piña, Samuel Houston, Ludimila Cavalcante,<br />
Theodore Lampidis, Timothy G. Murray<br />
1352 RB34<br />
VITREOUS INJECTION THERAPY OF MELPHALAN FOR<br />
RETINOBLASTOMA<br />
Shigenobu Suzuki, Akihiro Kaneko<br />
58 RB35<br />
A STUDY OF UNILATERAL RETINOBLASTOMA WITH<br />
AND WITHOUT HISTOPATHOLOGIC HIGH-RISK FEA-<br />
TURES AND THE ROLE OF ADJUVANT CHEMOTHERA-<br />
PY: A CHILDREN’S ONCOLOGY STUDY<br />
M. Chintagumpala, R. Eagle, D. Albert, B. Langholz, V.A. Reddy, V.<br />
Khetan, S. Honavar S, J. O’Brien, A. Leahey, K. Matthay, A. Meadows, P.<br />
Chevez-Barrios<br />
17.20-18.20 ISOO Business meeting
Posters Retinoblastoma<br />
2006 RBp100<br />
RETINOBLASTOMA ASSESSMENT BY DOPPLER SONOG-<br />
RAPHY - A FOLLOW-UP STUDY<br />
Maria Teresa B.C. Bonanomi, Osmar C. Saito, Tatiana Tanaka<br />
354 RBp101<br />
PATIENTS WITH UNILATERAL RETINOBLASTOMA AND<br />
HIGH-RISK PATHOLOGIC FEATURES DO NOT REQUIRE<br />
INTENSIVE METASTATIC WORK-UP OR AGGRESSIVE<br />
CHEMOTHERAPY<br />
Ibrahim Qaddoumi, Matthew W. Wilson, Catherine Billups, Jianrong<br />
Wu, Thomas Merchant, Barry Shulkin, Rachel Brennan, Barrett G. Haik,<br />
Carlos Rodriguez-Galindo, Erin Sullivan.<br />
1916 RBp103<br />
TEN YEARS OF EXPERIENCE IN THE TREATMENT OF<br />
INTRA-OCULAR RETINOBLASTOMA IN A SINGLE IN-<br />
STITUTION IN BRAZIL<br />
Carla R.D. Macedo, Luiz F. Teixeira, Camila H. Hashimoto, Virginia L.<br />
Torres, Juliana dos Santos Soares, Maria T. Seixas, Maria C. Martins,<br />
Clelia M. Erwenne<br />
60 RBp104<br />
DIFFERENT CHARACTERISTICS OF GERMLINE AND<br />
NON-GERMLINE RETINOBLASTOMA<br />
Fariba Ghassemi, Hormoz Chams, Siamak Sabour, Reza Karkhaneh,<br />
Farzad Farzbod, Mehdi Khodaparast, Parvaneh Vosough<br />
1833 RBp105<br />
RETINOBLASTOMA IN CHILDREN: ANALYSIS OF 518 CASES<br />
Z. Islamov, F. Islom<br />
102 RBp106<br />
MULTIDISCIPLINARY COORDINATED SERVICES:<br />
WHAT WE NEED TO IMPROVE IN THE MANAGEMENT<br />
OF RB<br />
M Naseripour, H Nazari, KH Ghasemi Falavarjani, R Soudi, A Maleki, S<br />
Ansari,<br />
40 RBp107<br />
EXPERIENCE IN TREATMENT OF METASTATIC & NON-<br />
METASTATIC ORBITAL RETINOBLASTOMA IN A SIN-<br />
GLE INSTITUTION<br />
Carlos A. Leal, Julieta Robles-Castro, Gabriela Isaac, Vanessa Bosch<br />
836 RBp108<br />
ERG MONITORING OF RETINAL FUNCTION DURING<br />
SYSTEMIC CHEMOTHERAPY FOR RETINOBLASTOMA.<br />
Scott E. Brodie, Yannis M. Paulus, Mrinali Patel, Y. Pierre Gobin, Ira J.<br />
Dunkel, Brian Marr, David H. Abramson<br />
RETINOBLASTOMA<br />
Posters<br />
32<br />
2117 RBp109<br />
UTERINE LEIOMYOSARCOMA IN RETINOBLASTOMA:<br />
HOW SHOULD WE COUNSEL OUR PATIENTS?<br />
Jasmine H. Francis, Ruth A. Kleinerman, David H. Abramson<br />
1700 RBp110<br />
MONITORING AND DISCUSSING QUALITY OF LIFE IN<br />
RETINOBLASTOMA ROUTINE PRACTICE<br />
A.C. Moll, M.I. Bosscha, G. LaRiviere, W.A. Kors, I. Verdonck-de Leeuw,<br />
J. van Dijk, J. Huisman<br />
242 RBp111<br />
DOES PARENTAL SOCIOECONOMIC AND EDUCA-<br />
TIONAL STATUS INFLUENCE RETINOBLASTOMA INI-<br />
TIAL PRESENTATION AND ITS SUBSEQUENT MOR-<br />
BIDITIES?<br />
Daniel Colicchio, Carla D. Macedo, Juliana dos Santos Soares, Luiz F.<br />
Teixeira<br />
1534 RBp112<br />
ARE SOCIOECONOMIC STATUS AND ETHNICITY RISK<br />
FACTORS FOR THE PRESENTATION OF ADVANCED RB<br />
IN THE UK?<br />
M. Ashwin Reddy, Rabia Bourkiza, Archana Kulkarni, Manoj Parulekar,<br />
Phillippa Cumberland, Mandeep Sagoo, John Hungerford, Jugnoo Rahi<br />
352 RBp113<br />
NEUROPSYCHOMOTOR DEVELOPMENT OF EYE<br />
ENUCLEATED CHILDREN WITH RETINOBLASTOMA<br />
Marcela Bagnatori Braga, Juliana dos Santos Soares, Carla R.D. Macedo,<br />
Walquyria de Almeida Santos<br />
345 RBp114<br />
NURSING GUIDELINES FOR SELF-CARE OF PATIENTS<br />
WITH PROSTHETIC RETINOBLASTOMA: AN EXPERI-<br />
ENCE REPORT<br />
Juliana dos Santos Soares, Carla R.D. Macedo, Adriana M. Duarte<br />
33 RBp115<br />
EYE SALVAGE RATE IN 166 PATIENTS WITH<br />
INTRAOCULAR RETINOBLASTOMA<br />
Luiz F. Teixeira, Carla R.D. Macedo, Virginia L. Torres, Camila H.<br />
Hashimoto, Rubens Belfort Neto, Juliana dos Santos Soares, Clelia<br />
Maria Erwenne<br />
933 RBp116<br />
SYSTEMIC CHEMOTHERAPY IN THE MANAGEMENT<br />
OF RETINOBLASTOMA<br />
John D McKenzie, Nisha Sachdev, Sandra Staffieri, Kary Suen, James E<br />
Elder, John Heath, Peter Downie
2225 RBp117<br />
COMPARISON BETWEEN OPHTHALMIC ARTERIAL IN-<br />
JECTION THERAPY AND CHEMOREDUCTION AS PRIMA-<br />
RY THERAPY FOR INTRAOCULAR RETINOBLASTOMA<br />
Takashi Yamane, Nobuyuki Suzuki, Makoto Mohri<br />
942 RBp118<br />
INTRA-ARTERIAL CHEMOTHERAPY FOR RETINOBLAS-<br />
TOMA: FIRST AUSTRALIAN EXPERIENCE<br />
John D McKenzie, Nisha Sachdev, Sandra Staffieri, James E Elder, John<br />
Heath, Peter Downie, Peter J Mitchell<br />
817 RBp119<br />
OUTCOMES OF GROUP D RETINOBLASTOMA EYES<br />
J.L. Berry, H. Almarzouki, S.R. Bababeygy, T.H. Lee, R. Jubran, A.L. Murphree<br />
417 RBp120<br />
THE FIRST EXPERIENCE OF RETINOBLASTOMA<br />
TREATMENT WITH THE USE OF SUPERSELECTIVE<br />
INTRA-ARTERIAL CHEMOTHERAPY IN RUSSIA<br />
S.V. Saakyan, S.B. Yakovlev, G.L. Kobyakov, N.K. Serova, A. Jarwa<br />
2317 RBp121<br />
MISSING INTRAOCULAR BLUSH IN AN ANGIOGRAPHY<br />
OF AN ADVANCED INTRAOCULAR RETINOBLASTOMA<br />
M. Holdt, S. Göricke, E. Biewald, M. Schündeln, N. Bornfeld, M.<br />
Schlamann<br />
2004 RBp122<br />
CONSERVATIVE TREATMENT OF INTRAOCULAR<br />
RETINOBLASTOMA: A PROSPECTIVE PHASE II TRIAL<br />
FOR BILATERAL RETINOBLASTOMA WITH MACULAR<br />
OR PARAMACULAR INVOLVEMENT<br />
Christine Levy-Gabriel, Livia Lumbroso-Le Rouic, Isabelle Aerts, David<br />
Hajaje, Alexia Savignoni, Nathalie Algret, François Doz, Laurence Desjardins<br />
1857 RBp123<br />
EXTRACTION OF RADIATION-INDUCED CATARACT IN<br />
PATIENTS WITH RETINOBLASTOMA<br />
Z. Islamov, F. Islom<br />
1533 RBp124<br />
OUTCOME OF CHILDREN WITH RETINOBLASTOMA<br />
AND ISOLATED CHOROIDAL INVASION<br />
Andrea Bosaleh, Claudia Sampor, Verónica Solernou, Adriana Fandiño,<br />
Julieta Domínguez, María TG de Dávila, Guillermo Chantada<br />
2336 RBp125<br />
HIGH RISK HISTOPATHOLOGY FOLLOWING INTRA-<br />
ARTERIAL (IA) CHEMOTHERAPY FOR RETINOBLAS-<br />
TOMA<br />
D. Gombos, C. Shields, J. Shields, P. Chevez Barrios, R. Eagle, C. Herzog,<br />
M. Chintagumpala, R. Hurwitz, P. Zage, R. Spencer<br />
RETINOBLASTOMA<br />
<strong>Program</strong><br />
33<br />
1613 RBp126<br />
DIFFUSE INFILTRATING RETINOBLASTOMA AFTER<br />
CHEMOREDUCTION FAILURE<br />
Hans E. Grossniklaus, Christopher K. Hwang, Thomas M. Aaberg,<br />
Jr., Patricia Chevez-Barrios, Dan Gombos, Evelyn Paysse, Murali<br />
Chintagumpala, Elizabeth Verner-Cole<br />
30 RBp127<br />
TREATMENT MODULATION IN RETINOBLASTOMA TU-<br />
MORIGENESIS AND ITS IMPACT ON TUMOR BURDEN<br />
Timothy G. Murray, Samuel Houston, Christina L. Decatur, Nikesh Shah,<br />
Ludimila Cavalcante, and Yolanda Piña<br />
1603 RBp128<br />
REPORT OF NINE NOVEL RB1 MUTATIONS IN<br />
PATIENTS WITH RETINOBLASTOMA REFERRED TO<br />
RASOUL-E-AKRAM UNIVERSITY HOSPITAL<br />
Babak Behnam, Ali Ahani, Masoud Naseripour<br />
1954 RBp129<br />
A NOVEL GERMLINE MUTATION OF THE RETINOBLAS-<br />
TOMA SUSCEPTIBILITY GENE IS ASSOCIATED WITH<br />
INCOMPLETE PENETRANCE<br />
Peter Hovland, Kami Schneider, Edythe Albano<br />
601 RBp130<br />
CNS ABNORMALITIES IN RTB PATIENTS<br />
T. Hadjistilianou, S. De Francesco, P. Galluzzi, A. Cerase, A. Renieri, F.<br />
Mari, L. Micheli, M. De Luca, G.Coriolani, C. Menicacci, M. Borri<br />
9 RBp131<br />
OPHTHALMOSCOPIC DIFFERENTIATION OF COATS’<br />
DISEASE FROM RETINOBLASTOMA<br />
Jerry A Shields, Carol L Shields<br />
2149 RBp132<br />
PROTON IRRADIATION FOR RETINOBLASTOMA<br />
W. Sauerwein, B. Timmerman, N. Bornfeld, J. Herault, J. Farr, B.<br />
Zimmermann, A. Wittig<br />
52 RBp133<br />
MULTIPLE PLAQUE TREATMENT IN RETINOBLASTO-<br />
MA<br />
Manoj Parulekar, Randhir Chavan, John Ainsworth, Helen Jenkinson, Dan<br />
Ford, David Spooner, Geoff Heyes<br />
2301 RBp134<br />
ASSESSMENT OF POST-OPERATIVE VOMITING IN<br />
RETINOBLASTOMA PATIENTS AND THEIR SIBLINGS<br />
UNDERGOING EYE EXAMS UNDER ANESTHESIA<br />
Pascal Owusu-Agyemang, Elizabeth Rebllo, Radha Arunkumar, Joseph<br />
Ruiz, Dan Gombos
120 RBp135<br />
MANAGEMENT OF AN ECTOPIC SELLAR TRILATERAL<br />
RETINOBLASTOMA<br />
Rana’a Al-Jamal, Sanna Seitsonen, Ulla Pihkala, Matti Tenhunen, Päivi<br />
Lindahl, Leena Koskinen, Tero Kivelä<br />
350 RBp136<br />
MOLECULAR PATHWAYS OF RETINOBLASTOMA RE-<br />
VEALED THROUGH GLOBAL PROTEOMICS ANALYSES<br />
OF Y79 AND CHLA215 CELL LINES: A DRUG RESIS-<br />
TANCE CASE STUDY<br />
Susan Lee, Robert Fanter, Narine Harutyunyan, Joanne Lee, A Linn<br />
Murphree<br />
1950 RBp137<br />
EVALUATING THE GLYCOLYTIC PATHWAY IN RETINO-<br />
BLASTOMA: A MECHANISTIC APPROACH USING THE<br />
GLYCOLYTIC INHIBITOR 2-DEOXY-D-GLUCOSE IN VIT-<br />
RO AND IN VIVO<br />
Christina L. Decatur, Yolanda Piña, Samuel Houston, Elizabeth Sullivan,<br />
RETINOBLASTOMA<br />
<strong>Program</strong><br />
34<br />
Huaping Liu, Theodore Lampidis, Timothy G. Murray<br />
101 RBp138<br />
REGIONAL AND TEMPORAL VARIATIONS IN GENE<br />
EXPRESSION AND VASCULATURE DURING RETINO-<br />
BLASTOMA TUMORIGENESIS AND ITS IMPACT ON<br />
OCULAR TREATMENT<br />
Yolanda Piña, Timothy G. Murray, Christina L. Decatur, Nikesh Shah,<br />
Ludimila Cavalcante, and Samuel Houston
152 RB1<br />
GUIDELINES FOR IMAGING OF RETINOBLASTOMA:<br />
DIAGNOSTIC IMAGING STRATEGY AND<br />
STANDARDIZED MR IMAGING PROTOCOL<br />
P. de Graaf1 , S. Göricke2 , F. Rodjan1, P. Galluzzi3, P. Maeder4 , J.A.<br />
Castelijns1, H.J. Brisse5 on behalf of the European Retinoblastoma<br />
Imaging Collaboration (ERIC) (p.degraaf@vumc.nl)<br />
1. Department of Radiology, VU University Medical Center, Amsterdam,<br />
The Netherlands<br />
2. Department of Diagnostic and Interventional Radiology and<br />
Neuroradiology, University Hospital, Essen, Germany<br />
3. Unit of Diagnostic and Therapeutic Neuroradiology, Azienda<br />
Ospedaliera e Universitaria Senese, Policlinico “Le Scotte”, Siena, Italy<br />
4. Service de Radiodiagnostic et Radiologie Interventionelle, CHUV,<br />
Lausanne, Switzerland<br />
5. Département d’Imagerie, Institut Curie, Paris, France<br />
Purpose. Diagnosis of retinoblastoma is usually established by<br />
the ophthalmologist on the basis of fundoscopy and ultrasound<br />
(US). Together with US, high-resolution MR imaging has emerged<br />
as an important imaging modality for the pretreatment assessment<br />
of retinoblastoma, i.e., for diagnostic confirmation, detection of<br />
local tumor extent and depiction of associated brain abnormalities<br />
(developmental malformation, or trilateral retinoblastoma, i.e.,<br />
intracranial primitive neuroectodermal tumor). MR imaging is<br />
currently performed in the work-up for retinoblastoma in many<br />
institutions around the world. However, diagnostic accuracy for<br />
detection of high-risk features, especially optic nerve infiltration, is<br />
highly dependend on technical quality of MR images. Thus, there is<br />
the need for a standardized protocol with minimal requirements for<br />
imaging retinoblastoma.<br />
Methods. In this imaging guideline, the minimum requirements for<br />
pretreatment diagnostic evaluation of retinoblastoma or mimicking<br />
lesions are presented, according to the consensus reached between<br />
members of the European Retinoblastoma Imaging Collaboration<br />
(ERIC).<br />
Results. The most appropriate techniques for state-of -the-art<br />
diagnostic imaging of a child with leukocoria are reviewed. CT is<br />
no longer recommended. A standardized MR imaging protocol was<br />
developed, including detailed technical requirements and specific<br />
imaging stategies for unilateral and bilateral disease.<br />
Conclusions. Implementation of a standardized MR imaging protocol<br />
for retinoblastoma in clinical practice will allow a state-of-the-art<br />
radiologic evaluation for the detection of tumor extent.<br />
Financial disclosure. None<br />
1831 RB2<br />
CHEMOTHERAPY FOCAL THERAPY AND BEYOND:<br />
THE IMPORTANCE OF CLINICAL TRIALS & THE<br />
ROLE OF A RETINOBLASTOMA CLINICAL STUDIES<br />
CONGLOMERATE<br />
Helen Dimaras1, Ashwin C. Mallipatna2, Brenda L. Gallie1, Helen S.L.<br />
Chan1.(helen.dimaras@utoronto.ca)<br />
1. The Hospital for Sick Children and The University of Toronto<br />
2. Narayana Nethralaya Hospital<br />
RETINOBLASTOMA<br />
Abstracts<br />
35<br />
Purpose<br />
The National Retinoblastoma Strategy Canadian Guidelines for Care<br />
point out the absence of Class A evidence (randomized clinical trials) to<br />
guide therapy. Consequently, consensus recommendations and current<br />
practice at Retinoblastoma Centres underpin the Guidelines. Because<br />
retinoblastoma is rare, few clinical trials have been completed.<br />
Methods. We undertook search of the NIH Clinical Trials Database<br />
using the search term ‘retinoblastoma’ (http://clinicaltrials.gov/<br />
ct2/results?term=retinoblastoma). The results of this search were<br />
categorized purpose, country, and number of centres involved, and<br />
publications that ensued. Results were used to inform suggested<br />
directives for retinoblastoma clinical research.<br />
Results. Our search yielded 54 hits, in which 19 trials studied the<br />
efficacy of a treatment specifically targeting retinoblastoma patients.<br />
Only 6 were multicentre trials, with most participating centres in highincome<br />
countries. There was little representation of middle-income<br />
countries (3/19 studies), and none of low-income countries (0/19<br />
studies), where most children with retinoblastoma reside. Most results<br />
were unpublished; those published were limited in scope and study<br />
numbers.<br />
Conclusions. Clinical trials are the gold standard for evidence-based<br />
care, as they ascertain utility, efficacy and safety of new methods.<br />
Despite this, the few retinoblastoma clinical trials target only a small<br />
proportion of affected children in rich countries, resulting in small<br />
and often homogenous study populations, with results that may<br />
not be applicable to children around the world. As shown in other<br />
pediatric cancers, conducting rigorous, significant, multicentre trials<br />
led by multidisciplinary teams will most effectively improve care for all<br />
retinoblastoma children. We propose a retinoblastoma clinical studies<br />
conglomerate to develop, conduct and evaluate novel clinical studies<br />
that contribute to evidence based care. Since only 9000 children<br />
each year are newly diagnosed, clinical trials could involve all eligible<br />
children.<br />
Financial disclosure. None<br />
1846 RB3<br />
RETINOBLASTOMA: ANALYSIS OF MORTALITY IN<br />
UZBEKISTAN<br />
Z. Islamov, F. Islom (dr_islamov@yahoo.com)<br />
National Center of Oncology, Uzbekistan<br />
Mercer University, United States<br />
Purpose. We sought to analyze mortality from retinoblastoma and<br />
identify factors that predispose to these deaths.<br />
Methods. From 2001 to 2010, 314 patients age
After treatment, 10 patients lived
egression. 2. Advanced tumours show acute ocular signs like resolved<br />
retinal detachment associated with spontaneous regression.<br />
The features that are useful in identifying regression become more<br />
subtle in younger children. Regression may be difficult to detect below<br />
14 months of age, as insufficient time has passed for clues to develop.<br />
As there is a risk of spontaneous reactivation in regressed tumours,<br />
careful monitoring is essential in all such cases.<br />
Financial disclosure. None<br />
47 RB7<br />
RETINOBLASTOMA PATIENTS WITH CHROMOSOME<br />
13Q DELETIONS HAVE INCREASED CHEMOTHERAPY-<br />
RELATED TOXICITIES<br />
R.C. Brennan1, 5, I. Qaddoumi1,5, C. Billups2, C. Odom1, T. Douglas3, W.<br />
Furman1,5 M.W. Wilson4,6 (rachel.brennan@stjude.org)<br />
Department of 1. Oncology, 2. Biostatistics, 3. Surgery and 4. Pathology,<br />
St. Jude Children’s Research Hospital, Memphis, TN, USA. Department<br />
of 5. Pediatrics and 6. Ophthalmology, University of Tennessee Health<br />
Science Center, College of Medicine, Memphis, TN, USA<br />
Purpose. Five-10% of retinoblastoma (RB) patients with RB1 germline mutations<br />
harbor various sized deletions of chromosome 13 (13q-). We reviewed our<br />
experience on a single protocol (RET5) to determine if the 13q- genotype<br />
influences toxicity for these patients during chemotherapy.<br />
Methods. From 2005-2010, 107 RB patients were treated on RET5: stratum<br />
A [low stage; Vincristine(V)/Caroboplatin(C)], stratum B [bilateral; subtenon<br />
C with either VC/Topotecan or VC/Etoposide(E)], and stratum C (unilateral/<br />
primary enucleation; high risk histology received V/Cyclophosphamide(Cy)/<br />
Doxorubicin(D) or VCyD/VCE) with focal therapy as needed. Twelve/107 patients<br />
had 13q- abnormalities (11%). One to two controls matched for age, stratum and<br />
treatment (n=16) were identified for each of 9/12 patients. Grade 3/4 hematologic<br />
(hemoglobin, platelets, and absolute neutrophil count [ANC]), infectious (febrile<br />
neutropenia, bacteremia), and gastrointestinal (GI) toxicities (anorexia/emesis)<br />
were reviewed.<br />
Results. In patients with 13q-, slow ANC recovery delayed chemotherapy (8/9)<br />
more often than in matched controls (9/16), leading to chemotherapy reductions<br />
in 4/9 patients compared with 1/16 controls. GI toxicity was more common<br />
(4/9 vs. 1/16), leading to cessation of chemotherapy in one 13q- patient. For<br />
13q- patients, those with microdeletions (n=5) had significantly more grade 3/4<br />
toxicities (mean 18.4 events) compared with patients who had macrodeletions<br />
(n=5, mean 9 events) (p=0.024). All patients are alive with no evidence of disease<br />
at last follow-up (range 4 to 70 months).<br />
Conclusions. Patients with retinoblastoma and 13q- abnormalities have<br />
more severe chemotherapy-induced toxicities compared to age and therapy<br />
matched controls. These patients may require more intensive supportive care<br />
during chemotherapy, prophylactic cytokine support and dose-reductions in<br />
chemotherapy.<br />
Financial disclosure. None<br />
358 RB8<br />
TOPOTECAN IS EFFECTIVE IN ADVANCED INTRAOCU-<br />
LAR RETINOBLASTOMA WITH MANAGEABLE TOXIC-<br />
ITY<br />
Ibrahim Qaddoumi 1,8, Catherine Billups 2, Clinton F. Stewart 3, Jianrong<br />
RETINOBLASTOMA<br />
Abstracts<br />
37<br />
Wu 2, Katherine Helton 4, Mary McCarville 4, Thomas E. Merchant 4,<br />
Rachel Brennan 1, Barrett G. Haik 5,7, Carlos Rodriguez-Galindo 1,8,<br />
Matthew W. Wilson 5,6,7. (ibrahim.qaddoumi@stjude.org)<br />
Departments of 1. Oncology; 2. Biostatistics; 3. Pharmaceutical Sciences;<br />
4. Radiological Sciences; 5. Surgery; 6. Pathology St. Jude Children’s<br />
Research Hospital, Memphis, TN<br />
Departments of 7. Ophthalmology (Hamilton Eye Institute) and 8.<br />
Pediatrics, University of Tennessee Health Sciences Center, Memphis,<br />
TN<br />
Dr. Rodriguez-Galindo is currently at Dana-Farber Cancer Institute,<br />
Boston, MA<br />
Purpose. To evaluate response rate of topotecan in intraocular<br />
retinoblastoma (RB).<br />
Methods. Patients with bilateral RB in whom at least one eye was<br />
Reese-Ellsworth IV or V were eligible to receive window therapy<br />
consisted that of 2 courses of vincristine and topotecan (VT with G-CSF<br />
support). Patients with ≥ partial response received 3 more courses of VT<br />
alternating with 6 courses of vincristine and carboplatin.<br />
The topotecan dose started at 3 mg/m2/day, and was adjusted to<br />
attain a target systemic exposure of 140 ± 20 ng/ml*hr. Carboplatin<br />
was administered to achieve an area under the curve of 6.5 mg/ml/min.<br />
The dose of vincristine dose was 0.05 mg/kg if age at diagnosis < 12<br />
months and 1.5mg/m2 if age at diagnosis > 12 months.<br />
Results. A total of 27 patients were enrolled with a median age of 8.1<br />
months (range, 0.7 to 22.1 months). Twenty-four of 27 patients responded<br />
(88.9%; 95% Blyth-Still-Casella CI, 71.3%-96.9%). Hematologic toxicity<br />
in the form of grade 4 neutropenia (n=27), grade 3 anemia (n=19)<br />
and grade 3-4 thrombocytopenia (n=16) were observed during the VT<br />
window. Thirteen patients developed grade 3 non-hematologic toxicity.<br />
G-CSF support was added after treating 10 patients. Patients treated with<br />
GCSF (n=17) had a significant shorter duration of grade 4 neutropenia<br />
(median, 7 days) compared to patients without G-CSF (n=10) (median,<br />
24 days) (Wilcoxon rank sum test p
Methods. Six cycles of carboplatin 560 mg/m2 on day 1, etoposide<br />
150 mg/m2 on days 1 and 2, and vincristine 1.5 mg/m2 on day 1 were<br />
prescribed. Patients less than 36 months of age were dosed on a per<br />
kilogram basis (conversion: 30 kg = 1 m2). Toxicity was graded according<br />
to the National Cancer Institute Common Toxicity and Adverse Event<br />
Criteria, Version 3.0.<br />
Results. Five hundred and twenty-one cycles were administered to 93<br />
patients. The median age was 28 months (range, 2-77). Three patients<br />
were under 6 months of age at initiation of chemotherapy. Grade 3-4<br />
myelosuppression (anemia or thrombocytopenia or neutropenia)<br />
was noted in 3% of cycles. Fever and neutropenia occurred in 2 % of<br />
cycles. All other Grade 3 and higher toxicities were seen in less than 1%<br />
of cycles administered. No patient had documented hearing loss and<br />
no patient developed a second malignancy. There were no treatment<br />
related deaths.<br />
Conclusions. Standard dose CEV is associated with a very low rate of<br />
toxicity. Pediatric ophthalmologists and oncologists should not hesitate<br />
to recommend this life preserving treatment.<br />
Financial disclosure. None<br />
1615 RB10<br />
CONSERVATIVE TREATMENT OF INTRAOCULAR<br />
RETINOBLASTOMA: A PROSPECTIVE PHASE II RAN-<br />
DOMIZED TRIAL OF NEOADJUVANT CHEMOTHERAPY<br />
FOLLOWED BY LOCAL TREATMENT<br />
Livia Lumbroso-Le Rouic1, Isabelle Aerts2, David Hajaje3, Christine Lévy-<br />
Gabriel1, Alexia Savignoni3, Nathalie Algret3, François Doz2, Laurence<br />
Desjardins1 (livia.lumbroso@curie.net)<br />
1. Department of ocular oncology, Institut Curie, Paris France<br />
2. Department of oncologic pediatry, Institut Curie, Paris France<br />
3. Department of Biostatistics, Institut Curie, Paris France<br />
Purpose. Intraocular retinoblastoma treatments often associate chemotherapy<br />
and focal treatments. The protocols vary and may combine two or three drugs,<br />
and different number of cycles associated to the local adjuvant treatments. A<br />
first prospective protocol of conservative treatments in our institution showed<br />
the efficacy of the use of two courses of chemoreduction with etoposide and<br />
carboplatin, followed by chemothermotherapy using carboplatin as a single<br />
agent. In order to decrease the possible long term toxicity of chemotherapy<br />
due to etoposide a prospective randomized chemoreduction protocol was<br />
conducted using vincristine and carboplatin vs. etoposide carboplatin<br />
Methods. The study was proposed when intial tumor characteristics<br />
did not allow front-line local treatments. The phase II randomized study<br />
of reduction chemotherapy used treatments vincristin carboplatin<br />
or etoposide carboplatin, and followed by local treatment including<br />
chemothermotherapy with carboplatin only. Primary endpoint was the<br />
need for secondary enucleation or EBRT not exceeding 40% at two years.<br />
Results. 55 children, 65 eyes were included in the study (May 2004- August 2009).<br />
32 eyes (27 children) were treated conservatively in the arm etoposidecarboplatin<br />
and 33 (28 children) eyes in the arm vincristin carboplatin.<br />
At two years after treatment 23/33 (69.7%) eyes were treated and salvaged<br />
without EBRT or enucleation in the arm vincristin-carboplatin and 26/32<br />
(81.2%) in the arm etoposide and carboplatin.<br />
Conclusions. Neoadjuvant chemotherapy by two cycles of vincristine and<br />
carboplatin followed by chemothermotherapy (laser diode hyperthermia<br />
combined to carboplatine as single drug) does not seem to offer an optimal<br />
local control.<br />
Financial disclosure. None<br />
RETINOBLASTOMA<br />
Abstracts<br />
38<br />
24 RB11<br />
OUTCOMES OF 105 EYES WITH INTRAOCULAR RETIN-<br />
OBLASTOMA TREATED WITH SYSTEMIC CHEMO-<br />
THERAPY AND/OR LOCAL THERAPY AS FIRST TREAT-<br />
MENT<br />
Luiz F. Teixeira1,2, Carla R. Donato Macedo2, Virginia L. L Torres1,2,<br />
Camila Hiromi Hashimoto2, Juliana dos Santos Soares2, Clelia M.<br />
Erwenne1,2 (luizfteixeira@hotmail.com)<br />
1. Department of ophthalmology/ Unifesp- Federal University of Sao<br />
Paulo<br />
2. Pediatric Oncology Institute/GRAACC/Unifesp<br />
Purpose. To evaluate the outcome of 105 eyes with intraocular<br />
retinoblastoma treated with conservative treatment.<br />
Methods. Retrospective review of 85 consecutive patients with<br />
intraocular retinoblastoma (34 unilateral cases and 51 bilateral cases).<br />
Results. A total of 105 eyes, 9 group A eyes (9%), 22 group B eyes (21%),<br />
17 group C eyes (16%), 43 group D eyes (41%) and 14 group E eyes (13%)<br />
were treated.<br />
Systemic chemotherapy associated with local therapy was performed<br />
as first treatment in 97 eyes (92%). Periocular carboplatin injection<br />
(20mg/2ml) was used in 13 group D eyes (30%) and in 7 group E eyes<br />
(50%) associated with systemic chemotherapy.<br />
Disease progression was observed in 57% (n=60 eyes) during the first<br />
treatment period (B-32%, C-35%, D-86% and E-86%). Enucleation was<br />
performed in 28 eyes (27%).<br />
Recurrence appeared in 18 eyes from 77 eyes initially saved, after<br />
a mean follow up of 7 months (range 4-12 months). Seven eyes were<br />
enucleated.<br />
Considering all forms of conservative treatments and excluding EBRT,<br />
the final eye salvage rate was respectively: 100%/100% for group A,<br />
95%/95% for group B, 88%/82% for group C, 49%/40% for group D,<br />
54%/54% for group D with periocular carboplatin and 28%/14% for<br />
group E.<br />
A total of 70 eyes (67%) were saved.<br />
Conclusions. Conservative treatment for intraocular retinoblastoma<br />
using systemic chemotherapy associated with local therapy is very<br />
efficient for initial disease. Most of the enucleations (80%) were<br />
indicated during the first treatment period. Recurrence appear most in<br />
the first year of follow up.<br />
Financial disclosure. None<br />
1546 RB12<br />
BRACHYTHERAPY IN THE TREATMENT OF RETINO-<br />
BLASTOMA. EXPERIENCE IN A SPANISH POPULA-<br />
TION<br />
Mónica Asencio-Duran, José Abelairas, José-María Peralta, José-Maria<br />
Fernández-Guardiola, Ernesto Sánchez-jacob (masedur@hotmail.com)<br />
Hopsital La Paz, Madrid, Spain<br />
Purpose. To study the efficacy of brachytherapy in retinoblastoma as a<br />
consolidation treatment in structural and functional terms.<br />
Methods. Descriptive, retrospective and longitudinal study in a series of<br />
86 treatments in 80 retinoblastomas belonging to 67 eyes in a Spanish<br />
reference Hospital.<br />
Results. There were 23 men/34 women, with a medium age at diagnosis
of 10.4 months. 53 % were unilateral, with involvement of the RE in 51<br />
%, and the most frequent symptom was leucocoria (49 %), followed by<br />
strabismus (35 %). The most frequent Reese-Ellsworth groups were Va<br />
(17 cases), IIa (15 cases) and IIb (12 cases). All patients were treated with<br />
VEC, with a 23 % reduction in tumour volume.<br />
76 % of the eyes received only 1 treatment, 21 % 2, and 1,5 % received<br />
3 and 4 treatments. 93 % were carried out once in a tumor, whereas in<br />
6 it was necessary to repeat the treatment. The most used plaque was<br />
Ruthenium in 95 %. The dose was 4000 cGy to the apex in all cases.<br />
With the combined regimen of QR and brachytherapy we have obtained<br />
a survival rate of 100 %, and a 0% rate of metastasis, trilateral<br />
retinoblastoma and second neoplasia with an average follow-up of 2.6 years.<br />
The conservation rate of the globe was high in the group treated with<br />
brachytherapy (66 % opposite to 34 % of non-treated). 95,5 % of the<br />
treated eyes had good tumour response, whereas only 3 were enucleated<br />
due to bad response to the brachytherapy (4,5 %).<br />
The complications associated were the appearance of retinopathy in 61<br />
%, optical neuropathy in 7,6 % and cataracts in 6 % of the cases.<br />
Conclusions. A consolidation treatment is necessary in spite of a good<br />
initial response to chemotherapy. Brachytherapy has demonstrated to<br />
be a “curative” treatment in a wide spectrum of disease due to the great<br />
availability of plaques and isotopes. In addition, the treatments are easy<br />
to realize, short and repeatable, being able to have a certain preventive<br />
effect of enucleation, since it supports more eyes and during more time<br />
than chemotherapy alone. Nevertheless, it is not capable of preventing<br />
the appearance of new tumors and massive seeding, main reasons for<br />
enucleation, and the complication rate is not negligible, being the main<br />
cause of vision loss.<br />
Financial disclosure. None<br />
2130 RB13<br />
THE RADIOTHERAPY IN COMPLEX TREATMENT OF<br />
ADVANCED RETINOBLASTOMA IN CHILDREN<br />
Tatiana Ushakova1, Igor Glekov2, Olga Gopovtzova3, Igor Dolgopolov4,<br />
Alentina Pavlovskaya5, Irina Matveeva6, Vladimir Polyakov3, Geordge<br />
Mentkevich2 (ushtat07@mail.ru)<br />
1. Institute of Pediatric Oncology and Haematology N.N. Blokhin Cancer<br />
Research Center Rams Moscow, Tumors Head and Neck; 2. Institute of<br />
Pediatric Oncology and Haematology, Radiology; 3. Institute of Pediatric<br />
Oncology and Haematology, Tumors Head and Neck; 4. Institute of<br />
Pediatric Oncology and Haematology, BMT; 5. N.N. Blokhin Cancer<br />
Research Center Rams, Pathology Anatomy; 6. N.N. Blokhin Cancer<br />
Research Center Rams, Cytology, Moscow, Russian federation<br />
Purpose. To determine the place of external beam radiotherapy (EBR) in<br />
treatment of children with advanced retinoblastoma (Rb).<br />
Methods. From 2001 to 2008, 65 of patients with Rb were treated in<br />
risk-adapted protocol at our institute. For group I there were 43 patients<br />
with unilateral Rb had undergone primary enucleation. 17 of 43 patients<br />
had insufficiency or minimum tumor invasion choroid and prelaminar<br />
invasion of the optic nerve (Ia – group). The adjuvant therapy was not<br />
administrated for patients of this group. 18 of 43 patients had invasion<br />
into the anterior chamber massive tumor invasion choroid, intra- and<br />
retrolaminar invasion of the optic nerve (Ib-group). The adjuvant CT<br />
included 4 courses of combination of CY, VP-16, Carbo. In addition to<br />
the above, only 4 from 11 patients who had retrolaminar invasion of the<br />
optic nerve received orbital EBR at a dose of 50 Grey. 8 of 43 had tumor<br />
invasion of optic nerve transection and extrascleral extention (Ic-group)<br />
and 7 of 8 received postenucleation EBR (50 Grey), 4 courses of the same<br />
RETINOBLASTOMA<br />
Abstracts<br />
39<br />
CT and high-dose CT included BU and MELPH followed by autologous<br />
peripheral blood stem cells transplantation (APBSCT). For group II there<br />
were 8 patients (unilateral Rb n=6) had initial extraocular disease and<br />
5 of them were treated with neoadjuvant CT and after they underwent<br />
operation followed by CT, EBR and high-dose CT also followed by<br />
APBSCT. Last III group there were 21 patients had undergone organsaving<br />
treatment of advanced intraocular Rb and 10 of them received<br />
combined CT (CY, VP-16, carbo) and EBR at a dose of 46 Gy (IIIa-group).<br />
Results. The patients from group Ia had disease free survival (DFS) of<br />
full 100% with a median period of follow-up of 45 m. The patients from<br />
group Ib had DFS of 89% with a median period of follow-up of 78 m. The<br />
patients from groups Ic and II had DFS of 64% with a median period of follow-up of<br />
56 mos. 4 of 16 patients in groups Ic and II were excluded from study. The patients<br />
from group IIIa had DFS of 80% with a median period of follow-up of 48 m.<br />
Conclusions. Revision of the indications to after initial enucleation in<br />
depends of histopathologic findings was done. EBR is one of effective<br />
methods for preventive of relapses in extraocular Rb after CT and<br />
operation. Combined CT and EBR generally employed in organ-saving<br />
treatment of advanced intraocular Rb.<br />
Financial disclosure. None<br />
1909 Rb14<br />
RESULTS OF PATIENTS WITH UNILATERAL RETINO-<br />
BLASTOMA TREATED WITH INITIAL ENUCLEATION: A<br />
SINGLE INSTITUTION IN BRAZIL<br />
Carla R. Donato Macedo1, Luiz F. Teixeira1,2, Camila H. Hashimoro1,<br />
Virginia L. L Torres 1,2, Juliana dos Santos Soares, Maria T. Seixas1,3,<br />
Maria C. Martins2, Clelia M. Erwenne1,2 (carladonatomacedo@uol.com.br)<br />
1. Pediatric Oncology Institute/GRAACC/Unifesp<br />
2. Ophthalmology Department/Unifesp<br />
3. Pathology Department /Unifesp<br />
Purpose. Evaluation of patients with unilateral retinoblastoma treated<br />
with initial enucleation.<br />
Methods. A retrospective analysis of patients with unilateral<br />
retinoblastoma that underwent enucleation as initial therapy from<br />
2001 to 2011 in a single institution in Brazil. Enucleation was indicated<br />
as primary treatment for patients with massive unilateral disease. The<br />
presence of pathology high risk features, such as massive choroidal<br />
invasion, any degree of concomitant choroid and optic nerve involvement,<br />
tumor involving the optic nerve posterior to the lamina cribosa, was<br />
indication of six cycles of adjuvant chemotherapy. If the surgical margin<br />
was compromised orbit radiotherapy was indicated.<br />
Results. In our data 123 patients had unilateral retinoblastoma (67,2 %<br />
of retinoblastoma patients). Of these, 80 patients underwent enucleation<br />
as initial therapy. Enucleation as single therapy was performed in 43<br />
patients, 37 patients received systemic chemotherapy as adjuvant<br />
treatment and one patient was treated with external beam radiotherapy<br />
with 45Gy. Systemic chemotherapy with carboplatin and vincristine was<br />
given to 25 patients and carboplatin and etoposide to 12 patients.<br />
All the patients are alive with a median follow up of 79 months , with no<br />
recurrence or death.<br />
Conclusions. For patients with unilateral massive disease, enucleation<br />
remains the standard of care. Adjuvant chemotherapy is beneficial for selected<br />
group of patients with higher risk of extraocular dissemination. Ideally, therapy<br />
should be structured to achieve maximal response with minimal toxicity. In our<br />
data, there were no difference in the treatment with carboplatin and vincristine<br />
or etoposide, but further prospective studies must be done.<br />
Financial disclosure. None
1940 RB15<br />
PROTON THERAPY FOR RECURRENT LOCALLY<br />
ADVANCED RETINOBLASTOMA: COMBINED RESULTS<br />
FROM THE RETINOBLASTOMA CENTER OF HOUSTON<br />
& INDIANA UNIVERSITY<br />
D.S. Gombos MD FACS; A.L. Chang MD; D.L. Andolino MD; H.P. Fontanilla<br />
MD; C. Herzog MD; M. Chintagumpala MD; P. Zage MD; R. Hurwitz MD;<br />
P. Chevez-Barrios MD; A. Mahajan MD (dgombos@mdanderson.org)<br />
The Retinoblastoma Center of Houston<br />
MD Anderson Cancer Center<br />
Indiana University<br />
Texas Children’’s Cancer Center<br />
The Methodist Hospital Research Insitute<br />
Baylor College of Medicine<br />
Purpose. Despite significant advances with systemic and local<br />
chemotherapeutic modalities, relapsed retinoblastoma can be salvaged<br />
with adjuvant radiotherapy. We present a cohort of patients treated with<br />
fractionated proton beam radiotherapy for recurrent locally advanced<br />
retinoblastoma.<br />
Methods. A review of all patients with recurrent retinoblastoma treated<br />
with proton beam radiotherapy at MD Anderson Cancer Center and the<br />
Midwest Proton Radiotherapy Institute.<br />
Results. 14 patients / 16 eyes were treated. Median treatment dose was<br />
45 CGE with a median dose to the bony orbit of 24 CGE. Local control<br />
was achieved in 6 of 16 eyes (38%). Median time to local failure was<br />
eight months. Toxicity included peri-orbital erythema, cataract, retinal<br />
vasculopathy and neovascular glaucoma.<br />
Conclusions. Proton beam radiotherapy can be used in the salvage<br />
setting for patients with advanced disease refractory to other treatments<br />
with results comparable to other series.<br />
Dosimetric planning is superior to other modalities.<br />
Financial disclosure. Dr Gombos is a member of the Children’s Oncology Group and has received<br />
reimbursement for travel. He has provided consultation for IMS Health.<br />
1828 RB16<br />
COMPARISON OF HIGH-RISK HISTOPATHOLOGY<br />
BETWEEN UNTREATED AND TREATED EYES OF PA-<br />
TIENTS WITH RETINOBLASTOMA<br />
M.W. Wilson1,2,5, R. Brennan3,6, C. Rodriguez-Galindo3,6, C. Billups4,<br />
B.G. Haik5, I. Qaddoumi3,6 (mwilson5@uthsc.edu)<br />
Departments of 1. Surgery, 2. Pathology, 3. Oncology, and 4. Biostatics,<br />
St Jude Children’s Research Hospital, Memphis, TN, USA<br />
Departments of 5. Ophthalmology and 6. Pediatrics, University of<br />
Tennessee Health Science Center, Memphis, TN, USA<br />
Purpose. To compare high risk histology between untreated and treated<br />
eyes of patients with retinoblastoma.<br />
Methods. A retrospective study identified 177 eyes of 172 patients<br />
enucleated between February 1986 and September 2010. Review of<br />
ocular histopathology focused on high risk features: tumor invasion of<br />
the anterior chamber, iris, ciliary body, choroid (massive), retro-laminar<br />
optic nerve, or sclera, and/or extraocular disease.<br />
Results. 116 eyes of 115 patients were primarily enucleated. The<br />
untreated group had a higher proportion of Reese-Ellsworth (RE) Group<br />
V eyes, 94% versus 59% (p0.19). Forty of the 52 patients were further<br />
treated with adjuvant chemotherapy (n=40) and/or external beam<br />
radiation (n=12). 3 patients died; 2 untreated from metastatic disease<br />
despite adjuvant therapy and 1 with metastatic disease at diagnosis<br />
from complications related to bone marrow transplant.<br />
Conclusions. Despite more favorable Reese-Ellsworth Grouping, treated<br />
eyes with retinoblastoma had an equal risk of harbouring HRH compared<br />
to untreated eyes, committing patients to further adjuvant therapy.<br />
Financial disclosure. None<br />
2 Rb17<br />
PATHOLOGY ASSESSMENT IN UNILATERAL RETINO-<br />
BLASTOMA WITH & WITHOUT HISTOPATHOLOGIC<br />
HIGH-RISK FEATURES & THE ROLE OF ADJUVANT<br />
CHEMOTHERAPY: A COG STUDY<br />
P. Chévez-Barrios1-3,11, R. Eagle1,4, D. Albert1,5, G. Vemuganti6, S.<br />
Krishnakumar7, B. Langholz1, S. Honavar6, J. O’Brien1,8,9, A. Leahey1,8,<br />
K. Matthay1,10, A. Meadows1,8, M. Chintagumpala1,3,11<br />
(pchevez-barrios@tmhs.org)<br />
1. Children’s Oncology Group<br />
2. The Methodist Hospital Research Institute, Houston, TX, USA<br />
3. Retinoblastoma Center of Houston, TX, USA<br />
4. Will’s Eye Institute, Philadelphia, PA, USA<br />
5. University of Wisconsin Hospital and Clinics, Madison, WI, USA<br />
6. LV Prasad Eye Institute, India<br />
7. Vision and Medical Research Foundation, Sankara Nethralaya, India<br />
8. Children’s Hospital of Philadelphia , PA , USA<br />
9. Scheie Eye Institute, Philadelphia, PA, USA<br />
10. University of California San Francisco Medical Center-Parnassus, CA, USA<br />
11. Baylor College of Medicine, Houston, TX, USA<br />
Purpose. Children’’s Oncology Group (COG) finalized a prospective<br />
multicenter international study in patients with unilateral retinoblastoma<br />
undergoing enucleation to determine the prevalence of specific, strictly<br />
defined histopathologic (high-risk) features (HRFs) and the role of<br />
chemotherapy to prevent recurrences.<br />
Methods. Eyes enucleated for unilateral retinoblastoma were submitted<br />
for central review and three pathologists (PCB, RE, DA) independently<br />
reviewed the slides. Additional slides were requested if material was<br />
thought inadequate for interpretation. Central pathology consensus<br />
stratified patients with one or more of the following: posterior uveal<br />
invasion >3mm, any degree of concomitant optic nerve and choroid<br />
involvement, and post-lamina optic nerve involvement. These patients<br />
received chemotherapy; others were observed.<br />
Results. Of 312 patients with central review, 49 patients had their risk<br />
classification changed (13% of initial non-risk had HRFs, 24% of initial<br />
HRFs had non-HRFs). The most important reason for discrepancy was<br />
initial inadequate sections and sampling. 92 patients (29.48%) had HRFs<br />
(post-laminar 16.35%, massive choroidal invasion 13.46 %, concomitant<br />
optic nerve and choroidal invasion 10.58%, others 10.89%) requiring<br />
adjuvant chemotherapy. Three of 312 patients developed recurrences.<br />
Conclusions. The study highlights the importance of histopathology
assessment of HRFs and the adequate handling and sampling of the<br />
enucleated eyes with retinoblastoma. The percentage of patients with<br />
HRFs is higher than reported in developed countries but lower than in<br />
developing countries. This percentage most likely represents a worldwide<br />
average, as this is a multicenter international prospective study.<br />
Financial disclosure. None<br />
2123 RB18<br />
LESSONS LEARNED AFTER 5 YEARS (AND 500 INFU-<br />
SIONS) OF CHEMOSURGERY: PREDICTORS OF SUC-<br />
CESS AND FAILURE<br />
David H. Abramson, MD, Brian P. Marr, MD, Scott E. Brodie, MD, PhD, Ira<br />
J. Dunkel, MD, Sotiria Palioura, MD, PhD, Pierre Gobin, MD (abramsod@<br />
mskcc.org)<br />
Memorial Sloan-Kettering Cancer Center; New York Presbyterian<br />
Hospital; Mt. Sinai School of Medicine, New York, N.Y., USA<br />
Purpose. To identify clinical factors that predict success and failure with<br />
chemosurgery for intraocular retinoblastoma<br />
Methods. Retrospective, single Institution review of 500 technically<br />
successful chemosurgery infusions for retinoblastoma performed<br />
between May 2006 and May 2011.<br />
Results. Ocular survival was 100% for Reese-Ellsworth Groups I, II , III<br />
and IV eyes, 78% for Group V and 100% for ICRB B and C eyes, 76% for D<br />
eyes and 92% for E eyes. Naïve eyes did better than previously treated<br />
eyes (87% vs. 77%) and retinal detachment eyes better than attached<br />
retina (86% vs. 79%). Kaplan Meier ocular survival at 2 years was 83% for<br />
naïve (95%CI=69-96%) and 68.1% for previously treated and resistant<br />
eyes (95%CI=53-83%) (p
4. Fluoroscopy for cannula placement was needed in all cases. Radiation<br />
exposure was far below toxic levels in all cases.<br />
5. Complications mainly involved retinal vascular pruning, often<br />
subclinical and only detected on fluorescein angiography. Occlusion of<br />
ophthalmic/retinal artery (5%) or choroidal vessels (10%) was noted.<br />
Conclusions. IAC provides satisfactory control for less advanced<br />
eyes with retinoblastoma. Retinal detachment often shows complete<br />
resolution. Complications of vascular occlusion should be monitored.<br />
Financial disclosure. None<br />
1527 RB21<br />
COMPARATIVE PHARMACOKINETICS OF TOPOTECAN<br />
AND MELPHALAN AFTER INTRA-ARTERIAL ADMINIS-<br />
TRATIONS IN THE SWINE MODEL<br />
Paula Schaiquevich, PhD, Emiliano Buitrago, Bsc, Ana Torbidoni PhD,<br />
Alejandro Ceciliano, MD, Adriana Fandino, MD, Javier Opezzo, PhD,<br />
Marcelo Asprea, DVM, Sergio Sierre, MD, Flavio Requejo, David H.<br />
Abramson, MD, Guillermo F. Bramuglia, PhD, Guillermo L. Chantada,<br />
MD. (gchantada@yahoo.com)<br />
Hospital JP Garrahan<br />
Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET)<br />
Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires,Agencia<br />
de Promocion Cientifica y Tecnologica, Argentina<br />
Memorial Sloan Kettering Cancer Center, New York, NY, USA<br />
Purpose. To compare the vitreous and plasma pharmacokinetics of<br />
topotecan and melphalan after ophthalmic artery infusion (OAI) following<br />
super-selective artery catheterization.<br />
Methods. The ophthalmic artery of 8 Landrace pigs was super-selectively<br />
catheterized and 1 mg of topotecan in one group and 7 mg of melphalan in<br />
the other group were infused over 30 minutes. Serial vitreous specimens<br />
were obtained by microdialysis with simultaneous plasma samples. Drug<br />
levels were measured by HPLC and pharmacokinetic analysis was carried<br />
out with the obtained data. IC50 for each drug were estimated in vitro from<br />
retinoblastoma cell line Y79.<br />
Results. Maximum median vitreous (Cmax) topotecan concentration in<br />
the vitreous was 288 nM, (range 247-303) and that of melphalan 650 nM,<br />
(range 160-1360). The ratio between the vitreous and plasma Cmax and area<br />
under the curve were 15.4 versus 3.4 and 29 versus 3.2 for topotecan and<br />
melphalan respectively. Systemic exposure was low for both drugs (median<br />
plasma Cmax: 0.018 and 0.2 uM for topotecan and melphalan respectively).<br />
The IC50 for topotecan was 10 nM and for melphalan 1000 nM. Topotecan<br />
levels higher than the IC50 were detected for up to 4 hours.<br />
Conclusions. Super-selective OAI resulted in vitreous concentrations of<br />
topotecan that exceeds the IC50, while melphalan levels are slightly below<br />
that range. Topotecan vitreous/plasma concentration is almost 10 times<br />
higher than of melphalan.<br />
Financial disclosure. Universidad de Buenos Aires, CONICET, Agencia de Promocion Cientifica y<br />
Tecnologica, (Argentina). Fund for Ophthalmic Knowledge, New York, USA. Fundacion Natali<br />
Flexer, Buenos Aires, Argentina, Hospital JP Garrahan, Buenos Aires, Argentina<br />
539 RB22<br />
RELAPSES FOLLOWING INTRA-ARTERIAL CHEMO-<br />
THERAPY WITH MELPHALAN<br />
T. Hadjistilianou1, S. De Francesco1, S. Bracco2, P. Galluzzi2, P. Toti3,<br />
P. Gennari2, A. D’Ambrosio4, M. Caini4, D. Galimberti4, A. Cerase2, C.<br />
Venturi2 (hadjistilian@unisi.it)<br />
RETINOBLASTOMA<br />
Abstracts<br />
42<br />
1. Ophthalmology Unit, Retinoblastoma Referral Center<br />
2. Neuroradiology Unit<br />
3. Dept.of Pathology<br />
4. Dept.of Pediatrics<br />
AOUS-Azienda Ospedaliera Universitaria Senese.<br />
Purpose. To report the incidence of relapses following intra-arterial<br />
chemotherapy with melphalan for advanced retinoblastoma at diagnosis<br />
and after systemic neoadjuvant chemotherapy.<br />
Methods. From may 2008 to may 2011, 41 patients (45 eyes, 25 eyes<br />
with relapses and 20 at first diagnosis) have been treated at the Referral<br />
Center for Retinoblastoma (University of Siena) with intra-arterial<br />
chemotherapy using melphalan alone. All patients had an advanced<br />
stage of disease (VB Reese Classification, D ABC Classification). Twenty<br />
eyes were at first diagnosis and twenty five eyes were relapses after<br />
systemic neoadjuvant chemotherapy. All patients had received 3 to 6<br />
infusions of Melphalan. The dose varied from 3 to 7 mg. Five out of 41<br />
had “tandem” therapy for bilateral relapses. All patients received focal<br />
therapy (argon laser, thermotherapy, cryotherapy, and plaques).<br />
Results. Six out of 20 (30%) eyes at first diagnosis had relapses<br />
following intra-arterial chemotherapy with melphalan. Six out of 20 (30%)<br />
underwent enucleation for progressive disease. Six out of 20 (30%)<br />
obtained complete remission; two were lost to follow up. Fifteen out of<br />
25 eyes (60%) which relapsed after systemic neoadjuvant chemotherapy<br />
had new relapses following intra-arterial chemotherapy with melphalan;<br />
one out of 15 eyes (6%) has been successfully treated with focal therapy<br />
alone, fourteen out 15 required one more cycle (3 infusions) of melphalan<br />
and focal therapy. Nine out of 25 eyes (36%) obtained complete remission<br />
with one cycle of melphalan; 1 patient was lost to follow-up.<br />
Conclusions. Intra-arterial chemotherapy with melphalan may represent<br />
a potential treatment option for advanced retinoblastoma, but more<br />
investigations with new chemotherapeutic agents are necessary when<br />
diffuse vitreous and/or subretinal seeding are present.<br />
Financial disclosure. None<br />
2257 RB23<br />
FACTORS INFLUENCING RESPONSE RATE FOLLOWING<br />
INTRA-OPHTHALMIC ARTERY MELPHALAN SALVAGE<br />
THERAPY FOR RELAPSE AFTER PRIMARY TREATMENT<br />
OF RETINOBLASTOMA<br />
John Hungerford1, Judith Kingston2,3, Stefan Brew4, Ashwin Reddy2,<br />
Mandeep Sagoo1,2, Fergus Robertson4, Jane Herod5 (john.hungerford@<br />
btopenworld.com)<br />
1. Oncology Service, Moorfields Eye Hospital<br />
2. Retinoblastoma Service, St Bartholomew’s and the London Hospital<br />
3. Paediatric Oncology Service, Great Ormond Street Hospital<br />
4. Interventional Neuroradiology Service, Great Ormond Street Hospital<br />
5. Anaesthetics Service, Great Ormond Street Hospital, London, UK<br />
Purpose. To evaluate intra-ophthalmic artery Melphalan (IAM) as a<br />
salvage treatment.<br />
Methods. Consecutive, retrospective chart review.<br />
Results. Between December 2008 and May 2011, 39 treatment episodes,<br />
each comprising 1-3 infusions of intra-ophthalmic artery Melphalan<br />
(IAM), were undertaken in 36 eyes of 34 patients for relapsed (34) or<br />
refractory (5) retinoblastoma. Of 34 treatment episodes for relapse,<br />
7 were for vitreous relapse alone whilst a further 10 were for patients<br />
with vitreous disease associated with recurrence of the primary tumour.
Seventeen episodes were for isolated relapse of the primary tumour.<br />
The number of courses of IAM treatment received per episode were 1 (in<br />
3), 2 (in 28) and 3 (in 8) episodes. The dose of IAM varied between 3mg-<br />
7.5 mg depending on age.<br />
With a median follow-up of 16 months post IAM, 10/36 (28%) treated<br />
eyes have required enucleation.<br />
All 5 eyes treated for tumours refractive to primary treatment have<br />
also failed IAM and subsequently required enucleation whilst 4/5 of<br />
the other eyes requiring enucleation had been treated with IAM for an<br />
early relapse within 4 months of previous treatment. The remaining<br />
eye treated after a relapse at 8/12, had no viable tumour at the time of<br />
enucleation.<br />
Of the total of 17 eyes (47%) with vitreous disease 4/17 (23%) have been<br />
enucleated.<br />
Five children had abnormal vascular anatomy, 3 with middle meningeal<br />
artery arising from ophthalmic artery, 2 of whom were enucleated.<br />
Conclusions. Refractory disease or early relapse appear to be the major<br />
factors predicting poor response to IAM applied as a salvage treatment.<br />
Financial disclosure. None<br />
60 RB24<br />
INTRAVITREAL CHEMOTHERAPY WITH MELPHALAN<br />
FOR VITREOUS DISEASE IN ADVANCED RETINOBLAS-<br />
TOMA: EVIDENCE FOR SAFETY AND EFFICACY<br />
Francis L. Munier1, Marie-Claire Gaillard1, Aubin Balmer1, Susan<br />
Houghton1, Maja Beck-Popovic1<br />
1. Jules-Gonin Eye Hospital, Lausanne Switzerland<br />
2. Pediatric Hemato-Oncology Unit, CHUV, Lausanne, Switzerland<br />
Purpose. The presence of active vitreous seeding following state-ofthe-art<br />
conservative treatment of intraocular retinoblastoma leads<br />
in the vast majority of cases to either external beam irradiation (EBR)<br />
and/or enucleation. Intravitreal chemotherapy (IVC) is theoretically<br />
the best route for delivering the highest vitreous concentration of a<br />
chemotherapeutic drug, over intravenous, periocular and ophthalmic<br />
artery chemotherapy. It has however remained highly controversial due<br />
to the risk of tumor exteriorization. In 1995 Kaneko and Susuki were the<br />
first to inject Melphalan in the vitreous of 41 eyes and reported a 51.3%<br />
eye preservation rate.<br />
Methods. We retrospectively reviewed all consecutive patients treated<br />
with IVC between April 2009 and July 2011. IVC was performed on<br />
a weekly basis up to 8 injections of Melphalan /event, using a novel<br />
injection technique characterized by the prevention of vitreous reflux<br />
and sterilization of the needle track. Results. 23 eyes from 23<br />
patients with resistant vitreous seeding, even following ophthalmic<br />
artery Melphalan chemotherapy (13 eyes), were included. Mean followup<br />
was 17 months. Complete seeding regression was achieved in 21<br />
patients. Success rate, defined as absence of enucleation and/or EBR,<br />
was 87% (20/23). No ocular IVC-related complications or extraocular<br />
dissemination were experienced.<br />
Discussion. These preliminary results appear promising in terms of<br />
safety and efficacy with unprecedented success rates for resistant<br />
vitreous disease. It must be emphasized that such a delicate procedure<br />
should imperatively be carried out only in tertiary referral centres, due<br />
to the risk of dissemination. IVC needs to be further investigated and its<br />
indications more precisely defined.<br />
Financial disclosure. None<br />
RETINOBLASTOMA<br />
Abstracts<br />
43<br />
7 RB25<br />
SELECTIVE INTRA-ARTERIAL CHEMOTHERAPY AS A<br />
TREATMENT FOR INTRAOCULAR RETINOBLASTOMA:<br />
ALTERNATIVES TO DIRECT OPHTHALMIC ARTERY<br />
CANNULATION<br />
Michael A. Klufas, MD1, Y. Pierre Gobin, MD1, Brian Marr, MD2, Scott<br />
E. Brodie, MD, PhD2, Ira J. Dunkel, MD2, David H. Abramson, MD2<br />
(mak2049@nyp.org)<br />
1. New York-Presbyterian Hospital/Weill Cornell Medical College, New York,<br />
NY, USA<br />
2. Memorial Sloan-Kettering Cancer Center, New York, NY, USA<br />
Purpose. Report results of intra-arterial chemotherapy for retinoblastoma<br />
when delivery of drug was not via direct cannulation of the ophthalmic<br />
artery.<br />
Methods. Retrospective review of 110 eyes treated with 351 intraarterial<br />
infusions at a single institution identified 18 eyes of 14 patients<br />
who received a total of 67 intra-arterial infusions with at least one<br />
intra-arterial chemotherapy infusion not through the ophthalmic artery<br />
(OA). Alternatives included cannulation of the middle meningeal artery<br />
(MMA), or temporary balloon occlusion of the internal carotid artery<br />
distal to the origin of the OA.<br />
Results. Patient survival: 100%; all patients are alive. Ocular survival:<br />
100%; no eye has been enucleated. Mean follow-up was 12.1 months<br />
(median 11, range 3-28). Eyes received a mean of 3.7 intra-arterial<br />
infusions (median 3, range 2-9). Reese-Ellsworth Group included: RE II,<br />
3 eyes; RE III, 4 eyes; and RE V, 11 eyes (ICRB: Group B, 5; Group C,<br />
3; Group D, 10). Treatment routes included: MMA only, 3 eyes; MMA +<br />
OA, 4 eyes; MMA + balloon, 2 eyes; balloon only, 1 eye; balloon + OA, 7<br />
eyes; balloon + OA + MMA, 1 eye. Intra-arterial chemotherapies included<br />
melphalan, topotecan, and carboplatin. Electroretinogram readings<br />
were: stable, 10 eyes; improved, 3 eyes; reduced, 5 eyes. Neutropenia<br />
(CTCAE v3.0 ≥ grade 3) occurred after 37.5% of treatments. One patient<br />
was hospitalized twice, and once was transfused blood products.<br />
Conclusions. Treatment via the MMA or balloon-assisted infusion allows<br />
salvage of eyes and life, without unacceptable local or systemic side<br />
effects in cases where direct OA cannulation is precluded.<br />
Financial disclosure. None<br />
1448 RB26<br />
INTRA-ARTERIAL CHEMOTHERAPY USING SIMUL-<br />
TANEOUS MULTI AGENT CHEMOTHERAPY, THREE<br />
DRUGS, FOR RESCUE OF EYES WITH INTRAOCULAR<br />
RETINOBLASTOMA<br />
Brian P. Marr, M.D.1 , Y. Pierre Gobin, M.D.2, Scott E. Brodie, M.D. ,<br />
Ph.D.1, Ira J. Dunkel, M.D. 3, David H. Abramson, M.D.1 (marrb@mskcc.org)<br />
1. Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer<br />
Center<br />
2. Division of Interventional Neuroradiology, Department of Radiology,<br />
Neurosurgery, and Neurology, Weill Cornell Medical College<br />
3. Dept. of Pediatrics, Memorial Sloan-Kettering Cancer Center, New<br />
York, N.Y.<br />
Purpose. To report our experience with super selective intraarterial<br />
chemotherapy (SSIAC) using simultaneous multi agent chemotherapy<br />
(three drugs) for advanced intraocular retinoblastoma.
Methods. A retrospective chart review of 26 eyes of 25 patients receiving<br />
three-drug (melphalan, topotecan, and carboplatin) multi agent SSIAC<br />
was conducted between May 2006 and June 2011.<br />
Results. Twenty-six eyes, Reese-Ellsworth group 5b (22) 5a (1) 4a (2)<br />
and 3a (1), received 61 infusions of 3 drug multiagent chemotherapy<br />
for rescue of eyes with advanced retinoblastoma. The dose range for<br />
melphalan was 2.5 to 7.5 mg, 0.3 to 0.6 mg for topotecan, and 30 to 50<br />
mg for carboplatin. The median number of multi drug infusions was 2<br />
with a maximum of 4 and minimum of 1 averaging 2.3 per eye. Fourteen<br />
of 25(56%) patients presented after failing intravenous chemotherapy<br />
(IVC), 2/25(8%) after failing IVC and external beam radiotherapy and<br />
1/25(4%) after failing IVC and plaque brachytherapy. Twenty-four /26<br />
(92)% of eyes were salvage over a mean follow up period of 14 mo. (1-43<br />
mo.) Electroretinogram (ERG) showed improvement greater than in 25mv<br />
in 4/26 eyes (15%), greater than 25-mv loss in 12/26 eyes(46%), no<br />
change greater than 25mv in 10/26 eyes(39%).<br />
Conclusions. We have successfully used three-drug multiagent SSIAC to<br />
rescue eyes that have failed IVC and/ or single or double agent SSIAC.<br />
A significant portion of eyes avoided enucleation and retained ERG<br />
function. . Further investigation into multiagent SSIAC is required to<br />
determine its role in treatment of advanced retinoblastoma.<br />
Financial disclosure. None<br />
1550 RB27<br />
OCULAR COMPLICATIONS OF DIRECT INTRA-OPH-<br />
THALMIC ARTERY MELPHALAN TREATMENT FOR RE-<br />
FRACTORY RETINOBLASTOMA<br />
M Ashwin Reddy1,2, Wisam J. Muen1, Judith Kingston1,3, John<br />
Hungerford2, Fergus Robertson4, Stefan Brew4, Mandeep Sagoo1,2,<br />
Dorothy Thompson5 (mashwinreddy@hotmail.com)<br />
1. Retinoblastoma Unit, Barts & the London NHS Trust, Royal London<br />
Hospital, Whitechapel Road<br />
2. Moorfields Eye Hospital, City Road<br />
3. Oncology Department, Great Ormond Street Children’s Hospital<br />
4. National Hospital for Neurology and Neurosurgery, Queens Square<br />
5. Ophthalmology Department, Great Ormond Street Children’s Hospital,<br />
London, UK<br />
Purpose. We report on patients receiving Intra-ophthalmic Artery<br />
Melphalan (IAM), which was delivered via direct catheterisation of the<br />
ophthalmic artery in cases of retinoblastoma refractory to systemic<br />
chemotherapy +/- radiation .<br />
Methods. All cases undergoing IAM between May 09 to August 10 were<br />
included and the results of ocular complications including reduced<br />
vision were recorded. Minimum follow-up was 11 months.<br />
Results. 15 eyes of 14 patients were treated. 5 developed IIIrd nerve<br />
palsies which resolved within 6 months. 5 patients with prior radiation<br />
developed more severe ocular complications. 2 patients demonstrated<br />
good ERG function post-treatment but a subtle deterioration of patternonset<br />
VEPs. 1 child had her vision reduce from 20/20 to 20/40 with<br />
treatment. 10 of 15 eyes (66%) showed a good tumour response. 2<br />
patients with vitreous seeding required enucleation despite systemic<br />
chemotherapy and intraarterial melphalan.<br />
Conclusions. Potentially amblyogenic complications may occur when<br />
using direct IAM. Complications are exacerbated with prior radiation.<br />
Families undergoing this experimental treatment need to be counselled<br />
accordingly.<br />
Financial disclosure. None<br />
RETINOBLASTOMA<br />
Abstracts<br />
44<br />
438 RB28<br />
LIMITATIONS OF THE INTERNATIONAL CLASSIFICA-<br />
TION IN PREDICTING SUCCESS OF INTRA-ARTERIAL<br />
CHEMOTHERAPY FOR GROUP D/E INTRAOCULAR<br />
RETINOBLASTOMA<br />
Sotiria Palioura, MD, PhD, Y. Pierre Gobin, MD, Scott E. Brodie, MD, PhD,<br />
Brian P. Marr, MD, Ira J. Dunkel, MD, and David H. Abramson, MD (sotiria.<br />
palioura@gmail.com)<br />
Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center,<br />
New York. Currently, Department of Ophthalmology, Massachusetts Eye<br />
and Ear Infirmary, Boston. Division of Interventional Neuroradiology,<br />
Departments of Radiology, Neurosurgery and Neurology, Weill Cornell<br />
Medical College, New York Presbyterian Hospital, New York; Ophthalmic<br />
Oncology Service, Memorial Sloan-Kettering Cancer Center, New York;<br />
and Department of Ophthalmology, Mount Sinai School of Medicine,<br />
New York; Brian P. Marr: Ophthalmic Oncology Service, Memorial<br />
Sloan-Kettering Cancer Center, New York; Department of Pediatrics,<br />
Memorial Sloan-Kettering Cancer Center, New York; David H. Abramson:<br />
Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center,<br />
New York, NY, USA.<br />
Purpose. To report the success rate of superselective ophthalmic<br />
artery chemotherapy for International Classification group D and E<br />
retinoblastoma eyes and to compare it to reported success rates of<br />
systemic chemoreduction.<br />
Methods. Retrospective review of 41 group D (n=33) and E (n=8) eyes of<br />
40 retinoblastoma patients who were treated (May 2006-June 2011) with<br />
intra-arterial chemotherapy as primary treatment. Kaplan Meier data<br />
analysis on ocular event-free (enucleation or external beam radiation)<br />
survival is reported. The PubMed database was searched through June<br />
2011 for studies reporting success rates of systemic chemoreduction for<br />
Group D and E eyes.<br />
Results. The Kaplan-Meier estimates of ocular event-free survival at 2<br />
years were 75.5% (95% confidence interval, 58.2%-92.9%) for group D<br />
eyes and 100% (95% confidence interval, 62.5%-100%) for group E eyes.<br />
The success rates of systemic chemoreduction for group D eyes reported<br />
in the literature range from 23% to 47%. According to our literature<br />
search, all group E eyes were enucleated either at presentation or after<br />
failed systemic chemoreduction and/or external beam radiation.<br />
Conclusions. The high success rate of intra-arterial chemotherapy for<br />
group D and E eyes suggests that the International Classification falls<br />
short when predicting intra-arterial treatment success. It seems that<br />
clinical features used by the International Classification that would deem<br />
an eye “hopeless” for chemoreduction are not predictors of treatment<br />
failure when intra-arterial chemotherapy is used instead.<br />
Financial disclosure. None<br />
2330 RB29<br />
INTRA-ARTERIAL MELPHALAN DOSING REGIMENS<br />
FOR THE TREATMENT OF RETINOBLASTOMA<br />
Timothy G. Murray1, Samuel K. Houston1, Mohammad A. Aziz-Sultan2,<br />
Christina E. Fernandes3, Christina Decatur1, Yolanda Pina1 (TMurray@<br />
med.miami.edu)<br />
1. Bascom Palmer Eye Institute; 2. University of Miami, Department of<br />
Neurosurgery<br />
3. University of Miami, Department of Pediatrics
Purpose. The purpose of this study is to demonstrate dosing protocols for<br />
intraarterial chemotherapy for the treatment of children with retinoblastoma.<br />
Methods. his is an interventional case series of 21 patients with<br />
advanced retinoblastoma (Reese-Ellsworth Vb) treated with intraarterial<br />
chemotherapy and focal laser ablation. Dosing regimens included 3<br />
different strategies. Patients were treated with either: (1) single dose<br />
of 7.5mg if unilateral disease; (2) repetitive treatment with 5mg or<br />
7.5mg for 3 sessions; (3) tandem, bilateral therapy with 7.5mg to the<br />
more advanced eye for a total of 12.5mg. Six patients were treated with<br />
3mg initially, then retreated at higher doses. Patients were evaluated by<br />
indirect ophthalmoscopy and wide-field photography for tumor response.<br />
Results. Patients tolerated treatment well, without severe side effects of<br />
stroke or death. Mild local toxicities were observed, as well 4 cases of<br />
vitreous hemorrhage. However, vitreous hemorrhage occurred in patients<br />
who were treated with lower doses (less than 5mg), then retreated with<br />
higher doses secondary to a lack of response at the lower dose. Systemic<br />
side effects were mild, with mild cytopenias not requiring hospitalization.<br />
75% of patients avoided enucleation or radiation therapy, with patients<br />
treated at lower doses (3 or 5mg) requiring enucleation 36% of the time<br />
versus 0% for those treated at higher doses (7.5mg).<br />
Conclusions. Superselective intraarterial chemotherapy offers an<br />
exciting globe-salvaging technique for the primary and salvage treatment<br />
of retinoblastoma. Standard dosing regimens have not been determined<br />
and vary between institutions. The current study presents dosing<br />
strategies for intraarterial melphalan in the treatment of retinoblastoma<br />
at a single specialized center.<br />
Financial disclosure. None<br />
15 RB30<br />
THE GENERAL HEALTH AND PSYCHOSOCIAL FUNC-<br />
TIONING OF ADULT SURVIVORS OF RETINOBLAS-<br />
TOMA: PRELIMINARY RESULTS OF THE RETINOBLAS-<br />
TOMA SURVIVOR STUDY<br />
Ira J Dunkel1, Jennifer S Ford1, Charles A Sklar1, Kevin C Oeffinger1,<br />
Joanne F Chou1, Yuelin Li1, Danielle Novetsky Friedman1, Mary McCabe1,<br />
Nancy Kline1, Leslie L Robison 2, Ruth A Kleinerman3, Brian P Marr1,<br />
David H Abramson1 (dunkeli@mskcc.org)<br />
1. Memorial Sloan-Kettering Cancer Center, New York, NY, United States,<br />
2. St. Jude Children’s Research Hospital, Memphis, TN, United States, 3.<br />
National Cancer Institute, Bethesda, MD, United States<br />
Purpose. To describe the health status, quality of life, and psychosocial<br />
functioning of adult retinoblastoma survivors.<br />
Methods. A self-report descriptive study (modified CCSS questionnaire<br />
with added VFQ-25 vision questions) was conducted via mail and/or<br />
telephone interview with adult retinoblastoma survivors who had been<br />
treated in New York.<br />
Results. 470 (48%) of 987 potential subjects participated. Mean age at<br />
study entry was 43.4 years (SD 11); 52.1% are female, 90.4% white/non-<br />
Hispanic, and 53.6% had bilateral retinoblastoma. Most were currently<br />
employed full-time (72.2%), married (54.4%), and had at least some<br />
college education (81.0%). The majority endorsed having good overall<br />
health (94.4%), having good eyesight (61.4%), and having no physical<br />
disabilities (61.8%), but 15.4% reported difficulty obtaining health<br />
insurance. A history of psychological dysfunction was reported by 30.7%,<br />
and 35.4% reported having anxiety as a result of their retinoblastoma.<br />
Many worried about passing retinoblastoma to their children (52.3%),<br />
had concerns about their future health (69.9%) or developing a cancer<br />
RETINOBLASTOMA<br />
Abstracts<br />
45<br />
(70.5%), and were dissatisfied with their facial appearance (78.2%).<br />
Participants who reported any disability, poor health, anxiety due to<br />
retinoblastoma, worry about passing retinoblastoma to their children,<br />
concerns about future health or developing a cancer, were significantly<br />
more likely to have been diagnosed with bilateral than unilateral<br />
retinoblastoma.<br />
Conclusions. Most adult retinoblastoma survivors are high functioning<br />
and healthy, but many expressed concerns about the long-term<br />
implications of their retinoblastoma. Future analyses will be conducted<br />
to compare these results to a control (CCSS sibling) population.<br />
Financial disclosure. None<br />
2323 RB31<br />
LATE MEDICAL OUTCOMES IN SURVIVORS OF EXTRA-<br />
OCULAR RETINOBLASTOMA: THE MEMORIAL SLOAN-<br />
KETTERING CANCER CENTER (MSKCC) EXPERIENCE<br />
D. Novetsky-Friedman1, C.A. Sklar1, K.C. Oeffinger1, N.A. Kernan1,<br />
Y. Khakoo1, B.P. Marr2, S.L. Wolden3, D.H. Abramson2, I.J. Dunkel1<br />
(friedmad@mskcc.org)<br />
1. Department of Pediatrics, 2. Ophthalmic Oncology Service; 3.<br />
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer<br />
Center, New York, New York, USA<br />
Purpose. To provide the first report characterizing chronic health<br />
conditions among survivors of extra-ocular retinoblastoma.<br />
Methods. Retrospective analysis of late medical outcomes in 20 survivors<br />
of extra-ocular retinoblastoma diagnosed between 1990 and 2009.<br />
Late effects were graded using the NCI’s CTCAE v4.0 scale. All patients<br />
received intensive multimodality therapy, which included conventional<br />
chemotherapy (n=20, 100%), radiation therapy (n=14, 70%), and/or<br />
high-dose chemotherapy with autologous stem cell transplant (n=18,<br />
90%).<br />
Results. The median follow-up was 10.9 years from initial diagnosis<br />
of intra-ocular RB (range 1.8-18.8 years) and 7 years from diagnosis of<br />
extra-ocular RB (range 0.9-18.4 years). After excluding visual defects,<br />
which were present in 100% of survivors, the most common long-term<br />
complications were hearing loss (n=14, 70%), short stature (n=8,<br />
40%), and neurocognitive delay (n=7, 35%). Eighty-percent of survivors<br />
exhibited ≥2 non-visual long-term effects of any grade. Except short<br />
stature, which was not graded for severity, grade 3-4 toxicities were<br />
limited to: ototoxicity (n=8; n=4 require hearing aids), secondary<br />
malignancies (n=5), ovarian dysfunction (n=1), and unequal limb length<br />
(n=1). Grade 4 secondary malignant neoplasms (SMNs) developed at a<br />
median of 11.6 years after initial diagnosis; two of the five patients died<br />
of their SMN. Cardiac, pulmonary, hepatobiliary or renal toxicities were<br />
not identified in any survivors.<br />
Conclusions. Late effects are commonly seen in survivors of extra-ocular<br />
retinoblastoma but the majority are mild-moderate in their severity.<br />
Longer comprehensive follow-up is needed to fully assess treatmentrelated<br />
chronic health conditions in this population.<br />
Financial disclosure. None<br />
1755 RB32<br />
VARIATION OF SECOND CANCER RISK BY FAMILY<br />
HISTORY OF RETINOBLASTOMA AMONG LONG-TERM<br />
SURVIVORS
Ruth A. Kleinerman1, Chu-ling Yu1, Mark P. Little1, Yi Li2, David H.<br />
Abramson3, Johanna H. Seddon4, and Margaret A. Tucker1 (kleinerr@<br />
mail.nih.gov)<br />
1. Division of Cancer Epidemiology and Genetics, National Cancer Institute,<br />
National Institutes of Health, Department of Health and Human Services,<br />
Rockville, MD<br />
2. Department of Biostatistics and Computational Biology, Dana Farber<br />
Cancer Institute, Boston, MA<br />
3. Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer<br />
Center, New York, NY<br />
4. Ophthalmic Epidemiology and Genetics Service, Tufts-New England<br />
Medical Center, Boston, MA<br />
Purpose. To evaluate the risk of a non-ocular second cancer (SC) in<br />
long-term survivors of retinoblastoma (Rb) according to classification of<br />
germline mutation, based on family history of Rb and laterality.<br />
Methods. We assembled a cohort of 1,852 1-year survivors of<br />
retinoblastoma. SCs were confirmed by pathology reports. Classification<br />
of RB1 germline mutation, inherited or de novo, was inferred by laterality<br />
of Rb and positive family history of Rb. Standardized incidence ratios and<br />
cumulative incidence for all SCs combined and for soft tissue sarcomas,<br />
bone cancers and melanoma were calculated. The influence of host and<br />
therapy related risk factors for SC was assessed by Poisson regression<br />
for bilateral survivors.<br />
Results. We observed a relative risk (RR) of 1.10 (95% Confidence<br />
interval (CI), 0.84-1.44) for SCs in bilateral survivors associated with a<br />
family history of Rb, adjusted for treatment, age and length of followup.<br />
The risk for melanoma was elevated for survivors with a family<br />
history of Rb (RR=2.38, 95%CI 1.04-5.09), but not for bone or soft tissue<br />
sarcomas. The cumulative incidence of SCs at 50 years after diagnosis<br />
of bilateral Rb, with adjustment for competing risk of death, was higher<br />
for survivors with a family history (44%, 95%CI, 35%-54%) than without<br />
(38%, 95%CI, 31-44%).<br />
Conclusions. Rb survivors with bilateral disease and an inherited<br />
germline mutation may be at slightly higher risk of a SC compared<br />
to those with a de novo germline mutation, in particular melanoma,<br />
perhaps due to shared genetic alterations.<br />
Financial disclosure. None<br />
2039 RB33<br />
A NOVEL, ORAL, NON-INVASIVE METHOD OF DELIV-<br />
ERY FOR THE GLYCOLYTIC INHIBITOR 2-DEOXY-D-<br />
GLUCOSE IN THE TREATMENT OF RETINOBLASTOMA<br />
Christina L. Decatur, Yolanda Piña, Samuel Houston, Ludimila Cavalcante,<br />
Theodore Lampidis, Timothy G. Murray (cdecatur@med.miami.edu)<br />
Bascom Palmer Eye Institute, University of Miami Miller School of<br />
Medicine, Miami, Florida, USA.<br />
Purpose. The aim of the current study is to assess the impact of oral<br />
delivery of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on tumor<br />
burden and hypoxia in the LHBETATAG retinal tumor model.<br />
Methods. The study protocol was approved by the University of Miami<br />
Institutional Animal Care and Use Review Board Committee. LHBETATAG<br />
transgenic mice (n=25) received oral delivery of either 2-DG (0.02%) in<br />
custom made food pellets, or control food pellets without 2-DG, and<br />
were divided into three groups: (1) a group treated for 8 weeks, from 4<br />
to 12 weeks of age (8 weeks early tx); (2) a group treated for 18 weeks,<br />
from 4 to 22 weeks of age (18 weeks early tx); and (3) a group treated<br />
RETINOBLASTOMA<br />
Abstracts<br />
46<br />
for 8 weeks, from 17 to 25 weeks of age (8 weeks late tx). At the time of<br />
enucleation, all eye samples were snap frozen and analyzed for tumor<br />
burden and hypoxia using histopathology and immunohistochemistry<br />
techniques. Percentages of the different variables were statistically<br />
analyzed using ANOVA.<br />
Results. Following oral delivery of 2-DG, there was a significant<br />
difference between all treatment groups on tumor burden (p=0.049). A<br />
78% reduction of tumor burden was found in the 18 weeks early treated<br />
group (p=0.0034). Both the early and late treated groups did not show<br />
any difference from the control (p=0.61 and p=0.58, respectively). A<br />
91% reduction in hypoxia was found in the 18 weeks early treated group<br />
(p=0.061). Although there was a large reduction in hypoxia in both the 8<br />
weeks early and late treated groups (85% and 45%, respectively), they<br />
did not show any difference from the control (p=0.4 and p=0.37, respectively).<br />
Conclusions. Reduction of tumor burden and hypoxia with oral delivery<br />
of 2-DG presents a novel approach as a potential therapeutic treatment<br />
of retinoblastoma. The use of glycolytic inhibitors as adjuvants to<br />
therapeutic strategies, (e.g., chemotherapy, vessel targeting) as a<br />
therapeutic strategy offers a new approach for enhancing current<br />
retinoblastoma treatments.<br />
Financial disclosure. This work was supported by the American Cancer Society and the<br />
University of Miami Sylvester Comprehensive Cancer Center. NIH center grant P30EY014801 and<br />
by the unrestricted grant to the University of Miami from Research to Prevent Blindness.<br />
1352 RB34<br />
VITREOUS INJECTION THERAPY OF MELPHALAN FOR<br />
RETINOBLASTOMA<br />
Shigenobu Suzuki, Akihiro Kaneko (sgsuzuki@ncc.go.jp)<br />
1. Department of Ophthalmic Oncology, National Cancer Center Hospital<br />
2. Yokohama City University Hospital<br />
Purpose. To describe the adverse events and prognosis of retinoblastoma<br />
patients treated with vitreous injection therapy.<br />
Methods. A retrospective review of retinoblastoma patients treated with<br />
vitreous injection therapy until 2009. Injected drug was melphalan, and<br />
the dose ranged from 8 to 24 microgram. All vitreous injections were<br />
performed as salvage treatments, and concomitant treatments were<br />
selected depend on the eye condition: radiotherapy, chemotherapy,<br />
arterial injection, laser therapy, cryotherapy, brachytherapy, and ocular<br />
hyperthermia.<br />
Results. 896 injections were performed for 237 eyes of 227 patients.<br />
Mean follow-up period was 91 months.<br />
Adverse events: Extraocular tumor extension occurred in one eye treated<br />
at the early time of this technique (0.4%), which had anterior chamber<br />
spread and dense vitreous seeds. Systemic metastasis occurred in ten<br />
patients, but nine of them were not related to vitreous injections, and<br />
only in one patient (0.4%) we could not eliminate the association of<br />
vitreous injection. Other adverse events were vitreous hemorrhage (two<br />
eyes, 0.8%), retinal detachment (one eye, 0.4%), chorioretinal atrophy<br />
(two eyes, 0.8%), and iris atrophy (three eyes, 1.3%). There was no case<br />
of endophthalmitis.<br />
Prognosis: In total, 135 eyes (58%) were salvaged. For 83 eyes with active<br />
vitreous seeds without large residual retinal tumors, 68% of eyes were<br />
salvaged. More than half eyes without initial macular tumor kept visual<br />
acuity better than 0.5 (Landolt ring).<br />
Conclusions. Vitreous injection therapy is effective for vitreous seeds,<br />
and causes few adverse events. Good visual acuity means the limited<br />
damage for the eye.<br />
Financial disclosure. None
58 RB 35<br />
A STUDY OF UNILATERAL RETINOBLASTOMA WITH<br />
AND WITHOUT HISTOPATHOLOGIC HIGH-RISK FEA-<br />
TURES AND THE ROLE OF ADJUVANT CHEMOTHERA-<br />
PY: A CHILDREN’S ONCOLOGY STUDY<br />
M. Chintagumpala, R. Eagle, D. Albert, B. Langholz, V.A. Reddy, V.<br />
Khetan, S. Honavar S, J. O’Brien, A. Leahey, K. Matthay, A. Meadows, P.<br />
Chevez-Barrios (mxchinta@txch.org)<br />
Baylor College of Medicine, Houston, Texas; Children’s Hospital of<br />
Philadelphia; University of Wisconsin Hospital; Children’s Oncology<br />
Group;<br />
LV Prasad Eye Institute, Hyderabad, India; Sankaranethralaya, Chennai,<br />
India; University of California San Francisco Medical Center;<br />
The Methodist Hospital, Houston, Texas<br />
Purpose. The COG completed a prospective study in patients with<br />
unilateral retinoblastoma who undergo enucleation to determine the<br />
prevalance of specific, strictly defined histopathologic (high-risk)<br />
features that are predictors of recurrence and the role of chemotherapy<br />
to prevent recurrences.<br />
Methods. All patients who underwent enucleation for unilateral<br />
retinoblastoma were eligible for the study. Pathology slides were<br />
submitted for central review within 21 days of enucleation. Patients with<br />
evidence of one or more high-risk features (posterior uveal invasion<br />
grades IIC and D, concurrent optic nerve and choroid involvement and<br />
post-lamina optic nerve involvement) as determined by central review,<br />
received 6 cycles of chemotherapy consisting of carboplatin, vincristine<br />
and etoposide. All others were observed. All patients were followed for<br />
extraocular or metastatic recurrences.<br />
Results. Patients were enrolled from February of 2005 until May<br />
2010. Of 312 patients with central review, 49 patients had their risk<br />
classification changed. 92 patients with high-risk features received<br />
adjuvant chemotherapy. Three of 312 patients developed recurrences;<br />
two of them had received chemotherapy for massive uveal and postlaminar<br />
involvement, and the third one was observed after enucleation.<br />
Conclusions. Preliminary results of this study suggest that prophylactic<br />
chemotherapy after enucleation for selected patients with unilateral<br />
retinoblastoma can lead to an excellent outcome.<br />
Financial disclosure. None<br />
RETINOBLASTOMA<br />
Abstracts<br />
47
2006 RBp100<br />
RETINOBLASTOMA ASSESSMENT BY DOPPLER<br />
SONOGRAPHY - A FOLLOW - UP STUDY<br />
Maria Teresa B.C. Bonanomi, Osmar C. Saito, Tatiana Tanaka<br />
(mtbonanomi@uol.com.br)<br />
Hospital das Clínicas da Faculdade de Medicina da Universidade de São<br />
Paulo (HCFMUSP) São Paulo - BRAZIL<br />
Purpose. Chistian Andreas Doppler (1803-1853) first described the<br />
physical principle that permits to assess the velocity of an object by<br />
using the change of frequency of waves. This principle was applied in<br />
medicine to study the large vessels in 1957. Color Doppler imaging (CDI)<br />
is an ultrasound technique that combines B-scan images with velocity<br />
information obtained from the Doppler shift of the moving erythrocytes.<br />
The intrinsic circulation of tumors has been reliably imaged in<br />
melanomas before and after treatment. The Purpose of this study is to<br />
assess the retinoblastoma volume and its vascularization by CDI before<br />
and during treatment.<br />
Methods. Retinoblastoma tumors in children with bilateral disease were<br />
studied with the “Toshiba Aplio XG, 16 MHz Transducer. Tumors stage<br />
B or higher were assessed before and after three cycles of the operative<br />
protocol treatment in the HCFMUSP. Tumor volume was calculated<br />
by a multiplication of three manually obtained ultrassonographic<br />
measurements (transversal, longitudinal and antero-posterior in<br />
centimetres) and the mathematical constant 0.52. Vascularization<br />
was indicated as present or absent. Data was compared with the<br />
ophthalmoscopy findings.<br />
Results. There were 14 eligible tumors in 5 children (2 males and 3<br />
female). The mean age of presentation was 10 months (3 to 21months).<br />
Only two lesions were excluded due to unreliable data. The initial mean<br />
volume of the twelve tumors was 0.37cm3 ± 0.68 cm3 (0.004 cm3 to<br />
2.36 cm3). Intrinsic vessels were detected in 9 lesions with mean<br />
volume of 0.49 cm3±0.76 cm3 while in three lesions, mean volume<br />
of 0.01cm3±0.01cm3, tumor vessels could not be demonstrated, the<br />
difference was statistically significant ( p=0.036 Mann-Whitney).The<br />
mean volume at three months was 0.04cm3 ± 0.06cm3 (zero to 0.172<br />
cm3), corresponding to a mean reduction of 86%. The tumor vessels<br />
pattern was exuberant showing variable degrees of turbulence before<br />
treatment. The vascularization at 3 months, considered only in 6 tumors<br />
that were not flat, was still present in 1 (29%) and totally absent in 5.<br />
All 6 tumors showed features of viability at fundus examination in the<br />
third month, meaning opaque tissue sometimes with visible vessels.<br />
Movement of the child and the presence of calcium inside the tumor<br />
hamper the vessel imaging. After treatment, vascularization shrinkage<br />
can be demonstrated by CDI, even in small lesions.<br />
Conclusions. Echodoppler is able to assess size and vascularization of<br />
the tumor in the same session. Intrinsic vessels may be overlooked in<br />
too small tumors. Lack of vascularization in the follow-up does not imply<br />
total involution of the tumor. This diagnostic tool should be considered<br />
in assessing retinoblastoma.<br />
Financial disclosure. None<br />
354 RBp101<br />
PATIENTS WITH UNILATERAL RETINOBLASTOMA AND<br />
HIGH-RISK PATHOLOGIC FEATURES DO NOT REQUIRE<br />
INTENSIVE METASTATIC WORK-UP OR AGGRESSIVE<br />
CHEMOTHERAPY<br />
RETINOBLASTOMA<br />
Posters<br />
48<br />
Ibrahim Qaddoumi1,7, Matthew W. Wilson2,3,6, Catherine Billups4,<br />
Jianrong Wu4, Thomas Merchant5, Barry Shulkin5, Rachel Brennan1,<br />
Barrett G. Haik3,6, Carlos Rodriguez-Galindo1,7, Erin Sullivan1. (ibrahim.<br />
qaddoumi@stjude.org)<br />
Departments of 1. Oncology, 2. Pathology, 3. Surgery, 4. Biostatistics,<br />
5. Radiological Sciences St. Jude Children’s Research Hospital; 6.<br />
Ophthalmology (Hamilton Eye Institute) and 7. Pediatrics, University of<br />
Tennessee Health Sciences Center, Memphis, TN.<br />
Dr. Rodriguez-Galindo is currently at Dana-Farber Cancer Institute,<br />
Boston, MA<br />
Purpose. To describe the work-up, treatment, and outcome of patients<br />
with advanced unilateral intraocular retinoblastoma.<br />
Methods. Patients received up-front enucleation, then were assigned to<br />
Low-Risk (LR), Intermediate-Risk (IR), or High-Risk (HR) groups according<br />
to histology of enucleated eyes. LR patients underwent observation. IR<br />
patients received 4 courses of chemotherapy that included vincristine,<br />
doxorubicin, and cyclophosphamide (VDC). HR patients received 6<br />
courses of chemotherapy: VDC alternated with vincristine, carboplatin,<br />
and etoposide (VCE). The IR and HR groups also received granulocytecolony<br />
stimulating factor.<br />
Results. Fifty patients were treated: LR, 36 patients; IR, 7 patients;<br />
HR, 7 patients. The median age at enrollment was 26 months. All eyes<br />
were classified as Reese-Ellsworth group V. All bone scans (n=79),<br />
lumbar punctures (n=17), and bone marrow aspirates (n=16) were<br />
negative. Chemotherapy-related toxicity was well tolerated. Grades 3<br />
and 4 hematologic toxicities were seen in all patients; grades 3 and 4<br />
nonhematologic toxicities were seen in 7 of 14 patients (in the IR and HR<br />
groups). Chemotherapy dose modifications or delays due to neutropenia<br />
or thrombocytopenia were needed in only 4/67 (6%) courses. Only1<br />
patient in the HR group received radiation therapy.<br />
All patients were alive at the time of analysis; 1 patient was still on active<br />
therapy, and none had experienced recurrence. Median follow-up was<br />
2.5 years (range, 0.2-5.7 years).<br />
Conclusions. Nonmetastatic retinoblastoma with high risk pathologic<br />
features may be cured with a short course of chemotherapy with good<br />
toxicity profile. Thus, intensive metastatic work-up and aggressive<br />
chemotherapy are not required.<br />
Financial disclosure. None<br />
1916 RBp103<br />
TEN YEARS OF EXPERIENCE IN THE TREATMENT OF<br />
INTRA-OCULAR RETINOBLASTOMA IN A SINGLE<br />
INSTITUTION IN BRAZIL<br />
Carla R. Donato Macedo1, Luiz F. Teixeira1,2, Camila H. Hashimoto1, Virginia<br />
L. L Torres1,2, Juliana dos Santos Soares1, Maria T. Seixas1,3, Maria C.<br />
Martin 2, Clelia M. Erwenne1,2 (carladonatomacedo@uol.com.br)<br />
1. Pediatric Oncology Institute/GRAACC/Unifesp<br />
2. Ophthalmology Department/ Unifesp<br />
3. Pathology Department /Unifesp<br />
Purpose. Present clinical and epidemiological features, treatment<br />
modalities and survival of patients with intra-ocular retinoblastoma<br />
Methods. Data as epidemiological features, laterality, international<br />
staging of retinoblastoma, treatment modalities, survival and the<br />
incidence of second malignancies were collected.<br />
The best initial and subsequent treatments were based on whether the<br />
child has unilateral or bilateral disease, the stage of the disease, and<br />
the age of the child.
Results. A total of 183 patients with retinoblastoma, 50,3% male<br />
and 49,7% female. 63% of white ethnicity. Leucocoria was the most<br />
commom initial presentation (65%). 67,2% had unilateral and 33%<br />
bilateral retinoblastoma (243 eyes).<br />
43% of eyes underwent enucleation as primary treatment, of these,<br />
19% received chemotherapy as adjuvant treatment. Chemotherapy<br />
with focal therapy FT was given to 52% of eyes as first treatment,<br />
associated with periocular carboplatin in 8%, brachytherapy in 3%,<br />
external beam radiotherapy (EBRT) in 1%, and one eye received EBRT<br />
and brachytherapy, 12% of these eyes underwent enucleation during<br />
the treatment. 4% received FT alone. None of the patients died with<br />
chemotherapy toxicity.<br />
Intra-ocular recurrent disease occurred in 23% of the eyes with 57% of<br />
eye salvage. 2 patients had recurrent extra-ocular disease with orbital<br />
disease, and bone and bone marrow disease, respectively. Two patients<br />
presented with a bone tumor as second malignancy.<br />
Conclusions. There are several options for treatment of retinoblastoma,<br />
and the multidisciplinary team should be thoroughly familiar with the<br />
indications, technique, and expected Results of all treatment Methods<br />
as well as the expected systemic and visual problems.<br />
Financial disclosure. None<br />
60 RBp104<br />
DIFFERENT CHARACTERISTICS OF GERMLINE AND<br />
NON-GERMLINE RETINOBLASTOMA<br />
Fariba Ghassemi MD1, Hormoz Chams MD1, Siamak Sabour MD2,3,<br />
Reza Karkhaneh MD1, Farzad Farzbod MD1, Mehdi Khodaparast MD1,<br />
Parvaneh Vosough MD4<br />
1. Ocular Oncology and Retina &Vitreous Service, Farabi Hospital,<br />
Tehran University of Medical Sciences.<br />
2. Department of Epidemiology, Faculty of Health, Shahid Beheshti<br />
University of Medical Sciences.<br />
3. Health Promotion and Injury Prevention Research Centre, Shahid<br />
Beheshti University of Medical Sciences.<br />
4. Oncology Service, Mahak Hospital, The Society for Supporting the<br />
Children Suffering from Cancer, Tehran, IR Iran.<br />
Purpose. Retinoblastoma (RB) is a relatively common childhood tumor.<br />
This report discusses clinical characteristics, treatments and outcome<br />
of Germline and Non-germline retinoblastoma patients from a referral<br />
centre in Iran.<br />
Methods. A retrospective study was carried out on cases treated in<br />
Farabi Hospital between 1979 and 2007. The variables analyzed were<br />
age, sex, affected eyes, time of the diagnosis, treatment modalities,<br />
pathological findings and the survival in two groups, i.e. Germline and<br />
Non-germline patients.<br />
Results. We analyzed 557 cases (734 eyes) with a mean age of 32.2<br />
months (Standard Deviation = 22). Male predominance was especially<br />
observed in the Germline group (P< 0.05). There were 380 unilateral<br />
cases (68.6%). Germline cases were different than Non-germline group<br />
in mean age, symptoms, and outcome (P
months. Mean delay between beginning of symptoms and first visit<br />
by a physician was about 3 months. The most common presenting<br />
signs were leukocoria (68%), strabismus (20%) and red eye (7%).<br />
86.8% of unilateral cases and 46.3% of bilateral cases presented<br />
with advanced Rb (groups D-E). Enucleation was done primarily<br />
for 77% of unilateral cases and 35% of bilateral cases. Secondary<br />
enucleation was necessary in 6% and 7% of unilateral and bilateral<br />
cases respectively.<br />
The 5-year cumulative patients survival rate was 94% and 84% for<br />
unilateral and bilateral cases respectively. Overall 5-year survival<br />
rate was 89%.<br />
Conclusions. Prognosis of Rb cases in developing countries is<br />
promising in terms of both globe and patients survival because of<br />
established multidisciplinary coordinated services.<br />
Financial disclosure. None<br />
40 RBp107<br />
EXPERIENCE IN TREATMENT OF METASTATIC &<br />
NON-METASTATIC ORBITAL RETINOBLASTOMA IN A<br />
SINGLE INSTITUTION<br />
Carlos A. Leal, Julieta Robles-Castro, Gabriela Isaac, Vanessa Bosch<br />
(drcarlosaleal@msn.com)<br />
Retinoblastoma Clínic Instituto Nacional de Pediatra Mexico<br />
Purpose. Orbital Retinoblastoma is an infrequent condition in<br />
developed countries, while, on the contrary, in developing countries,<br />
it is diagnosed in 50% of patients. We evaluated the prognosis of<br />
metastatic & no metastatic orbital disease treated with radio- and<br />
chemotherapy.<br />
Methods. A prospective study of the last 15 years regarding treatment<br />
with chemotherapy and radiotherapy.<br />
Results. Five hundred patients with Retinoblastoma were studied.<br />
Thirty percent presented with orbital disease, and of these, 50% were<br />
metastatic. The two-year overall survival of patients with metastatic<br />
disease to the central nervous system was 10%.<br />
The presence of only a positive optic nerve had a better prognosis<br />
than gross orbital disease.<br />
Overall survival of patients with positive optic nerve without<br />
metastatic disease treated with chemo and radiotherapy was 65%.<br />
Neoadjuvancy avoided exenteration and did not affect prognosis.<br />
We evaluated 4 different chemotherapy schemes. The best one was<br />
carboplatin, etoposide, cyclophosfamide.<br />
Conclusions. A positive nerve has a better prognosis than orbital<br />
disease. BMT is necessary for metastatic disease. Carbo vp CFA is<br />
appropiate scheme for advance disease. Neoadjuvancy does not<br />
affect prognosis.<br />
Financial disclosure. None<br />
836 RBp108<br />
ERG MONITORING OF RETINAL FUNCTION DURING<br />
SYSTEMIC CHEMOTHERAPY FOR RETINOBLASTOMA<br />
Scott E. Brodie, M.D., Ph.D.1,4 , Yannis M. Paulus, M.D.1, Mrinali Patel,<br />
M.D.1, Y.<br />
Pierre Gobin, M.D.3, ,1 , Ira J. Dunkel, M.D.2, Brian Marr, M.D.1, David H.<br />
Abramson, M.D.1 (scott.brodie@mssm.edu)<br />
RETINOBLASTOMA<br />
Posters<br />
50<br />
1. Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center,<br />
New York, N.Y.<br />
2. Dept. of Pediatrics, Memorial Sloan-Kettering Cancer Center, New<br />
York, N.Y.<br />
3. Division of Interventional Neuroradiology, Department of Radiology,<br />
Neurosurgery, and Neurology, Weill Cornell Medical College, New York, N.Y.<br />
4. Dept. of Ophthalmology, Mt. Sinai School of Medicine, New York, N.Y.<br />
Purpose. To assess the effect of systemic chemotherapy as initial<br />
treatment for retinoblastoma on retinal function by ERG testing.<br />
Methods. Patients referred for initial treatment of retinoblastoma<br />
who were considered unsuitable for local ablative treatment or intraarterial<br />
chemotherapy received intravenous carboplatin (18.7 mg/kg IV<br />
over one hour) treatment every 3-5 weeks for two to four cycles. ERG<br />
recordings were obtained at baseline and at susbsequent examinations<br />
under anesthesia using a hand-held ganzfeld stimulator, according to<br />
a modified ISCEV standard protocol. The responses to 30-Hz flicker<br />
stimulation were adopted as a proxy for the entire set of ERG responses,<br />
as photopic and scotopic responses were highly correlated. A change in<br />
response amplitude of 25 µV was considered clinically significant.<br />
Results. We report ERG findings in 4 patients (8 eyes) who received<br />
primary IV carboplatin for bilateral retinoblastoma. Retinas were<br />
attached at presentation and throughout IV chemotherapy in all 8 eyes.<br />
All four patients (8 eyes) responded well to initial IV chemotherapy. 30-<br />
Hz flicker ERG responses improved in all eyes, significantly in 6 of 8 eyes<br />
(at least one eye of each patient).<br />
Conclusions. These findings suggest that retinal function may improve<br />
following initial treatment of retinoblastoma with IV carboplatin, quite<br />
apart from improvements due to resolution of retinal detachment. This<br />
observation suggests a deleterious effect on retinal function of the presence<br />
of untreated tumors. The potential for functional improvement argues for<br />
globe-preserving therapy even in the presence of extensive retinoblastoma,<br />
as such eyes may retain significant potential for useful vision.<br />
Financial disclosure. None<br />
2117 RBp109<br />
UTERINE LEIOMYOSARCOMA IN RETINOBLASTOMA:<br />
HOW SHOULD WE COUNSEL OUR PATIENTS?<br />
Jasmine H. Francis1, Ruth A. Kleinerman2, David H. Abramson1<br />
(jasminehfrancis@gmail.com)<br />
1. Ophthalmic Oncology Service, Memorial Sloan-Kettering Cancer Center,<br />
New York, NY;<br />
2. Division of Cancer Epidemiology and Genetics, National Cancer<br />
Institute, National Institutes of Health, Rockville, MD<br />
Purpose.. We have previously reported a substantial excess risk for<br />
leiomyosarcomas (LMS) of the corpus uteri more than 30 years after<br />
diagnosis of hereditary retinoblastoma. Here, we describe updated<br />
patient and risk characteristics for uterine LMS (ULMS) and discuss<br />
patient management relative to these findings.<br />
Methods. A cohort study and retrospective chart review. The excess risk<br />
was calculated as the observed number of uterine leiomyosarcoma minus<br />
the expected number based on general population rates times 10,000.<br />
Results. In our cohort of 900 female retinoblastoma survivors, 8 patients<br />
developed ULMS and seven (87.5%) of these patients had hereditary<br />
retinoblastoma. In this latter group, the average age of ULMS diagnosis<br />
was 41.4 (+/- 7.9 years) and the average age of death was 44.2 (+/-<br />
2.9) years. The excess risk of ULMS was 3.87 per 10,000 women with<br />
hereditary retinoblastoma over all ages. However, as patients enter the
age when at risk for ULMS, this excess risk increased dramatically: to<br />
20/10,000 for female hereditary retinoblastoma patients aged between<br />
30-39 years, and to 27/10,000 for patients aged 40+ years. Cumulative<br />
risk at 50 years of age for ULMS in hereditary retinoblastoma patients<br />
was 3.18% (95%CI 0.91%-7.98%).<br />
Conclusions. There is a substantial excess risk of ULMS in female<br />
hereditary retinoblastoma patients, particularly over 30 years of age.<br />
As more patients survive into their thirties, this number is likely to<br />
increase. Relative to these findings, we provide a perspective on how<br />
best to counsel hereditary retinoblastoma patients on lifestyle risk<br />
factors, early childbearing, screening and even prophylactic measures;<br />
all topics that are important, but not well-established for this group of<br />
patients.<br />
Financial disclosure. None<br />
1700 RBp110<br />
MONITORING AND DISCUSSING QUALITY OF LIFE IN<br />
RETINOBLASTOMA ROUTINE PRACTICE<br />
A.C. Moll, M.I. Bosscha, G. LaRiviere, W.A. Kors, I. Verdonck-de Leeuw, J.<br />
van Dijk, J. Huisman (a.moll@vumc.nl)<br />
VU University Medical Center, Department of Ophthalmology,<br />
Amsterdam, The Netherlands<br />
Purpose. To assess feasibility of routine monitoring of quality of life<br />
(QOL) in retinoblastoma patients and their parents to facilitate early<br />
detection of problems and optimize referral to supportive care.<br />
Methods. Just before the yearly follow-up visit retinoblastoma patients<br />
were asked to complete QOL (SDQ, GHQ28) questionnaires and to<br />
answer some specific retinoblastoma questions via a desktop computer<br />
touch-screen, in separate quiet rooms, supervised by a trained staff<br />
member. Outcomes were discussed face-to-face during consultation<br />
with the ophthalmologists. Feasibility of RetinoQuest was evaluated<br />
using study specific questionnaires.<br />
Results. The questionnaire was completed by 36 patients or parents and<br />
by 2 physicians. Retinoquest increased the awareness of patients, parents<br />
and physicians for psychosocial problems and improved communicating<br />
between patient/parent and physician. The 10 adolescents (11-17 year)<br />
were able to fill in the questionnaire independently. The 20 parents of<br />
young children (4-11 year) were all very content about the attention for<br />
psychosocial problems. The 6 adults (21-62 year) ranged from positive<br />
to neutral to negative. The scores of the QOL questionnaires could be<br />
divided in 3 groups: patients with no problems, patients with known<br />
problems and a third group, who had the most benefit because of the<br />
shared awareness of psychosocial problems. They were immediately<br />
referred to our psychologist, a member of the retinoblastoma team, to<br />
set up an individualized supportive care plan.<br />
Conclusions. Touch-screen computer-assisted health-related quality of<br />
life data collection in retinoblastoma patients has yielded positive Results<br />
it is feasible and can be used for clinical and scientific documentation.<br />
Financial disclosure. None<br />
242 RBp111<br />
DOES PARENTAL SOCIOECONOMIC AND EDUCA-<br />
TIONAL STATUS INFLUENCE RETINOBLASTOMA INI-<br />
TIAL PRESENTATION AND ITS SUBSEQUENT MOR-<br />
BIDITIES?<br />
RETINOBLASTOMA<br />
Posters<br />
51<br />
Daniel Colicchio1,2, Carla D. Macedo2, Juliana dos Santos Soares2, Luiz<br />
F. Teixeira1,2 (dcolicchio@gmail.com)<br />
1. Department of Ophthalmology - Federal University of São Paulo -<br />
UNIFESP - EPM<br />
2. Pediatric Oncology Institute - GRACC - UNIFESP<br />
Purpose. To evaluate the relationship between socioeconomic and<br />
parental educational status with retinoblastoma initial grouping<br />
presentation and its morbidities.<br />
Methods. Retrospective analysis of 105 randomly selected patients<br />
presenting with intraocular retinoblastoma.<br />
The following socioeconomic variables were evaluated through selfanswering<br />
questionnaires: parental educational status, family income,<br />
rural or urban living, State of birth, first person to note any symptom,<br />
first sign/symptom noted.<br />
Results. Analyzing the socioeconomic and environmental correlations<br />
with the tumor stage at the initial presentation and the subsequent<br />
morbidities, the following conditions didn’t have any influence in the<br />
earlier diagnosis and better prognosis: rural or urban living, parental<br />
educational status, family income, State of birth, first sign/symptom<br />
noted. The only variable with statistical meaning showed that when<br />
health care professionals were the first person to note any symptom/<br />
sign, the child presented higher rates of non-group D/E stage (43% vs.<br />
9.3%) and less enucleation rates (50.0% vs. 83.7%).<br />
Conclusions. Although there are some theories that low cultural and<br />
financial aspects are related with risk factors for late presentation of<br />
retinoblastoma, the data collected did not show anything that would<br />
contribute to these theories. It also denoted that the patients didn’t<br />
benefit in prevention or early detection despite the money and education<br />
of their parents, probably because retinoblastoma is a rare disease and<br />
even well-educated groups have little information about it.<br />
Eye examination by health care professionals (eg. Pediatricians,<br />
Ophthalmologists) performed during the entire childhood could be<br />
effective in earlier diagnosis and better prognosis of retinoblastoma.<br />
Financial disclosure. None<br />
1534 RBp112<br />
ARE SOCIOECONOMIC STATUS (SES) AND ETHNICITY<br />
RISK FACTORS FOR THE PRESENTATION OF<br />
ADVANCED RB (RB) IN THE UK?<br />
M. Ashwin Reddy1, Rabia Bourkiza1, Archana Kulkarni2, Manoj<br />
Parulekar2, Phillippa Cumberland3, Mandeep Sagoo1, John Hungerford1,<br />
Jugnoo Rahi3 (mashwinreddy@hotmail.com)<br />
1. Barts and the London NHS Trust<br />
2. Birmingham Children Hospital<br />
3. University College London Institute of Child Health<br />
Purpose. To identify features of patients in the UK with advanced RB as<br />
designated by the International Intraocular RB Classification.<br />
Methods. Retrospective review of sporadic cases presenting with early<br />
RB (B&C) and advanced RB (D&E) over 3 years. SES was identified via<br />
zip code and quintile categories of the Index of Multiple Deprivation:<br />
analysed via multinomial regression.<br />
Results. Of 122 patients, the most deprived had an increased likelihood<br />
of having groups D&E compared to B&C. After adjustment for ethnicity<br />
this was marginally significant in group E (Risk Ratio, most deprived<br />
compared to mid-quintile, 3.7 [95% CI 0.8, 16] p = 0.08). Ethnicity was
not associated with severity of RB.<br />
Conclusions. Directing awareness campaigns to low SES groups may be<br />
of benefit in the UK but ethnicity was not a factor.<br />
Financial disclosure. None<br />
352 RBp113<br />
NEUROPSYCHOMOTOR DEVELOPMENT OF EYE<br />
ENUCLEATED CHILDREN WITH RETINOBLASTOMA<br />
Marcela Bagnatori Braga, Juliana dos Santos Soares, Carla R. Donato<br />
Macedo, Walquyria de Almeida Santos (mabagnatori@uol.com.br)<br />
Purpose. Retinoblastoma is the most common malignant ocular tumor<br />
of childhood, usually presenting before four years of age. The incidence<br />
in Brazil shows an average of 3 to 5 cases/million in children younger<br />
than 14 years old.<br />
Currently, the cure rates of Retinoblastoma are higher because<br />
of the advances in diagnosis and treatment. However, aesthetic,<br />
ophthalmologic, neurocognitive and social effects, as well as visual<br />
impairment, makes eye enucleated children with Retinoblastoma<br />
likely to show deficits in Neuropsychomotor Development and/or<br />
Sensory Integration. The Purpose is present the possible changes in<br />
Neuropsychomotor Development and/or Sensory Integration of eye<br />
enucleated children with Retinoblastoma.<br />
Methods. A study was made at the Pediatric Oncology Institute - GRAACC<br />
/ UNIFESP - São Paulo - Brazil. Two assessment tools were used, the<br />
PEDI and the Sensory Profile.<br />
Results. It was possible to check that children in this sample showed<br />
deficits in Neuropsychomotor Development and/or Sensory Integration.<br />
These changes were graduated from minimal to maximum – following<br />
the assessments used.<br />
Conclusions. From this study was contested an alteration in<br />
Neuropsychomotor Development and/or Sensory Integration of these<br />
children related to the disease, treatment and consequences in the<br />
sensorial and motor system of this population.<br />
Financial disclosure. None<br />
345 RBp114<br />
NURSING GUIDELINES FOR SELF-CARE OF PATIENTS<br />
WITH PROSTHETIC RETINOBLASTOMA: AN EXPERI-<br />
ENCE REPORT<br />
Juliana dos Santos Soares, Carla R.D. Macedo, Adriana M. Duarte<br />
(js_soares3@hotmail.com)<br />
Purpose. Retinoblastoma (RB) is a rare cancer in retina, representing<br />
about 4% of all malignancies of childhood. The treatment modalities<br />
include chemotherapy, focal therapy, radiation and enucleation,<br />
according to the stage of disease. Upon receiving news of the<br />
enucleation, child and family tend to be fragile and frightened by the<br />
surgical procedure, the change in self-image and lifestyle after surgery.<br />
In this context, the role of nurse has great value in educating the patient<br />
and family providing support to deal with the new situation. The Purpose<br />
is to report the experience lived by a Nurse at a Brazilian Hospital of<br />
Pediatric Oncology with the orientation of a child with RB and her family<br />
for self-care after enucleation.<br />
Methods. It is an experience report. About 19 queries were held with<br />
the child and her family immediately after enucleation indication and<br />
throughout the adaptation process in the period from September<br />
2010 to July 2011. With appropriate language for the child age and<br />
RETINOBLASTOMA<br />
Posters<br />
52<br />
parents understanding, graphics and ocular prosthesis models were<br />
used for explanation of the whole procedure and required care after<br />
enucleation.<br />
Results. Subjects discussed in the meetings varies since surgery<br />
procedure to prosthetic eye care. After 10 months of starting the treatment,<br />
child and family became more calm and confident when talking about the<br />
experience of enucleation. The child showed to be able to perform selfcare<br />
under supervision of her mother.<br />
Conclusions. The sections were productive, with effective participation<br />
of patient and parents. As a result of these encounters, a plan for<br />
systematic and individualized care was prepared, with quality, by<br />
identifying the real needs of the child submitted to enucleation and her family.<br />
Financial disclosure. None<br />
33 RBp115<br />
EYE SALVAGE RATE IN 166 PATIENTS WITH INTRAOC-<br />
ULAR RETINOBLASTOMA<br />
Luiz F. Teixeira1,2, Carla R. Donato Macedo2, Virginia L. L Torres1,2,<br />
Camila H. Hashimoto2, Rubens Belfort Neto1,2, Juliana dos Santos<br />
Soares2, Clelia M. Erwenne1,2 (luizfteixeira@hotmail.com)<br />
1. Depatment of Ophthalmology, Federal University of Sao Paulo-<br />
UNIFESP<br />
2. Pediatric Oncology Institute/GRAACC/UNIFESP<br />
Purpose. To evaluate the eye salvage rate in 166 patients with<br />
intraocular retinoblastoma.<br />
Methods. Retrospective review of 217 consecutive eyes with intraocular<br />
retinoblastoma (115 unilateral cases and 51 bilateral cases).<br />
Results. A total of 217 eyes, 9 group A eyes (4%), 22 group B eyes<br />
(10%), 17 group C eyes (8%), 53 group D eyes (24%) and 116 group E<br />
eyes (54%) were treated.<br />
112 eyes (52%), (10 eyes (19%) of group D and 102 eyes (88%) of group<br />
E) were treated with enucleation as primary treatment.<br />
Systemic chemotherapy and/or local therapy were performed as first<br />
treatment in 105 eyes (46%), (9 group A, 22 group B, 17 group C, 43<br />
group D and 14 group E). External beam radiotherapy (EBRT) was used<br />
for major tumor recurrence. Analysing conservative therapies the eye<br />
salvage rate considering all forms of treatments and excluding EBRT<br />
was respectively: 100%/100% for group A, 95%/95% for group B,<br />
88%/82% for group C, 49%/40% for group D and 28%/14% for group<br />
E.<br />
From 217 eyes diagnosed with intraocular disease, 70 eyes (32%) were<br />
saved.<br />
The final eye salvage rate was 100% for group A (n=9), 95% for group<br />
B (n=21), 88% for group C (n=15), 40% for group D (n=21) and 3% for<br />
group E (n=4).<br />
Conclusions. Advanced intraocular disease, group D and E represent<br />
more than 70% of the intraocular disease treated in our institution<br />
with a high rate of primary or secondary enucleation. Groups A, B and<br />
C present excellent outcomes but represent only 28% of the eyes.<br />
Financial disclosure. None<br />
933 RBp116<br />
SYSTEMIC CHEMOTHERAPY IN THE MANAGEMENT<br />
OF RETINOBLASTOMA<br />
John D. McKenzie1, Nisha Sachdev1, Sandra Staffieri1,4, Kary Suen1 , James<br />
E. Elder1,2, John Heath2,3, Peter Downie3 (jdmckenzieonline@gmail.com)
1. Department of Ophthalmology, Royal Children’s Hospital, Melbourne<br />
2. Department of Paediatrics, University of Melbourne<br />
3. Children’s Cancer Centre, Royal Children’s Hospital, Melbourne<br />
4. Centre for Eye Research Australia, University of Melbourne<br />
Purpose. To demonstrate the utility of utilising systemic chemotherapy<br />
as adjunctive therapy for the management of retinoblastoma.<br />
Methods. Nine consecutive patients treated with systemic<br />
chemotherapy are described. All have presented with differing<br />
classification of retinoblastoma (according to International<br />
Classification or Retinoblastoma) including 3 with optic nerve<br />
involvement at presentation. No patients had bone marrow infiltration<br />
or CSF involvement.<br />
Results. Each case will be presented individually. Chemotherapy<br />
regimes varied according to “aggressiveness” of tumour and whether<br />
optic nerve invasion was evident. The number of cycles of chemotherapy<br />
changed according to the clinical response as evident on serial EUA’s.<br />
Conclusions. Systemic chemotherapy has revolutionised the<br />
management of retinoblastoma, providing excellent tumour regression<br />
allowing focal therapy to be applied. This therapy frequently avoids<br />
the previously “gold standard” of enucleation.<br />
Financial disclosure. None<br />
2225 RBp117<br />
COMPARISON BETWEEN OPHTHALMIC ARTERIAL<br />
INJECTION THERAPY AND CHEMOREDUCTION AS<br />
PRIMARY THERAPY FOR INTRAOCULAR RETINOBLAS-<br />
TOMA<br />
Takashi Yamane, Nobuyuki Suzuki, Makoto Mohri (joecool777jp@<br />
yahoo.co.jp)<br />
Saiseikai Yokohamashi Tobu Hospital<br />
Purpose. For retinoblastoma patients, we have performed ophthalmic<br />
arterior injection therapy (OPAI) by using melphalan from 1988. We<br />
compared OPAI as primary therapy with OPAI after chemoreduction<br />
retrospectively, and examined the validity of OPAI.<br />
Methods. 128 eyes were treated by chemoreduction (VEC 2-6 course)<br />
before OPAI. ICRB A: 2, B: 45 C: 22 D: 46 E: 13 eyes<br />
49 eyes were treated by OPAI from start of therapy. A: 2, B: 30, C: 5, D:<br />
9, E: 3 eyes<br />
Each eye preservation rate was examined. Most of OPAI were combined<br />
with laser therapy.<br />
Results. Eye preservation rate was as follows:<br />
OPAI after chemoreduction, A: 100%, B: 82% C: 59% D: 41% E: 31%.<br />
OPAI as primary therapy, A: 100%, B: 93% C: 40% D: 78% E: 33%<br />
Conclusions. Ophthalmic arterial injection chemotherapy using<br />
melphalan can expect eye preservation more than an equivalence<br />
compared with chemoreduction following OPAI. We would like to add<br />
statistically examination furthermore.<br />
Financial disclosure. None<br />
942 RBp118<br />
INTRA-ARTERIAL CHEMOTHERAPY FOR RETINOBLAS-<br />
TOMA: FIRST AUSTRALIAN EXPERIENCE<br />
John D. McKenzie1, Nisha Sachdev1, Sandra Staffieri1,4, James E. Elder1,2, John<br />
Heath2,3, Peter Downie3, Peter J Mitchell5,6 (jdmckenzieonline@gmail.com)<br />
RETINOBLASTOMA<br />
Posters<br />
53<br />
1. Department of Ophthalmology, Royal Children’s Hospital; 2. Department<br />
of Paediatrics, University of Melbourne; 3. Children’s Cancer Centre, Royal<br />
Children’s Hospital;<br />
4. Centre for Eye Research Australia, University of Melbourne; 5.<br />
Department of Radiology, Royal Melbourne Hospital, Parkville; 6.<br />
Neurointervention Service, University of Melbourne, Melbourne<br />
Purpose. To present the first Australian case of using intra-arterial<br />
chemotherapy for primary treatment of Retinoblastoma<br />
Methods. A child was referred with leukocoria to Royal Children’s Hospital in<br />
Melbourne. Examination revealed a large lobulated posterior segment mass<br />
occupying more than 50% of the globe. IOP and anterior examination was<br />
normal. MRI showed no extrascleral extension, no optic nerve involvement.<br />
LP, Bone Marrow Aspirate and trephine biopsy was normal.<br />
Standard treatment of primary enucleation was offered to the parents,<br />
which was denied. Globe preservation was strongly desired by the parents<br />
due to the child’s previous history of self-induced wound dehiscence.<br />
It was decided that intra-arterial chemotherapy could be offered as<br />
primary therapy for this large retinoblastoma. Clinical Ethics Committee<br />
approval was obtained to offer this treatment.<br />
Results. Four cycles of intra-arterial chemotherapy (Melphalan 5mg,30<br />
min infusion) were administered monthly. Serial EUA’s and MRI’s were<br />
arranged during this time period. Apart from significant sterile orbital<br />
cellulitis after the inital treatment the intra-arterial chemotherapy was<br />
well tolerated. MRI following the fourth cycle revealed an inferotemporal<br />
orbital mass on the revealed a retinoblastoma deposit. Bone marrow<br />
aspirate and trephine biopsy showed bone marrow infiltration. He<br />
has subsequently had 4 cycles of quadruple systemic chemotherapy<br />
(Vincristine, Etoposide, Carboplatin, Cyclophosphamide).<br />
Conclusions. Intra-arterial chemotherapy for retinoblastoma is an<br />
emerging treatment modality as primary therapy for retinoblastoma;<br />
however, as this case illustrated, further study into the precise<br />
chemotherapeutic agents that should be used and frequency for these<br />
require to be established.<br />
Financial disclosure. None<br />
817 RBp119<br />
OUTCOMES OF GROUP D RETINOBLASTOMA EYES<br />
J.L. Berry1, H. Almarzouki2, S.R. Bababeygy1, T.H. Lee1, 2, R. Jubran2,<br />
A.L. Murphree1, 2 (jesse.berrymd@gmail.com)<br />
1. Doheny Eye Institute, Los Angeles, CA<br />
2. Childrens Hospital of Los Angeles, Los Angeles, CA<br />
Purpose. To determine treatment outcomes of Group D retinoblastoma eyes.<br />
Methods. Retrospective chart review.<br />
Results. All patients diagnosed with retinoblastoma and classified as<br />
Group D in at least one eye during a ten-year period from January 1, 2000<br />
to December 31, 2009 at Childrens Hospital Los Angeles were included.<br />
107 eyes of 94 patients were included in the study; 44 patients had<br />
unilateral disease and 50 had bilateral disease, 13 of which had bilateral<br />
Group D disease. 50 of 107 Group D eyes were enucleated primarily. 57<br />
eyes were treated with systemic and local chemotherapy, as well as local<br />
consolidation. 27 of 57 eyes (47%) were salvaged with chemotherapy and<br />
consolidation therapy. 30 eyes had recurrences; 5 eyes were enucleated<br />
and 25 eyes were treated with 36 Gy intensity modulated radiotherapy<br />
(IMRT). Of the 25 irradiated eyes, 20 (80%) were salvaged. 5 eyes were<br />
enucleated after IMRT treatment. Two patients died from retinoblastoma,<br />
1 from a midline primitive neuroectodermal tumor and the other from CNS<br />
metastases without ocular recurrence. Final visual acuity ranged from<br />
20/20 to light perception with 10 eyes having 20/80 vision or better. 4<br />
eyes had 20/200 vision. Mean length of follow up was 42.6 months.
Conclusions. During a ten-year period, 47 of 57 (82%) treated Group D<br />
eyes were salvaged. 47% (27/57) were salvaged with systemic and local<br />
chemotherapy alone. 20 of 57 (35%) eyes required IMRT for salvage.<br />
In our series, systemic treatment for retinoblastoma even in advanced<br />
eyes can salvage a majority of eyes, many with functional vision.<br />
Financial disclosure. Doheny core grant support: NIH Grant EY03040 and Research to Prevent<br />
Blindness<br />
417 RBp120<br />
THE FIRST EXPERIENCE OF RETINOBLASTOMA TREAT-<br />
MENT WITH THE USE OF SUPERSELECTIVE INTRA-AR-<br />
TERIAL CHEMOTHERAPY IN RUSSIA<br />
S.V. Saakyan1 , S.B. Yakovlev2, G.L. Kobyakov2, N.K. Serova2, A. Jarwa1<br />
(svsaakyan@yandex.ru)<br />
1. Moscow Helmholtz Research Institute of Eye Diseases<br />
2. Moscow Scientific Neurosurgery Institute named after Burdenko<br />
Purpose. Evaluate the effectiveness of SSIAC in treatment of patients<br />
with multifocal retinoblastoma with vitreal seeding.<br />
Methods. 12 children of 1- 6 years of age with retinoblastoma of Stages<br />
D and E, including 9 children with binocular retinoblastomas, were<br />
managed. 10 patients underwent unsuccessful systemic chemotherapy<br />
previously. On average 3 single injections of SSIAC using a 50 mg dose<br />
of carboplatinum were conducted in each case.<br />
Results. Preservation of 8 eyes was achieved with the use of SSIAC (1<br />
eye in a patient with monocular retinoblastoma and 7 eyes in patients<br />
with binocular retinoblastoma), resulting in 67% ocular preservation<br />
rate. Observed findings included a decrease in prominension and<br />
a development of calcifications in the main focus and the vitreal<br />
seedings.<br />
Conclusions. Conclusion: Our first experience demonstrated that SSIAC<br />
allows for ocular preservation and improves the effectiveness of therapy<br />
in children with advanced stages of retinoblastoma.<br />
Financial disclosure. None<br />
2317 RBp121<br />
MISSING INTRAOCULAR BLUSH IN AN ANGIOGRAPHY<br />
OF AN ADVANCED INTRAOCULAR RETINOBLASTOMA<br />
M. Holdt, S. Göricke, E. Biewald, M. Schündeln, N. Bornfeld, M.<br />
Schlamann (markus.holdt@uk-essen.de)<br />
Department of Ophthalmology, Department of Radiology, Department<br />
of Pediatric Oncology<br />
Purpose. To find out therapeutical option for a single case with<br />
advanced bilateral sporadic retinoblastoma (both eyes classified E)<br />
Methods. In a case of a 13 month old girl with bilateral sporadic<br />
retinoblastoma, both eyes were classified E (International Intraocular<br />
Retinoblastoma Classification) or Vb (Reese-Ellsworth-Classification)<br />
without light perception. All examinations including MRI showed no<br />
extraocular pathology. The more affected eye was primary enucleated<br />
without revealing histopathological risk factors. The attempt to<br />
preserve the less affected eye with superselective ophthalmic artery<br />
chemotherapy was discontinued due to not demarcated intraocular<br />
blush beside expanded exophytic tumor masses with retinal<br />
detachment. Angiography showed broad perfusion of periocular<br />
tissues like lacrimal gland or nasal mucosa and a strong anastomosis<br />
RETINOBLASTOMA<br />
Posters<br />
54<br />
to anterior meningeal artery. This eye was also primary enucleated<br />
without revealing histopathological risk factors. Hence no adjuvant<br />
chemotherapy, no other therapy was necessary.<br />
Results. The approach of superselective ophthalmic artery<br />
chemotherapy has limitations when intraocular blush is not<br />
definable.<br />
Conclusions. Primary enucleation with histopathological confirmed<br />
absence of risk factors still offers a therapy without any additional<br />
burden in these rare cases with clinical advice for germline mutation.<br />
Financial disclosure. None<br />
2004 RBp122<br />
CONSERVATIVE TREATMENT OF INTRAOCULAR<br />
RETINOBLASTOMA: A PROSPECTIVE PHASE II TRIAL<br />
FOR BILATERAL RETINOBLASTOMA WITH MACULAR<br />
OR PARAMACULAR INVOLVEMENT<br />
Christine Levy-Gabriel 1, Livia Lumbroso-Le Rouic 1, Isabelle Aerts 2,<br />
David Hajaje3, Alexia Savignoni 3, Nathalie Algret 3, François Doz 2,<br />
Laurence Desjardins 1 (christine.levy@curie.net)<br />
1. Department of ocular oncology, Institut Curie<br />
2. Department of oncologic pediatry, Institut Curie<br />
3. Department of Biostatistics, Institut Curie, Paris France<br />
Purpose. Intraocular retinoblastoma treatments often associate<br />
chemotherapy and focal treatments. The protocols vary and may<br />
combine two or three drugs, and different number of cycles associated<br />
to the ocular treatments. In order to decrease the possible long term<br />
sequels of laser scars for macular or paramacular tumors, a protocol of<br />
laser reduction was initiated.<br />
Methods. Monocentric prospective phase II study including children<br />
with bilateral retinoblastoma and macular or paramacular involvement.<br />
The protocol combines 6 cycles of of 3 drugs (vincristin carboplatin and<br />
etoposide), diode laser thermotherapy sparing macula is associated<br />
from the third cycle.<br />
Results. 19 children, 23 eyes with 23 macular or paramacular tumors were<br />
included in the study (July 2004-Sept 2009). Six tumors were treated<br />
with chemotherapy alone, 2 of them presented a local recurrence. 17<br />
tumors were treated with diode laser hyperthermy sparing macula, one<br />
of them reccured. 20 eyes were salvaged without EBRT, 1 needed EBRT,<br />
and 1 eye was enucleated<br />
Conclusions. Six cycles of of 3 drugs (vincristin carboplatin and<br />
etoposide) associated with diode laser thermotherapy sparing macula<br />
achieves good local control while probably decreasing laser macular<br />
scar. Visual function evolution will need longer follow-up.<br />
Financial disclosure. None<br />
1857 RBp123<br />
EXTRACTION OF RADIATION-INDUCED CATARACT IN<br />
PATIENTS WITH RETINOBLASTOMA<br />
Z. Islamov, F. Islom (dr_islamov@yahoo.com)<br />
National Center of Oncology, Uzbekistan<br />
Mercer University, United States<br />
Purpose. Analysis of Results of radiation-induced cataract extractions in<br />
patients with retinoblastoma.
Methods. From 2001 through 2010, 314 patients age 2 but
30 RBp127<br />
TREATMENT MODULATION IN RETINOBLASTOMA TUM-<br />
ORIGENESIS AND ITS IMPACT ON TUMOR BURDEN<br />
Timothy G. Murray, Samuel Houston, Christina L. Decatur, Nikesh Shah,<br />
Ludimila Cavalcante, and Yolanda Piña (tmurray@med.miami.edu)<br />
Bascom Palmer Eye Institute, University of Miami Miller School of<br />
Medicine, Miami, Florida, USA.<br />
Purpose. The Purpose of the current study is to examine vessel targeting,<br />
chemotherapy, and mammalian target of rapamycin (mTOR) inhibitor<br />
agents in LHBETATAG retinal tumors and their impact on tumor burden.<br />
Methods. Group A: Ten-week-old, LHBETATAG mice (n=30) received a<br />
single subconjunctival injection of anecortave acetate (AA; 1200, 600,<br />
300, and 150 µg) delivered to right eyes only. Group B: Ten-week-old,<br />
LHBETATAG mice (n=30) received a single subconjunctival injection of<br />
AA (600, 300, and 150 µg) delivered to right eyes only, either during<br />
a cycle of carboplatin (six subconjunctival deliveries) or after the<br />
completed cycle. Carboplatin was delivered at the subtherapeutic<br />
concentration of 62.5 µg. All animals were euthanatized at 16 weeks of<br />
age, and the eyes were examined histopathologically. Group C: Eighteenweek-old,<br />
LHBETATAG mice received (n=30) subconjunctival injections<br />
of rapamycin once weekly for two consecutive weeks (0.00333, 0.167,<br />
3.33, and 6.67 mg/kg). Tumor sections were analyzed for tumor burden<br />
with immunohistochemistry techniques.<br />
Results. A statistically significant reduction in tumor burden was<br />
detected after a single periocular injection of AA. The reduction of<br />
tumor burden followed a U-shaped dose-response curve. Tumor burden<br />
was significantly decreased when AA and carboplatin were combined.<br />
However, varying doses and delivery schedule of these agents had<br />
significant impact on the effectiveness of the combined treatment.<br />
The most effective scheme was delivering a low dose (150-300 µg) of<br />
AA after a complete cycle of carboplatin. Reduction in tumor burden<br />
were significantly different between rapamycin doses and control<br />
(pA, at the (-23) position of the<br />
intron 9 of the coding sequence of the retinoblastoma gene, RB1. This
ase substitution has not been previously documented as a germ line<br />
mutation associated with retinoblastoma.<br />
Conclusions. Bio-informatic analysis suggests this single base<br />
substitution creates a cryptic splice donor site in intron 9 leading<br />
to aberrant transcription of the RB1 gene. The significance of this<br />
mutation and mechanism to explain the incomplete penetrance is not<br />
known.<br />
Financial disclosure. None<br />
601 RBp130<br />
CNS ABNORMALITIES IN RTB PATIENTS<br />
T. Hadjistilianou1, S. De Francesco1, P. Galluzzi 2, A. Cerase2, A. Renieri3,<br />
F. Mari3, L. Micheli1, M. De Luca1, G.Coriolani4, C. Menicacci1, M. Borri1<br />
(hadjistilian@unisi.it)<br />
1. Ophthalmology Unit, Retinoblastoma Referral Center; 2.<br />
Neuroradiology Unit; 3. Genetics; 4. Dept.of Pediatrics, AOUS-Azienda<br />
Ospedaliera Universaitaria Senese<br />
Purpose. The presence of CNS abnormalities on MR images in a large<br />
group of consecutive patients with retinoblastoma is evaluated. Mental<br />
retardation and congenital brain anomalies are reported in patients with<br />
retinoblastoma, mostly in combination with 13q deletion syndrome.<br />
Pineoblastoma is the most important and “life threatening” condition<br />
associated with hereditary retinoblastoma, but recent studies suggest<br />
an association with pineal cysts.<br />
Methods. MR images of 320 consecutive patients with retinoblastoma<br />
from 2000 to 2010 were evaluated by neuroradiologists for tumors,<br />
structural anomalies, myelinization, and coincidental findings. Clinical<br />
records were reviewed for laterality, heredity, and the presence of the<br />
13q deletion syndrome.<br />
Results. The hereditary group (patients with bilateral and unilateral<br />
proved RB1-germline mutation) included 42 (48%) out of 87 patients.<br />
Nine patients had 13q deletion syndrome. Normal findings on brain<br />
MR images were seen in 307 (96%) patients. One pineoblastoma was<br />
detected in a patient with hereditary retinoblastoma. One arachnoid<br />
cyst in a sporadic unilateral RTB girl. One cerebral and corpus callosum<br />
atrophy, 3 pineal cysts were detected (2 non hereditary, 1 in 13q deletion<br />
syndrome). Corpus callosum agenesis was found in 3 patients (2 13q<br />
deletion syndrome, 1 hereditary RTB), corpus callosum hypoplasia in 3<br />
patients (2 twins, 1 sporadic RTB), both in combination with 13q deletion<br />
syndrome.<br />
Conclusions. Pineoblastoma is associated with hereditary retinoblastoma,<br />
and structural brain abnormalities are associated not only to patients<br />
with the 13q deletion syndrome. Pineal cysts can be detected in patients<br />
with sporadic retinoblastoma and/or with 13q deletion syndrome.<br />
Financial disclosure. None<br />
9 RBp131<br />
OPHTHALMOSCOPIC DIFFERENTIATION OF COATS’<br />
DISEASE FROM RETINOBLASTOMA<br />
Jerry A. Shields, Carol L. Shields (jerryshields@comcast.net)<br />
Wills Eye Institute, Philadelphia PA<br />
Purpose. Coats’disease (CD) and retinoblastoma (RB) are clinically<br />
similar but it is important to differentiate them for clinical and legal<br />
reasons. This study was done to elucidate the clinical differentiate of<br />
these 2 conditions.<br />
RETINOBLASTOMA<br />
Posters<br />
57<br />
Methods. All patients with RB (>1500 cases) and CD (>200 cases)<br />
seen over 30 years were reviewed to establish relative clinical criteria that<br />
serve to differentiate them.<br />
Results. Clinical features that differed in CD and RB included nature of<br />
the pupillary reflex, color of subretinal fluid, and caliber and distribution<br />
of the retinal blood vessels. The pupillary reflex and color of subretinal<br />
material is generally yellow in CD and white to gray with RB. Macular<br />
involvement with CD generally shows yellow lipoproteinaceous<br />
exudation, whereas macular involvement with RB shows a white mass<br />
without exudation. The retinal blood vessels in CD are irregular in<br />
caliber, whereas in RB the retinal vessels are more uniformly dilated and<br />
more tortuous. The blood vessels in CD tend to remain visible from the<br />
posterior pole to the peripheral fundus, whereas the vessels in RB tend<br />
to disappear as dip into the adjacent or underlying neoplasm.<br />
Conclusions. Despite their superficial similarities, CD and RB have<br />
ophthalmoscopic features that differ from one another. Recognition of<br />
these differences can avoid erroneous diagnosis, misdirected therapy,<br />
and legal repercussions.<br />
Financial disclosure. None<br />
2149 RBp132<br />
PROTON IRRADIATION FOR RETINOBLASTOMA<br />
W. Sauerwein1, B. Timmerman2, N. Bornfeld3, J. Herault4, J. Farr2, B.<br />
Zimmermann1, A. Wittig5 (w.sauerwein@uni-due.de)<br />
1. University Duisburg- Essen, University Hospital Essen, Department of<br />
Radiation Oncology, Essen, Germany; 2. WPE gGmbH, Essen, Germany;<br />
3. University Duisburg- Essen, University Hospital Essen, Department of<br />
Ophthalmology, Essen, Germany<br />
4. Cyclotron Biomédicale, Centre Antoine-Lacassagne, 06200 Nice,<br />
France<br />
3. University Duisburg- Essen, University Hospital Essen, Department of<br />
Ophthalmology, Essen, Germany; 5. Klinikum der Philipps-Universität<br />
Marburg. Department of Radiation Oncology Marburg, Germany<br />
Purpose. External beam radiotherapy is a curative treatment in<br />
retinoblastoma leading to excellent functional Results at long term but<br />
burdened by the appearance of secondary cancers. Chemotherapy often<br />
has to be locally supported by coagulative treatments jeopardizing<br />
visual acuity. Furthermore, an increasing number of publication reports<br />
secondary malignancies after cytotoxic drugs in retinoblastoma<br />
patients. There is a need for radiotherapy techniques that reduce the<br />
irradiated volume limiting the dose to the eyeball and sparing normal<br />
tissues. Brachytherapy using radioactive plaques is a well-established<br />
modality but limited to small tumor lesions. Proton therapy offers a<br />
hypothetical approach for further improvements.<br />
Methods. Only 4 retinoblastoma patients received proton treatment by<br />
our group in the last decade. Three were able to collaborate and the<br />
treatment was performed similar to conventional proton irradiation for<br />
uveal melanoma. A five-year-old boy suffered from a recurrent tumor<br />
close to the papilla after a full course of external beam irradiation.<br />
After enucleation of one eye in early childhood, we had to treat a late<br />
recurrence on the other eye that involved not only the retina but also<br />
the anterior chamber. Finally a primary retinoblastoma of the posterior<br />
pole in an adult was irradiated by protons. Another indication was<br />
the irradiation of the orbit in a 1-year-old boy by a ventral field after<br />
enucleation of an eye with involvement of the orbit.<br />
Results. In the first case, vitreal spreading occurred 2 years after PT<br />
and the eye was lost. The histomorphological evaluation showed a<br />
complete control of the proton-irradiated lesion. In the second case,<br />
irradiation with 50 Gy in 25 fractions resulted in a complete remission
(follow-up 5 years). Two years after PT, the adult patient had a<br />
recurrent tumor that was controlled by brachytherapy. Proton therapy<br />
of the orbit in very young patients leads to bad cosmetic Results and<br />
should be avoided.<br />
Conclusions. Further efforts are necessary to find techniques that can<br />
be applied in very young children unable to collaborate. The technique<br />
has to include positioning without using ionizing radiation. In principle,<br />
a dose distribution limited to the eye and not damaging the growing<br />
bones can be achieved using two fields and an isocentric gantry.<br />
Financial disclosure. None<br />
52 RBp133<br />
MULTIPLE PLAQUE TREATMENT IN RETINOBLASTOMA<br />
Manoj Parulekar, Randhir Chavan, John Ainsworth, Helen Jenkinson, Dan<br />
Ford, David Spooner, Geoff Heyes (manojparulekar@aol.com)<br />
Birmingham Children’s Hospital, and University Hospitals Birmingham, UK<br />
Purpose. 106 Ruthenium plaque brachytherapy is a useful tool in salvage<br />
treatment of retinoblastoma with limited lateral irradiation and ease of<br />
use. To determine the safety and efficacy of multiple 106 Ruthenium<br />
plaque treatment for eyes with persistent or recurrent retinoblastoma.<br />
Methods. Retrospective review of all children treated in a single<br />
retinoblastoma centre over an eight year period (2002-2010).<br />
Results. 26 tumours in 21 eyes required brachytherapy as salvage<br />
treatment. 11.5mm (65%), 15.5mm (23%) and notched (12%) plaques<br />
were used. 52% tumours regressed after application of one plaque,<br />
and 25% required a further plaque to control disease. Although some<br />
radiation related complications were noted in the 5 eyes receiving more<br />
than one plaque, 4 of these eyes were salvaged with useful vision (<br />
mean visual acuity 0.6 logMAR).<br />
Conclusions. The main aim of salvaging eyes was achieved in most<br />
cases treated with multiple plaques. Despite the risk of complications,<br />
this high risk strategy might be suitable is some cases to avoid<br />
enucleation.<br />
Financial disclosure. None<br />
2301 RBp134<br />
ASSESSMENT OF POST-OPERATIVE VOMITING IN<br />
RETINOBLASTOMA PATIENTS AND THEIR SIBLINGS<br />
UNDERGOING EYE EXAMS UNDER ANESTHESIA<br />
Pascal Owusu-Agyemang, Elizabeth Rebllo, Radha Arunkumar, Joseph<br />
Ruiz, Dan Gombos (poagyemang@mdanderson.org)<br />
University of Texas M.D. Anderson Cancer Center; Retinoblastoma Center<br />
of Houston<br />
Purpose. To evaluate the incidence of emesis in the PACU in pediatric<br />
patients undergoing eye exams of minimal stimulation under<br />
anesthesia.<br />
Methods. We analyzed data from ophthalmologic procedures that<br />
did not involve a surgical incision, laser, and cryotherapy from our<br />
Automated Anesthesia Information System. Between January 2006 and<br />
July 2010 we found 76 patients with a diagnosis of or need for screening<br />
for retinoblastoma. Our endpoint was administration of an antiemetic<br />
or the documentation of emesis in the PACU. Descriptive statistics were<br />
used in data analysis.<br />
Results. Sixty-three percent of patients received prophylactic antiemetics:<br />
40/76 (53%) received ondansetron alone, 6/76(8 %) received<br />
RETINOBLASTOMA<br />
Posters<br />
58<br />
both ondansetron and dexamethasone, and 2/76 (2.6%) patients<br />
received dexamethasone alone. The overall incidence of emesis in this<br />
study group was 1.3% (1/76 patients). The incidence of emesis in the<br />
group of patients receiving anti-emetics and those not receiving antiemetics<br />
was 0% and 3% respectively.<br />
Conclusions. In our study where identified risk factors were present<br />
but with essentially no surgical stimulation the incidence of POV in the<br />
PACU was lower than the baseline of 9% with no risk factors2. However,<br />
the discomfort associated with POV may justify prophylactic anti-emetic<br />
administration.<br />
Financial disclosure. None<br />
120 RBp135<br />
MANAGEMENT OF AN ECTOPIC SELLAR TRILATERAL<br />
RETINOBLASTOMA<br />
Rana’a Al-Jamal, Sanna Seitsonen, Ulla Pihkala, Matti Tenhunen, Päivi<br />
Lindahl, Leena Koskinen, Tero Kivelä (ranaa.aljamal@hus.fi)<br />
Departments of Ophthalmology, Paediatrics and Oncology, Helsinki<br />
University Central Hospital, Helsinki, Finland<br />
Purpose. To report successful management of an ectopic sellar<br />
trilateral retinoblastoma.<br />
Methods. A 10-month-old girl with strabismus and leukokoria had<br />
bilateral retinoblastoma (Group E, OD; group D, OS). MRI revealed an<br />
enhancing 20x24 mm sellar tumour which protruded to the suprasellar<br />
cistern and pushed the chiasm. Spinal MRI, bone marrow aspirate and<br />
lumbar puncture revealed no metastases.<br />
Results. Combination chemotherapy was started eight days after<br />
diagnosis.<br />
The 1st, 3rd and 5th cycles consisted of intravenous topotecan (2 mg/<br />
m2 on days 1 and 2), cisplatin (120 mg/m2 on day 1), vincristine (2 mg/<br />
m2 on day 3) and intrathecal thiotepa (5 mg on day 5). In the 2nd cycle,<br />
cisplatin was substituted with carboplatin (560 mg/m2 on day 1) and<br />
the 4th cycle consisted of vincristine, topotecan and thiotepa.<br />
The intraocular tumours responded promptly and were consolidated<br />
with TTT. Before the 2nd cycle, she underwent autologous<br />
hematopoietic stem cell harvesting. Stem cell rescue was executed at<br />
5 and 7 months, preceded by high dose chemotherapy (carboplatin<br />
500 mg/m2, thiotepa 300 mg/m2, and topotecan 2 mg/m2 on days<br />
1-3). Stereotactic radiotherapy was given between the stem cell<br />
transplantations (6 MV photons, 1.8 Gy fraction size, 17 fractions) from<br />
a linear accelerator (30.6 Gy) from five conformal dynamic fields.<br />
Latest brain and spinal MRI 3 years after termination of treatment show<br />
full regression. Binocular VA is 20/40. She receives growth hormone,<br />
thyroxine and hydrocortisone substitution.<br />
Conclusions. The patient is one of three known longer term survivors<br />
after an ectopic sellar trilateral retinoblastoma.<br />
Financial disclosure. None<br />
350 RBp136<br />
MOLECULAR PATHWAYS OF RETINOBLASTOMA RE-<br />
VEALED THROUGH GLOBAL PROTEOMICS ANALYSES<br />
OF Y79 AND CHLA215 CELL LINES: A DRUG RESIS-<br />
TANCE CASE STUDY<br />
Susan Lee1,2, Robert Fanter1, Narine Harutyunyan1, Joanne Lee1, A Linn<br />
Murphree1,3 (sulee@chla.usc.edu)
1. Children’s Hospital Los Angeles; 2. Department of Pathology and<br />
Laboratory Medicine;<br />
3. Department of Ophthalmology, Keck School of Medicine, University of<br />
Southern CA, Los Angeles, CA, USA<br />
Purpose. To provide molecular insights into retinoblastoma using global<br />
proteomics analyses of retinoblastoma cell lines, Y79 and CHL215.<br />
Methods. Cell lines were characterized by DIMSCAN drug testing<br />
using carboplatin and topotecan and proteomic analyses using liquid<br />
chromatography coupled to tandem mass spectrometry (LC-MS/MS).<br />
Results. At all concentrations and time points tested, CHLA215 were<br />
much more drug resistant than Y79. One stark example was the<br />
comparison between Y79 and CHLA215 survival fractions, 0.016 versus<br />
0.86, after 4 days in 24 micromolar carboplatin.<br />
The cellular proteomes of Y79 and CHLA215 were characterized using<br />
LC-MS/MS. 724 proteins were identified, with 410 proteins (57 %) in<br />
common. Of these, 27 have been previously shown to have a role in<br />
tumorigenesis. Additionally, 199 and 115 proteins were identified as<br />
unique to Y79 and CHLA215, respectively.<br />
Multiple members of the glutathione-S-transferase (GST) pathway were<br />
shown to be upregulated in CHLA215, including GSTP1, GSTM2, and<br />
GSTM3.<br />
Conclusions. Though retinoblastoma has been associated with cancer<br />
predisposing mutations in the RB1 gene for more than 30 years, there<br />
is still a need to understand the molecular processes of retinoblastoma,<br />
particularly those independent of the RB1 mutation.<br />
Here we have shown that unbiased proteomic analyses can identify<br />
that the GST pathway is upregulated in drug resistant CHLA215<br />
retinoblastoma. This pathway has been implicated in drug resistance of<br />
other malignancies such as breast and lung cancer.<br />
These studies will form the foundation for targeted studies on the<br />
molecular differences between retinoblastoma tumors and their clinical<br />
implications.<br />
Financial disclosure. None<br />
1950 RBp137<br />
EVALUATING THE GLYCOLYTIC PATHWAY IN RETINO-<br />
BLASTOMA: A MECHANISTIC APPROACH USING THE<br />
GLYCOLYTIC INHIBITOR 2-DEOXY-D-GLUCOSE IN VIT-<br />
RO AND IN VIVO<br />
Christina L. Decatur, Yolanda Piña, Samuel Houston, Elizabeth Sullivan,<br />
Huaping Liu, Theodore Lampidis, Timothy G. Murray (cdecatur@med.<br />
miami.edu)<br />
Bascom Palmer Eye Institute, University of Miami Miller School of<br />
Medicine, Miami, Florida, USA.<br />
Purpose. To assess the molecular mechanism of glycolytic inhibition: (1) in<br />
vivo employing the LHBETATAG retinoblastoma (RB) animal model, and (2)<br />
in vitro using two established human RB cell lines Y-79 and WERI-Rb-1.<br />
Methods. (1) 17-week-old mice received one periocular injection of<br />
2-deoxy-D-glucose (2-DG; 500 mg/kg). Two hours post injection,<br />
animals were euthanized and crude retinal tumor extracts were analyzed<br />
for HIF and HKII expression. (2a) Y-79 and WERI-Rb-1 cells were exposed<br />
to either normoxia or hypoxia (0.5% O2) conditions for 24 hours. Cells<br />
were harvested and basal levels of HIF and HKII were measured. (2b)<br />
To assay 2-DG cytotoxicity at increasing concentrations, Y-79 and WERI-<br />
Rb-1 cells were treated with 3 mM, 6 mM, or 12 mM of 2-DG and placed<br />
in a hypoxic chamber for 72 hours.<br />
RETINOBLASTOMA<br />
Posters<br />
59<br />
Results. (1) There was a 41% reduction in HKII levels and 37% increase<br />
in HIF levels compared to the non-treated tumors (p
8.30-9.00 Poster presentations ECOp101-111<br />
(Moderator: S. Frenkel, H. Tsuji)<br />
9.30-11.00 papers<br />
(Moderators: B. Esmaeli, S. Heegaard)<br />
1621 EC1<br />
EVALUATION OF THE “HEDGEHOG” SIGNAL-<br />
LING PATHWAYS (SHH, PTCH-1, GLI-1 LEVELS) IN<br />
SQUAMOUS AND BASAL CELL CARCINOMAS OF THE<br />
EYELIDS AND CONJUNCTIVA.<br />
Hayyam Kiratli, Ali Rıza Cenk Çelebi, Figen Söylemezoğlu<br />
1246 EC2<br />
MARGIN CONTROL IN EYELID TUMOR EXCISION: IS<br />
FROZEN SECTION OPTIMAL?<br />
David T.L. Liu, Kelvin K.L. Chong, Gary M.K. Tse, N.M. Luk, Dennis S.C. Lam<br />
1407 EC3<br />
RADIOTHERAPY FOR MANAGEMENT OF MEDIAL<br />
CANTHAL BASAL CELL CARCINOMA<br />
Hatem Krema, Caroline Chung, Evelyn Herrmann, Rand Simpson, David<br />
Payne, Normand Laperriere<br />
1756 EC4<br />
DOES THE SIZE OF EYELID SEBACEOUS CARCINOMA<br />
CORRELATE WITH NODAL METASTASIS AND SURVIVAL?<br />
Bita Esmaeli, Qasiem Nasser, Hilda Cruz, Melissa Felman, Carla L.<br />
Warneke, Doina Ivan<br />
2244 EC5<br />
LYMPHOMA OF THE EYELIDS – A NATION-BASED<br />
STUDY<br />
Steffen Heegaard, Peter K. Rasmussen, Elisabeth Ralfkiaer, Lene D. Sjö<br />
and Jan U. Prause<br />
143 EC6<br />
DIAGNOSIS AND FOLLOW-UP OF OCULAR SURFACE<br />
SQUAMOUS NEOPLASIA BASED ON NON-INVASIVE<br />
IN VIVO BIOPSY USING CONFOCAL MICROSCOPY<br />
J. Oscar Croxatto, Carolina Gentile<br />
1459 EC7<br />
OCULAR SURFACE SQUAMOUS NEOPLASIA IN A<br />
PATIENT WITH HIV INFECTION: REGRESSION AFTER<br />
RESTARTING ANTIRETROVIRAL THERAPY WITH<br />
DEVELOPMENT OF SPECIFIC T-CELLS<br />
M. Marinkovic, A. Rengifo Coolman, M.J..P Schoenmaekers-Welters, S.<br />
van der Burg, M.J. Jager, G.P.M. Luyten<br />
Wednesday November 16, 2011<br />
EYELID, CONJUNTIVA & ORBIT<br />
<strong>Program</strong><br />
61<br />
12 EC8<br />
RUTHENIUM PLAQUE THERAPY IN THE MANAGEMENT<br />
OF CONJUNCTIVAL SQUAMOUS CELL CARCINOMA<br />
INVADING THE EYE<br />
Priscilla L Ballalai, Virginia L Torres, Roberto Segretto<br />
1059 EC9<br />
INVASIVE SQUAMOUS CELL CARCINOMA OF THE<br />
CONJUNCTIVA TREATED BY PROTONS<br />
W. Sauerwein, J. Herault, P. Chauvel, H. Westekemper, R. Darawsha, B.<br />
Zimmermann, C. Maschi, A. Wittig, L. Brualla, J-P. Caujolle<br />
1505 EC10<br />
PROSPECTIVE STUDY OF SENTINEL LYMPH NODE BI-<br />
OPSY FOR CONJUNCTIVAL MALIGNANT MELANOMA<br />
Victoria M.L. Cohen, Maria Tsimpida, Norbert Avril, John L. Hungerford,<br />
Grahem Moir<br />
2202 EC11<br />
EXENTERATION FOR CONJUNCTIVAL MELANOMA IN<br />
LIVERPOOL: 1993-2010<br />
Nihal Kenawy, Sarah E. Coupland, Bertil E. Damato<br />
2311 EC12<br />
TEENAGE ELEVATED CONJUNCTIVAL LESIONS IN THE<br />
PLICAL AREA – LYMPHOMA OR REACTIVE LYMPHOID<br />
HYPERPLASIA?<br />
Shahar Frenkel, Jacob Pe’er<br />
11.00-11.20 BREAK<br />
11.20-12.45 Papers: Other Intraocular Tumors<br />
(Moderators: J. Elizalde, J. Shields)<br />
1933 OT1<br />
CLINICAL SURVEY OF 3680 SOLID AND CYSTIC TU-<br />
MORS OF THE IRIS<br />
Carlos Bianciotto, Carol L. Shields, Swarupa Kancherla, Mayerling<br />
Suriano, Margaret V. Shields, Priya Sharma, Jinali Patel, Jerry A. Shields<br />
111 OT2<br />
CLINICAL AND OCT FINDINGS ON SYMPTOMATIC<br />
MACULAR NAEVI TREATED WITH INTRAVITREAL ANTI-<br />
VEGF<br />
Sonia A. Callejo, Mikael Sebag, Marc Blouin, Christine Corriveau<br />
1340 OT3<br />
RISK FACTORS FOR GROWTH OF POSTERIOR UVEAL<br />
MELANOCYTIC LESIONS WITH THICKNESS GREATER<br />
THAN 2 MM IN 161 CONSECUTIVE PATIENTS<br />
Patrick De Potter, Audrey Noel, Jacques Jamart
6 OT4<br />
THE EXPANDING SPECTRUM OF RETINAL VASOPRO-<br />
LIFERATIVE TUMOURS<br />
Jerry A. Shields, David Reichstein, Arman Mashayekhi, Carol L. Shields<br />
518 OT5<br />
DIFFUSE CHOROIDAL HEMANGIOMA: CLINICAL<br />
MANIFESTATIONS AND VISION OUTCOME IN 60<br />
PATIENTS<br />
H.K. Li, C.L. Shields, N. Ni, J. Iturralde, J.A. Shields<br />
504 OT6<br />
SD-OCT AND AUTOFLUORESCENCE CHARACTERIS-<br />
TICS OF CANCER-ASSOCIATED AUTOIMMUNE RETIN-<br />
OPATHY<br />
Prithvi Mruthyunjaya and Kathryn L. Pepple<br />
1801 OT7<br />
NEAR-INFRARED AUTOFLUORESCENCE OF<br />
NEUROFIBROMATOSIS TYPE 1<br />
Minoru Furuta, Tetuju Sekiryu, Tomohiro Iida<br />
2340 OT8<br />
VASOPROLIFERATIVE LESIONS (VPLS) OF THE RETINA<br />
AND THE OPTIC DISC<br />
Vicktoria Vishnevskia-Dai, Josef Moisseiev, Amir Elhalel, Iris Moroz,<br />
Roth Sigal, Mordechai Rosner<br />
2113 OT9<br />
VITREORETINAL SURGERY FOR TRACTIONAL<br />
COMPLICATIONS ASSOCIATED WITH JUXTAPAPILLARY<br />
COMBINED HAMARTOMA OF THE RETINA AND<br />
RETINAL PIGMENT EPITHELIUM<br />
Javier Elizalde<br />
206 OT10<br />
RISK OF RADIATION RETINOPATHY IN PATIENTS WITH<br />
ORBITAL AND OCULAR LYMPHOMA<br />
Megha Kaushik, Jose S. Pulido, Khushboo K. Agrawal, Steven E. Schild,<br />
Scott Stafford<br />
2324 OT11<br />
VITREORETINAL LYMPHOMA TREATED BY<br />
INTRAVITREAL INJECTIONS OF METHOTREXATE: 80<br />
EYES OVER 14 YEARS<br />
Jacob Pe’er, Shahar Frenkel<br />
2329 OT12<br />
COMBINATION INTRAVITREAL RITUXIMAB AND<br />
METHOTREXATE FOR PRIMARY VITREORETINAL<br />
LYMPHOMA<br />
David J. Wilson, and Justine Smith<br />
EYELID, CONJUNTIVA & ORBIT<br />
<strong>Program</strong><br />
62<br />
12.45-13.15 Poster presentations OTp101-110<br />
(Moderator: J. Pe’er, D. Gombos)<br />
13.15-14.15 LUNCH<br />
14.15-14.35<br />
Keynote Lecture: Dr. Steffen Heegaard<br />
LYMPHOMA OF THE OCULAR ADNEXA.<br />
14.35-17.35 Rapid Fire Cases<br />
(Chair J. Shields)<br />
Retina<br />
(Moderators: C. Shields, A. Schefler)<br />
2128 RF1<br />
RETINOBLASTOMA<br />
David H. Abramson<br />
1941 RF2<br />
EXTRA-OCULAR RETINOBLASTOMA WITH INVASION<br />
OF THE OPTIC CHIASMA: CAN BE SAVED?<br />
Camila H. Hashimoto<br />
54 RF3<br />
SEVEN-YEARS-OLD BOY WITH PERSISTENT PAINFUL<br />
RED RYE AND PARS PLANA LESION<br />
Patricia Chévez-Barrios<br />
1830 RF4<br />
MALIGNANT TRANSFORMATION OF RETINOCYTOMA<br />
Eduardo F. Marback<br />
1937 RF5<br />
SUDDEN VITREOUS HAEMORRHAGE<br />
Tero Kivelä<br />
2044 RF6<br />
SPONTANEOUS ISCHEMIA AND PIGMENT RELEASE<br />
IN AN ADVANCED CASE OF RETINOBLASTOMA<br />
Dan Gombos<br />
121 RF7<br />
SUPRA-SELECTIVE CATHETERIZATION OF THE<br />
OPHTHALMIC ARTERY FOR INTRA-ARTERIAL<br />
CHEMOTHERAPY INJECTION IN RETINOBLASTOMA<br />
Vicktoria Vishnevskia-Dai<br />
1957 RF8<br />
PARANEOPLASTIC VITELLIFORM RETINOPATHY<br />
M. Turell
Uvea<br />
(Moderators: B. Damato, M. Sagoo)<br />
214 RF9<br />
CILIARY BODY TUMOR IN A CHILD<br />
Adriana C. Fandiño<br />
418 RF10<br />
RETINAL DETACHMENT AFTER FNAB<br />
Arturo Irarrazaval<br />
2047 RF11<br />
DIFFUSE MELANOCYTIC NEOPLASM IN A 9 YEAR-OLD<br />
FEMALE WITH OCULODERMAL MELANOCYTOSIS<br />
Amy C. Schefler<br />
2251 RF12<br />
A CASE OF ADENOMA OF THE NON-PIGMENTED<br />
CILIARY EPITHELIUM CAUSING NEOVASCULAR<br />
GLAUCOMA<br />
Vasilios P. Papastefanou<br />
1934 RF13<br />
CHOROIDAL NEVUS...CHOROIDAL NEVUS?<br />
Miguel A. Materin<br />
2312 RF14<br />
MUSHROOM SHAPED TUMOR. MELANOMA OR NOT?<br />
Jerry Shields<br />
104 RF15<br />
AMELANOTIC INTRAOCULAR LESION IN A 26 YEAR-<br />
OLD FEMALE PATIENT<br />
Luiz F. Teixeira<br />
2328 RF16<br />
PIGMENTED ANTERIOR SEGMENT TUMOR IN A<br />
YOUNG MAN<br />
Carolina M. Gentile<br />
2254 RF17<br />
AMELANOTIC CHOROIDAL MASS EXTENDING TO THE<br />
FOVEA<br />
Zelia M Correa<br />
29 RF18<br />
PIGMENTED CHOROIDAL TUMOR<br />
Jacob Pe’er<br />
2028 RF19<br />
RAPID REGRESSION OF POST-BRACHYTHERAPY<br />
CHOROIDAL MELANOMA IN RESPONSE TO INTRAVIT-<br />
REAL AVASTIN<br />
Peter Hovland<br />
EYELID, CONJUNTIVA & ORBIT<br />
<strong>Program</strong><br />
63<br />
1845 RF20<br />
LIGHT AND ELECTRON MICROSCOPY OF TWO CILIARY<br />
BODY TUMORS<br />
Lynn Schoenfield<br />
513 RF21<br />
RETINAL DETACHMENT AFTER TTT FOR ACTIVE CHOR-<br />
OIDAL MELANOMA<br />
Prithvi Mruthyunjaya<br />
55 RF22<br />
TREATMENT OF DIFFUSE IRIS MELANOMA<br />
Bertil Damato<br />
62 RF23<br />
LATE RECURRENCE OF A PRESUMED IRIS MELANO-<br />
MA<br />
John McWhae<br />
45 RF24<br />
HOLY TUMOR<br />
Carol Shields<br />
1848 RF25<br />
RESECTION OF AN IRIS TUMOR<br />
Arun D Singh<br />
410 RF26<br />
MELANOMA OR MELANOCYTOMA?<br />
Arturo Irarrazaval<br />
Eyelid<br />
(Moderators: H. Demerci, M. Naseripour)<br />
1655 RF27<br />
MALIGNANT TRANSFORMATION OF CELLULAR BLUE<br />
NEVUS IN AN 8-YEAR-OLD GIRL<br />
Alexander P. Moulin<br />
1618 RF28<br />
ORBITAL MELANOMA AND NAEVUS OF OTA<br />
Victoria M.L. Cohen<br />
558 RF29<br />
MANAGEMENT OF A RARE ADNEXAL TUMOR<br />
Sonul Mehta<br />
Conjunctiva<br />
(Moderators: E. Midena, M. Manquez)
19 RF30<br />
AMELANOTIC CONJUNCTIVAL TUMOR - MALIGNANT OR<br />
BENIGN?<br />
Priscilla Ballalai<br />
1809 RF31<br />
65-YEAR OLD WOMAN WITH DIFFUSE CONJUNCTIVAL<br />
NEOPLASM<br />
J. William Harbour<br />
23 RF32<br />
DIFFUSE CONJUNCTIVAL MALT LYMPHOMA<br />
Shahar Frenkel<br />
Orbit<br />
(Moderators: B. Esmaeli, P. de Potter)<br />
1510 RF33<br />
PAEDIATRIC TUMOUR WITH SCLERAL INVASION<br />
Maria Tsimpida<br />
1227 RF34<br />
STEREOTACTIC-GUIDED TRANSCRANIAL<br />
CRYOEXTRACTION OF CAVERNOUS HEMANGIOMA IN<br />
THE ORBITAL APEX<br />
Mordechai Rosner<br />
1352 RF35<br />
MYSTERIOUS ORBITAL CASE<br />
Patrick De Potter<br />
1802 RF36<br />
ORBITAL INVOLVEMENT FROM AN UNUSUAL<br />
CONDITION<br />
Manquez Maria<br />
112 RF37<br />
REPONSE OF METASTATIC PANCREATIC<br />
ADENOCARCINOMA TO CHEMOTHERAPY<br />
Scott Oliver<br />
127 RF38<br />
A CASE OF TEARING AND SWELLING OF THE EYE<br />
AFTER RESOLUTION OF ORBITAL CELLULITIS<br />
Daniel Moreno-Páramo<br />
EYELID, CONJUNTIVA & ORBIT<br />
<strong>Program</strong><br />
64<br />
Miscellaneous and unknown<br />
(Moderators: M. Giblin, A. Singh)<br />
124 RF39<br />
MYSTERY CASE<br />
Masood Naseripour<br />
158 RF40<br />
A PATIENT WITH MULTIPLE CANCER HISTORY<br />
Helen K. Li<br />
110 RF41<br />
MULTIPLE OCULAR VASCULAR ANOMALIES IN A<br />
CHILD<br />
Mandeep S. Sagoo<br />
1938 RF42<br />
MYSTERY CASE<br />
M. Ashwin Reddy<br />
1834 RF43<br />
MYSTERY CASE<br />
Edoardo Midena<br />
1255 RF44<br />
MYSTERY CASE<br />
Michael E. Giblin<br />
1309 RF45<br />
METASTATIC CHOROIDAL PARAGANGLIOMA<br />
Ann Schalenbourg<br />
67 RF46<br />
MYSTERY CASE<br />
Sara Lally<br />
68 RF47<br />
MYSTERY CASE<br />
Hakan Demirci
Morning<br />
8.30-9.00 Poster presentations ECOp101-111<br />
(Moderator: S. Frenkel, H. Tsuji)<br />
1849 ECp101<br />
FIVE CASES OF CARCINOMA METASTATIC TO THE<br />
EYELIDS<br />
Hiroya Kashiwagi, Hirohisa Katagiri, Takuya Takagi, Hideki Murata,<br />
Mitsuru Takahashi, Toshiaki Takahashi, Masato Matsuzaki<br />
1516 ECp102<br />
NATURAL KILLER/T-CELL LYMPHOMAS IN OCULAR<br />
LESION<br />
Hideki Tsuji, Megumi Kobayashi, Kengo Takeuchi, Kazuhiro Oshitari,<br />
Keigo Shikishima<br />
2337 ECp103<br />
CONJUNCTIVAL SQUAMOUS CELL CARCINOMA<br />
ARISING IN IMMUNOSUPPRESSED PATIENTS (ORGAN<br />
TRANSPLANT, HUMAN IMMUNODEFICIENCY VIRUS<br />
INFECTION)<br />
Carol L. Shields, Aparna Ramasubramanian, Phoebe L. Mellen, Jerry A.<br />
Shields<br />
1822 ECp104<br />
SQUAMOUS NEOPLASIA OF THE OCULAR SURFACE<br />
INVADING THE EYE AND ORBIT: A STUDY OF 30 CASES<br />
Eduardo F. Marback, Ediney Vila Nova Silva, Roberto L. Marback<br />
1150 ECp105<br />
A PROPOSAL FOR A NEW TREATMENT OF ORBITAL<br />
LOW GRADE MALIGNANT LYMPHOMA<br />
Akihiro Kaneko<br />
59 ECp106<br />
ORBITAL EXENTERATION RECONSTRUCTION WITH<br />
RADIAL FOREARM AND<br />
ANTEROLATERAL THIGH FREE FLAP: A<br />
MULTIDISCIPLINARY APPROACH<br />
Sara E. Lally, Carol L. Shields, Joseph Curry, Ryan Heffelfinger, David<br />
Cognetti, Howard Krein, Jerry A. Shields<br />
243 ECp107<br />
A HUGE OCULAR ADNEXAL MALT LYMPHOMA WHICH<br />
AROSE FROM IGG4 RELATED ORBITAL LESION<br />
Koh-ichi Ohshima<br />
223 ECp108<br />
HIGH-RESOLUTION ULTRASONOGRAPHY IN THE<br />
DIAGNOSIS OF ORBITAL MALIGNANT LYMPHOMA<br />
S.V. Saakyan, A.G. Amiryan, V.R. Alikhanova<br />
EYELID, CONJUNTIVA & ORBIT<br />
Posters<br />
65<br />
1752 ECp109<br />
CONJUNCTIVA MALIGNANT MELANOCYTIC TUMORS.<br />
RECURRENCE AND SURVIVAL RATE IN 15 PATIENTS<br />
FROM CHILE<br />
Maria E. Manquez, Pablo Vigorena, Bruno Nervi, Pablo Zoroquiain,<br />
Jeannie Slater, Arturo Espinoza<br />
66 ECp110<br />
LYMPHOPROLIFERATIVE TUMORS OF THE LACRIMAL<br />
GLAND: ANALYSIS OF CLINICAL FEATURES AND<br />
SYSTEMIC INVOLVEMENT<br />
Hakan Demirci, Shivani Gupta, Carol L. Shields, Jerry A. Shields, Victor M. Elner<br />
224 ECp111<br />
IMMUNOHISTOCHEMICAL AND MOLECULAR STUDY<br />
OF OPTIC PATHWAY GLIOMAS<br />
Charles G. Eberhart, J. Douglas Cameron, Elizabeth J. Rushing, Matthias<br />
Karajannis, Fausto J. Rodriguez<br />
Posters Other Intra-ocular Tumors<br />
12.45-13.15 Poster presentations OTp101-110<br />
(moderator J. Pe’er, D. Gombos)<br />
131 OTp101<br />
PHOTODYNAMIC THERAPY FOR ACQUIRED<br />
ASTROCYTOMA<br />
Cinzia Mazzini, Maria Carla Donati, Giulia Pieretti, Ugo Menchini<br />
530 OTp102<br />
MANAGEMENT OF PERIPAPILLARY HEMANGIOMA IN<br />
PEDIATRIC VHL DISEASE<br />
Prithvi Mruthyunjaya<br />
105 OTp103<br />
MEK Inhibitor-associated serous retinopathy -<br />
clinical features of a new retinal disorder<br />
Scott C.N. Oliver, Raul Velez Montoya, Wells Messersmith, Jeffrey L.<br />
Olson, Naresh Mandava<br />
1450 OTp104<br />
BENIGN TUMORS OF CILIARY BODY IN KOREAN<br />
PATIENTS<br />
Christopher Seungkyu Lee, Hee Jung Kwon, Hyae Min Jeon, Min Kim,<br />
Sung Chul Lee<br />
321 OTp105<br />
TREATMENT OF SEROUS MACULAR DETACHMENT<br />
ASSOCIATED WITH CIRCUMSCRIBED CHOROIDAL<br />
HEMANGIOMA<br />
Sung Chul Lee, Hee Jung Kwon, Min Kim, Christopher Seungkyu Lee
2132 OTp106<br />
INTRAOCULAR RELAPSE OF MULTIPLE MYELOMA<br />
RESPONSIVE TO BORTEZOMIB<br />
Tero Kivelä<br />
1923 OTp107<br />
TUBEROUS SCLEROSIS COMPLEX: CHARACTERIZA-<br />
TION OF OCULAR MANIFESTATIONS AND CORRELA-<br />
TIONS WITH SYSTEMIC DISEASE<br />
M.E. Turell, E.I. Traboulsi, A. Gupta , A.D. Singh<br />
248 OTp108<br />
INTERLEUKIN LEVELS IN AQUEOUS OF UNTREATED<br />
AND TREATED EYES WITH VITREORETINAL LYMPHO-<br />
MA<br />
Jose S. Pulido, Joseph Balsanek, Brian Peters, Melissa Snyder<br />
304 OTp109<br />
INTRAVITREAL RITUXIMAB FOR PRIMARY INTRAOCU-<br />
LAR LYMPHOMA (PIOL)<br />
V. Kakkassery, G. Willerding, K. Jahnke, A. Korfel, U. Pleyer, N. Stübiger,<br />
A.M. Joussen<br />
EYELID, CONJUNTIVA & ORBIT<br />
Posters<br />
66
1621 EC1<br />
EVALUATION OF THE “HEDGEHOG” SIGNALLING<br />
PATHWAYS (SHH, PTCH-1, GLI-1 LEVELS) IN<br />
SQUAMOUS AND BASAL CELL CARCINOMAS OF THE<br />
YYELIDS AND CONJUNCTIVA<br />
Hayyam Kiratli1, MD, Ali Rıza Cenk Çelebi1, MD, Figen Söylemezoğlu2, MD<br />
(hkiratli@hacettepe.edu.tr)<br />
1. Ocular Oncology Service, Department of Ophthalmology (and Çelebi)<br />
and 2. Department of Pathology, Hacettepe University School of<br />
Medicine, Ankara, Turkey.<br />
Purpose. To assess the role of hedgehog signalling pathways in the<br />
carcinogenesis of eyelid skin and conjunctival epithelial malignant tumors.<br />
Methods. Shh, the major secreted morphogen protein of the pathway,<br />
Ptch-1, its transmembrane receptor and Gli-1, the target gene involved<br />
in stem cell proliferation were evaluated in paraffin-embedded tissues<br />
using immunohistochemical stainings. The study was conducted on the<br />
specimens of 41 patients with eyelid basal cell carcinoma, 22 with eyelid<br />
and conjunctival squamous cell carcinoma and 12 with conjunctival<br />
intraepithelial neoplasia. For each specimen, the percentage (50%) and the intensity of stainings (graded between 0 to 3) were<br />
calculated and the scores obtained by the multiplication of the two values<br />
were analyzed using Kruskall-Wallis test.<br />
Results. The Shh and Ptch-1 expressions were statistically significantly<br />
lower in the basal cell carcinoma group. In the conjunctival squamous cell<br />
carcinoma group, the Ptch-1 score was 0 in 25% of specimens and Gli-1<br />
score was 3 in 66% of cases. In the conjunctival intraepithelial neoplasia<br />
group, the Ptch-1 score was >2 in 66% of specimens and the Gli-1 score<br />
was 3 in 87.5% of cases.<br />
Conclusions. Ptch-1 mutations may contribute to the development of eyelid<br />
basal cell carcinoma. Alterations in the hedgehog signaling pathways may<br />
lead to transformation of the conjunctival intraepithelial neoplasia into<br />
invasive squamous cell carcinoma.<br />
Financial disclosure. None<br />
1246 EC2<br />
MARGIN CONTROL IN EYELID TUMOR EXCISION: IS<br />
FROZEN SECTION OPTIMAL?<br />
David T.L. Liu, Kelvin K.L. Chong, Gary M.K. Tse, N.M. Luk, Dennis S.C.<br />
Lam (david_tlliu@yahoo.com)<br />
Department of Ophthalmology & Visual Sciences, the Chinese University<br />
of Hong Kong; Department of Anatomical & Cellular Pathology, the<br />
Chinese University of Hong Kong; Dermatology Institute, Department of<br />
Medicine & Therapeutics, the Chinese University of Hong Kong<br />
Purpose. To report the surgical outcomes of periocular basal cell<br />
carcinoma (BCC) patients managed with quick Mohs micrographic<br />
surgery (MMS)<br />
Methods. Prospective series of periocular BCC were enrolled and<br />
managed by quick MMS, which is a simple technique of collapsing<br />
thickness of the specimen, single sectioning and one tissue-level<br />
histopathological examination.<br />
Results. Six female and one male, with age ranged from 58 to 88 were<br />
recruited. Median operation time was 30 minutes. Five patients were<br />
free from postoperative complication. At 18 months, no patient showed<br />
sign of recurrence.<br />
EYELID, CONJUNTIVA & ORBIT<br />
Abstracts<br />
67<br />
Conclusions. In the strike for maximal tumor clearance and aesthetic<br />
preservation, Quick Mohs micrographic surgery may be an express<br />
surrogate for the labor-intensive conventional MMS in the management<br />
of periocular BCC.<br />
Financial disclosure. None<br />
1407 EC3<br />
RADIOTHERAPY FOR MANAGEMENT OF MEDIAL<br />
CANTHAL BASAL CELL CARCINOMA (BCC)<br />
Hatem Krema, Caroline Chung, Evelyn Herrmann, Rand Simpson, David<br />
Payne, Normand Laperriere<br />
(htmkrm19@yahoo.com)<br />
Ocular Oncology and Radiation Oncology Department, Princess Margaret<br />
Hospital/ UHN Toronto, Ontario, Canada<br />
Purpose. To report the efficacy and toxicity of fractionated external<br />
beam radiotherapy for management of medial canthal BCC.<br />
Methods. Retrospective case series analysis. We included consecutive<br />
patients with medial canthal BCC treated with orthovoltage radiotherapy<br />
using direct apposition technique. Patients were included whether<br />
radiotherapy was delivered as a primary treatment or for recurrent<br />
cases after surgical excision, between 1998 and 2009. Kaplan-Meier<br />
estimates were used to calculate actuarial rates.<br />
Results. Included in this study were 92 patients with a median follow-up<br />
of 70 months. The median dose was 35 Gys and the median fraction dose<br />
was 7 Gys. The local control rate was 96% for BCCs treated primarily by<br />
radiotherapy, and 78% for recurrent BCCs after prior surgery. There were<br />
transient post radiotherapy complications in 72% of patients. Chronic<br />
epiphora was present in 19% and chronic dry eye symptoms in 15 %.<br />
Conclusions. Radiotherapy provides an alternative management to<br />
surgical excision and major reconstruction procedures for medial<br />
canthal BCC, with manageable post irradiation side effects.<br />
Financial disclosure. None<br />
1756 EC4<br />
DOES THE SIZE OF EYELID SEBACEOUS CARCINOMA<br />
CORRELATE WITH NODAL METASTASIS AND<br />
SURVIVAL?<br />
Bita Esmaeli1, Qasiem Nasser 1, Hilda Cruz1, Melissa Felman1, Carla L.<br />
Warneke4, Doina Ivan2.3 (besmaeli@mdanderson.org)<br />
1. Section of Ophthalmology, Department of Head and Neck Surgery,<br />
2. Department of Pathology,<br />
3. Department of Dermatology,<br />
4. Department of Biostatistics<br />
The University of Texas MD Anderson Cancer Center, Houston, Texas.<br />
Purpose. To evaluate whether the American Joint Committee on Cancer<br />
(AJCC) 7th edition T designation for eyelid carcinomas correlates with<br />
lymph node metastasis, distant metastasis, and survival in patients with<br />
sebaceous carcinoma of eyelid.<br />
Methods. The records of 50 consecutive patients who were treated by<br />
the principal investigator (BE) for a diagnosis of sebaceous carcinoma<br />
of eyelid between May 1999 and August 2010 were reviewed. Each<br />
patient was staged using the AJCC 7th edition TNM (Tumor, Nodal<br />
status, Distant Metastasis) criteria based on clinical, pathologic, and<br />
radiographic data.
Results. The study included 37 women and 13 men with a median age<br />
of 68.5 years (range: 44 to 86 years). There were 44 whites, 5 hispanics,<br />
and 1 Asian. Tumor location was in the upper eyelid in 28 patients, in the<br />
lower eyelid in 15 patients, and involved both upper and lower eyelids in<br />
7 patients. AJCC 7th edition TNM designations were: TxN0M0,7 patients<br />
(pts); T1N0M0,4 pts.;T2aN0M0,12 pts.;T2bN0M0,11 pts.; T2bN1M0, 2<br />
pts; T2bN1M1,1 patient (pt.);T3aN0M0,2 pt.; T3aN1M0,5 pts.; T3bN0M0,<br />
1 pt; T3bN1M0,1 pt; T3bN0M1,2 pt.; T4N0M0,1 pt.; and T4N0M1,1pt.<br />
Regional lymph node metastasis was seen in 9 patients (18%). The<br />
TNM designation for these 9 patients at last contact were: T2bN1M0<br />
(2 pts), T2bN1M1 (1pt.), T3aN1M0 (5 pts.), T3bN1M0 (1 pt). Presence<br />
of lymph node metastasis was significantly associated with T-stage<br />
at presentation (P = 0.0079). No tumors less than T2b had nodal<br />
metastasis. No tumors less than 9 mm in greatest dimension had nodal<br />
metastasis. Distant metastasis was documentable in 4 patients and<br />
death from disease occurred in 5 patients (10%). The TNM designations<br />
for these 5 patients were: T2bN1M1 (1pt.), T3bN0M1 (2pts.), T4N0M0 (1<br />
pt), and T4N0M1 (1pt). No tumors less than 12 mm in greatest dimension<br />
were associated with distant metastasis or death. Disease-specific<br />
survival (DSS) was significantly associated with T-stage of the primary<br />
tumor (P = 0.0009). DSS was poorer among patients who presented<br />
with a tumor > T3a using the 2-category t-stage (P = 0.035).<br />
Conclusions. The 7th edition AJCC criteria for eyelid carcinomas correlate<br />
with outcomes for sebaceous carcinoma of eyelid. Tumor size correlates<br />
with regional lymph node metastasis with tumors >10 mm in greatest<br />
dimension being at risk. Sebaceous carcinomas > T3a are associated<br />
with poorer survival.<br />
Financial disclosure. None<br />
2244 EC5<br />
LYMPHOMA OF THE EYELIDS – A NATION-BASED STUDY<br />
Steffen Heegaard1,3, Peter K. Rasmussen 1, Elisabeth Ralfkiaer2, Lene<br />
D. Sjö2 and Jan U. Prause1 (sthe@sund.ku.dk)<br />
1. Department of Neuroscience and Pharmacology, Eye Pathology<br />
Institute, University of Copenhagen, Denmark<br />
2. Department of Pathology, Copenhagen University Hospital, Denmark<br />
3. Department of Ophthalmology, University of Copenhagen, Glostrup Hospital,<br />
Denmark<br />
Purpose. To characterize the clinicopathological features of lymphoma<br />
of the eyelids<br />
Methods. All cases of eyelid lymphoma between 1980 and 2008 were<br />
retrieved from the Danish Registry of Pathology. Histological specimens<br />
were re-evaluated using a panel of monoclonal antibodies. Clinical files<br />
from all patients with confirmed lymphoma were collected.<br />
Results. Twenty-five patients with lymphoma of the eyelids were<br />
identified. Thirteen of the patients were males and the median age was<br />
66 years (range 31 to 83 years). The distribution of lymphoma subtypes<br />
were: extranodal marginal zone lymphoma (EMZL) 44% (11), mantle<br />
cell lymphoma (MCL) 20% (5), follicular lymphoma (FL) 12% (3), diffuse<br />
large B-cell lymphoma (DLBCL) 8% (2), peripheral T-cell lymphoma,<br />
unspecified (PTCL, NOS) 8% (2), chronic lymphocytic leukemia/ small<br />
lymphatic lymphoma (CLL/SLL) 4% (1) and anaplastic large T-cell<br />
lymphoma (T-ALCL) 4% (1).<br />
Fourteen patients (56%) presented with Stage I/II lymphoma. Two<br />
patients (8%) had Stage III lymphoma and nine patients (36%) presented<br />
with Stage IV lymphoma.<br />
The 5-year overall survival rate (OS) was 42%. The patients with lowgrade<br />
lymphoma subtypes (EMZL; FL; PTCL, NOS; CLL/SLL) had a<br />
EYELID, CONJUNTIVA & ORBIT<br />
Abstracts<br />
68<br />
significantly better 3-year OS rate (77%) than patients with high-grade<br />
lymphoma (MCL; DLBCL; T-ALCL) (3-year OS rate, 21%).<br />
Conclusions. Lymphoma of the eyelids is relatively rare and is mainly<br />
prevalent in elderly patients. Most patients had unilateral involvement.<br />
The occurrence of MCL was relatively high compared to the distribution of<br />
lymphoma subtypes of the orbit. The prognosis for the whole population<br />
was relatively poor, however, patients with low-grade lymphoma had a<br />
significantly better survival.<br />
Financial disclosure. None<br />
143 EC6<br />
DIAGNOSIS AND FOLLOW-UP OF OCULAR SURFACE<br />
SQUAMOUS NEOPLASIA BASED ON NON-INVASIVE<br />
IN VIVO BIOPSY USING CONFOCAL MICROSCOPY<br />
J. Oscar Croxatto, MD, Carolina Gentile, MD (juan.croxatto@gmail.com)<br />
Oncology Unit, Hospital Italiano de Buenos Aires, Fundación<br />
Oftalmológica Argentina J. Malbran and Laboratorios Pörtner, Buenos<br />
Aires, Argentina.<br />
Purpose. To analyze the tissue findings, diagnosis and follow-up of<br />
corneal and conjunctival epithelial neoplasia in a large series of patients<br />
examined with in vivo confocal microscopy.<br />
Methods. Fifty-five patients with a presumed diagnosis of corneal<br />
and conjunctival epithelial neoplasia underwent examination with<br />
in vivo confocal microscopy (CCFM) (Rostock corneal module/HRTII,<br />
Heildelberg). The CCFM findings were compared with histology and<br />
cytology in those cases which underwent surgical excision or ocular<br />
surface impression cytology. The main outcome measures were CCFM<br />
findings, diagnosis, resolution after therapy, and histopathologic and<br />
cytologic findings.<br />
Results. The CCFM diagnoses were cornea and conjunctival<br />
intraepithelial neoplasia (38 cases), early invasive epithelial neoplasia<br />
(4 cases), intraepithelial neoplasia and pterygium (3 cases), stem cell<br />
deficiency (3 cases), UV-related keratosis (4 cases), pterygium without<br />
epithelial atypia (2 cases), and squamous cell carcinoma (1 case).<br />
CCFM findings showed a precise correlation with histopathological and<br />
cytological specimens. The post-medication examination procedure<br />
could confirm resolution ad integrum in patients treated with mitomycin<br />
C, and periodic evaluation until complete resolution in those patients<br />
receiving interferon alfa2-b. Subclinical recurrences were identified in<br />
3 cases.<br />
Conclusions. CCFM provides an excellent non-invasive in vivo image<br />
method to confirm the diagnosis of cornea and conjunctival neoplasia, to<br />
detect early invasion, to guide medical treatment in patients undergoing<br />
topical therapy, and to differentiate limbal and corneal simulating diseases.<br />
Financial disclosure. None<br />
1459 EC7<br />
OCULAR SURFACE SQUAMOUS NEOPLASIA IN A<br />
PATIENT WITH HIV INFECTION: REGRESSION AFTER<br />
RESTARTING ANTIRETROVIRAL THERAPY WITH<br />
DEVELOPMENT OF SPECIFIC T-CELLS<br />
M. Marinkovic, A. Rengifo Coolman, M.J.P. Schoenmaekers-Welters, S.<br />
van der Burg, M.J. Jager, G.P.M. Luyten (m.marinkovic@yahoo.com)<br />
Dept. of Ophthalmology and Dept. of Oncology, Leiden University<br />
Medical Centre, Leiden , The Netherlands
Purpose. Ocular surface squamous neoplasia (OSSN) refers to<br />
precancerous and cancerous lesions of the conjunctiva ranging form<br />
conjuctival intraepithelial neoplasia (CIN) to an invasive tumor with<br />
destruction of the orbital tissues. OSSN used to affect elderly men, yet<br />
this pattern has changed. In Africa the incidence is rising in younger<br />
persons, mostly women around 35 years of age. This increasing<br />
prevalence is probably due to HIV infection and HPV co-infections.<br />
Methods. Clinical and immunological analysis including testing of<br />
specific T cell interferon-gamma immune responses, and tissue HPV<br />
type analysis.<br />
Results. A 50 year-old female presented with complaints of chronical<br />
blepharoconjunctivitis which had existed for a couple of years. She was<br />
HIV positive and used antiretroviral medication infrequently. An eye<br />
examination revealed extensive leukoplakia of the palpebral and bulbar<br />
conjunctiva and cornea in the left eye. As a biopsy revealed squamous<br />
cell carcinoma with infiltration of the tarsal and bulbar conjunctiva of<br />
the left eye, exenteration of the left orbit was planned.<br />
When admitted to the hospital after a patients delay of a couple of<br />
months, the lesion of the conjunctival lesion had almost disappeared.<br />
The patient mentioned that she had restarted to take her HAART<br />
medication conscientiously.<br />
Earlier biopsies showed the presence of HPV 16, and at the time of tumor<br />
regression, anti-HPV16 T-cell responses were found to be present.<br />
Conclusions. Meticulous use of antiretroviral medication may cause<br />
regression of OSSN. It is unclear whether the medication targets the<br />
underlying HIV or HPV infection, or indirectly led to healing by allowing<br />
the recurrence of an anti-HPV16 T cell immune response. The lack of<br />
compliance in the use of therapy could be added to the list of risk factors<br />
for OSSN. Further research is needed to confirm this suggestion.<br />
Financial disclosure. None<br />
12 EC8<br />
RUTHENIUM PLAQUE THERAPY IN THE MANAGEMENT<br />
OF CONJUNCTIVAL SQUAMOUS CELL CARCINOMA<br />
INVADING THE EYE<br />
Priscilla L. Ballalai, Virginia L. Torres, Roberto Segretto (pbbordon@<br />
terra.com.br)<br />
Ocular Oncology Section - Federal University of Sao Paulo<br />
Radiotherapy - Federal University of Sao Paulo<br />
Purpose. To describe the outcome of patients with conjunctival<br />
squamous cell carcinoma invading the eye treated with Ruthenium<br />
(Ru106) plaque therapy.<br />
Methods. Retrospective, non-comparative review of charts of patients<br />
referred to the University and private office with conjunctival squamous<br />
cell carcinoma (SCC) invading the eye, from January 2001 to July 2011.<br />
Patients with focal invasions at the cornea, sclera or iris and ciliary body<br />
were included. Patients with orbital infiltrations or extensive intraocular<br />
infiltrations were excluded. All patients were submitted to Ru 106 plaque<br />
therapy, and the treatment dose was 50 Gy. The duration of the treatment<br />
was calculated according to the UBM measurements with a 1 mm safety<br />
margin. The patients were followed with a complete ophthalmological<br />
examination and systemic evaluation after the treatment.<br />
Results. Twenty patients with conjunctival SCC invading the eye were<br />
seen by the authors from January 2001 to July 2011. Six of them were<br />
eligible for salvage therapy with ruthenium plaque therapy. One patient<br />
was HIV positive. The mean age was 58 yo (range 29-82 yo), 4 were<br />
females and 2 males. The mean follow up of was 31,5 mo (range 6 -108<br />
EYELID, CONJUNTIVA & ORBIT<br />
Abstracts<br />
69<br />
mo). All of them had been treated previously with surgery or surgery and<br />
topical chemotherapy (Mitomycin C and/or Interferon). The mean number<br />
of surgeries was 2,1 (range 1-4). The pathological evaluation confirmed<br />
the diagnosis of SCC in all patients. Infiltration of the corneal stroma<br />
was observed in 3 patients, deep scleral infiltration in 4 patients and<br />
iris and ciliary body infiltration in 1 patient. All patients had regression<br />
of the tumor after the treatment without recurrence in the treatment<br />
site or elsewhere. None of them presented distant metastasis. The only<br />
complication observed with this treatment was cataract, in 3 patients.<br />
Conclusions. Ruthenium plaque therapy is safe and effective in the<br />
management of eyes with focal infiltrations by conjunctival squamous<br />
cell carcinoma.<br />
Financial disclosure. None<br />
1059 EC9<br />
INVASIVE SQUAMOUS CELL CARCINOMA OF THE<br />
CONJUNCTIVA TREATED BY PROTONS<br />
W. Sauerwein1, J. Herault2, P. Chauvel2, H. Westekemper3, R.<br />
Darawsha3, B. Zimmermann1, C. Maschi4, A. Wittig5, L. Brualla1, J.-P.<br />
Caujolle4 (w.sauerwein@uni-due.de)<br />
1. University Duisburg- Essen, University Hospital Essen, Department of<br />
Radiation Oncology, Essen, Germany<br />
2. Cyclotron Biomédicale, Centre Antoine-Lacassagne, Nice, France<br />
3. University Duisburg- Essen, University Hospital Essen, Department of<br />
Ophthalmology, Essen, Germany<br />
4. Service d’Ophtalmologie, CHU Saint Roch, Nice, France<br />
5. Klinikum der Philipps-Universität Marburg, Department of Radiation<br />
Oncology Marburg, Germany<br />
Purpose. Squamous cell carcinoma (SCC) of the conjunctiva is an<br />
extremely rare disease. The disease is suspected to be associated<br />
with atrophic dermatitis and HIV in young women. After local excision<br />
the tumor often recurs instead of adjuvant therapies such as cryocoagulation,<br />
local chemotherapy or radiotherapy. Conventional external<br />
beam radiotherapy with electrons or photons is not conducive as the<br />
dose needed to control the tumor will destroy the eye. A sufficient dose<br />
can only be delivered by brachytherapy if the tumor is localized on the<br />
eyeball and if the target volume can be covered by a radioactive plaque.<br />
Therefore, exenteration is often the only curative approach. Protons<br />
might offer an alternative as they can be collimated and modulated to<br />
cover a complex area of the conjunctiva including fornix and tarsus while<br />
protecting the inner part of the eye and radiosensitive structures in the<br />
neighbourhood.<br />
Methods. The irradiation technique was initially developed to treat<br />
melanoma of the conjunctiva. The target volume to be considered is<br />
large and individually shaped. It includes often more than half of the total<br />
surface of the conjunctiva, with the goal to avoid further relapses at the<br />
margin of the treated volume. Because of the large volume, the number of<br />
fractions has been extended as compared to conventional proton therapy of<br />
uveal melanoma. The dose applied is given in 6 fractions of 5.2 Gy (36 Gy<br />
RBE) followed by a boost of 2 fractions of 7 Gy (16 Gy RBE). The technical<br />
principles of the treatment are as follows: - the clips are inserted on the eye<br />
for localization of the target volume and positioning. A bolus is set-up on the<br />
lid to give a homogeneous flat entrance for the proton beam collimated to<br />
the size of the tumor, - the beam passes through a semi-spherical acrylic<br />
glass compensator to adapt the range of the proton beam to the shape<br />
the inner sclera and let the protons irradiate the thickness of sclera and<br />
conjunctiva. The compensator is individually customized from an acrylic<br />
glass block by a computerized milling machine. The resulting dose distribution is
homogeneous and gives the whole dose to the bulbar and tarsal conjunctiva.<br />
Results. We report results from 24 HIV negative patients who received<br />
proton radiotherapy in Nice between 2001 and 2010. Mean follow up is<br />
40 months. None of the patients died for metastases. Tumor control was<br />
achieved for 19 patients (79%). 5 recurrent tumors were observed 2 – 8<br />
years after the irradiation. None of them occurred inside the irradiated<br />
volume. In one case, a second proton irradiation could control the<br />
disease. Exenteration was performed in the other cases.<br />
Conclusion. Proton irradiation offers the possibility to successfully<br />
treat SCC of the conjunctiva with acceptable side effects and can be<br />
considered as an alternative to traditional treatments.<br />
Financial disclosure: None<br />
1505 EC10<br />
PROSPECTIVE STUDY OF SENTINEL LYMPH NODE BI-<br />
OPSY FOR CONJUNCTIVAL MALIGNANT MELANOMA<br />
Victoria M.L. Cohen, Maria Tsimpida, Norbert Avril, John L. Hungerford,<br />
Grahem Moir (victoria.lendrum@gmail.com)<br />
Ocular Oncology Service. St Bartholomew’s and Moorfields eye Hospital,<br />
London UK<br />
Department of Nuclear Medicine, St Bartholomew’s Hospital, London UK<br />
Department of Plastic Surgery, St Bartholomew’s Hospital London UK<br />
Purpose. To report our experience with sentinel lymph node biopsy for<br />
staging patients with conjunctival malignant melanoma.<br />
Methods. All patients with conjunctival malignant melanoma who<br />
had sentinel lymph node biopsy at St. Bartholomew’s Hospital from<br />
May 2008 to May 2011 were included in this study. The main outcome<br />
measures were the incidence of sentinel lymph node positivity, the<br />
procedure-related complications and the metastasis free survival rate.<br />
Results. In 3 years, 23 patients met the selection criteria for sentinel<br />
lymph node biopsy. 4 patients declined and 19 patients were consented<br />
for the procedure. Technetium-99m failed to identify the lymph nodes<br />
in 4 of the 19 patients (21%). Of the remaining 15 patients, 2 were<br />
found to have subclinical micrometastasis in regional lymph nodes. No<br />
false-negative events were observed. Complications of the procedure<br />
included transient blue staining of the epibulbar surface in 3 patients<br />
and transient facial nerve palsy in 1 patient.<br />
Conclusions. Sentinel lymph node biopsy is a safe procedure with<br />
minimal complications. It should be considered for the staging of<br />
conjunctival melanoma, especially non-limbal melanoma or conjunctival<br />
melanoma more than 2mm thick.<br />
Financial disclosure. None<br />
2202 EC11<br />
EXENTERATION FOR CONJUNCTIVAL MELANOMA IN<br />
LIVERPOOL: 1993-2010<br />
Nihal Kenawy, Sarah E. Coupland, Bertil E. Damato (nkenawy@liverpool.ac.uk)<br />
Liverpool Ocular Oncology Centre, Royal Liverpool University Hospital,<br />
Prescot Street, Liverpool, UK<br />
Purpose. To report the incidence and causes of exenteration in patients<br />
with conjunctival melanoma treated at the Liverpool Ocular Oncology<br />
Centre (LOOC) between 1993 and 2010.<br />
Methods. Database review of all patients with conjunctival melanocytic<br />
disease treated in LOOC between 1993 and 2010. Patients treated<br />
with exenteration were identified and the case notes were reviewed to<br />
EYELID, CONJUNTIVA & ORBIT<br />
Abstracts<br />
70<br />
identify the reasons for exenteration.<br />
Results. We treated 99 patients (52 females, 47 males; median age 62<br />
years, range 24-95) for conjunctival melanoma between 1993 and 2010.<br />
Four patients required exenteration. Two were males and two females. At<br />
initial presentation, three patients had biopsy-proven invasive melanoma<br />
and one patient had melanoma in situ (C-MIN score 9). One patient had<br />
primary exenteration because of advanced disease at presentation and<br />
three had secondary exenteration because of uncontrollable disease<br />
and/or pain. One of the three patients commenced treatment in 1995<br />
prior to our updated policy of brachytherapy for invasive melanoma<br />
and the condition was uncontrolled with multiple sessions of topical<br />
mitomycin C and cryotherapy. The caruncle and lacrimal passages<br />
were involved in the two other patients with invasive melanoma, both<br />
of whom had undergone excision biopsy with inadequate clearance<br />
prior to referral to LOOC. Both patients had received adjunctive orbital<br />
radiotherapy but one developed distant metastasis.<br />
Conclusions. Exenteration for conjunctival melanoma is rare in patients<br />
undergoing primary treatment with adjunctive brachytherapy and topical<br />
chemotherapy. The main causes of exenteration were uncontrollable<br />
disease and pain.<br />
Financial disclosure. None<br />
2311 EC12<br />
TEENAGE ELEVATED CONJUNCTIVAL LESIONS IN THE<br />
PLICAL AREA – LYMPHOMA OR REACTIVE LYMPHOID<br />
HYPERPLASIA?<br />
Shahar Frenkel, MD, PhD, Jacob Pe’er, MD(shahar.frenkel@gmail.com)<br />
Specialized Ocular Oncology Service, Department of Ophthalmology,<br />
Hadassah - Hebrew University Medical Center, Jerusalem, Israel<br />
Purpose. Ocular adnexal lymphoma (OAL) comprises 2.5% of extranodal<br />
non-Hodgkin lymphomas, and is most commonly a marginal zone<br />
lymphoma of mucosa-associated lymphoid tissue (MALT). The mean<br />
age at diagnosis is 63, with only 1.4% of cases younger than 21 years<br />
of age. We describe a series of cases with a similar clinical presentation<br />
but with a different final diagnosis in teenage patients.<br />
Methods. Retrospective chart review of patients with a clinical<br />
presentation of indicative of teenage OAL, presenting to our clinic in the<br />
past 5 years.<br />
Results. Five teenagers aged 14-17, all male, presented with bilateral<br />
large elevated pink conjunctival masses immediately adjacent to or even<br />
connected to the plica. None of them complained of allergic symptoms<br />
on presentation, but 3 (cases 3-5) confirmed symptoms on questioning.<br />
Cases 1-3 did not respond to anti-allergic medications and underwent<br />
excisional biopsies that revealed MALT lymphoma in cases 1 and 2, and<br />
reactive lymphoid hyperplasia in case 3. Cases 4 and 5 were treated<br />
with anti-allergic medication with resolution of the findings, and were<br />
clinically diagnoses as reactive lymphoid hyperplasia.<br />
Conclusions. OAL is rare in the pediatric group, but reactive lymphoid<br />
hyperplasia can present in teenage (male) patients with large plical<br />
masses that can resemble OAL.<br />
Financial disclosure. None<br />
1933 OT1<br />
CLINICAL SURVEY OF 3680 SOLID AND CYSTIC TU-<br />
MORS OF THE IRIS<br />
Carlos Bianciotto, Carol L Shields, Swarupa Kancherla, Mayerling<br />
Suriano, Margaret V. Shields, Priya Sharma, Jinali Patel, Jerry A. Shields
(cargusale@yahoo.com)<br />
Oncology Service, Wills Eye Institute, Philadelphia<br />
Purpose. To report the spectrum of iris lesions from a single ocular<br />
oncology center<br />
Methods. Retrospective review of medical records<br />
Results. Of 3451 patients, the mean age at presentation was 48 years<br />
(median 50 years, range 2 week to 95 years). There were 1423 males<br />
(41%) and 2028 females (59%). Of 3680 lesions, 2907 (79%) were<br />
benign and 773 (21%) were malignant, while 768 were cystic (21%)<br />
and 2912 (79%) solid. Specific diagnoses included nevus (41%), iris<br />
pigment epithelium (IPE) cyst (18%), melanoma (18%), freckle (3%),<br />
Lisch nodules (2%), melanocytoma (2%), melanocytosis (2%), and<br />
other (15%). Lesions were located in the iris stroma (80%) and IPE<br />
(20%). Most common diagnostic categories within solid lesions were<br />
melanocytic (68%), non-melanocytic (11%), vascular (2%), metastasis<br />
(2%) and pseudotumors (5%).<br />
Conclusions. Of 3680 iris lesions, 79% were benign; and the most<br />
common diagnosis included nevus (41%), IPE cyst (18%), melanoma<br />
(18%), and freckle (3%).<br />
Financial disclosure. None<br />
111 OT2<br />
CLINICAL AND OCT FINDINGS ON SYMPTOMATIC<br />
MACULAR NAEVI TREATED WITH INTRAVITREAL<br />
ANTI-VEGF<br />
Sonia A. Callejo, Mikael Sebag, Marc Blouin, Christine Corriveau<br />
(guilleyso@hotmail.com)<br />
Centre Hospitalier de l’Universite de Montreal CHUM Canada<br />
Purpose. To report the clinical and OCT findings of patients with<br />
symptomatic macular naevi treated with intraocular anti-VEGF.<br />
Methods. Retrospective small case series of 8 patients diagnosed<br />
with macular choroidal naevus with impared visual acuity treated<br />
with intravitreal anti-VEGF. Clinical information, serial color<br />
fundus photography, FA, OCT findings and ultrasonographic tumor<br />
measurements were reviewed and compared before and after anti-VEGF<br />
treatment.<br />
Results. 8 patients: 4 males and 4 females. Mean age at presentation:<br />
63 years (range 49 to 54). Mean follow up: 3 ½ years (range 7 months-9<br />
1/2 years). Mean number of anti-VEGF injections: 7.5 (range: 1 to 17).<br />
The largest naevus basal diameter was 7.3mm and the median thickness<br />
was 2.1mm. No ultrasonographic evidence of tumor enlargement or<br />
transformation into melanoma was documented following treatments.<br />
Large fluctuations in VA were recorded prior to anti-VEGF injections.<br />
Reduction in the degree of fluctuation was noticed during anti-VEGF<br />
treatments. Anti-VEGF treatment was associated with resolution or<br />
decreased of exudative retinal detachment, retinal thickness, cystic<br />
retinal changes (4 cases), subretinal fluid (6 cases), pigmented<br />
epithelium detachment (PED) (3 cases) and subretinal/intraretinal<br />
blood associated (1 case) or not (2 cases) to the presence of a choroidal<br />
endovascular membrane.<br />
Conclusions. Although a larger study is needed, the use of intraocular<br />
anti-VEGF treatment of symptomatic macular naevi is promising based<br />
on the improvement of clinical and OCT parameters as well as the<br />
stability of tumor measurements.<br />
Financial disclosure. None<br />
EYELID, CONJUNTIVA & ORBIT<br />
Abstracts<br />
71<br />
1340 OT3<br />
RISK FACTORS FOR GROWTH OF POSTERIOR UVEAL<br />
MELANOCYTIC LESIONS WITH THICKNESS GREATER<br />
THAN 2 MM IN 161 CONSECUTIVE PATIENTS<br />
Patrick De Potter, Audrey Noel, Jacques Jamart<br />
(patrick.depotter@uclouvain.be)<br />
Ocular Oncology Unit, Centre du Cancer, Cliniques Universitaires St Luc,<br />
Brussels, Belgium.<br />
Centre de Biostatistique et de Documentation médicale, Cliniques<br />
Universitaires de Mont-Godinne, Yvoir, Belgium<br />
Purpose. To better define the clinical and ultrasonographic risk factors<br />
predictive of growth of small melanocytic posterior uveal tumors<br />
presenting with a thickness of 2 mm or more as the only clinical suspicious<br />
factor predictive of tumor growth at first visit.<br />
Methods. Non comparative observational cases series including 161<br />
patients with suspicious choroidal or cilio-choroidal tumors measuring<br />
2 mm or more in thickness and no other clinical factors predicting of<br />
growth such as orange pigment, subretinal fluid, tumor margin touching<br />
disc, or tumor-related visual symptoms at initial visit. Those 161 patients<br />
were followed since October 1997 to document growth prior to treatment.<br />
Kaplan-Meier analysis was used to assess time to tumor growth and Cox<br />
proportional hazards regressions evaluated factors predictive of tumor<br />
growth<br />
Results. The mean age at diagnosis was 65 years old. The mean largest<br />
tumor diameter was 9 mm (range, 3 to 16 mm) and tumor thickness 2,6<br />
mm (range, 2 to 5,6 mm). The mean distance to the disc was 5,7 mm<br />
(range, 0,5 to 15 mm) and to the fovea 5,2 mm (range, 0 to 16 mm). Of<br />
the 161 small melanocytic lesions, 31 (19%) demonstrated growth after a<br />
mean follow-up of 32 months (range, 6 to 116 months). One patient (0.6%)<br />
developed systemic metastasis. The factors predictive of growth included<br />
greater tumor diameter, greater tumor thickness, lack of drusen, and<br />
acoustic hollowness. The global cumulative risks for tumor growth were<br />
4% at one year, 17% at 3 years, 22% at 5 years, and 27% at 10 years.<br />
Conclusions. Among posterior uveal melanocytic lesions with tumor<br />
thickness greater than 2.0 mm as the only clinical factor predictive of<br />
growth at initial visit, those with greater diameter, greater thickness,<br />
acoustic hollowness and lack of overlying drusen carried a significant risk<br />
for growth and should be monitored with regular surveillance.<br />
Financial disclosure. None<br />
6 OT4<br />
THE EXPANDING SPECTRUM OF RETINAL VASOPRO-<br />
LIFERATIVE TUMOURS<br />
Jerry A. Shields MD, David Reichstein MD, Arman Mashayekhi MD, Carol<br />
L. Shields MD (jerryshields@comcast.net)<br />
Wills Eye Institute<br />
Purpose. Retinal vasoproliferative tumor (RVPT) was originally<br />
described as an idiopathic fundus lesion with distinct clinical features.<br />
Subsequently, it found to be associated with a variety of ocular and<br />
systemic conditions and was subdivided into primary and secondary types.<br />
Methods. Review of lesions coded as retinal RVPT on the Oncology<br />
Service of Wills Eye Institute and literature search for causes of<br />
secondary retinal RVPTs<br />
Results. The secondary form of RVPT has now been associated with a
variety of ophthalmic disorders such as intermediate uveitis, retinitis<br />
pigmentosa, choroidal coloboma, longstanding retinal detachment,<br />
Coats’ disease, retinopathy of prematurity, familial exudative<br />
vitreoretinopathy, neurofibromatosis type 1, x-linked retinoschisis and<br />
other disorders.<br />
Conclusions. Lesions similar to idiopathic RVPT have now been recognized<br />
with an array of well known fundus entities and ophthalmologists should<br />
be aware of these associations.<br />
Financial disclosure. None<br />
518 OT5<br />
DIFFUSE CHOROIDAL HEMANGIOMA: CLINICAL MANI-<br />
FESTATIONS AND VISION OUTCOME IN 60 PATIENTS<br />
H.K. Li1,2,3, C.L. Shields1, N. Ni1, J. Iturralde1, J.A. Shields1 (hlimed@<br />
mac.com)<br />
1. Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA.<br />
2. The Methodist Hospital / Weil Cornell Medical College, Houston, TX<br />
3. The University of Texas Health Science Houston, Houston, TX<br />
Purpose. Evaluation of diffuse choroidal hemangioma clinical features<br />
and vision outcome.<br />
Methods. Retrospective clinic-based study.<br />
Results. 73 eyes of 60 patients with diffuse choroidal hemangioma<br />
were diagnosed on the Oncology Service at Wills Eye Hospital between<br />
1969 and 2010. Median age was 15 years (range, 21 to 88 years). Eye<br />
history included glaucoma (66%), amblyopia (29%) and strabismus<br />
(14%). Associated clinical findings included facial nevus flammeus<br />
(95%) and brain angioma (28%). Angioma involved both upper and<br />
lower lids (68%), upper lid only (29%), lower lid only (4%), conjunctiva<br />
(53%) and episclera (67%). Diffuse choridal hemangioma involved<br />
both eyes (22%), right eye only (32%), and left eye only (47%). Median<br />
thickness was 4.3mm (range, 1.3 to 11mm). Other features included<br />
circumscribed nodule (34%), venous dilatation and tortuosity (22%),<br />
and subretinal fluid (52%).<br />
Median follow-up of 57 eyes of 47 patients was 5 years (range, 0.3 to<br />
24.3 years). Fifteen eyes (21%) had subretinal fluid management prior<br />
to referral and 29 eyes (51%) after referral. Median age of patients<br />
diagnosed with subretinal fluid was 13 years (range 3.5 to 48 years).<br />
At final visit, 8 (14%) eyes had improved visual acuity, 43 (75%) were<br />
stable, and 6 (11%) had worsened. Final visual acuity was ≤ 20/200<br />
in 29 (51%) eyes, 20/50-20/200 in 9 (16%) eyes, and 20/20-20/40 in<br />
19 (33%) eyes. At final visit, eyes with subretinal fluid at initial visit<br />
showed poor vision of ≤ 20/200 in 21 (62%) eyes compared to those<br />
without subretinal fluid at initial visit in 8 (35%) eyes.<br />
Conclusions. Diffuse choroidal hemangioma commonly produces<br />
vision-threatening subretinal fluid. Eyes with diffuse choroidal<br />
hemangioma should be monitored closely for detection and treatment<br />
of subretinal fluid.<br />
Financial disclosure. None<br />
504 OT6<br />
SD-OCT AND AUTOFLUORESCENCE CHARACTER-<br />
ISTICS OF CANCER-ASSOCIATED AUTOIMMUNE<br />
RETINOPATHY<br />
Prithvi Mruthyunjaya MD and Kathryn L. Pepple MD, PhD (mruth001@<br />
mc.duke.edu)<br />
EYELID, CONJUNTIVA & ORBIT<br />
Abstracts<br />
72<br />
Ocular Oncology and Vitreoretinal Surgery Services, Duke Eye Center,<br />
Durham, North Carolina<br />
Purpose. To identify the SD-OCT and fundus autofluorescence (AF)<br />
characteristics found in patients diagnosed with cancer associated<br />
autoimmune retinopathy (c-AIR).<br />
Methods. Retrospective review of patients diagnosed with AIR at the<br />
Duke Eye center. Patients were included that demonstrated bilateral<br />
visual field loss, had abnormal electroretinograms (ERGs), had serum<br />
autoantibodies against retinal antigens demonstrated on western blot,<br />
and had SD-OCT and AF imaging of the fundus obtained at the time of<br />
presentation. Imaging studies were reviewed and the group of patients<br />
with abnormal findings was compared to the normal imaging cohort.<br />
Cancer status and autoantibody profiles were tested for correlation with<br />
abnormal imaging.<br />
Results. 12 patients were identified that met the inclusion criteria.<br />
Average age was 57 +/- 16 years (range 24 to 80), 4 males and 8<br />
females, 7 of 12 had a prior or recent diagnosis of systemic cancer. Ten<br />
of 12 patients were identified with AF abnormalities consisting of central<br />
or paracentral macular hypo-autofluorecence surrounded by hyperautofluorescence.<br />
SD-OCT imaging in these patients was also abnormal<br />
demonstrating peripheral loss of the photoreceptor layer with sparing<br />
of the central macula. The boundary of abnormal AF corresponds to the<br />
boundary of photoreceptor layer loss on SD-OCT. Comparison of the<br />
group of patients with imaging changes to those without did not reveal<br />
a significant correlation of imaging abnormalities with the any specific<br />
autoantibody.<br />
Conclusions. This is the first study to identify both SD-OCT and AF<br />
imaging abnormalities in patients with c-AIR. Vision loss corresponds<br />
with outer retinal dysfunction and RPE loss.<br />
Financial disclosure. None<br />
1801 OT7<br />
NEAR- INFRARED AUTOFLUORESCENCE OF NEUROFI-<br />
BROMATOSIS TYPE 1<br />
Minoru Furuta, Tetuju Sekiryu, Tomohiro Iida (furuta@fmu.ac.jp)<br />
Department of Ophthalmology, Fukushima Medical University School of<br />
Medicine, Fukushima, Japan<br />
Purpose. To determine presence of melanin pigment using near-infrared<br />
(NIR) autofluorescence in patients with choroidal neurofibromatosis<br />
type1 (NF-1).<br />
Methods. This case series includes ten eyes of five patients (one man<br />
and four females) with NF-1. Diagnosis was given under the National<br />
Institute of Health criteria for the diagnosis of NF-1. The patients were<br />
taken complete ophthalmic examination including spectral-domain<br />
optical coherence tomography, fluorescein angiography, indocyanine<br />
green angiography, and NIR autofluorescence (excitation 788<br />
nanometers; emission > 800-900 nanometers) imaging which was<br />
performed using HRA2 (Heidelberg Retina Angiogram 2, Heidelberg<br />
Engineering, Heidelberg, Germany).<br />
Results. Mean age of five patients was 38 year-old, ranging from 18 to<br />
60 year-old. NIR reflectance of posterior ocular fundus revealed highreflective<br />
patchy choroidal lesion in ten of all eyes. NIR autofluorescence<br />
was detected in every lesions observed in NIR reflectance imaging.<br />
Conclusions. NIR autofluorescence originates from oxidized melanin, or<br />
compounds closely associated with melanin in retinal pigment epithelium<br />
and choroid.1) Recent clinical observations reveal that the choroid is one
of the tissues most commonly affected by NF-1. Because the multiple,<br />
bright patchy spots were detected in 100% of cases under NIR reflectance<br />
imaging.2) In NF-1 patients, to prove presence of abnormal pigment<br />
accumulation which may originates from choroidal Schwann cells or<br />
nevoid cells will lead to better understandings of disease.<br />
1) Keilbauer CN, et al. IOVS 2006, 2)Yasunari T, et al. Lancet 2000<br />
Financial disclosure. None<br />
2340 OT8<br />
VASOPROLIFERATIVE LESIONS (VPLS) OF THE RETINA<br />
AND THE OPTIC DISC<br />
Vicktoria Vishnevskia-Dai1, Josef Moisseiev1, Amir Elhalel1, Iris Moroz1 ,<br />
Roth Sigal2, Mordechai Rosner1 (vivida65@gmail.com)<br />
1. Goldschleger Eye Institute, Sheba Medical center, Sackler School of<br />
medicine, Tel-Aviv University Israel.<br />
2. Rabin Medical center, Sackler School of medicine, Tel-Aviv University<br />
Israel.<br />
Purpose. Vasoproliferative lesions (VPLs) of the Retina and the Optic Disc<br />
consist of four rare clinical entities: Retinal capillary hemangioma, other<br />
retinal vasoproliferative lesions, retinal cavernous hemangiom and retinal<br />
arteriovenous communications (Wyburn-Mason syndrome).<br />
Our purpose is to report our experience with the management of patients with VPLs.<br />
Methods. Consecutive case series of 10 patients with VPLs treated at the<br />
Sheba medical center, Tel Aviv University, between the years 2004-2011.<br />
Results. The series included 14 eyes of 10 patients (8 males and 2<br />
females). The average age of the patients was 40.2 years (9-74years). The<br />
follow up time was 4-84 months (mean 29.8 months).<br />
Five of the patients had associated systemic disease. Two patients had<br />
associated ocular condition.<br />
Five eyes needed observation only. Of the eyes that needed intervention<br />
3 were injected with anti VEGF, 3 were treated with cryo-ablation, 3 were<br />
treated with argon laser photocoagulation, one with trans papillary<br />
thermo therapy and 3 eyes needed vitrectomy.<br />
The final visual acuity was 6/6 or better in 8 eyes (57%) 6/12 or better in<br />
11 eyes (78%) and less then 6/60 in 3 eyes (21%).<br />
Conclusions. Vasoproliferative lesions of the retina and the optic disc are<br />
rare ocular pathologies with a wide clinical spectrum of presentation.<br />
Proper systemic workup and patient tailored management can prevent<br />
ocular and systemic morbidity, and result in good visual acuity in most<br />
of the patients.<br />
Financial disclosure. None<br />
2113 OT9<br />
VITREORETINAL SURGERY FOR TRACTIONAL COMPLI-<br />
CATIONS ASSOCIATED WITH JUXTAPAPILLARY COM-<br />
BINED HAMARTOMA OF THE RETINA AND RETINAL<br />
PIGMENT EPITHELIUM<br />
Javier Elizalde (jem25@telefonica.net)<br />
Ocular Oncology Service, Barraquer Institute, Barcelona, SPAIN<br />
Purpose. To describe clinical features of tractional complications<br />
associated with combined hamartoma of the retina and retinal pigment<br />
epithelium (CHRRPE) and to discuss the surgical indications and<br />
technique, and the functional outcome after vitreoretinal surgery.<br />
Methods. Our Ocular Oncology database and the clinical data were<br />
EYELID, CONJUNTIVA & ORBIT<br />
Abstracts<br />
73<br />
reviewed. Microincisional vitreoretinal surgery with 23G instruments<br />
was performed to relieve the tractional component when the patient<br />
complained of progressive visual loss.<br />
Results. Clinical findings indicating retinal traction associated with<br />
CHRRPE include progressive distortion and displacement of the<br />
neighboring retina, stretching of the blood vessels, telangiectasias,<br />
retinal striae, exudation, superficial hemorrhages, retinal pigment<br />
epithelium abnormalities and full-thickness retinal folds. Vitreoretinal<br />
surgery usually improves the anatomical aspect of the retina although<br />
the functional improvement can be limited.<br />
Conclusions. Surgical dissection is partially effective in the treatment<br />
of vitreomacular traction associated with CHRRPE because amblyopia,<br />
long-standing intraretinal abnormalities and chronic photoreceptor<br />
damage usually limit the functional outcome. Early detection and<br />
intervention for cases presenting a recent vision loss are thought to<br />
show more positive results.<br />
Financial disclosure. None<br />
206 OT10<br />
RISK OF RADIATION RETINOPATHY IN PATIENTS WITH<br />
ORBITAL AND OCULAR LYMPHOMA<br />
Megha Kaushik, MBBS(hons) BSci(med)hons1, Jose S. Pulido1, MD<br />
MS MPH, Khushboo K. Agrawal1, MD, Steven E. Schild2, MD, Scott<br />
Stafford2, MD<br />
(megha.ka@gmail.com)<br />
1. Department of Ophthalmology<br />
2. Department of Radiation Oncology<br />
Mayo Clinic<br />
Purpose. The aim of this study is to identify the risk of developing radiation<br />
retinopathy at increasing radiation doses.<br />
Methods. A 40 year retrospective review was performed of patients who<br />
received external beam radiation therapy for ocular/orbital non-Hodgkin’s<br />
lymphoma (NHL).<br />
Results. Sixty-seven patients who had at least one ophthalmic follow up<br />
examination were included in this study. Most patients were diagnosed<br />
with NHL involving the orbit (52%). The patients received external beam<br />
radiation therapy at doses between 1886 to 5400cGy (mean 3033 ± 782<br />
cGy). 12% of patients developed radiation retinopathy with the mean time<br />
to diagnosis of 60 ± 76 months. The mean radiation dose in patients with<br />
retinopathy was 3309 ± 585cGy and the estimated retinal dose (derived by<br />
formulae) was 3087 ± 1030cGy. The incidence of retinopathy increased with<br />
dose. The mean visual acuity of the eyes that received radiation was worse<br />
than the eyes that did not (p=0.027). More patients with post-radiation<br />
retinopathy had comorbid diabetes mellitus type 2 compared to patients<br />
without retinopathy (p=0.015). Other post-radiotherapy ocular findings in<br />
our study included keratitis (7%), dry eyes (39%), and cataract (33%).<br />
Conclusions. Radiation retinopathy is a known complication of therapy for<br />
tumors within the orbit appears related to co-morbidities and dose. When<br />
treating an orbital tumor, one should always use the lowest effective dose<br />
and spare the eye to the greatest extent possible.<br />
Financial disclosure. None<br />
2324 OT11<br />
VITREORETINAL LYMPHOMA TREATED BY INTRAVIT-<br />
REAL INJECTIONS OF METHOTREXATE: 80 EYES OVER<br />
14 YEARS<br />
Jacob Pe’er, MD, Shahar Frenkel, MD, PhD (peer@hadassah.org.il)
Specialized Ocular Oncology Service, Department of Ophthalmology<br />
Hadassah - Hebrew University Medical Center, Kiryat Hadassah,<br />
Jerusalem, Israel<br />
Purpose. Vitreoretinal lymphoma is the most common type of intraocular<br />
lymphoma, and in most cases accompanies CNS lymphoma. Radiation<br />
therapy and systemic chemotherapy are the traditional methods<br />
of treating vitreoretinal lymphoma, but in recent years intravitreal<br />
chemotherapy has been used successfully in several centers.<br />
Methods. Since 1997 we have treated all our patients with vitreoretinal<br />
lymphoma by intravitreal injections of 400 µg/0.1 ml methotrexate<br />
alone. Our protocol includes twice-weekly injections for 4 weeks, a<br />
weekly injection for 8 weeks, and a monthly injection for 9 months, for<br />
a total of 25 injections.<br />
Results. Over the last 14 years we have treated 80 eyes of 45 patients;<br />
in three-quarters of them the disease was bilateral. In 41 patients the<br />
lymphoma was of the B-cell type, and in 4 the T-cell type. In one-third of<br />
the patients the vitreoretinal lymphoma preceded the CNS lymphoma,<br />
and in the rest the brain lymphoma was diagnosed earlier. All our<br />
patients responded to the treatment with total disappearance of the<br />
lymphoma cells from the vitreous and the infiltrates from the retina after<br />
3 – 16 injections. In all but one patient no recurrence was noticed. In<br />
one patient recurrence was diagnosed in one of the two affected eyes,<br />
and was treated again by our protocol, with complete response. Irritated<br />
conjunctiva and corneal epitheliopathy were the most common side<br />
effects. Four patients, two of them diabetics, developed neovascular<br />
glaucoma that recently was treated using intravitreal injections of<br />
Avastin.<br />
Conclusions. Intravitreal injection of methotrexate is a very successful<br />
method of treating vitreoretinal lymphoma, with almost no recurrence<br />
and reasonable ocular side effects.<br />
Financial disclosure. None.<br />
EYELID, CONJUNTIVA & ORBIT<br />
Abstracts<br />
74<br />
2329 OT12<br />
COMBINATION INTRAVITREAL RITUXIMAB AND<br />
METHOTREXATE FOR PRIMARY VITREORETINAL<br />
LYMPHOMA<br />
David J. Wilson, MD and Justine Smith, MD, PhD (wilsonda@ohsu.edu)<br />
Casey Eye Institute, Oregon Health and Science University<br />
Purpose. To determine the response rate and ocular effects of monthly<br />
intravitreal injection of a combination of methotrexate and rituximab in<br />
the treatment of primary vitreoretinal lymphoma.<br />
Methods. This is a retrospective chart review of a consecutive case series<br />
from one institution of patients with primary vitreoretinal lymphoma that<br />
were treated with combined methotrexate (.4mg/.1ml.) and rituximab (1<br />
mg/.1ml) by intravitreal injection. Injections were given on a monthly<br />
basis. Inclusion criteria consisted of biopsy proven vitreous or CNS.<br />
CD20 positive lymphoma.<br />
Results. Ten patients met the inclusion criteria. Five patients achieved<br />
a complete remission (defined as complete absence of vitreous cellsor<br />
sub RPE infiltrates). Five patients achieved partial remission (defined<br />
as markedly reduced but still detectable vitreous cells). Median follow<br />
up is 11 months. No ocular side effects directly attributable to the<br />
intravitreous agents were detected.<br />
Conclusions. Intravitreal injection of a combination of Rituximab and<br />
Methotrexate apppears to be a safe method for inducing partial or<br />
complete remission of a high percentage of patients with primary<br />
vitreoretinal lymphoma.<br />
Financial disclosure. None
2128 RF1<br />
RETINOBLASTOMA<br />
David H. Abramson, MD (abramsod@mskcc.org)<br />
Memorial Sloan-Kettering Cancer Center, New York, N.Y. USA<br />
Financial disclosure. None<br />
1941 RF2<br />
EXTRA-OCULAR RETINOBLASTOMA WITH INVASION<br />
OF THE OPTIC CHIASMA: CAN BE SAVED?<br />
Camila H. Hashimoto1, Carla R.D. Macedo1, Luiz F. Teixeira1,2, Virginia<br />
L. Torres1,2, Juliana dos Santos Soares1, Maria T. Seixas1,3, Clelia M.<br />
Erwenne1,2<br />
(camilahashimoto@yahoo.com.br)<br />
1. Pediatric Oncology Institute/GRAACC/Unifesp<br />
2. Ophtalmology Department/ Unifesp<br />
3. Pathology Department /Unifesp<br />
Purpose. To describe an unusual case of a six year old boy with atypical extra-ocular<br />
retinoblastoma with invasion of the optic chiasma<br />
Methods. A case report of an atypical extra-ocular retinoblastoma.<br />
Results. A 6 year old boy was referred to our service with a 7 months history of<br />
gradual redness, photophobia, tearing, and pain in the right eye, ptosis and impaired<br />
eye movements for the last 2 months. He had no family history of retinoblastoma.<br />
At physical exam he had axial proptosis of the right eye. It was impossible to perform<br />
fundoscopy in the right eye, and the fundoscopy of the left eye was normal.<br />
Brain and orbit CT showed no calcification. The brain and orbit MRI showed an<br />
enlargement of the right optic nerve until optic chiasma with a small tumor in the<br />
right eye, with invasion of the subarachnoid space.<br />
The differential diagnosis were atypical retinoblastoma, optic nerve tumor with<br />
intraocular invasion, optic glioma, optic disc tumor with optic nerve invasion and<br />
optic disc medulloepithelioma.<br />
Systemic workup was normal.<br />
We perform anterior approach enucleation and intraorbital segment of optic nerve<br />
resection. The diagnosis was poorly differentiated retinoblastoma with extensive<br />
choroidal invasion, invasion of the ciliary body and iris and invasion of tumor cells<br />
into the optic nerve posterior to the lamina cribosa.<br />
The treatment was chemotherapy and external beam radiotherapy of the orbit with<br />
45Gy and CNS and spine with 24Gy.<br />
He is alive without disease in a 8 years of follow-up.<br />
Conclusions. Multimodality treatment with surgery, chemotherapy and radiotherapy<br />
were primordial for the good result.<br />
Financial disclosure. None<br />
54 RF3<br />
SEVEN-YEARS-OLD BOY WITH PERSISTENT PAINFUL<br />
RED RYE AND PARS PLANA LESION<br />
P. Chévez-Barrios, I. Hernandez, M. Chintagumpala, R. Hurwitz R, S.<br />
Wittenberg, D. Moreno E. Passey, J. Edmond, C. Herzog, P. Zage, D. Gombos<br />
(pchevez-barrios@tmhs.org)<br />
Retinoblastoma Center of Houston; The Methodist Hospital Research<br />
Institute; Baylor College of Medicine; Houston Eye Associates;<br />
University of Texas, MD Anderson Cancer Center, Houston, TX, USA<br />
Purpose. The case is presented as an unknown to highlight the<br />
differential diagnosis and the importance of a team approach in the<br />
Rapid Fire Cases<br />
Abstracts<br />
75<br />
diagnosis of this masquerading presentation.<br />
Methods. Seven-year-old boy presented with red eye and pain that<br />
exquisitely responded to topical steroids for about a year. He also had<br />
smoldering peripheral retina/pars plana lesion that in the last 2 months<br />
increased in size. The most recent findings were anterior chamber debris<br />
and increased intraocular pressure.<br />
Results. The patient underwent anterior chamber tap with intraoperative<br />
cytologic interpretation that will be presented.<br />
Conclusions. The multidisciplinary approach, cytopathologic diagnosis<br />
and management of the patient will be discussed.<br />
Financial disclosure. None<br />
1830 RF4<br />
MALIGNANT TRANSFORMATION OF RETINOCYTOMA<br />
Eduardo F. Marback, MD, Epaminondas de Souza Mendes Jr, MD,<br />
Roberto L. Marback, MD (eduardomarback@uol.com.br)<br />
Federal University of Bahia, Brazil<br />
Purpose. To present a case of retinocytoma with malignant<br />
transformation<br />
Methods. Case report<br />
Results. 37 year old man, was seen for an ocular oncology evaluation<br />
because of having pain around the right eye for the past 15 days and<br />
a progressive decrease in visual acuity for the past 3 years. He had<br />
been evaluated in our service in 2001, after having two sons diagnosed<br />
with bilateral retinoblastoma. At that time he had an ophthalmoscopic<br />
appearance suggestive of bilateral retinocytoma and was adviced to<br />
have regular ophthalmologic follow up at least once a year. Now he<br />
returns with fundus pictures taken in 2008, showing a enlargement of<br />
the tumors in the right eye. His evaluation showed a blind painful right<br />
eye, with corneal edema, a mydriatic pupil with ectropion uvea and hazy<br />
media. Ultrasonography and CT scan revealed an enlarged intraocular<br />
mass, retinal detachment and an enlarged optic nerve. The right eye was<br />
enucleated.<br />
Conclusions. Retinocytoma patients should have periodical ophthalmic<br />
evaluation. The authors pose a question about possible benefits of<br />
prophylactic treatment is such cases.<br />
Financial disclosure. None<br />
1937 RF5<br />
SUDDEN VITREOUS HAEMORRHAGE<br />
Tero Kivelä (tero.kivela@helsinki.fi)<br />
Department of Ophthalmology, Helsinki University Central Hospital,<br />
Helsinki, Finland<br />
Purpose. A medium-aged woman presented with sudden vitreous<br />
haemorrhage, a choroidal mass in the papillomacular area and retinal<br />
vascular malformations. The case will be presented as an unknown.<br />
Financial disclosure. None<br />
2044 RF6<br />
SPONTANEOUS ISCHEMIA AND PIGMENT RELEASE<br />
IN AN ADVANCED CASE OF RETINOBLASTOMA<br />
D. Gombos MD FACS, P. Chevez-Barrios MD, P. Zage MD, C. Herzog MD,<br />
M. Chintagumpala MD, R. Hurwitz (dgombos@mdanderson.org)
The Retinoblastoma Center of Houston; MD Anderson Cancer Center;<br />
Texas Children’s Cancer Center; The Methodist Hospital Research<br />
Institute; Baylor College of Medicine, Houston, Texas, USA<br />
Purpose. Massive ischemia and necrosis can occur in advanced cases<br />
of retinoblastoma. Few reports have documented clinical findings just<br />
prior to and just after the ischemic event.<br />
Methods. A single case report.<br />
Results. The case will demonstrate the clinical findings just prior<br />
to and after a massive ischemic event in a patient with bilateral<br />
retinoblastoma. Photographic, radiographic and histologic correlation<br />
will be presented.<br />
Conclusions. This case demonstrates the atypical findings that can<br />
occur in advanced eyes with retinoblastoma that develop a massive<br />
ischemic event.<br />
Financial disclosure. Dr. Gombos is a member of the Children’s Oncology Group and has<br />
received reimbursement for travel. He is a paid consultant for IMS Health.<br />
121 RF7<br />
SUPRA-SELECTIVE CATHETERIZATION OF THE OPH-<br />
THALMIC ARTERY FOR INTRA-ARTERIAL CHEMO-<br />
THERAPY INJECTION IN RETINOBLASTOMA<br />
Vicktoria (Vicky)Vishnevskia-Dai1, Iris Moroz1 , Joseph Moisseiev,<br />
Mordechai Rosner1, Mati Bakon2<br />
(vivida65@gmail.com)<br />
1.Goldschleger Eye Institute, Sheba Medical center, Sackler School of<br />
medicine, Tel-Aviv University Israel.<br />
2. Invasive neuro-radiology center, Sheba Medical center, Sackler<br />
School of medicine, Tel-Aviv University Israel.<br />
Purpose. A 3-year old girl with unilateral group D retinoblastoma was<br />
treated with Supra-selective catheterization of the ophthalmic artery<br />
and intraarterial melphalan injections.<br />
Financial disclosure. None<br />
1957 RF8<br />
PARANEOPLASTIC VITELLIFORM RETINOPATHY<br />
M. Turell1, G. Adamus2, Y. Wang3, C.C. Chan3, A. Singh1<br />
(turellm2@ccf.org)<br />
1. Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland<br />
Clinic, Cleveland, OH<br />
2. Casey Eye Institute, Oregon Health & Science University, Portland, OR<br />
3. Laboratory of Immunology, National Eye Institute, National Institutes<br />
of Health, Bethesda, MD<br />
Purpose. An 80-year old man was referred for evaluation of choroidal<br />
metastases. The case will be presented as an unknown for opinions<br />
from the audience.<br />
Methods. Fundus photos, Fluorescein angiography, and OCT are<br />
presented.<br />
Results. Ophthalmic imaging exludes the possibility of choroidal<br />
metastases. Serum autoantibodies additionally confirm the<br />
paraneoplastic nature of the disease.<br />
Conclusions. The clinical picture is consistent with the rare disease,<br />
paraneoplastic vitelliform retinopathy.<br />
Financial disclosure. None<br />
Rapid Fire Cases<br />
Abstracts<br />
76<br />
214 RF9<br />
CILIARY BODY TUMOR IN A CHILD<br />
Adriana C. Fandiño MD, Raslawsky E. Cristina MD, Chantada Guillermo<br />
MD (acfandino@gmail.com)<br />
Ophthalmology Department; Radiotherapy Department;<br />
Hematooncology Department, Hospital de Pediatria J.P.Garrahan,<br />
Buenos Aires, Argentina<br />
Purpose. When a 10-year-old boy presented with rapid visual loss<br />
because of progressive astigmatism, a ciliary body mass with rapid<br />
progression was found.<br />
Methods. It was assumed to be a medulloepithelioma and treated with<br />
brachytherapy.<br />
Results. The patient had an excellent course with more than eight year<br />
follow-up.<br />
Conclusions. The case will be presented for opinions from the audience<br />
Financial disclosure. None<br />
418 RF10<br />
RETINAL DETACHMENT AFTER FNAB<br />
Arturo Irarrazaval, Pablo Cazón (artuira@consultoresoftalmologicos.com)<br />
Consultores Oftalmológicos<br />
Purpose. To show a case where after the FNAB a retinal detachment that<br />
did not resolve occurred.<br />
Methods. Retrospective study of the patient chart<br />
Results. The patient was first treated with pneumatic retinopexy, and<br />
after that with vitrectomy, which resolved the detachment.<br />
Conclusions. FNAB, although rarely, can produce a retinal detachment,<br />
that can be succesfully treated with retina surgery.<br />
Financial disclosure. None<br />
2047 RF11<br />
DIFFUSE MELANOCYTIC NEOPLASM IN A 9 YEAR-OLD<br />
FEMALE WITH OCULODERMAL MELANOCYTOSIS<br />
A.C. Schefler, A.M. Schimel, A. Abbey, E. Hodapp, S.R. Dubovy<br />
(aschefler@med.miami.edu)<br />
Bascom Palmer Eye Institute, University of Miami Miller School of<br />
Medicine, Miami, Florida, U.S.A.<br />
Purpose. This is an unusual case of a diffuse melanocytic malignancy<br />
involving 360 degrees of the ciliary body and the entire choroid in a 9<br />
year-old girl with oculodermal melanocytosis. The patient presented with<br />
melanocytomalytic glaucoma and ultimately underwent enucleation.<br />
Extensive clinical photographs and histopathology will be shown.<br />
Financial disclosure. None<br />
2251 RF12<br />
A CASE OF ADENOMA OF THE NON-PIGMENTED<br />
CILIARY EPITHELIUM CAUSING NEOVASCULAR<br />
GLAUCOMA<br />
Vasilios P. Papastefanou, Victoria ML Cohen (bazmed@hotmail.com)
Ocular Oncology Service, St Bartholomew`s Hospital and Moorfields Eye<br />
Hospital, London, UK<br />
Purpose. A 67-year old Caucasian man presented with rapidly reducing<br />
vision in the right eye. Reduced vision was attributed to cataract and he<br />
underwent routine cataract surgery. However, intraoperatively a solid<br />
mass was noted. The patient was referred to the Ocular Oncology Service.<br />
Methods. Transillumination did not reveal a clear shadow and B scan<br />
ultrasound revealed a ciliary body mass with internal blood flow and<br />
medium internal reflectivity. An incisional biopsy was performed. The<br />
histology results are discussed. A diagnosis of ciliary body adenoma of<br />
the non-pigmented epithelium (NPCE adenoma) was made.<br />
Results. One year later, patient developed hyperemia with blurred vision<br />
in the affected eye. He had marked episcleral injection, an oedematous<br />
cornea, marked rubeosis and angle closure. The intraocular pressure<br />
was 42 mmHg. The ciliary body adenoma remained unchanged .<br />
The tumour was treated with plaque radiotherapy (Ru-106) in order to<br />
restrict the neovascular response. Treatment was successful in reducing<br />
the tumour size on B-scan ultrasonography. Intracameral injections of<br />
bevacizumab where required pre- and postoperatively to control the rubeosis.<br />
Conclusions. To our knowledge, this is the first report of neovascular<br />
glaucoma secondary to a ciliary body adenoma.<br />
Financial disclosure. None<br />
1934 RF13<br />
CHOROIDAL NEVUS...CHOROIDAL NEVUS?<br />
Miguel A. Materin, Ruth Halaban, Antonella Bacchiocchi (miguel.materin@yale.edu)<br />
Yale School of Medicine<br />
Purpose. 10 years follow up on a typical choroidal nevus<br />
Conclusions. To be discussed at the meeting.<br />
Financial disclosure. None<br />
2312 RF14<br />
MUSHROOM SHAPED TUMOR. MELANOMA OR NOT?<br />
Jerry Shields, MD (jerryshields@comcast.net)<br />
Wills Eye Institute<br />
Purpose. To present a mushroom shaped tumor<br />
Methods. Review of case<br />
Results. Diagnosis and management<br />
Conclusions. A mushroom shaped tumor could be melanoma or<br />
something else.<br />
Financial disclosure. None<br />
104 RF15<br />
AMELANOTIC INTRAOCULAR LESION IN A 26 YEAR-<br />
OLD FEMALE PATIENT<br />
Luiz F. Teixeira1,2, Carla R. D. Macedo2, Carlos A.G. Filho1, Camila H.<br />
Hashimoto2, Marcia Lowen3, Maria C. Martins1 (luizfteixeira@hotmail.com)<br />
1. Department of Ophthalmology- Federal University of Sao Paulo-<br />
UNIFESP<br />
2. Pediatric Oncology Institute/GRAACC/UNIFESP<br />
3. Department of Pathology- Federal University of Sao Paulo<br />
Rapid Fire Cases<br />
Abstracts<br />
77<br />
Purpose. A 26 year-old female patient presented with an unusual<br />
intraocular lesion. It will be presented as a mysterious case for<br />
discussion.<br />
Financial disclosure. None<br />
2328 RF16<br />
PIGMENTED ANTERIOR SEGMENT TUMOR IN A YOUNG<br />
MAN<br />
Carolina M. Gentile, Camila Challiol, Atilio Lombardi, J. Oscar Croxatto<br />
(carolina.gentile@gmail.com)<br />
Hospital Italiano de Buenos Aires, Argentina<br />
Purpose. The aim of the presentation is to discuss the diagnosis and<br />
management of an anterior melanocytic segment tumor in a young adult.<br />
Methods. A 38 years-old male high mountain climber presented with a<br />
growing anterior segment pigmented mass. Diagnosis and management<br />
will be discussed with the audience. It will be presented as an unknown<br />
case for opinions.<br />
Results. Fine needle aspiration biopsy was performed and the diagnosis<br />
was melanocytoma.<br />
Conclusions. Anterior uveal melanocytomas are uncommon benign<br />
melanocytic tumors. Despite the benign nature of iris melanocytoma,<br />
growth was observed and histologic confirmation was necessary to<br />
establish a diagnosis and ruled out malignancy.<br />
Financial disclosure. None<br />
2254 RF17<br />
AMELANOTIC CHOROIDAL MASS EXTENDING TO THE<br />
FOVEA<br />
Zelia M. Correa, MD, PhD, James J. Augsburger, MD (correazm@uc.edu)<br />
Dept of Ophthalmology, University of Cincinnati, Cincinnati, OH, USA<br />
Purpose. Case presentation<br />
Methods. A 66-year-old asymptomatic Caucasian female was found to<br />
have a choroidal mass measuring 14 X 12 mm in base and 2.5 mm in<br />
thickness, extending to the fovea +/- SRF on routine eye exam.<br />
Results. The importance of accurate diagnosis will be discussed.<br />
Conclusions. Clinical diagnosis impacts management decision.<br />
Financial disclosure. None<br />
29 RF18<br />
PIGMENTED CHOROIDAL TUMOR<br />
Jacob Pe’er, MD, Shahar Frenkel, MD, PhD<br />
(peer@hadassah.org.il)<br />
Specialized Ocular Oncology Service, Department of Ophthalmology,<br />
Hadassah - Hebrew University Medical Center, Jerusalem, Israel<br />
Purpose. An 84-year-old woman presented with elevated (6.9 mm)<br />
pigmented lesion with retinal and choroidal hemorrhage around it.<br />
The lesion was diagnosed as choroidal melanoma and treated using<br />
brachytherapy, with good response.<br />
One year later regrowth was noticed, and the eye was enucleated.<br />
There was a surprise in the histopathologic examination.<br />
Financial disclosure. None
2028 RF19<br />
RAPID REGRESSION OF POST-BRACHYTHERAPY<br />
CHOROIDAL MELANOMA IN RESPONSE TO<br />
INTRAVITREAL AVASTIN<br />
Peter Hovland MD PhD (peterhovland@gmail.com)<br />
Colorado Retina Associates, Denver CO<br />
Purpose. To describe the rapid decrease in tumor volume seen in a<br />
patient treated with intravitreal avastin following brachytherapy.<br />
Methods. A 65 year old woman with anteriorly located choroidal<br />
melanoma of 10 mm thickness was treated with I-125 brachytherapy.<br />
After 6 months, persistent symptomatic sub-retinal fluid was treated<br />
with intravitreal avastin. Tumor thickness was monitored by b-scan<br />
ultrasound.<br />
Results. FNAB analysis of the tumor confirmed it to be a melanoma with<br />
a GEP Class 1. Tumor volume gradually reduced from a pre-treatment<br />
10.3 thickness to 8.0 mm in the first 6 months. Following 2 injections of<br />
intravitreal avastin, the tumor thickness decreased to less than 1 mm.<br />
Conclusions. Intravitreal avastin injections were associated with a rapid<br />
decrease in tumor volume in a patient with a large choroidal melanoma<br />
post-brachytherapy.<br />
Financial disclosure. None<br />
1845 RF20<br />
LIGHT AND ELECTRON MICROSCOPY OF TWO CILIARY<br />
BODY TUMORS<br />
L. Schoenfield, J. McMahon, A. Singh (schoenl@ccf.org)<br />
Cleveland Clinic<br />
Purpose. To discuss the differential diagnosis of two ciliary body<br />
tumors.<br />
Methods. Two cases of ciliary body tumors were evaluated with routine<br />
H&E stains, immunoperoxidase stains, and electron microscopy.<br />
Results. To be discussed at rapid fire section.<br />
Conclusions. Two tumors from the ciliary body of a 70 year old male and<br />
a 77 year old female will be presented with light microscopy (including<br />
immunoperoxidase stains) and electron microscopy. Discussion and opinions<br />
from the audience will be welcomed as to the nature of these lesions.<br />
Financial disclosure. None<br />
513 RF21<br />
RETINAL DETACHMENT AFTER TTT FOR ACTIVE<br />
CHOROIDAL MELANOMA<br />
Prithvi Mruthyunjaya, MD (mruth001@mc.duke.edu)<br />
Ocular Oncology and Vitreoretinal Surgery Services, Duke Eye Center,<br />
Durham, NC<br />
Purpose. 54 yo male with choroidal melanoma and exudative retinal<br />
detachment has undergone plaque brachytherapy with continued<br />
growth. Transpupillary thermotherapy is applied and a subsequent<br />
rhegmatogenous retinal detachment develops. What is the ideal timing<br />
of RD repair in the setting of an active melanoma?<br />
Methods. Case report<br />
Results. Audience participation requested<br />
Conclusions. What is the ideal timing of RD repair in the setting of an<br />
Rapid Fire Cases<br />
Abstracts<br />
78<br />
active melanoma?<br />
Financial disclosure. None<br />
55 RF22<br />
TREATMENT OF DIFFUSE IRIS MELANOMA<br />
B. Damato (bertil.damato@gmail.com)<br />
Liverpool, UK.<br />
Purpose. Succesfull treatment of diffuse iris melanoma after proton<br />
beam radiotherapy of the entire anterior segment<br />
Financial disclosure. None<br />
62 RF23<br />
LATE RECURRENCE OF A PRESUMED IRIS MELANO-<br />
MA<br />
John McWhae, Ryan Steinke (jmcwhae@gmail.com)<br />
Purpose. A 65-year old woman presented with a spontaneous hyphema<br />
OD. She has a history of iris melanoma treated with iridectomy 35 years<br />
prior. She was found to have 5 small amelanotic angle lesions. The<br />
patient refused any interventions. A second hyphema occurred 3 years<br />
later. The patient has now been followed for 5 years without any growth<br />
of the lesions. Possible explanations for this unusual tumor behaviour<br />
will be discussed.<br />
Financial disclosure. None<br />
45 RF24<br />
HOLY TUMOR<br />
Carol Shields, M.D. (carol.shields@shieldsoncology.com)<br />
Wills Eye Institute<br />
Purpose. An interesting case.<br />
Methods. Patient with uveal melanoma.<br />
Results. Halo nevi developed.<br />
Conclusions. An interesting cutaneous phenomenon developed<br />
following treatment of uveal melanoma in a young woman.<br />
Financial disclosure. None<br />
1848 RF25<br />
RESECTION OF AN IRIS TUMOR<br />
Arun D Singh, Laura Snyder, Linda Brodell, Mary B. Turell (singha@ccf.org)<br />
Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland<br />
Clinic, Cleveland, OH<br />
Purpose. A 71-year old Caucasian female was noted to have a small, light<br />
brown mass extending into the angle without iris deformity. On follow<br />
up examination sixteen months later, a new finding of iris distortion was<br />
observed.<br />
Financial disclosure. None<br />
410 RF26<br />
MELANOMA OR MELANOCYTOMA?
Arturo Irarrazaval, Pablo Cazon, Oscar Croxatto<br />
(artuira@consultoresoftalmologicos.com)<br />
Consultores Oftalmologicos<br />
Purpose. To show an unusual evolution of a plaque treated tumor of the<br />
posterior pole.<br />
Methods. A patient treated with plaque for a mushroom shaped choroidal<br />
melanoma, with characteristic ecography, that had quick growth after<br />
some years of stability, even after TTT adjuvant treatment.<br />
Results. The pathology of enucleated eye shows that the tumor was a<br />
melanocytoma<br />
Conclusions. A choroidal melanocytoma may have an unusual form of<br />
presentation and evolution.<br />
Financial disclosure<br />
None<br />
1655 RF27<br />
MALIGNANT TRANSFORMATION OF CELLULAR BLUE<br />
NEVUS IN AN 8-YEAR-OLD GIRL<br />
A P Moulin1, M Hamedani1, A Oberic1, M Mihm2, F Jakobiec3, V Prieto4, JN<br />
Myers4, F Demont4, RJ Skoracki4, S Woodman4, B Eemaeli4. (alexandre.<br />
moulin@fa2.ch)<br />
1. Jules Gonin Eye Hospital, Lausanne University, Switzerland<br />
2. Brigham and Women’s Hospital, Harvard Medical School, Boston<br />
3. Massachussetts Eye and Ear Infirmary, Harvard Medical School,<br />
Boston<br />
4. MD Anderson Cancer Center, University of Texas, Houston<br />
Purpose. To report a case of malignant transformation of blue nevus of<br />
eyelid into melanoma of orbit in an 8-year-old girl.<br />
Methods. Observational case report.<br />
Results. An 8-year-old girl was referred to Jules Gonin Eye Hospital<br />
for evaluation of an extensive blue nevus involving the right lower<br />
eyelid, the inferior conjunctiva and the orbit with evidence of recent<br />
growth into the orbit. Multiple palpebral and orbital biopsies were<br />
performed. The deepest lesions were consistent with cellular blue<br />
nevus with severe atypia. After 6 months observation, growth of the<br />
orbital mass led to repeat biopsies which confirmed transformation<br />
into invasive melanoma in the orbit. aCGH demonstrated a complete<br />
gain of chromosome 6. There were no mutations of BRAF (exon 15),<br />
GNAQ and GNA11 (exons 5). The patient was referred for evaluation<br />
and management to the University of Texas M.D. Anderson Cancer<br />
Center. The orbital tumor was found to involve the pterygopalatine<br />
fossa and other skull base structures. A multidisciplinary<br />
procedure including an orbital exenteration and skull base surgery<br />
was performed followed 4 weeks later by proton radiotherapy.<br />
Histopathology revealed atypical cellular blue nevus with foci of<br />
melanoma in the posterior orbit.<br />
Conclusions. Cellular blue nevi can rarely transform into malignant<br />
melanoma and can involve deeper structures in the orbital apex and<br />
skull base. To our knowledge, this may be the youngest patient to<br />
date documented to have a malignant transformation of cellular<br />
blue nevus into melanoma. The extent of involvement of atypical<br />
blue nevus required a complex multidisciplinary surgical approach<br />
followed by high-dose radiation therapy.<br />
Financial disclosure. None<br />
Rapid Fire Cases<br />
Abstracts<br />
79<br />
1618 RF28<br />
ORBITAL MELANOMA AND NAEVUS OF OTA<br />
Victoria M.L. Cohen (victoria.lendrum@gmail.com)<br />
Ocular Oncology Service, Moorfields and St Batholomew’s Hospital<br />
London, UK.<br />
Purpose. To report the management of an extensive orbital melanoma<br />
in a patient with naevus of Ota<br />
Methods. A 46-year old male with long standing pigmentation of the<br />
eye and eyelid presented with progressive proptosis. Orbital biopsy<br />
confirmed the presence of melanoma. Despite adjuvant radiotherapy,<br />
the lesion continued to enlarge. The subsequent radical surgical<br />
approach is described<br />
Results. Melanoma was found to be infiltrating the orbital bone,<br />
maxilla, nasopharynx and dura mata.<br />
Conclusions. Orbital and cerebral melanoma is very rare but the most<br />
lethal association of naevus of Ota.<br />
Financial disclosure. None<br />
558 RF29<br />
MANAGEMENT OF A RARE ADNEXAL TUMOR<br />
Sonul Mehta, MD1, John Harvey, MD, F.R.C.S.2 (sonulmehta@gmail.<br />
com)<br />
1. Division of Oculoplastics and Orbital Surgery, Department of<br />
Ophthalmology and Visual Sciences, University of Toronto<br />
2. Division of Oculoplastics and Orbital Surgery, Department of<br />
Ophthalmology and Visual Sciences, McMaster University<br />
Purpose. A 28 year old male who sustained a right upper brow and<br />
eyelid laceration after an injury that presented with a non-healing<br />
wound 3 months later. He was found to have a rare adnexal tumor.<br />
He will be presented to the audience as an unknown for opinions on<br />
management.<br />
Methods. Case Study<br />
Results. He was found to have a rare adnexal tumor that has failed<br />
multiple reconstructions and found to have recurrence of tumor.<br />
Conclusions. He will be presented to the audience as an unknown for<br />
opinions on management.<br />
Financial disclosure. None<br />
19 RF30<br />
AMELANOTIC CONJUNCTIVAL TUMOR - MALIGNANT OR<br />
BENIGN?<br />
Priscilla Ballalai, Maria C. Martins, Marcia Lowen (pbbordon@terra.com.br)<br />
Federal University of Sao Paulo<br />
Purpose. 82 yo female with a rapid growing conjunctival tumor<br />
Financial disclosure. None<br />
1809 RF31<br />
65-YEAR OLD WOMAN WITH DIFFUSE CONJUNCTIVAL<br />
NEOPLASM<br />
J. William Harbour, MD (harbour@vision.wustl.edu)
Washington University, St. Louis, Missouri<br />
Purpose. This case will be presented as an unknown for discussion of<br />
diagnosis and management.<br />
Methods. Case presentation.<br />
Results. This is a 65 year old Caucasian woman who presents with<br />
a diffuse conjunctival neoplasm involving her right eye. Three years<br />
prior to presentation, she noticed a loss of vision in her superior<br />
visual field in the right eye but did not seek medical attention<br />
because she was uninsured. Over the past 18 months she has noticed<br />
that the white part of the right eye has gradually become discolored.<br />
On examination, she had no pain. There was no light perception and<br />
the intraocular pressure was 56 in the right eye. Anterior segment<br />
examination revealed diffuse thickening and hypervascularity of<br />
the conjunctiva, which had a dark gelatinous appearance with an<br />
irregular, roughened surface. A view of the posterior segment was<br />
precluded by a dense cataract. Ultrasonography of the right eye<br />
revealed a total retinal detachment with diffuse thickening of the<br />
choroid and retina but no discrete mass. An intraconal orbital mass<br />
was also noted, which was discontinuous from the globe. The left eye<br />
examination was unremarkable.<br />
Conclusions. Final diagnosis and management will be discussed.<br />
Financial disclosure. None<br />
23 RF32<br />
DIFFUSE CONJUNCTIVAL MALT LYMPHOMA<br />
Shahar Frenkel, MD, PhD, Jacob Pe’er, MD<br />
(shahar.frenkel@gmail.com)<br />
Specialized Ocular Oncology Service, Department of Ophthalmology<br />
Hadassah - Hebrew University Medical Center, Jerusalem, Israel<br />
Purpose. A 40-year-old man was diagnosed as suffering from diffuse<br />
(almost 360deg) conjunctival lymphoma of the right eye. There<br />
was no evidence of other sites of lymphoma. He was treated via six<br />
courses of Rituximab, with complete response. No recurrence was<br />
seen in follow-up of four years.<br />
Any other ideas for treatment in such a case?<br />
Financial disclosure. None<br />
1510 RF33<br />
PAEDIATRIC TUMOUR WITH SCLERAL INVASION<br />
Maria Tsimpida, Amit Arora, Victoria Cohen, Mary Lendrum, John<br />
Hungerford(tsimpidam@yahoo.co.uk)<br />
The Ocular Oncology Service St. Bartholomew’s and Moorfield’s Eye Hospitals<br />
Purpose. A 15 year-old boy presented with a reddish-blue domed shaped<br />
intrascleral lesion in the upper temporal quadrant of the right eye. There<br />
was associated scleral thinning. A corresponding irregularly shaped, pale,<br />
choroidal mass was noted. Cells were present in the vitreous.<br />
Methods. B-scan ultrasonography showed an anterior choroidal mass with<br />
internal blood flow. This was further detailed with a UBM. There was no<br />
evidence of ocular inflammatory or systemic collagen vascular disorder.<br />
Results. The lesion was observed, as diagnostic biopsy would be hasardous<br />
in view of the overlying scleral thinning.A year later, the scleral nodule<br />
Rapid Fire Cases<br />
Abstracts<br />
80<br />
increased in size and the intraocular lesion had extended to involve the ciliary<br />
body. Interestingly, a cyst was found adjacent to the ciliary body mass.<br />
Conclusions. There was concern that this mass was a medulloepithelioma<br />
that was invading the sclera and the patient was offered enucleation. The<br />
surprising histopathological results are discussed.<br />
Financial disclosure. None<br />
1227 RF34<br />
STEREOTACTIC-GUIDED TRANSCRANIAL CRYOEXTRACTION<br />
OF CAVERNOUS HEMANGIOMA IN THE ORBITAL APEX<br />
Mordechai Rosner1, Sagi Harnof2, Vicktoria (Vicky) Vishnevskia-Dai1,<br />
Nachum Rosen1 (mrosner@post.tau.ac.il)<br />
1. Goldschleger Eye Institute, Sheba Medical center, Sackler School of<br />
medicine, Tel-Aviv University Israel.<br />
2. Department of Neurosergery, Sheba Medical center, Sackler School<br />
of medicine, Tel-Aviv University Israel.<br />
Purpose. A 55-year old man with cavernous hemangioma at the apex of his<br />
right eye underwent stereotactic guided transcranial cryoextraction with<br />
favorable results.<br />
Financial disclosure. None<br />
1352 RF35<br />
MYSTERIOUS ORBITAL CASE<br />
Patrick De Potter (patrick.depotter@uclouvain.be)<br />
Ocular Oncology Unit, Cliniques Universitaires St-Luc, Brussels, Belgium<br />
Purpose. Presentation of a mysterious orbital lesion<br />
Financial disclosure. None<br />
1802 RF36<br />
ORBITAL INVOLVEMENT FROM AN UNUSUAL CONDITION<br />
Manquez Maria (m_manquez@yahoo.com)<br />
Clinica Oftalmologica Pasteur, Santiago Chile<br />
Purpose. 58-year old Hispanic male with orbital mass and unusual<br />
liver condition<br />
Financial disclosure. None<br />
112 RF37<br />
REPONSE OF METASTATIC PANCREATIC<br />
ADENOCARCINOMA TO CHEMOTHERAPY<br />
Scott Oliver, MD scott.oliver@ucdenver.edu)<br />
Deparment of Ophthalmology, University of Colorado School of Medicine<br />
Purpose. A case of pancreatic adenocarcinoma presenting with<br />
circumpapillary choroidal metastasis will be presented. Management<br />
options will be discussed, and dramatic response to gemcitabine and<br />
ipilimumab will be shown.<br />
Financial disclosure. None<br />
127 RF38
A CASE OF TEARING AND SWELLING OF THE EYE AFTER<br />
RESOLUTION OF ORBITAL CELLULITIS<br />
Daniel Moreno-Páramo1, David M. Brown2, Robert W. Wong3, Dan S.<br />
Gombos1,2,4,5, Milton Boniuk4, Patricia Chévez-Barrios1,2,4,5<br />
(danomp@hotmail.com)<br />
1. The University of Texas, MD Anderson Cancer Center, Houston, Texas<br />
2. The Methodist Hospital, Weill Cornell Medical College of Cornell<br />
University, Houston, Texas<br />
3. Austin Retina Associates, Austin, Texas<br />
4. Baylor College of Medicine, Houston, Texas<br />
5. Retinoblastoma Center at Houston, Houston, Texas<br />
Purpose. To present as “mystery case” the findings of a 78-yearold<br />
woman with tearing and swelling of the left eye for discussion of<br />
differential diagnosis, pathology diagnosis and treatment.<br />
Methods. A 78-year old Caucasian woman presented with tearing and<br />
swelling of the left eye and history of orbital cellulitis of the same side.<br />
Imaging studies and fundoscopy showed a flat white lesion in the choroid<br />
and a larger lesion in the orbit.<br />
Results. Imaging, pathology and laboratory findings will be presented.<br />
Conclusions. Clinical and histopathologic differential diagnosis and<br />
management will be discussed.<br />
Financial disclosure. None<br />
124 RF39<br />
MYSTERY CASE<br />
Masood Naseripour MD (masoodnp@yahoo.com)<br />
Eye Research Center, Rassoul Akram Hospital, Tehran University of Medical<br />
Sciences<br />
Purpose. To report an interesting case<br />
Methods. A 5-month-old baby referred with an unusual black retinal<br />
mass. It will be presented as an unknown case for opinions from the<br />
audience.<br />
Conclusions. Will be presented<br />
Financial disclosure. None<br />
158 RF40<br />
A PATIENT WITH MULTIPLE CANCER HISTORY<br />
Helen K. Li, MD (hlimed@mac.com)<br />
1. The Methodist Hospital / Weil Cornell Medical College, Houston, TX<br />
2. The University of Texas Health Science Houston, Houston, TX<br />
3. Wills Eye Institute, Thomas Jefferson University, Philadelphia, PA.<br />
Purpose. To be presented as an unknown case for opinions from the<br />
audience.<br />
Financial disclosure. None<br />
110 RF41<br />
MULTIPLE OCULAR VASCULAR ANOMALIES IN A CHILD<br />
Mandeep S. Sagoo1,2,4 MB, PhD, MRCOphth, FRCS (Ed), Wisam J.<br />
Muen1,2 MRCS.Ed(Surg), FRCOphth, Clare Roberts3 MA, FRCOphth, M.<br />
Ashwin Reddy1,2 MD, FRCOphth (mandeep.sagoo@moorfields.nhs.uk)<br />
1. Retinoblastoma Unit, Barts & the London NHS Trust, Royal London<br />
Rapid Fire Cases<br />
Abstracts<br />
81<br />
Hospital, Whitechapel Road, London, UK<br />
2. Moorfields Eye Hospital, City Road, London, UK<br />
3. Moorfields Dubai Eye Hospital, Dubai, UAE<br />
4. UCL Institute of Ophthalmology, Bath Street, London, UK<br />
Purpose. A 2-year-old white female with ocular vascular anomalies is<br />
presented for discussion.<br />
Financial disclosure. None<br />
1938 RF42<br />
A MYSTERY CASE<br />
M. Ashwin Reddy MD FRCOph1,2, Sharola Dharmaraj PhD FRCS1,2,<br />
Mandeep Sagoo PhD FRCS FRCOph1,2,3, Himanshu Patel MS FRCS1,2,<br />
Phil Luthert PhD FRCP FRCPath2,3<br />
(mashwinreddy@hotmail.com)<br />
1. Barts and The London<br />
2. Moorfields Eye Hospital<br />
3. Institute of Ophthalmology<br />
Purpose. A 2-year old boy presented with a squint and an unusual red<br />
reflex. Fundus examination demonstrated a calcified mass with a fibrotic<br />
front of blood vessels. To be presented as a mystery case.<br />
Financial disclosure. None<br />
1834 RF43<br />
MYSTERY CASE<br />
Edoardo Midena1,2, Raffaele Parrozzani2 (edoardo.midena@unipd.it)<br />
1 Department of Ophthalmology, University of Padova, Padova, Italy.<br />
2 GB Bietti Eye Foundation, IRCCS, Roma, Italy.<br />
Purpose. A 46-year-old woman affected by a left choroidal successfully-treated<br />
mass underwent massive, perilesional, purely serous retinal detachment.<br />
Financial disclosure. None<br />
1255 RF44<br />
MYSTERY CASE<br />
Michael E. Giblin (emgiblin@ozemail.com.au)<br />
Sydney Eye Hospital, Sydney, Australia<br />
Purpose. To demonstrate an unusual presentation of a rare fundal tumour.<br />
Methods. A 29 year old white female patient presented with a<br />
pigmented fundal mass, considered suitable for Transpupillary Laser<br />
Thermotherapy (TTT). Immediately prior to the TTT some three weeks<br />
later, the mass had significantly altered.<br />
Conclusions. For audience to deduce<br />
Financial disclosure. None<br />
1309 RF 45<br />
METASTATIC CHOROIDAL PARAGANGLIOMA<br />
Ann Schalenbourg1, Alexandre Moulin1, Louis Guillou2 and Leonidas<br />
Zografos1 (ann.schalenbourg@fa2.ch)<br />
1. Jules-Gonin Eye Hospital, University of Lausanne, Switzerland<br />
2. University Institute of Pathology and University Hospital, University<br />
of Lausanne, Switzerland
Purpose. To describe a patient with metastatic choroidal paraganglioma,<br />
locally controlled with radiotherapy.<br />
Methods. Interventional clinico-pathological case report. Systematic<br />
search of the literature.<br />
Results. A 50-year-old man presented a non-pigmented atypical<br />
choroidal mass with secondary retinal detachment in the left eye.<br />
Following incisional biopsy, the diagnosis of paraganglioma was<br />
established. Metastatic work-up revealed vertebral, mediastinal and<br />
pulmonary metastases of a non secretory, malignant paraganglioma<br />
without tracer uptake. The primary tumor was not identified. The ocular<br />
tumor regressed after stereotaxic radiotherapy. Two years later, the<br />
patient developed recurrent lesions in the contralateral eye, which were<br />
also irradiated.<br />
Conclusions. Malignant paraganglioma can metastasize in the choroid<br />
and should be included in the differential diagnosis of a non pigmented<br />
choroidal mass. Stereotaxic radiation therapy is an effective treatment<br />
modality. To our knowledge, this is the first report of a patient with<br />
choroidal paraganglioma.<br />
Financial disclosure. None<br />
Rapid Fire Cases<br />
Abstracts<br />
82<br />
67 RF46<br />
MYSTERY CASE<br />
Sara Lally (saralally1@yahoo.com)<br />
Wills Eye Hospital, Philadelphia<br />
68 RF47<br />
MYSTERY CASE<br />
Hakan Demirci (hdemirc1@hfhs.org
1849 ECp101<br />
FIVE CASES OF CARCINOMA METASTASIC TO THE<br />
EYELIDS<br />
Hiroya Kashiwagi1, Hirohisa Katagiri2, Takuya Takagi2, Hideki Murata2,<br />
Mitsuru Takahashi2, Toshiaki Takahashi3 , Masato Matsuzaki4<br />
(h.kashiwagi@scchr.jp)<br />
1. Ophthalmology, 2. Orthopedics, 3. Thoracic Oncology, and 4. Urology,<br />
of Shizuoka Cancer Center<br />
Purpose. We report 5 rare cases of carcinoma metastasis to the eyelid.<br />
Methods. We reviewed the medical records of 5 patients with metastatic<br />
eyelid carcinoma who consulted the Shizuoka Cancer Center from April<br />
2007 to March 2011.<br />
Results. Four of the patients were male and one was female (age range,<br />
42–71 years; average age, 62.4 years). The primary tumors were a seminal<br />
vesicle leiomyosarcoma, an occult primary neuroendocrine carcinoma, a<br />
lung cancer, occult primary sarcoma, and a renal cell carcinoma. The site of<br />
carcinoma was the upper eyelid in 3 cases and the lower in 2 cases. The renal<br />
cell carcinoma was the only tumor that was discovered before the primary<br />
lesion was found. The treatment given was complete removal in 1 case,<br />
excisional biopsy in 1case, and incisional biopsy in 3 cases. Three patients<br />
died of systemic metastatic disease, and the time to death from discovery of<br />
the lesion was 2–3 months (average, 2.3 months). The leiomyosarcoma was<br />
resistant to chemotherapy and irradiation. The occult primary sarcoma was<br />
treated with macroscopic complete extraction. Therefore, chemotherapy<br />
was administered, and it was found to be effective with no recurrence. The<br />
renal cell carcinoma showed rapid growth even after the primary carcinoma<br />
was removed completely; therefore, complete resection with a safety margin<br />
of 5 mm was performed, and no recurrence has been reported to date.<br />
Conclusions. We think that early extraction are necessary for sarcoma.<br />
Oncologists should also understand that eyelid lesions may progress even<br />
if the primary tumor was removed.<br />
Financial disclosure. None<br />
1516 ECp102<br />
NATURAL KILLER/T-CELL LYMPHOMAS IN OCULAR<br />
LESION<br />
Hideki Tsuji, Megumi Kobayashi, Kengo Takeuchi, Kazuhiro Oshitari,<br />
Keigo Shikishima (tsuji-tky@umin.ac.jp)<br />
The Cancer Institute Hosptal<br />
Purpose. The importance of malignant lymphomas (ML) in ocular<br />
oncology is widely known. However, NK/T ML constitute a extremely<br />
small fraction of ocular adnexal lymphomas (OAL). We show the cases<br />
of NK/T in OAL.<br />
Methods. Case reports of NK/T malignant lymphomas (ML) of medial<br />
rectus muscle (68y.o.M) and of eyelid (60 y.o. F).<br />
Results. Both cases had aggressive clinical coarse even with radiation<br />
and chemotherapy, especially the medial rectus muscle case recurred<br />
and showed poor prognosis.<br />
Conclusions. NK/T ML in OAL have different clinical course compared with<br />
MALT lymphoma. These cases suggest us about clinical and pathological<br />
varieties of OAL and each subtype ML requires each prompt therapeutic strategies.<br />
Financial disclosure. None<br />
2337 ECp103<br />
CONJUNCTIVAL SQUAMOUS CELL CARCINOMA<br />
EYELID, CONJUNTIVA & ORBIT<br />
Abstract Posters<br />
83<br />
ARISING IN IMMUNOSUPPRESSED PATIENTS (ORGAN<br />
TRANSPLANT, HUMAN IMMUNODEFICIENCY VIRUS<br />
INFECTION)<br />
Carol L. Shields, M.D., Aparna Ramasubramanian, M.D., Phoebe L. Mellen,<br />
B.S., Jerry A. Shields, M.D. (carol.shields@shieldsoncology.com)<br />
Wills Eye Institute<br />
Purpose. To describe the relationship between chronic systemic immune<br />
suppression and conjunctival squamous cell carcinoma (SCC).<br />
Methods. Surgical excision in all cases plus additional topical interferon<br />
alpha 2B and/or mitomycin<br />
Results. There were three groups of patients with chronic<br />
immunosuppression and conjunctival SCC, including post organ<br />
transplant (n=8), human immunodeficiency virus (HIV) (n=4), and<br />
systemic lupus erythematosis (SLE) on long-term corticosteroids (n=1).<br />
The transplanted organ was kidney (n=4), lung (n=2), liver (n=1),<br />
and heart (n=1). The mean patient age at presentation for the organ<br />
transplant group was 60 years and the mean interval from transplant<br />
to conjunctival SCC was 8.2 years. Management included surgical<br />
excision (n=8) plus additional topical interferon alpha 2B (n=3) and<br />
mitomycin C (n=1). Three patients showed aggressive recurrence. In<br />
the HIV group, the mean patient age at presentation was 54 years and<br />
the mean interval from HIV diagnosis to conjunctival SCC was 5 years.<br />
Management included surgical excision (n=5) plus additional topical<br />
interferon alpha 2B (n=3) and mitomycin C (n=1). One patient showed<br />
aggressive extensive recurrence. Of the 5 patients treated with excision<br />
and prompt topical interferon alpha 2B, none showed recurrence or new<br />
tumor.<br />
Conclusions. Conjunctival SCC can occur in immune suppressed patients<br />
and can be more aggressive and invasive, requiring enucleation or<br />
exenteration. Surgical resection plus topical interferon alpha 2B might<br />
reduce the risk for recurrence/new tumor.<br />
Financial disclosure. None<br />
1822 ECp104<br />
SQUAMOUS NEOPLASIA OF THE OCULAR SURFACE<br />
INVADING THE EYE AND ORBIT: A STUDY OF 30 CASES<br />
Eduardo F. Marback, Ediney Vila Nova Silva, Roberto L. Marback<br />
(eduardomarback@uol.com.br)<br />
Federal University of Bahia - Brazil<br />
Purpose. To evaluate cases of squamous neoplasia of the ocular surface<br />
(SNOS) with orbital or intraocular invasion that required mutilating<br />
surgery.<br />
Methods. A review in the registry book from the Ophthalmic Pathology<br />
Laboratory at Federal University of Bahia – Brazil from January 2000 to<br />
December 2009 was conducted looking for entries with histopathologic<br />
diagnosis of SNOS. Cases with intraocular or orbital invasion that<br />
required mutilating surgery (eye enucleation or orbital exenteration)<br />
were selected. Collected data included age, sex, preoperative visual<br />
acuity, duration of symptoms and presence of previous surgery.<br />
Results. From 213 cases of SNOS, 30 (14%) had conjunctival squamous<br />
cell carcinoma that necessitated mutilating surgery. Thirteen (43%)<br />
patients required eye enucleation and 17 (57%) required orbital<br />
exenteration. In the enucleation group the mean age at diagnosis was<br />
62,9 years-old (ranging from 42 to 95), 10 (77%) patients were male,<br />
the mean duration of symptoms was 15,2 months (ranging from 3 to
36), 6 (46%) reported previous surgery. In the exenteration group the<br />
mean age at diagnosis was 67,8 years-old (ranging from 31 to 88), 11<br />
(64,7) patients were male, the mean duration of symptoms was of 28,5<br />
months (ranging from 3 to 94), 6 (35%) reported previous surgery.<br />
Conclusions. Mutilating surgery due to orbital or intraocular invasion<br />
by SNOS is uncommon (14%). History of previous surgery was detected<br />
in 40% of the cases. Duration of symptoms was 1.9 higher in cases<br />
undergoing exenteration, a factor that may be considered important for<br />
the occurrence of orbital invasion.<br />
Financial disclosure. None<br />
1150 ECp105<br />
A PROPOSAL FOR A NEW TREATMENT OF ORBITAL<br />
LOW GRADE MALIGNANT LYMPHOMA<br />
Akihiro Kaneko (akikaneko@jcom.home.ne.jp)<br />
Department of Ophthalmology, Teikyo University Hospital, Tokyo, Japan<br />
Purpose. TO propose a new treatment for orbital low grade lymphoma to<br />
avoid complications of radiotherapy<br />
Methods. A selective ophthalmic arterial injection with 3-5mg of<br />
melphalan (SOAI) is performed to eradicate orbital low grade malignant<br />
lymphoma.<br />
Results. The author has no chance to try this therapy until now.<br />
Conclusions. Melphalan is an old alkylating agent which has<br />
radiomimetic activity which means to work as radiotherapy.SOAI is<br />
developed by our group for eye-preservation therapy of retinoblastoma.<br />
It is performed more than 20 countries over the world, because very<br />
slight complications are recognized.<br />
Therefore good response is able to be expected for the treatment of<br />
localized orbital lymphoma. in addition to that ,many complications of<br />
radiotherapy must be avoidable.<br />
Financial disclosure. None<br />
59 ECp106<br />
ORBITAL EXENTERATION RECONSTRUCTION WITH<br />
RADIAL FOREARM AND ANTEROLATERAL THIGH FREE<br />
FLAP: A MULTIDISCIPLINARY APPROACH<br />
Sara E. Lally, M.D., Carol L. Shields, M.D., Joseph Curry, M.D., Ryan<br />
Heffelfinger, M.D., David Cognetti, M.D., Howard Krein, M.D., Jerry A.<br />
Shields, M.D. (saralally1@yahoo.com)<br />
Wills Eye Institute, Philadelphia PA<br />
Purpose.Orbital exenteration is a radical procedure to remove the eye<br />
and orbital contents, usually for invasive malignancies. When possible,<br />
eyelid skin and muscle are spared to aid in closure and healing. If tumor<br />
infiltrates the eyelid, then this tissue must be removed. Reconstruction<br />
of the socket with radial forearm and anterolateral thigh free flaps is<br />
performed.<br />
Methods. Review of technique and outcomes.<br />
Results. Over the past 5 years, exenteration was performed in 44<br />
cases for diagnoses of invasive eyelid squamous cell carcinoma (n=11),<br />
invasive eyelid basal cell carcinoma (n=1), eyelid sebaceous carcinoma<br />
(n=7), conjunctival melanoma (n=8), extraocular extension of uveal<br />
melanoma (n=5), lacrimal gland adenoid cystic carcinoma (n=3),<br />
primary orbital malignancies (n=7), and other extraocular extension of<br />
intraocular tumors (n=2). In 33 cases, eyelid sparing exenteration and<br />
EYELID, CONJUNTIVA & ORBIT<br />
Abstract Posters<br />
84<br />
reconstruction with primary closure was achieved. In 11 cases, eyelid<br />
sacrificing exenteration was performed and reconstruction with radial<br />
forearm (n=4) or anterolateral thigh (n=7) myocutaneous free flap was<br />
performed with anastomosis of large vessels with the temporal artery.<br />
In all cases (100%), reconstruction was successful and the graft survived,<br />
providing skin coverage over orbital bone.<br />
Conclusion. Radical exenteration for extensive orbital malignancies can<br />
lead to large open defects that require free myocutaneous flaps from the<br />
arm or leg with microvascular anastamosis.<br />
Financial disclosure. None<br />
243 ECp107<br />
A HUGE OCULAR ADNEXAL MALT LYMPHOMA WHICH<br />
AROSE FROM IGG4 RELATED ORBITAL LESION<br />
Koh-ichi Ohshima (koh-1125@po6.oninet.ne.jp)<br />
Section of Ophthalmology, Okayama Medical Center, Japan<br />
Purpose. For the treatment of the IgG4 related orbital disorders, steroid<br />
therapy is the first choice. On the other hand, ocular adnexal MALT<br />
lymphoma responds well to the radiation therapy. We should discuss<br />
how to treat MALT lymphoma which arose from IgG4 related orbital<br />
lesion.<br />
Methods. A 71-year-old woman visited our department for the treatment<br />
of eyelid swelling of the left eye which had been aggravating for two<br />
years. The left upper and lower eyelids were very swollen and the left<br />
eyeball had atrophied. The abnormal mass of left eyelid, the swelling of<br />
extra ocular muscle and the enlargement of major lacrimal gland were<br />
shown by orbital MRI. Auto-antibodies related to the thyroid gland were<br />
negative, and serum IgG4/IgG was 450/1844. The incisional biopsy of<br />
eyelid tumor revealed it to be MALT lymphoma with many IgG4 positive<br />
plasma cell infiltration.<br />
Results. The eyelid tumor was surgically removed and the deformity<br />
of the eyelid decreased. To prevent re-growth of the tumor, radiation<br />
therapy of 30Gy was added to the left orbit. The patient has been<br />
carefully followed up for one year.<br />
Conclusions. Excision and radiation therapy performed to treat a huge<br />
ocular adnexal MALT lymphoma which arose from an IgG4 related orbital<br />
lesion, with a good result.<br />
Financial disclosure. None<br />
223 ECp108<br />
HIGH-RESOLUTION ULTRASONOGRAPHY IN THE<br />
DIAGNOSIS OF ORBITAL MALIGNANT LYMPHOMA<br />
S.V. Saakyan, A.G. Amiryan, V.R. Alikhanova (svsaakyan@yandex.ru)<br />
Moscow Helmholtz Research Institute of Eye Diseases<br />
Purpose. To characterize the diagnostic criteria of orbital malignant<br />
lymphoma through the use of complex ultrasonography techniques.<br />
Methods. 21 patients with orbital lymphoma (mean age 55.2±16 years)<br />
were surveyed. The examination was performed on an ultrasonic system<br />
with volume-scanning, Voluson® 730 PRO (Kretztechnik’’s – GE Medical<br />
System, Austria). The Duplex scanning included B-mode examination,<br />
color Doppler Imaging (CDI), spectral Doppler analysis, and threedimensional<br />
reconstruction. In all cases, the diagnosis of lymphoma<br />
was morphologically verified.<br />
Results. The lymphoma was localized in the lacrimal glands in 11
patients. The isolated involvement of extraocular muscles was<br />
revealed in 4 patients. In 4 other cases the tumor was identified<br />
behind the sclerouveal ring surrounding the optic nerve. In 2 cases<br />
the tumor occupied all retrobulbar space. In B-mode examination<br />
the lymphoma presented as a complex formation, including small<br />
hyperechogenic inclusions and thin septations in the tumor. The<br />
acoustic density of the tumor estimated with densitometry was -44<br />
on average.<br />
Mixed arterio-venous flow imaging of tumor vessels demonstrated<br />
the average systolic flow velocity equaling 15,67cm/c; the indicators<br />
of resistance averaged RI=0,62±0,1 and PI=1,06±0,3. “Large” feeding<br />
arteries with the lower resistance indexes and diastolic flow were<br />
revealed in 50 % of cases.<br />
Conclusions. In concert with existing Methods, the echographic<br />
criteria presented enhance the diagnostic capabilities of malignant<br />
lymphoma of the orbit and allow for more precise determination of<br />
the extent of surgical intervention.<br />
Financial disclosure. None<br />
1752 ECp109<br />
CONJUNCTIVA MALIGNANT MELANOCYTIC TUMORS.<br />
RECURRENCE AND SURVIVAL RATE IN 15 PATIENTS<br />
FROM CHILE<br />
Maria E Manquez1, Pablo Vigorena2, Bruno Nervi3, Pablo Zoroquiain3,<br />
Jeannie Slater4, Arturo Espinoza5 (m_manquez@yahoo.com)<br />
1. Clinica Oftalmlogica Pasteur. Santiago, Chile<br />
2. Hospital Padre Hurtado, Santiago, Chile<br />
3. Universidad Catolica de Chile<br />
4. Hospital Militar Santiago, Chile<br />
5. Citolab, Santiago, Chile<br />
Purpose. To describe the clinical features of affected patients,<br />
regarding age, sex, systemic condition, prior treatment, and to<br />
describe the clinical features of the tumor, extension, presence of lid<br />
/ orbital invasion, and to report recurrence, metastasis and mortality<br />
rate at short term follow up.<br />
Methods. Review of 70 charts of patients with conjunctiva melanocytic<br />
lesions, 15 of them presented malignant tumors. Time of follow up was<br />
36 months ( 12-72).<br />
Results. Regarding patients: the age of presentation was 56 yo ( 33<br />
-88), 74% were female, 80% wiith dark hair, borwon iris. None were<br />
immunosuppressed.<br />
Regarding tumors: 74% of cases presented melanoma with pam with<br />
atypia, 26% with pam with severe atypia. 70% of cases had at least 1<br />
prior recurrence.<br />
Orbital involvement was observed in 20% of the cases<br />
Recurrence after treatment was observed in 8% of pts with prior<br />
surgery and 0% of those with no prior treatment.<br />
The survival rate was 94%.<br />
Conclusions. Mlaignant melanocytic are observed no only in caucasians<br />
but also in hispanic patients. Our patients seems to be younger at the<br />
time of presentation. Females are more often affected.<br />
Most of our patients are referred late, after at least 1 surgery.<br />
Those patients with no prior surgery, present good outcome with no<br />
recurrence at short term follow up.<br />
Financial disclosure. None<br />
EYELID, CONJUNTIVA & ORBIT<br />
Abstract Posters<br />
85<br />
66 ECp110<br />
LYMPHOPROLIFERATIVE TUMORS OF THE LACRIMAL<br />
GLAND: ANALYSIS OF CLINICAL FEATURES AND<br />
SYSTEMIC INVOLVEMENT<br />
Hakan Demirci, Shivani Gupta, Carol L. Shields, Jerry A. Shields, Victor<br />
M. Elner,<br />
(hdemirci@med.umich.edu)<br />
W. K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI<br />
Oncology Service, Wills Eye Institute, Philadelphia, PA<br />
Purpose. The lacrimal gland is an only ocular adnexal tissue that<br />
contains native lymphocytes. Despite its unique property, isolated<br />
primary involvement of the lacrimal gland is rare in lymphoproliferative<br />
tumors of the ocular adnexa. There is no information about the risk<br />
for systemic lymphoma in the patients with isolated lacrimal gland<br />
lymphoproliferative tumors.<br />
Methods. We retrospectively reviewed clinical features and treatment<br />
method of 40 patients with isolated lacrimal gland tumor. Data from 33<br />
patients without systemic disease at presentation were analyzed for<br />
their impact on the occurrence of systemic lymphoma.<br />
Results. At presentation, tumor was unilateral in 22 (55%) patients and<br />
bilateral in 18 (45%). Of 40 patients, 20 (50%) patients had marginal<br />
zone B-cell lymphoma, 13 (33%) patients had follicular lymphoma, 3<br />
(8%) patients had mantle cell lymphoma and 2 (5%) patients had diffuse<br />
large B-cell lymphoma. Thirty-five (88%) patients were managed with<br />
external beam radiotherapy, 2 (5%) patients were treated with systemic<br />
chemotherapy and 2 (5%) patients were managed with excisional<br />
biopsy.<br />
Systemic lymphoma was detected in 11 (28%) patients. Systemic<br />
involvement was diagnosed before the lacrimal gland tumor in 2 (5%)<br />
patients, at the time of diagnosis of the lacrimal gland tumor in 5 (13%)<br />
patients, and subsequent to the diagnosis of the lacrimal gland tumor in 4<br />
(10%) patients. Of 4 patients in whom systemic lymphoma subsequently<br />
developed, 3 (75%) patients had follicular lymphoma and 1(25) patient<br />
had diffuse large B- cell lymphoma. Using Kaplan-Meier estimates of 30<br />
patients without systemic involvement, systemic lymphoma developed<br />
in 16% at 3 and 5 years, and 58% at 10 years.<br />
Conclusions. The majority of lacrimal gland lymphoproliferative tumors<br />
were either marginal zone B-cell or follicular lymphoma. In patients<br />
with lacrimal gland lymphoproliferative tumor alone at presentation,<br />
systemic lymphoma eventually developed in 16% at 5 years and 58%<br />
at 10 years. Development of systemic lymphoma was associated with<br />
follicular or diffuse large B-cell lymphoma of the lacrimal gland.<br />
Financial disclosure. None<br />
224 ECp111<br />
IMMUNOHISTOCHEMICAL AND MOLECULAR STUDY<br />
OF OPTIC PATHWAY GLIOMAS<br />
Charles G. Eberhart, J. Douglas Cameron, Elizabeth J. Rushing, Matthias<br />
Karajannis, Fausto J. Rodriguez, (ceberha@jhmi.edu)<br />
Johns Hopkins University, Baltimore, MD; Armed Forces Institute of<br />
Pathology, Washington, DC; New York University, NYC<br />
Purpose. Optic pathway gliomas (OPG) represent a specific subtype of<br />
astrocytoma with unique clinicopathologic and biological properties.<br />
OPG may occur in the setting of NF1 syndrome or sporadically, and<br />
at the pathologic level are pilocytic astrocytomas. Recent studies
have highlighted a role for specific cell signaling pathways and the<br />
tumor microenvironment in the biology of this tumor. In this study we<br />
performed immunohistochemical studies in a relatively large series of<br />
OPG using tissue microarrays.<br />
Methods. Tumors from 59 patients with a median age of 9 years (range<br />
3 mo-66 years; 33 F,26 M) were tested using formalin-fixed paraffin<br />
embedded material in tissue microarrays. Immunohistochemistry<br />
was performed using antibodies recognizing mTOR pathway signaling<br />
components (total mTOR protein, Phospho-4E-BP1, PhosphoeIf4G,<br />
phosho-S6), microglia (CD68), markers of senescence (p16),<br />
and mutant IDH1 protein. Scoring was performed using a 4-tiered<br />
semiquantitative scale (0-4+). IDH1 was scored as positive or negative.<br />
Immunohistochemistry for GFAP was performed to evaluate for adequacy<br />
of immunoreactivity.<br />
Results. Immunohistochemical stains demonstrated frequent staining<br />
for mTOR pathway components, including moderate (2+) to strong (3+)<br />
staining for total mTOR (50%), phospho-4E-BP1 (42%), phospho-eIf4G<br />
(75%), and phospho-S6 (70%). Moderate to marked numbers of CD68<br />
positive microglia were identified in 44% of cases. Moderate to diffuse<br />
nuclear immunoreactivity for p16 was identified in 59% of cases. All<br />
cases (except for 1) were immunonegative for IDH1 mutant protein.<br />
Conclusions. OPG demonstrate increased total/activated levels of mTOR<br />
signaling components supporting an important role for this pathway<br />
in its biology. In addition, increased numbers of CD68+ microglia and<br />
markers of senescence (p16) were identified. These findings merit<br />
further study and correlation with additional molecular markers to<br />
evaluate their clinical and biological significance.<br />
Financial disclosure. None<br />
EYELID, CONJUNTIVA & ORBIT<br />
Abstract Posters<br />
86<br />
Other Intra-ocular Tumors Posters<br />
131 OTp101<br />
PHOTODYNAMIC THERAPY FOR ACQUIRED ASTRO-<br />
CYTOMA<br />
Cinzia Mazzini, Maria Carla Donati, Giulia Pieretti, Ugo Menchini (cinzia.<br />
mazzini@unifi.it)<br />
Department of Specialistic Surgery Sciences, Eye Clinic, University of<br />
Florence, Florence, Italy.<br />
Purpose. Retinal astrocytomas are glial tumours of the RNFL arising from<br />
retinal astrocytes, often associated with systemic disorders ( tuberous<br />
sclerosis or neurofibromatosis) but they can also be found on retinal<br />
examination as isolated tumour. We report the case of epipapillary<br />
retinal astrocytoma associated with serous retinal detachment treated<br />
with photodynamic therapy (PDT).<br />
Methods. A 32-years old man was referred for an elevated whitish<br />
epipapillary lesion associated with retinal detachment. He had a history<br />
of multicellular carcinoma and melanocytic nevus of the scapular region.<br />
Visual acuity was 20/20 in both eyes. Fluorescein angiography revealed<br />
a hyperfluorescence of the lesion; B-scan showed a solid epipapillary<br />
tumour with high reflectivity, posterior shadowing, and a contiguous<br />
serous retinal detachment. OCT showed a solid elevation of the retinal<br />
layers associated with raised neuro-epithelium at the edge of the lesion.<br />
The clinical picture was consistent with “acquired astrocytoma”.<br />
Four years later, the patient complained of a severe visual loss in left<br />
eye. BCVA was 20/50 and fundus examination, echography, fluorescein<br />
angiography and OCT showed an enlargement of the lesion and retinal<br />
detachment, with macular exudation. PDT with verteporfirin was performed.<br />
Results. Three months after treatment visual acuity remained stable;OCT<br />
and echography revealed a decrease of subretinal fluid. One year later<br />
BCVA was 20/30, and retinal detachment was disappeared.<br />
Conclusions. PDT with verteporfin can induce regression of aggressive<br />
retinal astrocytomas and may prevent their progression to total retinal<br />
detachment and enucleation. In selected severe cases, PDT may be<br />
considered a first-line treatment for acquired astrocytomas.<br />
Financial disclosure. None<br />
530 OTp102<br />
MANAGEMENT OF PERIPAPILLARY HEMANGIOMA IN<br />
PEDIATRIC VHL DISEASE<br />
Prithvi Mruthyunjaya, MD (mruth001@mc.duke.edu)<br />
Ocular Oncology and Vitreoretinal Surgery Services, Duke Eye Center,<br />
Durham, NC<br />
Purpose. To describe the management of a peripapillary retinal<br />
hemangioma in a pediatric patient with von-Hippel-Lindau disease and<br />
to describe the early development of epiretinal proliferations in this<br />
disease.<br />
Methods. Case report of a 2 yo male with a strong family history of VHL<br />
disease who presents with a new peripapillary hemangioma associated<br />
with a dome-shaped epimacular elevation.<br />
Results. Intraoperative photodynamic therapy was performed with<br />
verteporfin and intravitreal Avastin on 2 occasions with subsequent<br />
inactivation of the peripapillary hemangioma. The macular elevation<br />
was likely due to vitreous traction on the macular hyloid bursa with
exudative fluid from the hemangioma. Collapse of this structure may be<br />
the origin of an epiretinal membrane.<br />
Conclusions. Intraoperative PDT therapy is an option in pediatric VHL<br />
patients with peripapillary hemangiomas. Technique for this procedure<br />
performed under general anesthesia will be discussed.<br />
Financial disclosure. None<br />
105 OTp103<br />
MEK INHIBITOR-ASSOCIATED SEROUS RETINOPATHY<br />
- CLINICAL FEATURES OF A NEW RETINAL DISORDER<br />
Scott C. N. Oliver, Raul Velez Montoya, Wells Messersmith, Jeffrey L<br />
Olson, Naresh Mandava (scott.oliver@ucdenver.edu)<br />
Departments of Ophthalmology and Medical Oncology, University of<br />
Colorado School of Medicine, USA<br />
Purpose. MAPK/ERK kinase (MEK) inhibitors are a promising class<br />
of antineoplastic agents undergoing human clinical trial. This report<br />
describes new findings of serous retinopathy and outer retinal thickening<br />
not previously reported with these agents<br />
Methods. Retrospective review<br />
Results. Three patients with metastatic cancer had multiple central<br />
scotomas 1,3, and 14 days after study drug initiation. Subneurosensory<br />
fluid (SRF) was visible clinically and on optical coherence<br />
tomography(OCT). Additionally, OCT identified diffuse outer retinal<br />
thickening in areas not associated with fluid. FA and ICG angiography<br />
did not show leakage. Findings resolved with drug discontinuation.<br />
Conclusions. MEK inhibitor associated serous retinoapathy consists<br />
of rapid onset localized SRF and diffuse outer retinal thickening. It<br />
resembles, but is distinct from CSR, and requires further investigation.<br />
Financial disclosure. Dr. Oliver is a consultant with Array Bioscience, Inc.<br />
1450 OTp104<br />
BENIGN TUMORS OF CILIARY BODY IN KOREAN<br />
PATIENTS<br />
Christopher Seungkyu Lee1A, Hee Jung Kwon1A, Hyae Min Jeon1B, Min<br />
Kim1A, Sung Chul Lee1A (sklee219@yuhs.ac)<br />
(A) Department of Ophthalmology,<br />
(B) Department of Pathology,<br />
(1) Yonsei University College of Medicine, Seoul, Korea<br />
Purpose. To evaluate clinical features, management, histopathology,<br />
and prognosis of benign ciliary body tumors in Korean patients.<br />
Methods. A retrospective medical chart review was conducted on various<br />
benign tumors of ciliary body that were evaluated by the authors between<br />
2006 and 2011.<br />
Results. All 8 patients underwent transscleral local resection of ciliary<br />
body tumors, which were pathologically confirmed to be benign. Of 8, 3<br />
were diagnosed with adenoma of nonpigmented ciliary body epithelium<br />
(2 men, 1 woman; mean age 35 years; mean initial and final visual acuities<br />
(VAs) 20/25 and 20/32 over 2 years), 1 was adenoma of pigmented ciliary<br />
body epithelium (woman; 83 years; mean initial and final VAs 20/200<br />
and light perception over 1 month), 2 were melanocytoma (2 men; mean<br />
age 40 years; mean initial and final VAs 20/25 and 20/25 over 2 years),<br />
1 was schwannoma (woman; 30 years; initial and final VAs 20/100 and<br />
detecting hand movement over 5 years), and 1 was leiomyoma (woman;<br />
46 years; initial and final VAs 20/400 and 20/80 over 1.5 years).<br />
EYELID, CONJUNTIVA & ORBIT<br />
Abstract Posters<br />
87<br />
Conclusions. Various benign tumors can be found in the ciliary body<br />
that should be differentiated from malignant tumors, especially ciliary<br />
body melanoma. Benign ciliary body tumors are rare and each type of<br />
tumor has its characteristic clinical and histopathological features that<br />
can suggest the diagnosis. In the management of these tumors, local<br />
resection, rather than enucleation, should be considered first as the<br />
treatment of choice. The visual prognosis was fair without any systemic<br />
morbidity.<br />
Financial disclosure. None<br />
321 OTp105<br />
TREATMENT OF SEROUS MACULAR DETACHMENT<br />
ASSOCIATED WITH CIRCUMSCRIBED CHOROIDAL<br />
HEMANGIOMA<br />
Sung Chul Lee, Hee Jung Kwon, Min Kim, Christopher Seungkyu Lee<br />
(sunglee@yuhs.ac)<br />
Department of Ophthalmology, Institute of Vision Research, Yonsei<br />
University College of Medicine, Seoul, Korea<br />
Purpose. To evaluate the effect of transpupillary thermotherapy<br />
(TTT) and intravitreal injection of bevacizumab (IVB) on serous<br />
macular detachment (SMD) associated with circumscribed choroidal<br />
hemangioma (CCH).<br />
Methods. We retrospectively reviewed the records of CCH patients<br />
treated by TTT and/or IVB to reduce SMD. We assessed changes in<br />
visual acuity (VA), resolution of SMD and central fovea thickness (CFT) by<br />
optical coherence tomography (OCT).<br />
Results. Of 8 patients treated with TTT, 5 patients showed complete<br />
resolution of SMD in OCT with improvement of median LogMAR VA from<br />
0.7 to 0.22 (p=0.042). These 5 patients showed no recurrence of SMD<br />
for a mean duration of 51.8 months, but SMD finally recurred in 4 of<br />
them.<br />
Of 9 patients treated with IVB, 5 patients showed resolution of SMD with<br />
a decrease of median CFT from 514 µm to 330 µm (p=0.043). Of these 5<br />
patients, 2 patients showed recurrence of SMD after 6.2 months.<br />
In TTT group, 5 patients (3 patients in complete SMD resolution group,<br />
2 patients in persistent SMD group) received additional IVB and 4 of<br />
them also had cystoids macular edema (CME) with SMD before IVB.<br />
All the patients showed persistent CME after IVB despite the complete<br />
resolution of SMD in two of them.<br />
Conclusions. In some patients with SMD in CCH, both TTT and IVB may<br />
be used effectively. However, the duration of treatment effectiveness<br />
appears to be longer in TTT than that in IVB. IVB for recurred SMD after<br />
TTT Results in variable outcome but IVB had no effect on CME.<br />
Financial disclosure. None<br />
2132 OTp106<br />
INTRAOCULAR RELAPSE OF MULTIPLE MYELOMA<br />
RESPONSIVE TO BORTEZOMIB<br />
Tero Kivelä (tero.kivela@helsinki.fi)<br />
Department of Ophthalmology, Helsinki University Central Hospital,<br />
Helsinki, Finland<br />
Purpose. To report complete response to systemic bortezomib of a<br />
relapse of multiple myeloma in the iris.<br />
Methods. A 60-year-old man was diagnosed with multiple myeloma,
IgG λ type (stage IIIA) in 2000. He was first managed with vincristine,<br />
adriamycin and dexamethasone, resulting in partial response (PR), and<br />
then with cyclophosphamide and dexamethasone, resulting in complete<br />
response (CR), followed by autologous stem cell transplantation.<br />
No M-component was detected until May 2008, when a solitary<br />
plasmocytoma of the humerus appeared and was managed with<br />
thalidomide. Soon thereafter, a new, diffusely infiltrating unilateral iris<br />
lesion developed.<br />
Results. At diagnosis the patient was asymptomatic with 20/20 vision,<br />
IOP 14 mmHg, and cells in the anterior chamber. The iris was diffusely<br />
reddish with a circle of pigment epithelial cysts around the pupillary<br />
margin. The fundus was normal. He received two courses of bortezomib,<br />
a reversible proteasome inhibitor, with dexamethasone. After the 1st<br />
course, the cells and the redness of the iris disappeared. Two months<br />
after the 2nd course of bortezomib, while on lenalidomide maintenance<br />
therapy, he continued to be asymptomatic with an IOP of 14 mmHg and<br />
a normal iris.<br />
Conclusions. Bortezomib was effective in eradicating an intraocular<br />
replase of multiple myeloma in a patient who previously had received<br />
several types of conventional chemotherapy.<br />
Financial disclosure. None<br />
1923 OTp107<br />
TUBEROUS SCLEROSIS COMPLEX: CHARACTERIZA-<br />
TION OF OCULAR MANIFESTATIONS AND CORRELA-<br />
TIONS WITH SYSTEMIC DISEASE<br />
M.E. Turell1, E.I. Traboulsi1, A. Gupta2 , A.D. Singh1 (turellm2@ccf.org)<br />
1. Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH<br />
2. Department of Pediatric Epilepsy, Cleveland Clinic Foundation,<br />
Cleveland, OH<br />
Purpose. To evaluate genotype/phenotype correlations in individuals<br />
with astrocytic hamartoma (AH) and retinal achromic patch (AP) in the<br />
setting of tuberous sclerosis complex (TSC).<br />
Methods. Participants included 132 patients from the Cleveland Clinic<br />
Foundation Tuberous Sclerosis <strong>Program</strong> (CCF-TSCP) and 907 patients<br />
from the TSC Alliance (TSC-A). Gender, age at TSC diagnosis, presence<br />
of TSC1 or TSC2 mutations, ophthalmic examination, and systemic<br />
manifestations were analyzed.<br />
Results. No difference was found in the prevalence of AH in the CCF-<br />
TSCP (36.1%) and TSC-A (34.1%) groups (p = 0.743). AH were bilateral<br />
in 43.3% and 18.1% (p = 0.009) and multiple in 40.0% and 15.3% (p =<br />
0.008) in the CCF-TSCP and TSC-A groups respectively. In the CCF-TSCP<br />
group, AP was observed in 12.0% of patients (40.0% bilateral, 50.0%<br />
multiple). The presence of retinal features was associated with giant cell<br />
astrocytoma (37.1% vs 14.6%; p = 0.018), renal angiomyolipoma (60.0%<br />
vs 27.1%; p = 0.003), cognitive impairment (77.1% vs 43.8%; p = 0.002),<br />
and epilepsy (91.4% vs 70.8%; p = 0.022) in those with and without<br />
retinal findings respectively. In patients with retinal findings in the CCF-<br />
TSCP and TSC-A groups, mutations in TSC2 were more frequent than<br />
in TSC1, 3.3 times and 5.8 times, respectively. In those without retinal<br />
findings; the relative rates were 0.67 times and 2.3 times, respectively.<br />
Conclusions. Individuals with retinal findings are more likely to have<br />
subependymal giant cell astrocytomas, renal angiomyolipomas,<br />
cognitive impairment and epilepsy. TSC2 mutations are more frequent<br />
in patients with retinal findings than in those without.<br />
Financial disclosure. None<br />
EYELID, CONJUNTIVA & ORBIT<br />
Abstract Posters<br />
88<br />
Support: Research to Prevent Blindness<br />
Challenge Grant, Department of<br />
Ophthalmology, Cleveland Clinic Lerner<br />
College of Medicine<br />
248 OTp108<br />
INTERLEUKIN LEVELS IN AQUEOUS OF UNTREATED<br />
AND TREATED EYES WITH VITREORETINAL LYMPHO-<br />
MA<br />
Jose S. Pulido, MD, Joseph Balsanek, Brian Peters, Melissa Snyder, PhD<br />
(pulido.jose@mayo.edu)<br />
Department of Ophthalmology, Department of Laboratory Medicine and<br />
Pathology<br />
Purpose. To determine the levels of interleukin levels in aqueous<br />
samples taken at the time of intravitreal treatment in patients with<br />
vitreoretinal lymphoma<br />
Methods. Samples at the time of paracentesis were immediately placed<br />
on ice and then ELISA for interleukin levels were performed<br />
Results. 81 samples were tested. IL 10 levels had a mean of 62 with<br />
range of 0.69-624 pg/ml. IL-6 had a mean 123 pg/ml with range from<br />
1.67-960 pg/ml. Other levels that were elevated included were MCP-<br />
1,and IL-1ra.<br />
Conclusions. There are marked changes in interleukin levels depending<br />
upon treatment levels. IL-10 aqueous levels is a good measure of<br />
treatment response to intravitreal chemotherapeutic agents<br />
Financial disclosure. None<br />
304 OTp109<br />
INTRAVITREAL RITUXIMAB FOR PRIMARY INTRAOCU-<br />
LAR LYMPHOMA (PIOL)<br />
V. Kakkassery1, G. Willerding1, K. Jahnke2, A. Korfel2, U. Pleyer1, N.<br />
Stübiger1, A.M. Joussen1 (vk@charite.de)<br />
1. Department of Ophthalmology, Charité, Berlin, Germany<br />
2. Department of Hematology and Oncology, Campus Benjamin Franklin,<br />
Charité, Berlin, Germany<br />
Purpose. PIOL is a rare manifestation of primary central nervous system<br />
lymphoma (PCNSL). Due to its rarity, the optimal treatment of this<br />
condition has not yet been defined thus far. The chimeric monoclonal<br />
CD20 antibody rituximab offers a new intravitreal treatment option for<br />
PIOL. Here, we report on the clinical course after repeated intravitreal<br />
injections of rituximab for PIOL.<br />
Methods. Diagnosis of PIOL was confirmed by clinical investigation<br />
and vitreous biopsy in three cases. Two patients were pretreated with<br />
systemic chemotherapy for their PCNSL (ifosfamide or MTX). Ocular<br />
clinical findings (visual acuity, intraocular pressure, vitreous haze, extent<br />
of tumor) were recorded before and after rituximab therapy. Intravitreal<br />
1mg/0,1mL rituximab injections were conducted in accordance with the<br />
German Ophthalmic Society guidelines for intravitreal injections. Data<br />
were implemented in a nationwide open registry for PIOL supported by<br />
the German Federal Ministry of Education and Research.<br />
Results. Five eyes from 3 patients received a minimum of one to a
maximum of 7 rituximab injections. After a follow up of 4 -30 months, we<br />
observed a significant reduction of vitreous haze in all eyes (measured<br />
by the Nussenblatt classification), a preserved constant visual acuity<br />
or improvement (two eyes: finger count to 20/32; 20/40 to 20/32) and<br />
tumor remission. All patients reported about a reduction of discomfort<br />
after therapy. No intraocular adverse effects have been observed.<br />
Conclusions. In our case series, we demonstrated improvement of clinical<br />
symptoms and signs in PIOL and, to some extent, visual acuity without<br />
adverse intraocular side effects after intravitreal rituximab injections.<br />
Further long-term studies are necessary to further investigate local and<br />
systemic effects and possible side effects after rituximab therapy for<br />
intraocular lymphoma.<br />
Financial disclosure. None<br />
EYELID, CONJUNTIVA & ORBIT<br />
Abstract Posters<br />
89
8.30-9.00 Poster Presentations UMp101-113<br />
(Moderators: A. Singh, D. Pelayes)<br />
9.00-10.20 Papers<br />
(Moderators: N. Bornfeld, M.J. Jager)<br />
2253 UM1<br />
PRELIMINARY STUDY OF VASCULAR FLOW IN<br />
CHOROIDAL TUMORS AND PSEUDOTUMORS<br />
C.M. Gentile, M. Faria Dovasio , Lucila Tajtelbaum, Atilio Lombardi , J.<br />
Oscar Croxatto<br />
622 UM2<br />
AUSTRALIA AND NEW ZEALAND STUDY OF PDT IN<br />
CHOROIDAL AMELANOTIC MELANOMA (ANZSOPI-<br />
CAM) - TWO YEAR RESULTS<br />
William Glasson, William G. Campbell, Sid Finnigan, Michael Giblin,<br />
Peter Hadden, Timothy Isaacs, John D. McKenzie, James Muecke, Tanya<br />
M. Pejnovic<br />
1618 UM3<br />
PHOTODYNAMIC THERAPY AS ADJUVANT TREAT-<br />
MENT FOR AMELANOTIC CHOROIDAL MELANOMA<br />
DEBULKING<br />
Maria A. Blasi, Monica M. Pagliara, Andrea Scupola, Carmela G. Caputo,<br />
Emilio Balestrazzi<br />
1413 UM4<br />
MACROPHAGE INFILTRATION IN PREVIOUSLY-IRRA-<br />
DIATED UVEAL MELANOMA<br />
M.J. Jager, T.H.K. Vu, I.H.G. Bronkhorst, M. Versluis, M. Marinkovic, S.G.<br />
van Duinen, G.P.M. Luyten<br />
2131 UM4<br />
FINE NEEDLE ASPIRATION BIOPSY OF UVEAL MELA-<br />
NOMA : EVALUATION OF A CALIBRATED NEEDLE<br />
David E. Pelayes, Jorge O. Zárate, Charles V. Biscotti, Arun D. Singh<br />
56 UM5<br />
25G/23G TRANSRETINAL BIOPSY IN UVEAL TUMOURS<br />
N. Bornfeld, M. Gök, E. Biewald, M. Freistühler, M. Zeschnigk<br />
1601 UM7<br />
UVEAL TRACT MELANOMA: CORRELATION OF GENET-<br />
IC HETEROGENEITY WITH MACROSCOPIC MORPHOLOGY<br />
Vasilios P. Papastefanou, Ajay Patil, Marianne Grantham, Mandeep S.<br />
Sagoo, Victoria M.L. Cohen<br />
49 UM8<br />
DEVELOPMENTS IN PREDICTING METASTASIS FROM<br />
CHOROIDAL MELANOMA<br />
B.E. Damato, A. Eleuteri, A.F. Taktak, S.E. Coupland<br />
Thursday November 17, 2011<br />
UVEAL MELANOMA<br />
<strong>Program</strong><br />
91<br />
444 UM9<br />
FISH-BASED PROGNOSTICATION OF UVEAL MELA-<br />
NOMA<br />
M. Turell, R. Tubbs , C. Biscotti, L. Schoenfield, Y. Sun G. Bebek , Y.<br />
Saunthararajah, P. Triozzi, A. Singh<br />
1819 UM10<br />
FLUORESCENCE IN-SITU HYBRIDIZATION VS MULTI-<br />
PLEX LIGATION-DEPENDENT PROBE AMPLIFICATION<br />
FOR UVEAL MELANOMA PROGNOSTICATION: IN-VI-<br />
VO COMPARATIVE RESULTS<br />
Raffaele Parrozzani, Elisabetta Pilotto, Alessia Dario, Giacomo<br />
Miglionico, Edoardo Midena<br />
10.20-10.50 BREAK<br />
10.50-11.20<br />
THE STALLARD MEDAL<br />
Prof. ENRIQUE S. MALBRAN<br />
ANTERIOR SEGMENT SURGERY OF INTRAOCULAR TUMORS<br />
11.20-12.00 Papers<br />
(Moderator: J. Augsburger, B. Damato)<br />
2331 UM11<br />
UVEAL MELANOMA: AN ANALYSIS OF CELLULAR FEA-<br />
TURES AND COMPARISON TO MONOSOMY 3 STA-<br />
TUS.<br />
C.V. Biscotti, A. Lott-Limbach, R.R. Tubbs, M.E. Turell, Y. Sun, A.D.<br />
Singh<br />
2321 UM12<br />
RETROSPECTIVE ANALYSIS OF 700 FINE-NEEDLE<br />
ASPIRATION BIOPSIES OF SOLID INTRAOCULAR<br />
TUMORS: CHANGING INDICATIONS DURING LONG-<br />
TERM EXPERIENCE<br />
Zélia M. Corrêa, James J. Augsburger<br />
204 UM13<br />
PROSPECTIVE EVALUATION OF A GENE EXPRESSION<br />
PROFILE PROGNOSTIC ASSAY FOR UVEAL MELANOMA IN<br />
514 PATIENTS<br />
J. William Harbour, Michael D. Onken, Lori A. Worley, James J. Augsburger,<br />
Zelia M Correa, Devron H. Char, Eric Nudleman, Thomas M. Aaberg,<br />
Jr., Michael M. Altaweel, David S. Bardenstein, Paul T. Finger, Brenda<br />
L. Gallie, George J. Harocopos, Peter G. Hovland, Hugh D. McGowan,<br />
Tatyana Milman, Prithvi Mruthyunjaya, E. Rand Simpson, Morton E.<br />
Smith, David J. Wilson, William J. Wirostko
153 UM14<br />
PHENO-GENOTYPIC IDENTIFICATION OF CIRCULATING<br />
TUMOR CELLS IN UVEAL MELANOMA<br />
Cinzia Mazzini, Pamela Pinzani, Francesca Salvianti, Daniela Massi,<br />
Giulia Pieretti, Mario Pazzagli, Daniela Bacherini, Ugo Menchini<br />
12.00-12.30 Poster presentations UMp114-126<br />
(Moderators: J.W. Harbour, G. Chantada)<br />
12.30-14.00 LUNCH<br />
14.00-15.40 Papers<br />
(Moderators: T. Kivela, M. Materin)<br />
1245 UM15<br />
PROSPECTIVE FOLLOW-UP STUDY IN HIGH-RISK<br />
UVEAL MELANOMA (UM) PATIENTS: FINAL RESULTS.<br />
S. Piperno-Neumann, V. Servois, P. Mariani, J. Couturier, C. Plancher, C.<br />
Levy-Gabriel, L. Lumbroso-Le Rouic, R. Salmon, B. Asselain, L. Desjardins<br />
3 UM16<br />
PERSONALIZED TARGETED THERAPY FOR UVEAL<br />
MELANOMAS HARBORING GNAQ OR GNA11<br />
MUTATIONS<br />
Vasiliki Poulaki, Sue Anne Chew, Bin He, Nicholas Mitsiades<br />
132 UM17<br />
RATIONALE, STUDY DESIGN AND ACCRUAL STATUS<br />
OF A RANDOMIZED PHASE II STUDY OF AZD6244,<br />
A MEK INHIBITOR, VS TEMOZOMJDE IN ADVANCED<br />
UVEAL MELANOMA<br />
Richard D. Carvajal, Jedd D. Wolchok, Paul B. Chapman, Mark Dickson,<br />
Mark Bluth, Grazia Ambrosini, Brian Marr, Murk Heinemann, Annie<br />
Fusco, Marta Nalysnyk, Natasha Martin, Austin Doyle, Boris Bastian,<br />
David Abramson, Gary K. Schwartz<br />
2212 UM18<br />
A CLINICAL PROBE FOR TRANSSCLERAL OPTICAL<br />
SPECTROSCOPY OF INTRAOCULAR TUMOURS<br />
J. Krohn, P. Svenmarker, C.T. Xu, S. Andersson-Engels<br />
300 UM19<br />
OUR EXPERIENCE WITH TRANSPUPILLARY THERMO<br />
THERAPY FOR SUSPECTED OR SMALL CHOROIDAL<br />
MELANOMAS<br />
Mordechai Rosner, Iris Moroz , Josef Moisseiev, Victoria Vishnevskia-Dai<br />
1842 UM20<br />
RESECTION OF IRIS TUMOURS : INTERNAL APPROACH<br />
Arun D. Singh<br />
UVEAL MELANOMA<br />
<strong>Program</strong><br />
92<br />
1917 UM21<br />
PLAQUE RADIOTHERAPY TREATMENT WITH RUTHE-<br />
NIUM-106 FOR IRIS MALIGNANT MELANOMA<br />
Amit K. Arora, Maria Tsimpida, Victoria M.L. Cohen, John L. Hungerford<br />
1849 UM22<br />
RUTHENIUM BRACHYTHERAPY WITH THE 10 MM<br />
PLAQUE FOR SMALL POSTERIOR CHOROIDAL<br />
MELANOMAS<br />
Tero Kivelä, Susanna Salkola, Sebastian Eskelin, Jorma Heikkonen<br />
63 UM23<br />
REGRESSION OF UVEAL MELANOMA FOLLOWING<br />
IODINE 125 PLAQUE RADIOTHERAPY: PREDICTIVE<br />
FACTORS AND CORRELATION WITH METASTASIS<br />
Hakan Demirci, Fiorella Saponara, Adam Khan, Leslie Niziol, Grant<br />
Comer, David Musch<br />
1802 UM24<br />
TUMOUR REGRESSION AFTER BRACHYTHERAPY<br />
FOR UVEAL MELANOMA: ASSOCIATION WITH<br />
SURVIVAL<br />
M.M. Rashid, T. Kivelä<br />
2310 UM 25<br />
RESULTS OF VITREORETINAL SURGERY FOLLOWING<br />
A COMPLICATED COURSE AFTER PLAQUE<br />
BRACHYTHERAPY OF MALIGNANT MELANOMA OF<br />
THE UVEA<br />
C. Metz, T. Gkika, W. Sauerwein, N. Bornfeld<br />
2230 UM 26<br />
LONG-TERM RESULTS AFTER ENDORESECTION OF<br />
LARGE UVEAL MELANOMAS WITH PRETREATMENT<br />
BY SINGLE-DOSE STEREOTACTIC IRRADIATION AND<br />
ADJUVANT BRACHYTHERAPY<br />
E. Biewald, H. Lautner, M. Freistühler, M. Gök, W. Sauerwein, GA<br />
Horstmann, N. Bornfeld<br />
15.40-16.10 BREAK<br />
16.10-17.30 Papers Uveal Melanoma<br />
(Moderators: A. Irarrazaval, E. Midena)<br />
1447 UM27<br />
TREATMENT OF JUXTAPAPILLARY CHOROIDAL MELA-<br />
NOMA<br />
Maria Tsimpida, John Hungerford, Victoria M.L. Cohen
2307 UM28<br />
OPTIC NERVE DAMAGE AFTER IRRADIATION OF<br />
INTRAOCULAR TUMOURS<br />
Evangelos S. Gragoudas, Anne Marie Lane, Ivana Kim<br />
133 UM29<br />
PROTON BEAM RADIOTHERAPY OF PARAPAPILLARY<br />
CHOROIDAL MELANOMA<br />
G.D. Willerding, D. Cordini, N.E. Bechrakis, M.H. Foerster, J. Heufelder,<br />
A.M. Joussen N. Lakotka, L. Moser<br />
1414 UM30<br />
HEMODYNAMIC MODIFICATIONS OF THE RETINA<br />
AND THE CHOROÏD FOLLOWING PROTON BEAM<br />
IRRADIATION OF UVEAL MELANOMAS<br />
Leonidas Zografos, Ann Schalenbourg, Line Chamot<br />
2358 UM31<br />
PERIOCULAR TRIAMCINOLONE FOR PREVENTION<br />
OF MACULAR EDEMA FOLLOWING PLAQUE<br />
RADIOTHERAPY OF UVEAL MELANOMA: THREE YEAR<br />
FOLLOW-UP<br />
Noel Horgan, Carol L. Shields, Melissa Murphy, Arman Mashayekhi,<br />
Pedro F. Salazar, Miguel A. Materin, Myra O’Regan, Jerry A. Shields<br />
1825 UM32<br />
INTRAVITREAL BEVACIZUMAB VERSUS<br />
TRIAMCINOLONE ACETONIDE INJECTION FOR SEROUS<br />
RETINAL DETACHMENT SECONDARY TO POSTERIOR<br />
UVEAL MELANOMA<br />
Edoardo Midena, Raffaele Parrozzani, Elisabetta Pilotto, Alessia Dario,<br />
Giacomo Miglionico<br />
UVEAL MELANOMA<br />
<strong>Program</strong><br />
93<br />
2326 UM33<br />
INTRAVITREAL BEVACIZUMAB AS AN ADJUVANT<br />
AGENT WHEN USED IMMEDIATELY AFTER TREATMENT<br />
WITH PLAQUE BRACHYTHERAPY<br />
Samuel K. Houston, Timothy G. Murray, Arnold M. Markoe, Yolanda<br />
Pina, Christina Decatur<br />
2040 UM34<br />
INTRAVENOUS AND ORAL STEROID ADMINISTRATION<br />
FOR PAIN CONTROL IN PLAQUE PATIENTS: A<br />
RANDOMIZED TRIAL<br />
A.C. Schefler, D.G. Gologorsky, J. Fulgueira, W. Feuer<br />
1623 UM35<br />
UVEAL MELANOMA AMONG FINNISH CHILDREN AND<br />
ADOLESCENTS<br />
Rana’a Aljamal, Tero Kivelä<br />
406 UM 36<br />
RESULTS OF MELANOMA BRACHYTHERAPY IN<br />
ARGENTINA<br />
Arturo Irarrazaval, Pablo Cazon
8.30-9.00 Poster presentations UMp101-113<br />
(Moderator: A. Singh, D. Pelayes)<br />
1350 Ump101<br />
INDUCED EXPRESSION OF PIRES-EGR1-EGFP-OMI/<br />
HTRA2 AND ITS EFFECT ON APOPTOSIS OF HUMAN<br />
CHOROIDAL MELANOMA OCM-1 CELLS<br />
Xufang Sun, Tian Yu, Shu Yan<br />
2020 Ump102<br />
THE HISTONE DEACETYLASE INHIBITOR SAHA<br />
(VORINOSTAT) DOWNREGULATES HOMOLOGOUS<br />
RECOMBINATION REPAIR PROTEINS AND CAUSES<br />
APOPTOSIS IN UVEAL MELANOMA CELL<br />
Grazia Ambrosini, Oliver Surriga and Gary K. Schwartz<br />
1538 Ump103<br />
AN INITIAL STUDY OF THE MIRNA EXPRESSION<br />
PROFILE OF UVEAL MELANOMA<br />
Wenbin Wei, Cheng Hsun Yang<br />
1949 Ump104<br />
GENDER DIFFERENCES AND ESTROGEN AND<br />
PROGESTERONE RECEPTOR EXPRESSION IN UVEAL<br />
MELANOMA<br />
L. Schoenfield, M. Turell, P. Carver, S. Mackie, R. Tubbs, A. Singh<br />
2320 Ump105<br />
DOES INTERNAL BLOOD FLOW VELOCITY CORRELATE<br />
WITH KNOWN PROGNOSTIC FACTORS FOR PRIMARY<br />
UVEAL TRACT MELANOMA?<br />
Amit Arora, Vasilios P. Papastefanou, Mandeep S. Sagoo, Marie Restori,<br />
Marianne Graham, Victoria M.L. Cohen<br />
1425 Ump106<br />
EVALUATION OF IRIS AND CILIARY BODY LESIONS<br />
WITH ANTERIOR SEGMENT OPTICAL COHERENCE<br />
TOMOGRAPHY (AS-OCT) VERSUS ULTRASOUND B<br />
SCAN<br />
M.S. Sagoo, V. P. Papastefanou, S. Hau, S. Shah, M. Tsimpida, V.M.<br />
Cohen<br />
114 Ump107<br />
Β-RADIATION BRACHYTHERAPY FOR LARGE<br />
CHOROIDAL MELANOMA: DO WE NEED A HIGH DOSE<br />
TO THE APEX?<br />
M. Naseripour, K.H. Ghasemi Falavarjani, R. Jaberi, A.R. Irani, Z. Azma<br />
UVEAL MELANOMA<br />
Posters<br />
94<br />
2116 Ump108<br />
ACCURATE ESTIMATION OF THE DOSE DISTRIBUTION<br />
OF AN EYE IRRADIATED WITH RU/RH-106 EYE PLAQUE<br />
Wolfgang Sauerwein, Norbert Bornfeld, Andrea Wittig, Birthe<br />
Zimmermann, Dirk Flühs, Lorenzo Brualla<br />
1520 Ump109<br />
LOCAL IRRADIATION OF LARGE UVEAL MELANOMA<br />
WITH TUMOR HEIGHT OVER 6,5 MM<br />
Michael Freistühler, Eva Biewald, Mete Gök, Gkika Theodora, Dirk Flühs,<br />
Wolfgang Sauerwein, Norbert Bornfeld<br />
2332 Ump110<br />
COMPARISON OF MATCHED GROUPS OF PATIENTS<br />
TREATED WITH RUTHENIUM BRACHYTHERAPY<br />
WITH SIMULTANEOUS THERMOTHERAPY OR<br />
BRACHYTHERAPY ALONE<br />
A.A. Yarovoy, D.A. Magaramov, E.S. Bulgakova<br />
51 Ump111<br />
SURGICAL ATTENUATION OF RADIATION FROM<br />
I-125 BRACHYTHERAPY: PRELIMINARY SAFETY AND<br />
FEASIBILITY DATA<br />
Scott C. N. Oliver, Victor Hsu, Lucy Bollinger, Moyed Miften, Laurie<br />
Gaspar, Philip Boyer<br />
1110 Ump112<br />
IMAGE-BASED TREATMENT PLANNING OF UVEAL<br />
MELANOMA IN PROTON THERAPY<br />
J. Heufelder, D. Cordini, N.E. Bechrakis, M.H. Foerster, W. Hinkelbein, S.<br />
Höcht, B. Jamil, A.M. Joussen, B. Karle, R. Stark, A. Weber, G. Willerding,<br />
L. Moser<br />
1547 Ump113<br />
LONG-TERM OBSERVATIONS IN SMALL, POSTERIOR<br />
LOCATED MALIGNANT MELANOMAS OF THE CHOROID<br />
TREATED WITH TRANSPUPILLARY THERMOTHERAPY (TTT)<br />
B.M. Stoffelns, K. Schöpfer<br />
Afternoon<br />
12.00-12.30 Poster presentations Ump114-126 (moderators J.W.<br />
Harbour, G. Chantada)<br />
602 Ump114<br />
CANCER RISKS FOR PATIENTS WITH MYOTONIC<br />
DYSTROPHY<br />
Jose Pulido, Aung Ko Win, Promilla Perattur, Christine Pulido, Noralane Lindor
UVEAL MELANOMA<br />
Posters<br />
1053 Ump115<br />
CHOROIDAL NEOVASCULARIZATION SECONDARY TO<br />
A CHOROIDAL NAEVUS: A CASE SERIES<br />
Vasilios P. Papastefanou, Victoria M.L. Cohen, Martin Harris, Vanda<br />
Nogueira, Richard M. Andrews, Mandeep S. Sagoo<br />
1617 Ump116<br />
INCIDENCE OF METASTATIC DISEASE AND<br />
SURVIVAL OF 716 CONSECUTIVE PATIENTS WITH<br />
POSTERIOR UVEAL MELANOMA: A RETROSPECTIVE<br />
MONOCENTRIC REVIEW<br />
Fatima Hammouch, Patrick De Potter, David Francart, François<br />
Dall’Armellina, Jean-François Baurain<br />
25 Ump117<br />
LONG LASTING SURVIVAL OF UVEAL MELANOMA<br />
WITH EXTRAOCULAR EXTENSION<br />
Ignacio Zeolite, Carlos Zeolite, Juan Oscar Croxatto,<br />
2133 Ump118<br />
CLINICOPATHOLOGIC CORRELATIONS OF PLAQUE<br />
BRACHYTHERAPY FAILURE IN THE TREATMENT OF<br />
CHOROIDAL MELANOMA<br />
Jill R Wells, Chris S Bergstrom, Qing Zhang, Hans E Grossniklaus<br />
2038 Ump119<br />
VALUE OF DOPPLER ANALYSIS IN THE REGRESSION<br />
OF UVEAL MELANOMA AFTER PLAQUE<br />
Mónica Asencio-Duran, Pilar Garcia-Raya, Pilar Moreno, Isabel<br />
Rodriguez-Rodriguez, Eva Corredoira<br />
65 Ump120<br />
EVALUATION OF CHOROIDAL TUMORS BY OCT-<br />
ENHANCED DEPTH IMAGING<br />
Hakan Demirci, Dolly A. Padovani-Claudio, Alexis Smith, Brandon Smith,<br />
Grant M. Comer<br />
95<br />
1608 Ump121<br />
HISTOPATHOLOGIC FINDINGS IN EYES WITH<br />
CHOROIDAL MELANOMA TREATED WITH<br />
BEVACIZUMAB FOR RADIATION RETINOPATHY<br />
Hans E. Grossniklaus, Martina C. Herwig, Weiqing Gao<br />
64 Ump122<br />
TREATMENT OF RADIATION MACULOPATHY WITH<br />
INTRAVITREAL INJECTION OF BEVACIZUMAB<br />
Mosci Carlo, Francesca Nasciuti, Francesco Baldo Lanza<br />
327 Ump123<br />
EPIDEMIOLOGICAL ANALYSIS OF BRAZILIAN<br />
PATIENTS WITH UVEAL MELANOMA SUBMITTED TO<br />
PRIMARY ENUCLEATION IN A REFERRAL CENTER<br />
Priscilla L. Ballalai, Kelcia Kieffer, Ricardo Filippo, Rafaello Salla, Maria<br />
Cristina Martins, Márcia Lowen<br />
2252 Ump124<br />
UVEAL MELANOMA CLINICAL TRIALS AT MD<br />
ANDERSON CANCER CENTER<br />
Scott E. Woodman, Michael Tetzlaff, Xiaoxing Yu, Chandrani<br />
Chattopadhyay, Michelle Williams, NancyPoindexter, Elizabeth Grimm,<br />
Dan Gombos, Bita Esmaeli, Agop Bedikian, Sapna Patel<br />
1912 Ump125<br />
UVEAL MELANOMA: TRENDS IN INCIDENCE,<br />
TREATMENT, AND SURVIVAL<br />
Arun D. Singh, Mary E. Turell, Allan K. Topham<br />
453 Ump126<br />
FISH: MAKING HEADS OR TAILS OF TECHNIQUES<br />
M. Turell , R. Tubbs , C. Biscotti , Y. Sun, Y. Saunthararajah, P. Triozzi,<br />
A. Singh
2253 UM1<br />
PRELIMINARY STUDY OF VASCULAR FLOW IN CHOR-<br />
OIDAL TUMORS AND PSEUDOTUMORS<br />
C.M. Gentile, M. Faria Dovasio , Lucila Tajtelbaum, Atilio Lombardi , J.<br />
Oscar Croxatto (carolina.gentile@gmail.com)<br />
Hospital Italiano de Buenos Aires, Argentina<br />
Purpose. The aim of this study was to describe and analyze the<br />
hemodynamic findings pre and post treatment in choroidal melanocytic<br />
tumors and in pseudotumors using high resolution doppler color and<br />
spectral ultrasound.<br />
Methods. Twenty six patients (aged ranged from 38 and 86 years- old)<br />
with presumed<br />
diagnosis of choroidal tumour or pseudotumors were included. The<br />
B-Scan<br />
and Doppler ultrasound images were obtained with ESAOTE My Lab 70<br />
vision,<br />
Italia equipment. Intralesional vascularization and spectral doppler<br />
analysis from intratumoral vascular region and from tumoral base was<br />
performed using values of flow velocity in systole and diastole, and<br />
resistive index (systolic-diastolic/systolic, RI).<br />
Results. Vascular flow with low resistive index was observed in patients<br />
with untreated choroidal melanoma. After therapy, the intratumoral<br />
vascularization decreased and increased the RI. In three patients with<br />
treated melanomas, intratumoral vascularization in association with<br />
tumoral growing was observed. There was no tumoral vascularization<br />
in patients with choroidal nevus except for the base (choroid). Doppler<br />
ultrasound in patients with media opacity and presumed diagnosis<br />
of choroidal haematoma versus melanoma, revealed absence of<br />
intralesional vascularization and it showed presence of vascularization<br />
only on its base (choroidal vessels).<br />
Conclusions. Doppler color and spectral ultrasound is a non invasive<br />
and useful clinical technique which may be used in differential<br />
diagnosis between choroidal haematoma and advanced melanoma in<br />
patients with media opacity. It could be used as an additional tool for<br />
the differential diagnosis of choroidal nevus and melanoma and for<br />
evaluation of effectiveness in patients with choroidal melanoma after<br />
conservative therapy.<br />
Financial disclosure. None<br />
622 UM2<br />
AUSTRALIA AND NEW ZEALAND STUDY OF PDT IN<br />
CHOROIDAL AMELANOTIC MELANOMA (ANZSOPI-<br />
CAM) - TWO YEAR RESULTS<br />
William Glasson, William G. Campbell, Sid Finnigan, Michael Giblin,<br />
Peter Hadden, Timothy Isaacs, John D. McKenzie, James Muecke, Tanya<br />
M. Pejnovic. (glasson@terraceeyecentre.com.au)<br />
Dr William G. Campbell is the principal investigator, other authors are<br />
co-investigators.<br />
Purpose. ANZSOPICAM is an investigator-initiated prospective<br />
multicentre clinical trial of photodynamic therapy in choroidal amelanotic<br />
melanoma. This paper summarises the first two years’’ results.<br />
Methods. Patients presenting with posteriorly-located amelanotic<br />
melanoma were recruited into the study. After full ocular and systemic<br />
assessment photodynamic therapy was applied with the Zeiss Visulas<br />
laser, using verteporfin as the photosensitiser. PDT was repeated at<br />
UVEAL MELANOMA<br />
Abstracts<br />
96<br />
three monthly intervals intil the melanoma had completely regressed.<br />
Results. 31 patients were recruited in the first two years. Complete<br />
regression of the melanoma has been achieved in 19 patients to date;<br />
eight after just one treatment, five following two treatments, five<br />
required three sessions of PDT, whilst in one patient four treatments<br />
were necessary. The tumour in the remaining 12 patients demonstrated<br />
a response to PDT; of these 10 are still undergoing treatment, one was<br />
lost to follow-up and one, an 85 year old male, died of an unrelated<br />
condition three months after his initial PDT. Vision has remained stable<br />
or improved in all but three patients. Three participants developed<br />
small, local recurrences that responded favourably to a further session<br />
of PDT. So far no evidence of systemic metastatic disease has been<br />
found in any patients.<br />
Conclusions. The results of this study to date indicate PDT is effective<br />
in causing regression of amelanotic melanoma, in the majority of cases<br />
without compromising vision. The study is ongoing.<br />
Financial disclosure. None<br />
1618 UM3<br />
PHOTODYNAMIC THERAPY AS ADJUVANT TREAT-<br />
MENT FOR AMELANOTIC CHOROIDAL MELANOMA<br />
DEBULKING<br />
Maria A. Blasi, Monica M. Pagliara, Andrea Scupola, Carmela G. Caputo,<br />
Emilio Balestrazzi (mariaantonietta.blasi@rm.unicatt.it)<br />
Department of Ophthalmology, Catholic University, Rome, Italy<br />
Purpose. To evaluate the efficacy of photodynamic therapy (PDT) as adjuvant<br />
treatment to reduce tumour thickness before brachytherapy for amelanotic<br />
choroidal melanoma.<br />
Methods. Patients and Methods: Fourteen patients with amelanotic choroidal<br />
melanoma were recruited. Inclusion criterion was diagnosis of amelanotic<br />
choroidal melanoma based on ophthalmoscopy, ultrasonography (US),<br />
fluorescein angiography (FA), and ICGA. All patients underwent PDT treatment<br />
using verteporfin infused intravenously at a dose of 6mg/m2body surface<br />
area. Five minutes after infusion, a 689nm laser was applied with a light dose<br />
of 100 J/cm 2 at an irradiance of 600mW/cm2 over an interval of 166 seconds.<br />
One month after PDT all patients underwent brachytherapy.<br />
Results. One month after PDT treatment US showed reduction of tumour<br />
height in 9 patients (64.28%) (Group A), stable thickness in 3 patients (<br />
21.42%) (Group B) and minimal increase in thickness in 2 patients (14.28%)<br />
(Group C). The mean tumour thickness was 5.39mm at baseline, with a<br />
mean reduction of 25.33% in Group A; 4.60mm and no reduction in Group<br />
B; 2.63mm with a mean increase of 6.08% in Group C. In Group A, the mean<br />
dose of irradiation to macula and optic nerve calculated at baseline was 76.61<br />
and 54.2 Gy, after PDT it was 43.44 and 35.05 Gy, with a decrease of 43.3%<br />
and 35.3% respectively.<br />
Conclusions. The goal of treatment for uveal melanoma is to achieve local<br />
tumour control while minimizing damage to macula and optic nerve. Use of<br />
PDT as adjuvant therapy in order to reduce tumour thickness and consequently<br />
brachytherapy toxic effects is encouraging.<br />
Financial disclosure. None<br />
1413 UM4<br />
MACROPHAGE INFILTRATION IN PREVIOUSLY-IRRA-<br />
DIATED UVEAL MELANOMA<br />
M.J. Jager, THK Vu, IHG Bronkhorst, M Versluis, M Marinkovic, SG van<br />
Duinen, GPM Luyten (m.j.jager@lumc.nl)
Departments of Ophthalmology and Pathology, Leiden University<br />
Medical Center (LUMC), The Netherlands.<br />
Purpose. Previous studies at our department showed that uveal<br />
melanoma with a bad prognosis contained high numbers of infiltrating<br />
macrophages, especially of the M2 phenotype. We wondered whether<br />
prior treatment with irradiation would affect the degree of inflammation<br />
as displayed by the number of tumor-infiltrating macrophages and<br />
lymphocytes.<br />
Methods. We analyzed 46 eyes containing a uveal melanoma that were<br />
previously treated with radioactive plaque or proton beam therapy,<br />
and where the eye had to be enucleated due to tumor recurrence, nonresponsiveness,<br />
or complications after irradiation. Immunofluorescence<br />
staining was performed to determine the presence of CD68+ and<br />
CD68+CD163+macrophages, CD3+, CD8+ and Foxp3+ regulatory T<br />
lymphocytes. Outcomes were compared with known clinical and<br />
histological prognostic parameters.<br />
Results. Numbers of CD68+ and CD68+CD163+ macrophages in<br />
secondarily-enucleated eyes varied widely, but were not related to<br />
the reason for enucleation. When compared to primarily-enucleated<br />
eyes, the lymphocytic infiltration was significantly (p
Purpose. To determine the presence of genetic heterogeneity (for<br />
chromosomes 3 and 8) in uveal tract melanoma and correlate this with<br />
tumour size and morphology.<br />
Methods. Ninety-five patients who underwent enucleation for primary<br />
uveal melanoma in the period of 2009-2011 were included in the study.<br />
Tumour dimensions were preoperatively measured (height, maximal<br />
diameter). Corresponding areas and volumes were calculated. Tumour<br />
morphology was classified in separate subcategories (collar-stud,<br />
dome-shaped, bilobed, multilobed, diffuse and other) through B-mode<br />
ultrasonography.<br />
Double blind analysis of uveal tract melanoma by fine needle aspiration<br />
biopsy (FNAB) (from the centre of the tumour) vs punch biopsy (from<br />
the base of the tumour) to assess the presence of genetic heterogeneity<br />
of chromosomes 3 and 8 using the appropriate probes. Results were<br />
correlated with tumour dimensions, tumour size according to COMS<br />
classification and tumour morphology. In addition the yield of FNAB was<br />
determined and similar correlations were done.<br />
Results. Fine needle aspiration biopsy yield i.e. sufficient cells for<br />
diagnosis was seen in 77% (73/ 95) of tumours. Yield was higher in large<br />
tumours according to the COMS classification (83% of large melanomas).<br />
The yield was worst for bilobed tumours (36%, 4/11).<br />
Genetic heterogeneity (GH) between FNAB and punch biopsies was<br />
assessed in the remaining 72 patients. GH was 4% (3 out of 72 tumours)<br />
for chromosome 3 and 21% (15 out of 72 tumours) for chromosome 8.<br />
Genetic heterogeneity strongly correlated with collar-stud morphology<br />
for chromosome 3 (100%, 3 out of 3 tumours) and for chromosome 8<br />
(53%, 8 out of 15 tumours). In addition heterogeneity for chromosome<br />
8 strongly correlated with large melanomas, according to COMS<br />
classification (73%, 11 out of 15 tumours)<br />
Conclusions. Genetic heterogeneity for chromosomes 3 and 8 is<br />
strongly associated with collar-stud lesion morphology. Heterogeneity<br />
for chromosome 8 is correlated with large uveal melanoma.<br />
Financial disclosure. None<br />
49 UM8<br />
DEVELOPMENTS IN PREDICTING METASTASIS FROM<br />
CHOROIDAL MELANOMA<br />
B.E. Damato, A. Eleuteri, A.F. Taktak, S.E. Coupland (bertil.damato@<br />
gmail.com)<br />
Royal Liverpool University Hospital; University of Liverpool<br />
Purpose. We previously developed prognostic models using neural<br />
networks but these were inaccurate when baseline data were incomplete.<br />
We therefore devoped new models based on Accelerated Failure Time.<br />
The aim of this presentation is to evaluate our improved tool in terms of<br />
its ability to estimate survival probability after treatment of choroidal<br />
melanoma.<br />
Methods. Data from 3653 patients were used to generate models for<br />
predicting all-cause mortality.<br />
The program produced all-cause mortality curves for patients and<br />
controls, thereby allowing risk of metastatic mortality to be estimated.<br />
Results. The predicted morality correlated well with the observed<br />
mortality (Kolmogorov-Smirnov statistic, 0.79. p value 0.80). The C-index<br />
for discrimination (correlating predictions with risk factors) was 0.75 for<br />
the clinical model and 0.79 for the laboratory model (with fewer data).<br />
Conclusions. Our AFT model is a significant improvement over neural<br />
networks and provides reasonably reliable prognosis relevant to<br />
individual patients with choroidal melanoma.<br />
Financial disclosure. None<br />
UVEAL MELANOMA<br />
Abstracts<br />
98<br />
444 UM9<br />
FISH-BASED PROGNOSTICATION OF UVEAL MELA-<br />
NOMA<br />
M. Turell 1, R. Tubbs 2 , C. Biscotti 3 , L. Schoenfield 3, Y. Sun 2 , G. Bebek<br />
4 , Y. Saunthararajah 5, P. Triozzi 6, A. Singh1 (turellm2@ccf.org)<br />
1. Cole Eye Institute, Cleveland Clinic Foundation<br />
2. Department of Molecular Pathology, Cleveland Clinic Foundation<br />
3. Department of Anatomic Pathology, Cleveland Clinic Foundation<br />
4. Center for Proteomics and Bioinformatics, Case Western Reserve<br />
University<br />
5. Hematologic Oncology & Blood Disorders, Cleveland Clinic Foundation<br />
6. Solid Tumor Oncology, Cleveland Clinic Foundation, Cleveland, OH<br />
Purpose. To compare detection of monosomy 3 in uveal melanoma<br />
using single nucleotide polymorphism array (SNP-A) and fluorescence<br />
in situ hybridization (FISH)<br />
Methods. Consecutive cases of uveal melanoma treated by enucleation<br />
from 2004 to 2010 were analyzed. DNA was isolated from fresh frozen<br />
tissue and was analyzed by SNP-A (Illumina, San Diego, CA) and by FISH<br />
using both centromeric (CEP3) and locus-specific (3p26) probes (Abbott<br />
Molecular, Des Plains, IL). A total of 200 interphase cells were scored<br />
and a cut-point of 20% was used to determine monosomy 3 status.<br />
Results. In this series, there were 50 Caucasian patients including 28<br />
males (56%) and 22 females (44%) with an average age at diagnosis<br />
of 64 years. Tumor location was choroidal in 24 (48%), ciliochoroidal<br />
in 18 (36%), and iridociliochoroidal in 8 cases (16%). Monosomy 3<br />
was detected by either SNP-A or FISH (CEP3) in 33 cases (66%). SNP-A<br />
detected monosomy 3 in 31 tumors (94%). CEP3 probe detected 25<br />
cases of monosomy 3 (76%). Locus-specific FISH probe (3p26) detected<br />
deletion in 28 of 31 cases (90%) of monosomy 3 positive tumors by<br />
SNP-A and every case of of monosomy 3 by CEP3 probe.<br />
Conclusions. There is a strong correlation between monosomy 3 detected<br />
by SNP-A and by 3p26 deletion detected by locus-specific FISH probe.<br />
Financial disclosure. This work was supported by a Falk Trust grant<br />
and a Research to Prevent Blindness Challenge Grant, Department of<br />
Ophthalmology, Cleveland Clinic Lerner College of Medicine.<br />
1819 UM10<br />
FLUORESCENCE IN-SITU HYBRIDIZATION VS MULTI-<br />
PLEX LIGATION-DEPENDENT PROBE AMPLIFICATION<br />
FOR UVEAL MELANOMA PROGNOSTICATION: IN-VI-<br />
VO COMPARATIVE RESULTS<br />
Raffaele Parrozzani1, Elisabetta Pilotto2, Alessia Dario2, Giacomo<br />
Miglionico2, Edoardo Midena1,2 (parrozzani@libero.it)<br />
1. GB Bietti Eye Foundation, IRCCS, Roma, Italy.<br />
2. Department of Ophthalmology, University of Padova, Padova, Italy.<br />
Purpose. To compare fluorescence in-situ hybridization (FISH) and<br />
multiplex ligation-dependent probe amplification (MLPA) for uveal<br />
melanoma prognostication.<br />
Methods. Twenty-four patients affected by posterior uveal melanoma<br />
and scheduled for I125 brachytherapy were included in this prospective<br />
study. Patients underwent in-vivo 25-G transcleral FNAB (two passes)<br />
just before applying the radioactive plaque. Sampled material underwent<br />
both FISH and MLPA analysis using standard procedures. Follow-up was<br />
longer than 24 months.
Results. Follow-up was 31±8 months (range, 25-42 months). FISH<br />
analysis revealed monosomy 3 in twelve cases (50%). MLPA revealed<br />
monosomy 3 in thirteen cases (54%) and a 3p14-q29 deletion in one<br />
case (4%) (classified as monosomy 3 by FISH). Nine patients (41%)<br />
developed metastatic disease during follow-up, including the case<br />
showing monosomy 3 only by MLPA. Patient with partial chromosome 3<br />
deletion is still alive without metastases.<br />
Conclusions. MLPA allows to obtain more information than standard<br />
FISH in uveal melanoma prognostication. The biological and prognostic<br />
value of partial chromosome 3 deletion, as well as others subtle<br />
chromosomes alterations or complex MLPA results, remains unclear.<br />
Financial disclosure. None<br />
2331 UM11<br />
UVEAL MELANOMA: AN ANALYSIS OF CELLULAR<br />
FEATURES AND COMPARISON TO MONOSOMY 3<br />
STATUS<br />
C. V. Biscotti1, A Lott-Limbach1, R. R. Tubbs2, M. E. Turell3, Y Sun2, A. D.<br />
Singh3 (biscotc@ccf.org)<br />
1. Departments of Anatomic Pathology, 2. Molecular Pathology and 3.<br />
Ophthalmology, Cleveland Clinic, Cleveland, Ohio USA<br />
Purpose. Uveal melanoma patients segregate into two prognostic<br />
groups. Approximately half will eventually manifest metastases.<br />
Unfortunately, most experts agree that the die is cast by the time of<br />
diagnosis. We analyzed a series of uveal melanoma FNA samples to<br />
describe the cellular features and correlate these with the results of<br />
FISH analysis for monosomy 3.<br />
Methods. All patients had a clinical diagnosis of uveal melanoma<br />
based on history and physical examination including ophthalmoscopic<br />
examination performed by one of the authors (ADS).The patients<br />
consented to this study which was funded by the Falk Trust. FNA using<br />
a 25G needle was performed at the time of radiation therapy plaque<br />
placement or enucleation/excision by two of the authors (ADS and<br />
MET). In vivo samples were obtained by transvitreal or transscleral<br />
approach depending on tumour location. Aspirate samples were entirely<br />
rinsed into 2-3 ml of normal saline, visually examined for adequacy,<br />
and then entirely transferred to a cell preservative, CytoLyt (Hologic<br />
Corp, Marborough MA). ThinPrep® processing yielded 4 alcohol fixed<br />
Papanicolaou stained slides per case. One of the authors (CVB) analyzed<br />
the slides for cellular features including cell type (pure epithelioid,<br />
pure spindle, or mixed), nuclear grade (1, 2, or 3), and the presence or<br />
absence of necrosis, tumour infiltrating lymphocytes (Tils), and melanin.<br />
Slides with well preserved melanoma cells in sufficient numbers were<br />
destained and analyzed for monosomy 3 by FISH. An adequate FISH<br />
study required 200 cells. A positive result required monosomy 3 in at<br />
least 20% of cells.<br />
Results. Ninety patients with a clinical diagnosis of uveal melanoma<br />
consented to the study. This included 45 men and 45 women with<br />
ages ranging from 26 to 96 years (mean 62). Tumours involved the<br />
choroid 61(68%) cases, ciliochoroid 21(23%) cases, iridociliary 5(6%)<br />
cases and iris 3(3%) cases and ranged from 3 x 3 mm to 20 x 24 mm<br />
in basal dimensions and 1.2 mm to 15 mm in height. Fifty-eight (64%)<br />
patients had in vivo FNA either transvitreal 33 (57%) or transscleral 25<br />
(43%).While thirty-two (36%) patients had FNA of enucleation/excision<br />
specimens. FNA samples had diagnostic melanoma cells in 80 (89%)<br />
cases including 68 (76%) with a 200 cell FISH count. Six patients did<br />
not have data recorded for the specific cellular features. This yielded<br />
62 patients for the cytology-monosomy 3 correlation. Tumour cell type<br />
UVEAL MELANOMA<br />
Abstracts<br />
99<br />
included 40 (65%) mixed and 22(35%) spindle. There were no pure<br />
epithelioid tumours. Most (40 cases, 65%) tumours had grade 2 nuclei.<br />
Grade 3 and grade 1 nuclei occurred in only 13(21%) and 9(15%) tumors,<br />
respectively. Tils occurred in 18 (29%) tumours. FISH analysis identified<br />
monosomy 3 in 28(45%) tumours. Monosomy 3 occurred significantly<br />
more often in tumours with grade 3 nuclei (69% versus 39% in tumours<br />
with grade 1 or 2 nuclei, p=0.0498). Monosomy 3 occurred more often<br />
in tumours with TILs (61% versus 39% in tumours lacking TILs); this<br />
difference is not significant (p=0.11).<br />
Conclusions In our series most uveal melanomas had a relatively<br />
consistent cellular appearance characterized by at least some spindle<br />
cells, no more than moderate nuclear atypia, and melanin. In our<br />
experience monosomy 3 occurred more often in tumours with grade 3<br />
nuclei or Tils; however, the positive predictive value of these cellular<br />
features is low, limiting clinical utility.<br />
Financial disclosure. None<br />
2321 UM12<br />
RETROSPECTIVE ANALYSIS OF 700 FINE-NEEDLE<br />
ASPIRATION BIOPSIES OF SOLID INTRAOCULAR<br />
TUMORS: CHANGING INDICATIONS DURING LONG-<br />
TERM EXPERIENCE<br />
Zélia M. Corrêa, James J. Augsburger correazm@uc.edu<br />
Department of Ophthalmology, University of Cincinnati College of<br />
Medicine, Cincinnati, Ohio, USA<br />
Purpose. Describe the changing indications for and techniques of FNAB<br />
of intraocular tumours in a single group’s experience during a period of<br />
over 30 years.<br />
Methods. Retrospective records review and data analysis on 700 cases<br />
of FNAB of a solid intraocular tumour performed by the authors during<br />
the period 9/1980 through 6/2011.<br />
Results. During the first 5 years, most FNABs were investigational<br />
(including post-enucleation & post-resection to evaluated different<br />
calibers and lengths needles, different methods of aspiration, routes<br />
of needle passage, cellular yield, specimen processing, cytologichistologic<br />
correlation, and provide experience with cytology of the<br />
various types of tumours to the pathologists reading these samples).<br />
All clinical FNABs (diagnostic or confirmatory) during this period were<br />
performed under an IRB approved protocol in which clinical diagnostic<br />
accuracy, cytopathologic diagnostic accuracy, complications of FNAB,<br />
and percentage of cases in which the results of FNAB changed patient<br />
management were evaluated. In 1985, the IRB determined that FNAB<br />
of intraocular tumours by us no longer needed to be regarded as<br />
investigational. During the ensuing 10 to 15 years, most FNABs we<br />
performed were clinical diagnostic or confirmatory biopsies. Initially,<br />
amelanotic uveal melanoma versus metastatic cancer to uvea was the<br />
most common differential diagnosis, and later on, it became large uveal<br />
nevus versus small uveal melanoma. Our practice relocated to a different<br />
institution in 1999 prompting a new round of post-enucleation FNABs<br />
to familiarize our new pathologists with the cytopathologic features of<br />
intraocular tumours. In 2006, retrospective analysis of 25-year experience<br />
with FNAB of clinically diagnosed melanocytic uveal tumours showed that<br />
cytologic classification to be an independently significant prognostic<br />
factor for metastasis and metastatic death. From that point on, all of our<br />
FNABs on clinically diagnosed melanocytic uveal tumours have been<br />
regarded as prognostic. In 2007, we began to collaborate in a prospective<br />
IRB-approved multicenter (COOG) study of the prognostic significance of
gene expression profile of melanocytic uveal tumour cells obtained by FNAB.<br />
Since then, virtually all FNABs of clinically diagnosed uveal melanomas were<br />
simultaneously confirmatory, prognostic (cytology), and investigational for GEP<br />
while those performed on tumours diagnosed as nevus versus melanoma were<br />
simultaneously diagnostic, prognostic (cytology), and investigational for GEP.<br />
In late 2009, the COOG study validated the prognostic value of GEP of large and<br />
medium size uveal melanomas. A commercial laboratory (Castle Biosciences,<br />
Inc.) acquired the GEP test and all biopsies of similar tumours performed since<br />
then have been regarded as prognostic simultaneously for GEP and cytology.<br />
Conclusions. Indications for performing FNABs on solid intraocular tumours in<br />
this series changed substantially over the years. The FNAB method employed in<br />
a given case depends on indication for biopsy, timing of biopsy, and specimen<br />
size for a successful result.<br />
Financial disclosure. Research to Prevent Blindness, New York, NY, USA, and Quest for Vision<br />
Fund, University of Cincinnati, Cincinnati, OH. USA<br />
204 UM13<br />
PROSPECTIVE EVALUATION OF A GENE EXPRESSION<br />
PROFILE PROGNOSTIC ASSAY FOR UVEAL MELANOMA<br />
IN 514 PATIENTS<br />
J. William Harbour, Michael D. Onken, Lori A. Worley, James J. Augsburger,<br />
Zelia M Correa, Devron H. Char, Eric Nudleman, Thomas M. Aaberg,<br />
Jr., Michael M. Altaweel, David S. Bardenstein, Paul T. Finger, Brenda<br />
L. Gallie, George J. Harocopos, Peter G. Hovland, Hugh D. McGowan,<br />
Tatyana Milman, Prithvi Mruthyunjaya, E. Rand Simpson, Morton E.<br />
Smith, David J. Wilson, William J. Wirostko (harbour@vision.wustl.edu)<br />
Washington University, University of Cincinnati, Tumori Foundation,<br />
Michigan State University, University of Wisconsin, Case Western<br />
Reserve University, New York Eye Cancer Centre, Colorado Retina<br />
Associates, University of Toronto, New York Eye and Ear Infirmary, Duke<br />
University, Oregon Health & Science University, Medical College of<br />
Wisconsin<br />
Purpose. A 15 gene expression profiling (GEP) assay was developed to assign<br />
primary uveal melanomas to prognostic subgroups: class 1 (low metastatic<br />
risk) and class 2 (high metastatic risk). This study evaluated the prognostic<br />
performance of the 15-gene assay in a prospective, multicenter study.<br />
Methods. 514 patients with uveal melanoma were enrolled in a prospective,<br />
12-center study. Tumours were assigned to class 1 or class 2. 293 of the<br />
samples were also analyzed for chromosome 3 status using a single<br />
nucleotide polymorphism assay. Patients were managed for their primary<br />
tumour and monitored for metastasis.<br />
Results. The GEP was class 1 in 308 cases (60.0%) and class 2 in 206 cases<br />
(40.0%). Of the class 1 cases, 308 (87.0%) were class 1A and 67 (13.0%)<br />
were class 1B. Metastasis was detected in 2 (0.8%) class 1A patients, 7<br />
(10.4%) class 1B, and 61 (29.8%) class 2 (P
Purpose. Despite advances in the local treatment of UM, half of patients<br />
develop metastases typically to the liver with poor survival: 13 months<br />
in our large retrospective series of 470 unselected metastatic patients.<br />
Microscopic complete (R0) surgical resection of liver metastases improves<br />
survival to 22 months in high selected patients. Early identification highrisk<br />
patients might allow early detection of metastases, and increase R0<br />
liver surgery rate.<br />
Methods. From October 2006 to December 2009, we conducted a<br />
prospective study to detect early minimal lesions by liver MRI in<br />
asymptomatic high risk patients. High-risk was defined by thickness<br />
>8 mm or diameter >15 mm, or extrascleral extension, or monosomy<br />
3 for enucleated patients. Primary objective was to increase R0 liver<br />
resection rate from 10 to 30% (α risk=0.04 and β risk=0.05); secondary<br />
objectives were overall survival, metastasis-free survival, predictive<br />
value of MRI and liver functional tests (LFT’s).<br />
Results. 100 eligible patients were enrolled: median age 59 (32-83), sex<br />
ratio M 47/F 53. The median largest tumour diameter was 18 mm (11-<br />
26), median tumoral thickness was 11.7 mm (2.7-17); retinal detachment<br />
was present in 75 patients, extraocular spread in 8.<br />
Local treatment of the primary tumour consisted in proton beam therapy<br />
in 10 patients, enucleation in 90. Secondary enucleation was performed<br />
in 3 patients (2 for local relapse). The histotype was epithelioid in 20<br />
cases, spindle-cell in 21, mixed in 49. Monosomy 3 (FISH or array-CGH)<br />
was present in 55/86 (64%) analysed enucleations.<br />
With a median follow up of 32 months, the median metastasis-free<br />
survival was 31 months. Of 50 patients who became metastatic, 41 (82%)<br />
had exclusive liver metastasis. 5/21 operated patients had R0 liver<br />
surgery (24%). To date, 27 patients died (26 from metastasis, 1 myocardial<br />
infarction) and 24 patients are alive with metastasis. 3-year overall survival<br />
is 64%, median not reached. Univariate analysis showed gender, histotype<br />
and monosomy 3 to be prognostic factors for metastasis.<br />
For 85 patients with a complete follow-up dataset, 39 (46%) developed<br />
metastasis. LFT’s failed to detect metastasis before the first abnormal<br />
MRI; despite sensitivity and specificity rates of 100% and 83% for<br />
nodular lesions, liver MRI failed to detect capsular miliary in 7/13<br />
patients with peroperative confirmed liver miliary disease.<br />
Conclusions. MRI and LFT’s screening did not increase R0 liver surgery<br />
rate in 100 high risk patients; further studies will focus on molecular<br />
screening for detection of circulating tumour-derived DNA in sera from<br />
high-risk UM patients.<br />
Financial disclosure. None<br />
3 UM16<br />
PERSONALIZED TARGETED THERAPY FOR UVEAL<br />
MELANOMAS HARBORING GNAQ OR GNA11 MUTA-<br />
TIONS<br />
Vasiliki Poulaki1, Sue Anne Chew2, Bin He2, Nicholas Mitsiades2<br />
(poulakiv@gmail.com)<br />
1. Department of Ophthalmology, Veterans Affairs Boston Healthcare<br />
System, Jamaica Plain/Boston, MA 02130; and School of Medicine,<br />
Boston University, Boston 2. Departments of Medicine and Molecular<br />
and Cellular Biology, Baylor College of Medicine, Houston,USA<br />
Purpose. Inhibitors of B-Raf and MEK kinases hold promise for treatment<br />
of cutaneous melanomas harboring BRAF mutations. BRAF mutations are<br />
rare in uveal melanomas (UMs), but somatic mutations in the G protein<br />
α subunits Gαq and Gα11 (encoded by GNAQ and GNA11, respectively),<br />
occur, in a mutually exclusive pattern, in ~80% of UMs.<br />
Methods. Using cell viability, proliferation and apoptosis assays, and<br />
UVEAL MELANOMA<br />
Abstracts<br />
101<br />
immunoblotting, we assessed the impact of the B-Raf inhibitor PLX4720,<br />
the MEK inhibitor AZD6244, the Akt inhibitor MK2206 and the protein<br />
kinase C (PKC) inhibitors bisindolylmaleimide I (GF109203X), Gö6983<br />
and rottlerin on UM cell lines.<br />
Results. BRAF–mutant UM cells were sensitive to both PLX4720 and<br />
AZD6244, undergoing cell cycle arrest. The effect of these agents<br />
was enhanced when administered together or in combination with<br />
MK2206. UM cells with a Gα–protein mutation (GNAQ or GNA11) were<br />
mildly sensitive to AZD6244, but completely resistant to PLX4720 (even<br />
when administered in combination with AZD6244 or MK2206). In fact,<br />
PLX4720 paradoxically increased ERK phosphorylation in Gα–mutant<br />
UM cells. Conversely, Gα–mutant UM cells were more sensitive to all<br />
three PKC inhibitors than BRAF–mutant UM cells.<br />
Conclusions. The response of UM cells to inhibition of B-Raf, MEK, Akt<br />
and PKC is genotype-dependent. Our observation that Gα–mutant UM<br />
cells are sensitive to PKC inhibitors supports the design of future clinical<br />
trials of such targeted therapies for the treatment of carefully selected<br />
UM patients and provides the rationale for personalized therapy for this<br />
highly lethal malignancy.<br />
Financial disclosure. None<br />
132 UM17<br />
RATIONALE, STUDY DESIGN AND ACCRUAL STATUS<br />
OF A RANDOMIZED PHASE II STUDY OF AZD6244, A<br />
MEK INHIBITOR, VS TEMOZOMIDE IN ADVANCED UVEAL<br />
MELANOMA<br />
Richard D. Carvajal, Jedd D. Wolchok, Paul B. Chapman, Mark Dickson,<br />
Mark Bluth, Grazia Ambrosini, Brian Marr, Murk Heinemann, Annie<br />
Fusco, Marta Nalysnyk, Natasha Martin, Austin Doyle, Boris Bastian,<br />
David Abramson, Gary K. Schwartz (carvajar@mskcc.org)<br />
All from Memorial Sloan-Kettering Cancer Centre, New York, New York<br />
except for Austin Doyle who is from the Investigational Drug Branch,<br />
Cancer Therapy Evaluation <strong>Program</strong>, Bethesda, Maryland<br />
Purpose. Gain of function Gnaq/11 mutations are found in 80% of uveal<br />
melanomas (UM; vanRaamsdonk et al, Nature 2009/NEJM 2010) leading<br />
to MAPK activation. We demonstrated growth suppression associated<br />
with PERK and cyclinD1 down-regulation in Gnaq/11 mutant UM cell lines<br />
with MEK inhibition (MEKi; Ambrosini et al, AACR 2010). To rigorously<br />
assess clinical efficacy of MEKi, we are conducting a randomized<br />
multicenter phase II trial of AZD6244 (potent MEK1/2 inhibitor) versus<br />
temozolomide in advanced UM.<br />
Methods. 120 DTIC/temozolomide naïve patients will be randomized<br />
to AZD6244 75 mg PO BID or temozolomide 150 mg/m2 daily x 5 (28<br />
days cycles), with crossover to AZD6244 permitted. Stratification factors<br />
include Gnaq/11 mutation status. Up to 39 DTIC/temozolomide exposed<br />
patients may receive AZD6244 without randomization. Radiographic<br />
response is measured using RECIST 1.1, with exploratory fluoro-Lthymidine<br />
PET studies performed in 10 patients treated with AZD6244.<br />
Matched tumour biopsies will be collected from 30 patients receiving<br />
AZD6244 for in vivo pharmacodynamic assessment.<br />
Results. In the first year of accrual, 39 patients have provided informed<br />
consented from 4 participating centres, with 25 initiating study therapy.<br />
Another 14 centers are in the process of activating the trial. Baseline<br />
and post-AZD6244 FLT-PET scans have been performed in 8 cases, with<br />
paired tumour biopsies collected from 15 patients.<br />
Conclusions. MEKi is a rationale investigational therapeutic strategy<br />
in UM, with Gnaq/11 status a potential predictor of sensitivity. Despite
the rarity of UM, timely completion of this large trial with embedded<br />
correlative studies appears feasible in the multicenter setting.<br />
Financial disclosure. None<br />
2212 UM18<br />
A CLINICAL PROBE FOR TRANSSCLERAL OPTICAL<br />
SPECTROSCOPY OF INTRAOCULAR TUMOURS<br />
J Krohn1,2, P Svenmarker3, CT Xu3, S Andersson-Engels3 (joerkroh@<br />
online.no)<br />
1. Department of Clinical Medicine, Section of Ophthalmology, University<br />
of Bergen, Bergen, Norway<br />
2. Department of Ophthalmology, Haukeland University Hospital,<br />
Bergen, Norway<br />
3. Department of Physics, Lund University, Lund, Sweden<br />
Purpose<br />
To develop a fiber optic probe for in vivo diagnosis of intraocular<br />
tumours by means of diffuse reflectance spectroscopy, and to optimize<br />
its geometric parameters for transmitting and receiving light through<br />
the sclera.<br />
Methods<br />
Two probe parameters were investigated: the source-detector distance<br />
and the fiber protrusion, i.e. length of the fibers extending from the probe<br />
end. Fluorescence stained choroidal tumour phantoms in enucleated<br />
porcine eyes were measured with diffuse reflectance- and laser-induced<br />
fluorescence spectroscopy. To evaluate the amount of light entering the<br />
tumour phantom, rather than merely the scleral tissue, the fluorescence<br />
from the phantoms was compared with the transmitted excitation light.<br />
The IOP and tissue temperature were monitored, and the scleral surface<br />
was imaged by scanning electron microscopy.<br />
Results. A fiber source-detector distance of 5 mm with 0 mm fiber<br />
protrusion provided maximum contrast of light interacting with the<br />
tumour phantom relative to light propagating between the fibers without<br />
entering into the phantom volume. Scleral applanation by the probe led<br />
to a mean IOP rise of 15 mm Hg. During spectroscopy, a temperature rise<br />
of 0.3 ºC was measured between the sclera and the tumour phantom.<br />
The indentation of the optical fibers did not cause any visible damage<br />
to the sclera.<br />
Conclusions. A source-detector distance of 5 mm with 0.5 mm fiber<br />
protrusion was considered optimal in terms of clinical and spectroscopic<br />
parameters. The study indicates that transscleral spectroscopy can be<br />
safely performed in human eyes, without leading to unacceptable IOP<br />
elevation, significant temperature rise, or scleral damage.<br />
Financial disclosure. Supported by grants from the Western Norway Regional Health Authority<br />
300 UM19<br />
OUR EXPERIENCE WITH TRANSPUPILLARY THERMO<br />
THERAPY FOR SUSPECTED OR SMALL CHOROIDAL<br />
MELANOMAS<br />
Mordechai Rosner, Iris Moroz , Josef Moisseiev, Victoria Vishnevskia-Dai<br />
(mrosner@post.tau.ac.il)<br />
Goldschleger Eye Institute, Sackler Faculty of Medicine, Tel-Aviv<br />
University, Sheba Medical Center, Tel-Hashomer, Israel<br />
Purpose. Changes in treatment approaches to choroidal melanomas<br />
resulted in better preservation of the eyeball and the visual acuity,<br />
UVEAL MELANOMA<br />
Abstracts<br />
102<br />
without increasing the mortality. As it is assumed that the initial spread<br />
of metastases is during the proliferating stage, it might be vital to<br />
diagnose and treat choroidal melanomas during the very early stages.<br />
In this presentation we summarize our experience with treatment of<br />
posterior choroidal nevi suspected for malignant transformation or small<br />
choroidal melanomas, less than 2.5 mm in thickness using Transpupillary<br />
Thermo Therapy (TTT).<br />
Methods. Six patients affected by small posterior choroidal melanoma<br />
were treated with TTT as a sole treatment from 2007 to 2011, and are<br />
followed up.<br />
Results. Six patients affected by small posterior choroidal melanoma<br />
were treated with TTT as a sole treatment from 2007 to 2011, and are<br />
followed up.<br />
Conclusions. TTT might be the treatment of choice for selected, very<br />
small melanomas. However, studies with long follow-up and large<br />
number of patients are needed to evaluate it effectiveness.<br />
Financial disclosure. None<br />
1842 UM20<br />
RESECTION OF IRIS TUMOURS : INTERNAL APPROACH<br />
Arun D. Singh M.D. (singha@ccf.org)<br />
Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic<br />
Foundation, Cleveland, OH, USA<br />
Purpose. To describe a novel minimally invasive surgical technique for<br />
resection of small iris tumours.<br />
Methods. The surgical technique is described as “Small Incision Internal<br />
Resection and Aspiration.” Through a 3.0 mm beveled clear corneal<br />
incision a viscoelastic is instilled into the anterior chamber. Using 25 gauge<br />
horizontal vitrectomy scissors and vitrectomy forceps, the lesion is excised<br />
en bloc with a visible tumour free margin. A segment of clear plastic tubing<br />
(diameter 3.5 mm), primed with viscoelastic, is inserted into the anterior<br />
chamber through the enlarged corneal incision. Controlled aspiration<br />
allows removal of the entire lesion into the tube. The tube is then withdrawn<br />
from the anterior chamber and the lesion expressed onto filter paper. The<br />
iris defect is closed using a modified Siepser slip-knot technique. The larger<br />
corneal incision is closed with interrupted 10-0 nylon sutures.<br />
Results. This technique has been performed on 6 patients with localized<br />
iris tumours (base size : 5.0-1.7 mm) (hemangioma [1] and melanoma<br />
[5]). Reduced postoperative morbidity (inflammation, hypotony,<br />
astigmatism) allowed rapid uneventful recovery in all cases (Va 20/20).<br />
The histopathologic diagnosis could be established in each case and the<br />
margins were negative in all cases.<br />
Conclusions. Minimally invasive technique for resection of selected cases<br />
of iris tumours avoids the potential morbidity associated with a large<br />
corneoscleral incision allowing for rapid visual recovery.<br />
Financial disclosure. None<br />
1917 UM21<br />
PLAQUE RADIOTHERAPY TREATMENT WITH RUTHE-<br />
NIUM-106 FOR IRIS MALIGNANT MELANOMA<br />
Amit K. Arora, Maria Tsimpida, Victoria M.L. Cohen, John L. Hungerford<br />
(amitkarora@hotmail.com)<br />
St. Bartholomew’s Hospital and Moorfields Eye Hospital, London<br />
Purpose. To report results of Ruthenium-106 plaque radiotherapy for iris<br />
malignant melanoma
Methods. A retrospective study of 15 patients with pure iris melanoma<br />
treated with Ruthenium-106 plaque radiotherapy from June 1998 to June<br />
2006. The main outcome measures were tumour control and ocular<br />
complications.<br />
Results. Of the 15 patients, 8 had biopsy-proven melanoma (6 incisional<br />
and 2 excisional biopsies). In the remaining 7, patients enlargement<br />
of the lesion was documented. The median follow-up was 96 months<br />
(ranging from 14 months to 12 years). Common radiation-related<br />
complications included cataract in 9 (60%) patients, dry eyes in 3(20%)<br />
patients and elevated intraocular pressure in 4 (27%) patients. Vision<br />
was preserved in 80% of patients. Local tumour control was obtained<br />
in all patients.<br />
Conclusions. Ruthenium-106 plaque radiotherapy is an effective<br />
treatment for primary malignant iris melanoma , resulting in excellent<br />
local control with preservation of vision. Main complications included<br />
cataract ,dry eyes and glaucoma.<br />
Financial disclosure. None<br />
1849 UM22<br />
RUTHENIUM BRACHYTHERAPY WITH THE 10 MM<br />
PLAQUE FOR SMALL POSTERIOR CHOROIDAL MELA-<br />
NOMAS<br />
Tero Kivelä, Susanna Salkola, Sebastian Eskelin, Jorma Heikkonen<br />
(tero.kivela@helsinki.fi)<br />
Department of Ophthalmology and Oncology, Helsinki University Central<br />
Hospital, Helsinki, Finland<br />
Purpose. To assess tumour control and morbidity after brachytherapy<br />
with 10 mm ruthenium plaques for small posterior choroidal melanomas.<br />
Methods. In 1998-2009, forty-five consecutive choroidal melanomas were<br />
scheduled for irradiation with the 10 mm plaque. The median height and<br />
LBD were 1.9 (range, 0.4-5.2) and 7.0 (range, 3.3-9.6) mm, respectively.<br />
All tumours were T1aN0M0, Stage I (7th edition; 11 were T2, 6th edition).<br />
Median distance was 3.0 mm (range, 0-7.5) from disk and 2.0 mm (range,<br />
0-8.5) from foveola. The anterior margin was posterior to the equator for<br />
all except one. Median dose was 116 Gy (range, 80-194) to apex and 327<br />
Gy (range, 201-824) to base.<br />
Results. Four marginal recurrences developed a median of 1.4 years<br />
(range, 0.6-3.0) after irradiation; two were also vertical (apical and basal<br />
dose was 126-129 Gy and 266-324 Gy, respectively; median distance<br />
from disk 1.4 mm; range, 0.4-3.8). Kaplan-Meier recurrence rate was 10%<br />
(95% CI, 4-24) by 5 years. No patient developed signs of metastases. Six<br />
patients, one with a prior recurrence, died a median of 4.2 years (range,<br />
0.28-8.6) after treatment; 5-year all-cause mortality was 12% (95% CI<br />
5-29). Regarding complications by 5 years, 50% (95% CI, 32-66) were<br />
free of any maculopathy and 97% (95% CI, 80-100) were free or optic<br />
neuropathy. Mean visual acuity was 0.8 at diagnosis and 0.63 at 5 years,<br />
based on logMAR.<br />
Conclusions. The results compare favourably with an recurrence rate of<br />
0.25 by 5 years after transpupillary thermotherapy for tumours of similar<br />
size and location.<br />
Financial disclosure. None<br />
63 UM23<br />
REGRESSION OF UVEAL MELANOMA FOLLOWING<br />
IODINE 125 PLAQUE RADIOTHERAPY: PREDICTIVE<br />
FACTORS AND CORRELATION WITH METASTASIS<br />
UVEAL MELANOMA<br />
Abstracts<br />
103<br />
Hakan Demirci, Fiorella Saponara, Adam Khan, Leslie Niziol,Grant<br />
Comer,David Musch (hdemirci@med.umich.edu)<br />
W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI<br />
Purpose. To analysis uveal melanoma regression following iodine 125<br />
plaque radiotherapy, and evaluate its predictive factors and correlation<br />
with metastasis.<br />
Methods. Retrospective analysis of 124 eyes with > 3 years follow-up<br />
Results. By 50% increase in follow-up time, decrease in tumor thickness<br />
was 0.99 mm, 0.57 mm and 0.3 mm for tumors with initial thickness ><br />
8 mm, 3-8 mm and
C. Metz, T. Gkika, W. Sauerwein, N. Bornfeld (claudia.metz@uk-essen.de)<br />
1. University Hosital of Essen, Department of Ophthalmology, Essen,<br />
Germany<br />
2. University Hospital of Essen, Department of Radiation Oncology,<br />
Essen, Germany<br />
Purpose. Aim of this retrospective study is to analyze results of<br />
vitreoretinal surgery following a complicated course after plaque<br />
brachytherapy. Main focus of interest is the latency period between<br />
plaque brachytherapy and vitreoretinal surgery and the role of<br />
applied irradiation dosage.<br />
Methods. We present a retrospective analysis of vitreoretinal<br />
surgeries following brachytherapy of malignant uvea melanoma with<br />
Ruthenium, Iodine or Ruthenium/Iodine plaques between 1991 and<br />
2011.<br />
Results. A total number of 172 pars-plana-vitrectomies (126 patients)<br />
could be analyzed. Major indications for vitrectomy were massive<br />
vitreous bleeding (53%), retinal detachment (27%) and macular<br />
pucker (5%).<br />
Silicone oil tamponade was necessary in 27% of the cases. Average<br />
sclera irradiation dose was 950 Gy. The time period for irradiation<br />
retinopathy to develop in terms of rubeosis iridis, vitreous bleeding,<br />
intraretinal bleeding and proliferations was averagely 434 days. We<br />
observed an amaurosis in 24 cases; 16 of those had been treated<br />
with Ruthenium/ Iodine or CCB plaques and six cases were observed<br />
in juxtapapillary tumours. Better functional results could be achieved<br />
in those eyes that needed to be treated due to retinal detachment<br />
than in eyes with vitreous bleeding.<br />
Conclusions. Frequent controls are necessary after plaque<br />
brachytherapy not only for tumour control, but also for early<br />
recognition of secondary complications like irradiation retinopathy<br />
and retinal detachment. In many cases of complicated retinal<br />
detachment preservation of eyes and their function could be achieved<br />
applying a temporary silicone oil tamponade.<br />
Financial disclosure. None<br />
2230 UM 26<br />
LONG-TERM RESULTS AFTER ENDORESECTION OF<br />
LARGE UVEAL MELANOMAS WITH PRETREATMENT<br />
BY SINGLE-DOSE STEREOTACTIC IRRADIATION AND<br />
ADJUVANT BRACHYTHERAPY<br />
E. Biewald, H. Lautner, M. Freistühler, M. Gök, W. Sauerwein, GA<br />
Horstmann, N. Bornfeld (eva.biewald@web.de)<br />
1.University Hospital of Essen, Department of Ophthalmology, Essen,<br />
Germany<br />
2.Gamma Knife Centre, Krefeld, Germany<br />
3.University Hospital of Essen, Department of Radiation Oncology,<br />
Essen, Germany<br />
Purpose. The aim of this non-comparative, consecutive case series is<br />
to evaluate the long-term results after endoresection of large uveal<br />
melanomas in combination with pre-treatment with stereotactic gamma<br />
knife radiosurgery and adjuvant ruthenium brachytherapy in most<br />
cases.<br />
Methods. Between April 1999 and April 2010, 219 patients with large<br />
uveal melanomas underwent stereotactic radiosurgery followed by<br />
UVEAL MELANOMA<br />
Abstracts<br />
104<br />
endoresection of the tumour via a standard three-port vitrectomy<br />
including laser photocoagulation and silicone oil tamponade. 153<br />
patients were treated with adjuvant ruthenium brachytherapy. Patients<br />
with a juxtapapillary melanoma or an only eye usually did not receive<br />
a plaque. The average tumour height was 9.3 mm. The minimum dose<br />
delivered to the tumour volume was 25 Gy.<br />
Results. The median follow-up time was 34 months, with a range from<br />
10 years to 66 days. 48 patients showed a ciliary body involvement.<br />
Only 28 eyes (12.8%) with a mean tumour distance to the fovea of 4<br />
mm went blind after 15 months on average. All in all 24 (10.95%) eyes<br />
were enucleated due to serious complications such as pain, phthitical<br />
globe or loss to tumour control. In 12 of these eyes the histopathological<br />
report found vital toumor cells. After 3,7 years on average 39 (17.8%)<br />
patients developed liver metastases. Local tumour recurrences were<br />
observed in 12 cases leading to an additional treatment with ruthenium<br />
or a transpupillary thermotherapy.<br />
Conclusions. Eyes with large uveal melanomas can be salvaged by<br />
stereotactic radiotherapy followed by endoresection. A fair residual<br />
visual acuity was maintained in serveral patients.<br />
Financial disclosure. None<br />
1447 UM27<br />
TREATMENT OF JUXTAPAPILLARY CHOROIDAL MELA-<br />
NOMA<br />
Maria Tsimpida, John Hungerford, Victoria M.L. Cohen (tsimpidam@yahoo.co.uk)<br />
The Ocular Oncology Service St. Bartholomew’s and Moorfield’s Eye<br />
Hospitals<br />
Purpose. To compare the efficacy of proton beam radiotherapy (PBRT)<br />
and Ruthenium-106 notched plaque radiotherapy with or without<br />
adjuvant transpupillary thermotherapy (TTT) for the treatment of<br />
juxtapapillary choroidal melanoma.<br />
Methods. Retrospective case notes analysis of all juxtapapillary<br />
choroidal melanomas treated in London from May 2005 to February<br />
2011. Three treatment groups were identified: group 1 PBRT; group<br />
2 notched plaque with adjuvant TTT; group 3 notched plaque. Data<br />
analysis was based on tumour dimensions, length of follow-up, tumour<br />
control, radiation related complications, loss of 2 or more lines of Snellen<br />
visual acuity and secondary enucleation rates.<br />
Results. All juxtapapillary melanomas were ≤2mm from the optic disc.<br />
The tumour dimensions were similar in all 3 groups. 93 melanomas were<br />
identified. 52 with more than a year follow-up were included in the study.<br />
Tumour control was 100% in the proton beam group, 91% in the notched<br />
plaque with TTT group and 80% in the notched plaque group. However<br />
radiation-related complications were much more severe in the proton<br />
beam group, as 91% of patients lost 2 or more lines of vision, compared to<br />
43% of patients in the notched plaque group. The secondary enucleation<br />
rate of 9% was the same in all 3 groups.<br />
Conclusions. Juxtapapillary melanomas can be successfully treated using<br />
either proton beam or notched plaque combined with adjuvant TTT. However,<br />
vision is often sacrificed. Notched plaque alone provides reduced local tumour<br />
control but results in improved visual outcome.( word count: 245)<br />
Financial disclosure. None<br />
2307 UM28<br />
OPTIC NERVE DAMAGE AFTER IRRADIATION OF<br />
INTRAOCULAR TUMOURS
Evangelos S. Gragoudas, Anne Marie Lane, Ivana Kim<br />
(evangelos_gragoudas@meei.harvard.edu)<br />
Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical<br />
School, Boston, MA<br />
Purpose. To evaluate the tolerance of the intraocular optic nerve to<br />
different doses of proton irradiation.<br />
Methods. We evaluated 1121 patients with choroidal melanoma treated<br />
with protons in whom the optic nerve was exposed to doses between<br />
3.5 Gy and 70 Gy. The relationship between radiation exposure and<br />
incidence of radiation papillopathy and optic atrophy (disc pallor and<br />
visual acuity of NLP) was assessed. Vision loss (worse than 20/200)<br />
due to radiation-induced damage to the optic nerve was evaluated<br />
in a subgroup of 171 patients with tumours 46.7 Gy).<br />
Conclusions. These data suggest that exposure of the optic nerve<br />
to radiation doses up to 47 Gy is well-tolerated, with visual loss only<br />
observed in patients who received higher doses (> 47 Gy).<br />
Financial disclosure. None<br />
133 UM29<br />
PROTON BEAM RADIOTHERAPY OF PARAPAPILLARY<br />
CHOROIDAL MELANOMA<br />
G.D. Willerding1, D. Cordini2, N.E. Bechrakis4, M.H. Foerster5, J. Heufelder2,<br />
A.M. Joussen1, N. Lakotka1, L. Moser3(gregor.willerding@charite.de)<br />
1. Charité, BerlinProtonen am HZB, Berlin, Germany; 2. Charité,<br />
Augenklinik, Campus 1. Charité, Augenklinik, Campus Benjamin Franklin,<br />
Berlin, Germany; 2 Charité, BerlinProtonen am HZB, Berlin, Germany; 3<br />
Charité, Klinik für Strahlentherapie, Campus Benjamin Franklin, Berlin,<br />
Germany; 4. Department of Ophthalmology, Medical University of<br />
Innsbruck, Innsbruck, Austria; 5.Department of Ophthalmology, DRK<br />
Kliniken Berlin - Westend, Berlin, Germany<br />
Purpose. To report the results of optic disc involvement in proton beam<br />
radiotherapy of posterior choroidal melanoma.<br />
Methods. Retrospective case series of patients without endoresection<br />
following radiation, where treatment planning has been done with<br />
EYEPLAN. 159 patients, who received a cumulative dose of 50-60<br />
CGE to the optic disc during fractionated proton beam irradiation of<br />
choroidal melanoma between December 1998 and December 2005 were<br />
identified.<br />
Results. Radiation treatment controlled the tumour in 94 %. Medium<br />
follow-up was 64 (4 to 140) months. Mean visual acuity before<br />
radiotherapy was 0,3 and dropped to 0.05 and 0.04 after 3 and 5 years.<br />
Mean tumour thickness decreased from 3.7 to 2.5 and 2.1 after 3 and 5<br />
years. Recurrences occured in 6%. Main complications were radiation<br />
optic neuropathy in 81% and vitreous bleeding in 30% irrespective of<br />
secondary treatment. Secondary enucleation was performed in 3%.<br />
UVEAL MELANOMA<br />
Abstracts<br />
105<br />
Metastasis developed in 15% during follow-up.<br />
Conclusions. Significant decrease in visual acuity develops after optic<br />
disc irradiation in proton beam therapy. Rates of tumour control and eye<br />
retention in this group of patients are favourable.<br />
Financial disclosure. None<br />
1414 UM30<br />
HEMODYNAMIC MODIFICATIONS OF THE RETINA<br />
AND THE CHOROÏD FOLLOWING PROTON BEAM<br />
IRRADIATION OF UVEAL MELANOMAS<br />
Leonidas Zografos, Ann Schalenbourg, Line Chamot, (leonidas.<br />
zografos@fa2.ch)<br />
Jules-Gonin Eye Hospital, Lausanne, Switzerland<br />
Purpose. To study the mechanisms of hemodynamic modifications of<br />
the retina and the choroïd following proton beam irradiation of uveal<br />
melanomas.<br />
Methods. Panoramic ICG and panoramic fluorescein angiography was<br />
performed with the Staurenghi contact lens and the HRA2 camera.<br />
223cases of uveal melanomas, previously treated with proton beam<br />
irradiation. The main hemodynamic modifications of the choroïd and<br />
retina are: Partial choroïdal Ischemia 58%, vortex vein occlusion 49%,<br />
arterio venous communications between the posterior cilliary arteries<br />
and the vortex veins 29 %, localised retinal ischemia 54 %, diffuse<br />
retinal ischemia 18%, inferior retinal ischemia 22%.<br />
Results. Following laser coagulation a decrease of the vascular<br />
density of the choroïd was observed in all the cases associated to a<br />
decrease of the permeability of the previously observed arterio venous<br />
communications.<br />
Conclusions. Panoramic ICG and fluorescein angiography provide useful<br />
informations about the hemodynamic modifications of the retina and the<br />
choroïd following proton beam irradiation of uveal melanomas as well<br />
as after extensive laser coagulation witch allows to introduce valuable<br />
antivasoprolifératives strategies.<br />
Financial disclosure. None<br />
2358 UM31<br />
PERIOCULAR TRIAMCINOLONE FOR PREVENTION OF<br />
MACULAR EDEMA FOLLOWING PLAQUE RADIOTHER-<br />
APY OF UVEAL MELANOMA: THREE YEAR FOLLOW-<br />
UP<br />
Noel Horgan, Carol L. Shields, Melissa Murphy, Arman Mashayekhi,<br />
Pedro F. Salazar, Miguel A. Materin, Myra O’Regan, Jerry A. Shields<br />
(noelhorg@hotmail.com)<br />
Royal Victoria Eye and Ear Hospital, Dublin<br />
Wills Eye Institute, Philadelphia<br />
Trinity College, Dublin<br />
Purpose. To determine the efficacy and safety of periocular triamcinolone<br />
acetonide (40 mg) for the prevention of macular edema in patients<br />
undergoing plaque radiotherapy for uveal melanoma.<br />
Methods. A prospective randomized controlled clinical trial recruited nehundred<br />
and sixty-three patients with newly diagnosed uveal melanoma<br />
undergoing Iodine125 plaque radiotherapy . Fifty-five patients were<br />
randomized to the control group and 108 to the triamcinolone group.
Patients in the triamcinolone group received periocular injection of<br />
triamcinolone acetonide (40 mg in 1 ml) at the time of plaque radiotherapy<br />
and 4-months and 8-months later. Optical coherence tomography (OCT)<br />
was performed at each patient evaluation.<br />
Results. OCT-evident macular edema occurred significantly less often in<br />
the triamcinolone group compared to the control group up to 36-months<br />
following plaque radiotherapy (relative risk 0.61, 95% CI 0.46-0.81). At<br />
36-month follow-up however, rates of moderate vision loss (loss of 3 or<br />
more lines of best corrected visual acuity [BCVA]) and severe vision loss<br />
(BCVA 10 mm in LBD) were included in this<br />
prospective study. Patients were scheduled for I-125 brachytherapy<br />
and randomized for adjuvant IVTA (4mg/0.1mL) or IVA (1.25mg/0.05mL)<br />
injection performed at plaque removal. All patients underwent a 1, 3, 6<br />
month follow-up examination, and every 6 months thereafter, including<br />
fundus photography and A/B scan ultrasonography. Follow-up was<br />
longer than 24 months.<br />
Results. Follow-up was 37±7 months. Tumour regression was<br />
achieved in all patients. Complete SRD regression was documented in<br />
eighteen IVTA- treated patients (56%) vs eleven IVA-treated patients<br />
(34%) (p
control group received both an intravenous and oral placebo. Patients<br />
in both groups had access to standard medications for pain on a<br />
sliding scale as needed based on pain severity. Nurses were blinded<br />
to the patient’s group status. Patients were asked to score their pain<br />
experience using a visual analogue scale (VAS) three times per day<br />
during the inpatient admission while the plaque was in place as well as<br />
once the day after plaque removal and once at the 2-week postoperative<br />
visit. The nurse administering the steroid or placebo to the patient<br />
separately scored his/her perception of the patients’ pain using the<br />
Wong-Baker FACES scale.<br />
Results. Preliminary results indicate that there is a decreased pain in<br />
the patients in the steroid group both during plaque application and<br />
in the immediate post-operative period. Patient recruitment and data<br />
analysis is ongoing and full results will be presented at the ISOO.<br />
Conclusions. The use of intravenous and oral steroids should be<br />
considered both during the treatment period and post-operatively for<br />
plaque patients given the severe discomfort that many plaque patients<br />
experience.<br />
Financial disclosure. None<br />
1623 UM35<br />
UVEAL MELANOMA AMONG FINNISH CHILDREN AND<br />
ADOLESCENTS<br />
Rana’a Aljamal, Tero Kivelä (ranaa.aljamal@hus.fi)<br />
Departement of Ophthalmology, Ocular Oncology Service, Helsinki<br />
University Central Hospital,<br />
Purpose. To report uveal melanoma (UM) before the age of 25 years in<br />
Finland, a high incidence region for this cancer.<br />
Methods. A population-based study identified 24 patients (0.3%), aged<br />
between 13 and 24 years at diagnosis, treated in our hospital in 1963-<br />
2006. They were divided in two groups, the first consisted of 11 patients<br />
(9 females, 2 males) enucleated before 1997. The second was treated by<br />
irradiation after 1991, consisting of 11 patients (9 females, 2 males). Two<br />
other patients underwent local resection (male and female).<br />
Results. Tumour height was 4-11 mm (mean, 7) in the first and 4.4-13.7<br />
mm (mean, 8.5) in the second group and largest basal diameter ranged<br />
from 5-16 mm (mean, 10) and 2.5- 21 mm (mean, 15), respectively. Four<br />
patients died, 3 of UM (after 4, 12 and 21 years). All were female with<br />
spindle tumours. In the second group, 2 females died of UM (after 3<br />
and 4 years).<br />
Conclusions. UM is rarely seen among young children and adolescents.<br />
In this small series, females outnumbered males.<br />
Financial disclosure. None<br />
UVEAL MELANOMA<br />
Abstracts<br />
107<br />
406 UM 36<br />
RESULTS OF MELANOMA BRACHYTHERAPY IN AR-<br />
GENTINA<br />
Arturo Irarrazaval, Pablo Cazon (artuira@consultoresoftalmologicos.<br />
com)<br />
Consultores Oftalmologicos<br />
Purpose. To present our experience in 58 cases of choroidal melanoma<br />
treated with brachytherapy in Argentina.<br />
Methods. Retrospective study of the charts of 58 patients treated with<br />
brachytherapy.<br />
Results. There were, till today, 3 cases of metastases. We had 3<br />
recurrences, and could preserve the globe in 52 cases. 31 of our patients<br />
had a final visual acuity of 20/400 or better.<br />
Conclusions. Conservative treatment of melanoma, using brachytherapy,<br />
has good results in preserving the eye, without increase in mortality,<br />
and in more than half the patients, retaining useful vision.<br />
Financial disclosure. None
1350 Ump101<br />
INDUCED EXPRESSION OF PIRES-EGR1-EGFP-OMI/<br />
HTRA2 AND ITS EFFECT ON APOPTOSIS OF HUMAN<br />
CHOROIDAL MELANOMA OCM-1 CELLS<br />
Xufang Sun, Tian Yu, Shu Yan (applesxf@yahoo.com.cn)<br />
Department of Ophthalmology, Tongji Hospital, Tongji Medical College,<br />
Huazhong University of Science and Technology; Wuhan Aier Eye<br />
Hospital, Wuhan, China<br />
Purpose. The hydrogen peroxide induced and the kill characteristics of<br />
pIRES-Egr1-EGFP-Omi/HtrA2 in human choroidal melanoma OCM-1 cells<br />
were investigated.<br />
Methods. pIRES-Egr1-EGFP and pIRES-Egr1-EGFP-Omi/HtrA2<br />
recombinant plasmids were constructed and RT-PCR assays were<br />
used to identify, which were transfected into the cultured OCM-1 cells<br />
by lipofectamineTM2000. The cells transfected by both plasmids<br />
were stimulated respectively by hydrogen peroxide. pIRES-Egr1-EGFP<br />
transfected cells were used as control groups. The expression levels of<br />
Omi/HtrA2 and XIAP were examined by Western blotting. The rations of<br />
apoptotic cells were assessed by flow cytometry. The transfection rates<br />
was observed by fluorescence microscopy. MTT method was used for<br />
observing cell proliferation.<br />
Results. Our Results showed that the recombinant plasmids could<br />
successfully constructed and transferred into OCM-1 cells by<br />
lipofectamineTM2000. Compared with the control group, the Omi/<br />
HtrA2 and XIAP gene expression at the protein level were decreased<br />
53.5% and 31.9%, respectively. The apoptotic ratio of pIRES-Egr1-EGFP-<br />
Omi/HtrA2 transferred cells increased significantly after the induction<br />
(p
1949 Ump104<br />
GENDER DIFFERENCES AND ESTROGEN AND PRO-<br />
GESTERONE RECEPTOR EXPRESSION IN UVEAL MEL-<br />
ANOMA<br />
L. Schoenfield, M. Turell, P. Carver, S. Mackie, R. Tubbs, A. Singh<br />
(schoenl@ccf.org)<br />
Cleveland Clinic, Cleveland, OH; Pathology and Lab Medicine Institute; Cole<br />
Eye Institute<br />
Purpose. Older reports have not demonstrated estrogen receptor<br />
(ER) expression in uveal melanoma (UVM). A recent study reporting<br />
differences in incidence and metastasis-related mortality by gender<br />
prompted a re-examination of ER and progesterone receptor (PR)<br />
expression by immunohistochemistry with comparison to clinical<br />
outcome and chromosome 3 status.<br />
Methods. 33 cases of UVM from 2004-09 treated by enucleation were<br />
examined for incidence and survival. 23 cases were evaluated for ER and<br />
PR by immunohistochemistry. Chromosome 3 status was determined by<br />
FISH and SNP array analysis.<br />
Results. There were 19 men (58%) and 14 women (42%). 11 patients<br />
were DOD: 8 men (67%) and 3 women (25%); 1 woman was alive with<br />
metastasis. 10 men (56%) and 8 women (44%) were alive without<br />
metastasis. 3 patients died of other causes.<br />
ER was positive in 7 women (11 positive cases) and negative in UVM<br />
arising in men (8 of 12 negative cases). PR was negative in 20 of 23 cases<br />
and weakly positive or negative in 3. ER did not predict either clinical<br />
outcome or chromosome 3 status. Of the ER positive cases, 4 were DOD<br />
and 6 were alive without metastasis. Of the ER negative cases, 5 were<br />
DOD and 6 alive without metastasis. When compared to chromosome<br />
3 abnormalities, ER was positive in 9/18 monosomy 3 cases and 2/5<br />
disomy cases.<br />
Conclusions. Gender may play a role in UVM. ER expression was present<br />
in 48% of cases of uveal melanoma and more likely in women in this<br />
small study, but it does not appear to be prognostic. We propose further<br />
study, including quantitative evaluation using image analysis.<br />
Financial disclosure. None<br />
2320 Ump105<br />
DOES INTERNAL BLOOD FLOW VELOCITY CORRELATE<br />
WITH KNOWN PROGNOSTIC FACTORS FOR PRIMARY<br />
UVEAL TRACT MELANOMA?<br />
Amit Arora, Vasilios P. Papastefanou, Mandeep S Sagoo, Marie Restori,<br />
Marianne Graham, Victoria ML Cohen (amitkarora@hotmail.com)<br />
Ocular Oncology Service, St Bartholomew’s Hospital & Moorfields Eye<br />
Hospital, London<br />
Institute of Ophthalmology, University College London<br />
Cytogenetics Department, Barts and the London NHS Trust<br />
Purpose. To examine the association of internal blood flow velocity in<br />
primary uveal melanoma with tumour size, chromosomes 3/8 status and<br />
histopathology type.<br />
Methods. Between 2009 and 2011, all patients with large uveal tract<br />
melanoma scheduled for enucleation underwent internal blood flow<br />
velocity studies using B-mode Doppler ultrasound scans at the time of<br />
diagnosis. Tumour height and diameters were clinically determined.<br />
Corresponding areas and volumes were calculated for each tumour.<br />
UVEAL MELANOMA<br />
Posters<br />
109<br />
Punch biopsy tissue samples were obtained at the time of surgery<br />
for cytogenetic analysis for the status of chromosomes 3 and 8 with<br />
interphase FISH analysis. Cell type was determined by histopathology.<br />
Spearman correlation coefficient was used to examine the association<br />
of internal blood flow velocity with tumour dimensions.<br />
Results. Twenty-three enucleation specimens underwent preoperative<br />
blood flow velocity studies. Internal blood flow was not positively<br />
correlated with tumour height (r=0.061, p=0.786), area (r=-0.1.7,<br />
p=0.636) or volume (r=0.015, p=0.946). Similarly, no significant<br />
difference was noted in regards to cell type (12.25 ± 4.99 cm/sec for<br />
epithelioid cells, 16.1± 10.22 cm/sec for mixed cell and 11.7± 6.9 cm/sec<br />
for spindle cell tumours respectively [mean ± 1SD] or chromosome 3/8 status.<br />
Conclusions. Internal blood flow of primary uveal melanoma does not<br />
appear to be associated with uveal melanoma cell type or chromosome<br />
status. No positive correlation was found in relation to tumour<br />
dimensions.<br />
Financial disclosure. None<br />
1425 Ump106<br />
EVALUATION OF IRIS AND CILIARY BODY LESIONS<br />
WITH ANTERIOR SEGMENT OPTICAL COHERENCE<br />
TOMOGRAPHY (AS-OCT) VERSUS ULTRASOUND B<br />
SCAN<br />
M. S. Sagoo1,2,3, V. P. Papastefanou2,3, S. Hau2, S. Shah2, M.<br />
Tsimpida2,3, V.M. Cohen2,3 (mandeep.sagoo@moorfields.nhs.uk)<br />
1. UCL Institute of Ophthalmology<br />
2. Moorfields Eye Hospital, London<br />
3. Ocular Oncology Service, Barts and the London NHS Trust, London<br />
Purpose. To compare anterior segment optical coherence tomography (AS-<br />
OCT) versus ultrasound B scan for imaging iris and ciliary body lesions.<br />
Methods. We prospectively evaluated 66 eyes with AS-OCT and<br />
ultrasound B scan. Comparison of images between the two imaging<br />
modalities was made.<br />
Results. Thirty seven eyes (56%) had iris naevus, 13 (20%) iris pigment<br />
epithelial cyst, 6 (9%) iris melanoma, 2 (3%) iris haemangioma, 7 (10%)<br />
other iris lesions, and 1 (2%) ciliary body melanoma. Image analysis<br />
revealed (AS-OCT vs ultrasound B scan) the ability to detect lesion<br />
(62/66 (94%) vs 46/66 (70%), complete visualisation of the lesion in<br />
26/62 (42%) vs 46/46 (100%), and posterior lesion shadowing in 51/62<br />
(82%) vs 0/46 (0%).<br />
Conclusions. AS-OCT offers better detection and precise measurement<br />
but is less able to provide complete visualisation of iris lesions compared<br />
with ultrasound.<br />
Financial disclosure. None<br />
114 Ump107<br />
Β-RADIATION BRACHYTHERAPY FOR LARGE<br />
CHOROIDAL MELANOMA: DO WE NEED A HIGH DOSE<br />
TO THE APEX?<br />
M. Naseripour, K.H. Ghasemi Falavarjani, R. Jaberi, A.R. Irani, Z. Azma<br />
(masoodnp@yahoo.com)<br />
Eye Research Center, Rassoul Akram Hospital, Tehran University of Medical<br />
Sciences
Purpose. To report the Results of Ru-106 plaque radiotherapy for large (<br />
>7mm in thickness) choroidal melanoma.<br />
Methods. In this prospective interventional case series 23 patients<br />
with a diagnosis of large choroidal melanoma with a tumour thickness<br />
of more than 7 mm were studied. The off label use of Ru-106 plaque<br />
therapy for these tumour size and the safety concerns were discussed<br />
with the patients and inform consents were obtained. The estimated<br />
dose to the tumour apex was 100 Gy and maximum permitted sclera<br />
dose was considered 1450 Gy.<br />
Results. Twenty-three patients including 11 men and 12 women with a<br />
mean age of 55.6±13.7 years were treated. Patients were followed for a<br />
mean of 29.9±22.5 months. The mean apex dose was 70.7±15.5(40-100)<br />
Gy. Preoperative tumour thickness of 8±0.5 mm decreased to 4.1±2.1<br />
mm at last visit (P
Oncology Department, The S. Fyodorov Eye Microsurgery Complex,<br />
Moscow, Russia<br />
Purpose. To compare the outcomes of combined treatment of<br />
choroidal melanoma with Ru-brachytherapy (BT) simultaneously with<br />
transpupillary thermotherapy (TTT) and treatment with BT alone.<br />
Methods. Two matched groups of patients, one treated with BT and<br />
simultaneous TTT (group BT+TTT, n=63), the other treated with BT alone<br />
(group BT, n=70) were analyzed retrospectively. The main outcome<br />
measures were rate of tumour regression, recurrences, enucleations,<br />
metastases, recurrence-free and overall survival rate, assessed by<br />
Kaplan-Meier analysis.<br />
Results. Patients were matched according to mean age (P=0.22), mean<br />
tumour thickness (6.4 vs 6.25mm, range 2.5-10.8mm, P=0.59), and<br />
mean length of follow-up (42 vs 34.4 months, range 3-109, P=0.052).<br />
Tumour largest basal diameter (13.0 vs 12.9mm), tumour location, and<br />
mean radiation dose (apical 135 vs 136 Gy, scleral 1294 vs 1438 Gy) were<br />
also similar in both groups (P>0.1). Treatment with BT+TTT resulted in<br />
higher rate of tumour regression (63% vs 49% respectively, P=0.036),<br />
lower 5-year tumour recurrence rate (96% vs 83%, P
1547 Ump113<br />
LONG-TERM OBSERVATIONS IN SMALL, POSTERIOR<br />
LOCATED MALIGNANT MELANOMAS OF THE CHOROID<br />
TREATED WITH TRANSPUPILLARY THERMOTHERAPY<br />
(TTT)<br />
B.M. Stoffelns, K. Schöpfer (bernhard.stoffelns@unimedizin-mainz.de)<br />
Department of Ophthalmology, Universal Medical Center of Johannes<br />
Gutenberg - University, Mainz, Germany,<br />
Purpose. To evaluate the long-term Results of transpupillary<br />
thermotherapy (TTT) for small malignant choroidal melanomas.<br />
Methods. In the time period 1.1998 to 10.1999 in a prospective nonrandomized<br />
analysis 26 eyes with small malignant melanomas (located<br />
posterior to the equator with base ≤ 12 and thickness ≤ 4,5 mm) were<br />
primary treated with the TTT standard protocol (follow-up over a time<br />
span of 10 years minimally).<br />
Results. Thirteen women and thirteen men (mean age 64 years)<br />
underwent TTT. The mean preoperative tumor thickness was 2,45 mm<br />
(0,8 – 4,5 mm). Ten years postoperatively tumor regression without<br />
recurrence after 1,4 treatment sessions (mean) was achieved in 16/26<br />
eyes, primary regression followed by tumor regrowth in 6/26 eyes and<br />
primary failure of tumor regression in 4/26 eyes. Two patients died on<br />
liver metastasis. Ocular complications (with preference in posterior<br />
tumors after multiple TTT sessions) were observed in 14 eyes: macular<br />
pucker in 8, macular edema in 6, choroidal neovascularisation in 4 and<br />
posterior synechia with iris atrophy in one eye.<br />
Conclusions. Choroidal melanomas treated with TTT as stand-alone<br />
procedure need a close monitoring since these tumors developed a<br />
significant rate of local recurrences and ocular side-effects in the long<br />
run.<br />
Financial disclosure. None<br />
602 Ump114<br />
CANCER RISKS FOR PATIENTS WITH MYOTONIC<br />
DYSTROPHY<br />
Jose Pulido1, Aung Ko Win2, Promilla Perattur3, Christine Pulido3,<br />
Noralane Lindor3 pulido.jose@mayo.edu<br />
1. Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota,<br />
USA; 2. Centre for Molecular, Environmental, Genetic and Analytic<br />
Epidemiology, The University of Melbourne, Parkville, Victoria, Australia;<br />
3. Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota,<br />
USA.<br />
Purpose. Myotonic dystrophy (DM) types 1 and 2 are clinically similar<br />
autosomal dominant disorders and mainly characterized by myotonia,<br />
muscle weakness and early-onset cataracts. Several studies have<br />
suggested there may be increased risks for neoplasms associated with<br />
DM. We wished to quantify the risk<br />
Methods. A cohort of 307 DM patients identified from medical records<br />
from Mayo Clinic Rochester was retrospectively analyzed. We estimated<br />
standardized incidence ratios of specific cancers for DM patients<br />
compared with age- and sex-specific cancer incidences of the general<br />
population. Age-dependent cumulative risks were calculated using the<br />
Kaplan–Meier method.<br />
Results. A total of 54 cancers was observed at a median age at diagnosis<br />
of 55 years. DM patients were at an increased risk of thyroid cancer<br />
UVEAL MELANOMA<br />
Posters<br />
112<br />
(SIR 5.54, 95% CI 1.80-12.93, p=0.001), and choroidal melanoma (SIR<br />
27.54, 95% CI 3.34-99.49, p3 Snellen visual acuity lines. OCT scans indicated<br />
improvement in retinal thickness over the lesion and in central<br />
retinal thickness in all treated cases. Two cases (one untreated and<br />
one treated with anti-VEGF) presented with outer retinal tubulation.<br />
There was no evidence of malignant transformation during follow-up.<br />
Conclusions. Anti-VEGF treatment was effective in achieving stable<br />
visual acuity (loss of
1617 Ump116<br />
INCIDENCE OF METASTATIC DISEASE AND<br />
SURVIVAL OF 716 CONSECUTIVE PATIENTS WITH<br />
POSTERIOR UVEAL MELANOMA : A RETROSPECTIVE<br />
MONOCENTRIC REVIEW<br />
Fatima Hammouch1, Patrick De Potter2, David Francart3, François<br />
Dall’Armellina4, Jean-François Baurain5 (fatima.hammouch@uclouvain.be)<br />
1. Oncology Department, Centre du Cancer, Cliniques Universitaires<br />
Saint-Luc, Université Catholique de Louvain ; 2. Ophtalmology<br />
Department, Centre du Cancer, Cliniques Universitaires Saint-Luc; 3.<br />
Ophtalmology Department, Centre du Cancer, Cliniques Universitaires<br />
Saint-Luc ; 4. Oncology Department, Centre du Cancer, Cliniques<br />
Universitaires Saint-Luc, Université Catholique de Louvain ; 5.<br />
Oncology Department, Centre du Cancer, Cliniques Universitaires<br />
Saint-Luc, Université Catholique de Louvain, Brussels.<br />
Purpose. To determine the rate, time and location of systemic<br />
metastases in patients with posterior uveal melanoma and to evaluate<br />
risk factors and survival after diagnosis of systemic relapse.<br />
Methods. A retrospective review was performed on 716 consecutive<br />
patients, referred and managed at the Centre du Cancer, Brussels,<br />
for posterior uveal melanoma, between January 1998 and December<br />
2010. Data were analyzed with SPSS 18 for Mac. The rate of metastatic<br />
disease was calculated and patients survival was assessed by Kaplan-<br />
Meier method. The impact of metastatic diesase–related symptoms<br />
on survival was analyzed by the Log-Rank test. A multivariate Cox<br />
regression was performed to identify risk factors for metastatic<br />
disease.<br />
Results. The median age at diagnosis was 63 years. According to the<br />
COMS classification, there were 43 (6%) small tumors, 379 (53%)<br />
medium tumors, 232 (32%) large tumors and 62 (9%) tumors were<br />
unclassified. The treatment consisted in enucleation, radiotherapy<br />
+/- thermotherapy and thermotherapy alone in 24%, 66% and 10% of<br />
patients, respectively. The median time between tumor diagnosis and<br />
treatment was 9 days. The median time of follow up for the 716 patients<br />
was 3 years. Among them, 100 patients (14%) developed metastatic<br />
disease (71% exclusively liver localisation, 19% extraliver and liver<br />
localisations and 5% only extraliver localisation) with a median time<br />
to relapse of 32 months. The relapse free survival from diagnosis at 5<br />
and 10 years was 81% and 75%, respectively. Risk factors for systemic<br />
metastases (multivariate analysis) were: large tumor (p=0.035),<br />
epitheloid cell melanoma (p=0.002) and later age at diagnosis<br />
(p=0.002). The median follow-up from relapse was 34 months. Fourty<br />
patients (40%) died from their melanoma with a median survival time<br />
of 17 months. No difference in survival was observed between those<br />
patients with metastasis-related symptoms and those without (p><br />
0.05).<br />
Conclusions. Even with a relatively short follow-up time (36 months),<br />
our study showed a lower rate (14%) of metastatic disease with a<br />
higher median survival time than those previously reported. Our<br />
cohort seemed to be homogeneous, with classical risk factors<br />
identified. While the issue of regular systemic screening on patient<br />
survival was not assessed, we did not find a significant difference<br />
between asymptomatic and systemic metastasis-related symptomatic<br />
patients. The potential impact of the treatment(s) on prognosis among<br />
our patients with metastatic disease is under investigation.<br />
Financial disclosure. None<br />
UVEAL MELANOMA<br />
Posters<br />
113<br />
25 Ump117<br />
LONG LASTING SURVIVAL OF UVEAL MELANOMA<br />
WITH EXTRAOCULAR EXTENSION<br />
Ignacio Zeolite, Carlos Zeolite, Juan Oscar Croxatto (izeolite@yahoo.<br />
com)<br />
Oftar Mendoza, Universidad de Mendoza<br />
Purpose. To report a long term survival (over 60 months) of a patient<br />
with malignant melanoma with extraocular extension post diagnostic<br />
FNAB with no concomitant brachytherapy.<br />
Methods. A 80-year old female patient with malignant melanoma with<br />
extraocular extension post FNAB with no coadyuvant brachitherapy was<br />
treated with excisional biopsy of subconjunctival dark clumps diagnosed<br />
as extraocular extension of uveal melanoma. She refused any choice of<br />
treatment and was followed in a regular basis for 41 months.<br />
Results. Survival after FNAB with the diagnosis of malignant uveal<br />
melanoma was 51 months (46 months with extraocular extension). In this<br />
case we present an unusual pattern of extraoclar extension as multiple<br />
subconjunctival clumps with realatively long term stability while the<br />
general health status of the patient was well. At the time of the declining<br />
of the general health status the tumors grew fast and the patient died in<br />
2 months with liver metastases. Enucleation was performed 50 months<br />
after FNAB because of ocular infection and tumor necrosis. No other<br />
choice of treatment was authorized for the patient nor the family.<br />
Conclusions. Malignant melanoma of the choroid can spread<br />
extraocularly after FNAB.<br />
Co-adyuvant brachitherapy is indicated after FNAB. Different patterns of<br />
extraocular extension can be observed.<br />
Long-term stability of the lesion can be associeted with good general<br />
health status.<br />
Financial disclosure. None<br />
2133 Ump118<br />
CLINICOPATHOLOGIC CORRELATIONS OF PLAQUE<br />
BRACHYTHERAPY FAILURE IN THE TREATMENT OF<br />
CHOROIDAL MELANOMA<br />
Jill R. Wells, Chris S. Bergstrom, Qing Zhang, Hans E. Grossniklaus<br />
(jrwells14@hotmail.com)<br />
Emory Eye Center, Oncology and Pathology Service<br />
Purpose. To correlate the histopathologic findings in the enucleated<br />
eyes of three patients who failed treatment for choroidal melanoma with<br />
plaque brachytherapy.<br />
Methods. Three patients who had undergone enucleation for failure<br />
of plaque brachytherapy for choroidal melanoma were identified.<br />
The clinical and histopathologic features of the enucleated eyes were<br />
reviewed as well as immunohistochemical staining.<br />
Results. Based on the clinicopathologic correlations, case 1 failed<br />
secondary to inadequate radiation to the peripheral tumor; case 2 failed<br />
secondary to inadequate radiation to the tumor over the nerve; and case<br />
3 failed secondary to inherent radioresistance of the tumor.<br />
Conclusions. Careful attention to tumor ultrasound measurements and<br />
correct plaque design is important. Tumors overhanging the optic nerve<br />
are the difficult to treat. Further studies are needed to determine if and<br />
which cellular and genetic factors in choroidal melanomas underlie<br />
radioresistant cellular phenotypes.<br />
Financial disclosure. None
2038 Ump119<br />
VALUE OF DOPPLER ANALYSIS IN THE REGRESSION<br />
OF UVEAL MELANOMA AFTER PLAQUE<br />
Mónica Asencio-Duran, Pilar Garcia-Raya, Pilar Moreno, Isabel<br />
Rodriguez-Rodriguez, Eva Corredoira (masedur@hotmail.com)<br />
Hospital La Paz, Madrid, Spain<br />
Purpose. To study the vascularization of melanoma as a sign of tumoral<br />
activity.<br />
Methods. 50 cases of melanoma treated with brachytherapy from<br />
July 2005 to June 2010 were reviewed. The median follow-up was 29<br />
months (13.7-69 months). Doppler was performed at diagnosis and<br />
every 6 months. The average age was 60 years; there were 26 men and<br />
24 women. 70 % of tumors were melanotic, 18 % amelanotic and 12<br />
% mixed. Posterior location 30 %, equatorial 22 %, peripheral 20 %,<br />
ciliary body 12 % and postequatorial 16 %. The median basal size at<br />
diagnosis was 12.1 mm and median thickness 5.6 mm. The most used<br />
plaque was the COMS (70 %), Ruthenium (28 %) and in 10 cases TTT<br />
was associated. The apical dose was 85 cGy in all.<br />
Results. Doppler detected intratumoral vascularization at diagnosis in<br />
21 of 50 cases (42 %), of which 7 persisted at 6, 12 and 18 months. At<br />
24 months this was 5 of 31 (16 %), at 30 months 3/20 (15 %), at 36<br />
months 1/12 (8 %), at 42 months 1/6 (16.7 %), at 48 months 1/3 (33.3<br />
%), at 54 months 1 of 2 (50 %) and at 60 months 0/1 (0 %). 8 avascular<br />
tumors at diagnosis experienced new vascularization, of them, only 1<br />
recurred and was enucleated, and 7 presented with ophthalmoscopic<br />
and echographic regression. Of those with persistent vascularization<br />
during the follow-up (6), 1 case recurred and was enucleated, another<br />
developed metastasis, and 4 are regressed melanomas.<br />
Conclusions<br />
Results suggest that doppler is an important tool in management<br />
of melanoma after plaque. Persistent intratumoral vascularization<br />
seems to be associated with large tumour sizes, tumoral recurrence or<br />
appearance of vascular congestion in neovascular glaucoma. The new<br />
vascularized cases can be explained by the persistence of old vessels<br />
not found before (wrong angulation of the probe), tumour recurrence or NVG.<br />
Financial disclosure. None<br />
65 Ump120<br />
EVALUATION OF CHOROIDAL TUMORS BY OCT-<br />
ENHANCED DEPTH IMAGING<br />
Hakan Demirci, Dolly A. Padovani-Claudio, Alexis Smith, Brandon Smith,<br />
Grant M. Comer (hdemirci@med.umich.edu)<br />
W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, MI<br />
Purpose. To evaluate the role of OCT-enhanced imaging technique (OCT-<br />
EDI) in the imaging of choroidal tumors.<br />
Methods. Prospective, single-center case series of 30 patients<br />
Results. Hyporeflectivity was seen in choroidal nevus and melanoma,<br />
while hyper-reflectivity was seen in treated choroidal melanoma,<br />
choroidal metastasis, circumscribed choroidal hemangioma, posterior<br />
scleritis, and choroidal hemorrhage. OCT-EDI successfully imaged the<br />
tumors up to 1.5 mm in thickness.<br />
Conclusions. OCT-EDI is helpful in imaging of choroidal tumors up to 1.5 mm<br />
in thickness. It might be used in the differential diagnosis and follow-up of<br />
these tumors.<br />
Financial disclosure. None<br />
114<br />
1608 Ump121<br />
HISTOPATHOLOGIC FINDINGS IN EYES WITH<br />
CHOROIDAL MELANOMA TREATED WITH<br />
BEVACIZUMAB FOR RADIATION RETINOPATHY<br />
Hans E. Grossniklaus1, Martina C. Herwig1, 2, Weiqing Gao1 (ophtheg@<br />
emory.edu)<br />
1. Emory University School of Medicine, Atlanta, Georgia USA and 2.<br />
University of Bonn, Bonn, Germany<br />
Purpose. To describe the histopathological findings in two choroidal<br />
melanoma eyes treated with intravitreal bevacizumab for radiation<br />
retinopathy due to brachytherapy.<br />
Methods. The clinical course of two patients with choroidal<br />
melanoma who received intravitreal bevacizumab injections for<br />
radiation retinopathy following brachytherapy was evaluated. After<br />
enucleation for tumor recurrence (case 1) and secondary glaucoma<br />
(case 2), the eyes were routinely processed, stained with H&E and<br />
PAS, and immunostained for HMB45, VEGF, Ki67, CD31, and CD105.<br />
Results. An increased amount of fibrosis within the tumor and peritumoral<br />
tissue was found in both eyes in addition to the degenerative<br />
changes of radiation retinopathy. HMB45 and VEGF were expressed<br />
in both uveal melanomas, the latter particularly in macrophages.<br />
Proliferative activity measured by the Ki67 index and angiogenesis<br />
indicated by CD105+ vascular channels were related to tumor activity.<br />
Conclusions. Bevacizumab injections for radiation retinopathy<br />
seem to expedite fibrotic changes within uveal melanoma and the<br />
peri-tumoral tissue including the choroid and the overlying retina.<br />
Detection of tumor recurrence may be impaired by these bevacizumab<br />
induced changes leading to a delay until adequate treatment.<br />
Financial disclosure. None<br />
64 Ump122<br />
TREATMENT OF RADIATION MACULOPATHY WITH<br />
INTRAVITREAL INJECTION OF BEVACIZUMAB<br />
Mosci Carlo, Francesca Nasciuti, Francesco Baldo Lanza<br />
(carlo.mosci@galliera.it)<br />
Ocular Oncology Center, Galliera Hospital, Genova, Italy<br />
Purpose. To evaluate the safety and efficacy of intravitreal injection<br />
of bevacizumab as a treatment option for radiation maculopathy<br />
secondary to proton beam radiotherapy.<br />
Methods. Prospective case series of five patients affected by<br />
intraocular melanoma who developed radiation maculopathy after<br />
treatment with proton beam.<br />
Three intravitreal injections of bevacizumab (0.5 ml) were given,<br />
with an interval of one month between injections. The main outcome<br />
measures were visual acuity measured with ETDRS acuity chart,<br />
macular function with microperimetry test and optical coherence<br />
tomography.<br />
Results. The pre-injection visual acuity ranged from 46 to 13 with an<br />
average of 33 letters.<br />
The pre-injection central macular thickness measured by optical<br />
coherence tomography ranged from 321 m to 605 m with an average<br />
of 445 m. Three months after the first injection, the average visual<br />
acuity was 35 and the average thickness 418; after 6 months these<br />
numbers were 39 and 387, respectively. Microperimetry confirmed<br />
the improvement in visual function at six months.
Conclusions. In this series, treatment of radiation maculopathy with<br />
intravitreal injection of bevacizumab was useful in all the five patients;<br />
macular function and macular thickness were better since the second<br />
injection and resulted in a stable situation at six month of follow-up.<br />
Longer follow-up and a larger number of cases are necessary for definitive<br />
results.<br />
Financial disclosure. None<br />
327 Ump123<br />
EPIDEMIOLOGICAL ANALYSIS OF BRAZILIAN<br />
PATIENTS WITH UVEAL MELANOMA SUBMITTED TO<br />
PRIMARY ENUCLEATION IN A REFERRAL CENTER<br />
Priscilla L. Ballalai, Kelcia Kieffer, Ricardo Filippo, Rafaello Salla, Maria<br />
C. Martins, Márcia Lowen (pbbordon@terra.com.br)<br />
Ocular Oncology Unit, Federal University of Sao Paulo<br />
Pathology Unit, Federal University of Sao Paulo<br />
Purpose. To analyze the epidemiological characteristics of patients with<br />
uveal melanoma submitted to primary enucleation in a referral center<br />
in Brazil.<br />
Methods. Retrospective, non-comparative case series. Review of<br />
charts of patients submitted to primary enucleation from 2001 to 2011.<br />
Epidemiological data such as age, gender, race, histological type,<br />
presence of extra ocular extension and predisposing conditions were<br />
analyzed.<br />
Results. Eighty-four patients were submitted to primary enucleation<br />
from 2001 to 2011. The mean age was 48.8 years-old (range, 19-84 yo);<br />
45 were male and 39 females. Fifty-five patients were white, 11 black<br />
and 1 Brazilian Indian. The information about the race was not found in<br />
17 cases. Two patients had Oculodermal melanosis as a predisposing<br />
condition (2.3 %) and one tumor originated from a melanocytoma (1.2<br />
%). Nine patients had tumors at the cilliary body (11 %). Regarding<br />
the histological type, 63 (75 %) patients had mixed type tumors, with<br />
predominancy of epithelioid cells in 19 (30%), and spindle cells in 17<br />
(27%). Fifteen (18 %) tumors were epithelioid type and 5 were spindle<br />
cell type (6 %) . Extra-ocular extension was found in 7 patients (8 %).<br />
Conclusions. Although Brazilian population is multi-racial, in this group,<br />
uveal melanoma was more frequent in middle-aged white patients, as<br />
previously reported. The mixed type was more prevalent. Oculodermal<br />
melanosis and melanocytoma were rarely found as predisposing factors<br />
for uveal melanoma.<br />
Financial disclosure. None<br />
2252 Ump124<br />
UVEAL MELANOMA CLINICAL TRIALS AT MD<br />
ANDERSON CANCER CENTER<br />
Scott E. Woodman1A, Michael Tetzlaff1B, Xiaoxing Yu1A, Chandrani<br />
Chattopadhyay1A, Michelle Williams1B, Nancy Poindexter1A, Elizabeth<br />
Grimm1A, Dan Gombos3, Bita Esmaeli3, Agop Bedikian1A, Sapna Patel1A<br />
(sewmdphd@yahoo.com)<br />
1A. Melanoma Medical Oncology;1B, Pathology, MD Anderson Cancer<br />
Center, Houston, TX; 2. Ophthalmology, Leiden University Med Center,<br />
Leiden, The Netherlands; 3. Head & Neck Surgery/Ophthalmology, MD<br />
Anderson Cancer Center, Houston, TX.<br />
Purpose. Metastatic uveal melanoma has a very poor prognosis and<br />
115<br />
no effective treatment. We have designed two phase II clinical trials<br />
specifically for patients with metastatic uveal melanoma. The first<br />
study attempts to capitalize on the observation that metastatic uveal<br />
melanoma cells have a propensity for elevated IGF-1R levels which may<br />
be associated with worse outcome. The second study capitalizes on the<br />
observation that the anti-apoptotic molecule Bcl-2 may be a mediator of<br />
resistance to melanoma cell death after cytotoxic therapy.<br />
Methods. Study I is a pilot study of IMC-A12 in patients with metastatic<br />
uveal melanoma. It is designed as a prospective, multi-institutional,<br />
two-stage, Phase II trial with 18 patients in stage I and 14 patients in<br />
stage II. IMC-A12 is a recombinant human IgG1 monoclonal antibody<br />
which specifically targets the human IGF-1R resulting in blockade of<br />
ligand binding and internalization and degradation of IGF-1R. IMC A-12 is<br />
administered at 10 mg/kg by intravenous (IV) infusion over 1 hour every<br />
two weeks.<br />
A treatment cycle is defined as 4 weeks. Response evaluation is<br />
performed every two cycles. Study II is a pilot study of Genasense-<br />
Carboplatin-Paclitaxel (GCP) in patients with metastatic uveal<br />
melanoma. It is designed as a prospective, single-institution, twostage<br />
Phase II trial with 15 patients in each stage. Genasense is an<br />
antisense molecule that blocks Bcl-2 function. Genasense (900 mg) is<br />
administered on a fixed-dose basis as over 1 hour by IV infusion on days<br />
1, 3, and 5 of each cycle. Paclitaxel 175 mg/m2 is administered in 250 mL<br />
NS over 1 hour by IV infusion on Day 3 of each cycle immediately upon<br />
completion of administration of Genasense. Carboplatin (AUC= 6) is<br />
administered in150 mL D5W over 30 minutes (+/- 5 mins) by IV infusion<br />
after paclitaxel on day 3 of each cycle. A treatment cycle is defined as 3<br />
weeks. Response evaluation will be performed every two cycles.<br />
Results IMC-A12 study: The primary endpoint is objective response rate.<br />
The secondary endpoints are safety and tolerability, disease control rate,<br />
duration of response, progression-free survival, and overall survival.<br />
The exploratory endpoints are to correlate response to mutation status,<br />
correlate response to IGF-1R expression, determine the effect of IMC-<br />
A12 on expression of proteins involved in initiation, growth, and spread<br />
of uveal melanoma cells, determine potential resistance mechanisms to<br />
IMC-A12. GCP study: The primary endpoint is objective response rate.<br />
The secondary endpoints are overall survival, time to progression, time<br />
to treatment failure, duration of response, and safety profile of GCP<br />
in this patient population. The exploratory endpoints are correlation<br />
of response to blood and tumor markers and potential correlation of<br />
response to mutation status.<br />
Conclusions. We have designed two Phase II clinical trials using more<br />
targeted therapeutic approaches in an attempt to improve outcome.<br />
In addition, these studies have incorporated robust correlative studies<br />
to better interrogate molecular markers that may be associated with<br />
clinical outcome.<br />
Financial disclosure. None<br />
1912 Ump125<br />
UVEAL MELANOMA: TRENDS IN INCIDENCE,<br />
TREATMENT, AND SURVIVAL<br />
Arun D. Singh, Mary E. Turell, Allan K. Topham (singha@ccf.org)<br />
Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic,<br />
Cleveland, OH and Coalition of National Cancer Cooperative Group Inc.,<br />
Philadelphia, PA.<br />
Purpose. To determine trends in incidence, treatment, and survival with<br />
primary uveal melanoma in the<br />
United States over a 36-year period from 1973 to 2008.
Methods. A total of 4070 patients with primary uveal melanoma [ICD-<br />
O-2] codes C69.3 [choroid], C69.4 [ciliary body and iris], and C69.2<br />
[retina] derived from the Surveillance, Epidemiology, and End Results<br />
(SEER) database. The significance of trends were determined using chisquare<br />
test.<br />
Results. There were 4070 cases of uveal melanoma representing 3.1%<br />
of all recorded cases of melanoma.<br />
The majority of cases (98.3%) were reported by hospitals. Histopathologic<br />
confirmation was available in 72.1% of cases. The mean age-adjusted<br />
incidence was 5.1 per million, with 97.8% of cases occurring in the white<br />
population. No change in the 5-year relative survival rate (81.6%) was<br />
observed.<br />
Conclusions. The age-adjusted incidence (5.1 per million) has remained<br />
unchanged from 1973 to 2008. Despite a shift toward more conservative<br />
treatments, survival has not improved during this time period.<br />
Financial disclosure. None<br />
453 Ump126<br />
FISH: MAKING HEADS OR TAILS OF TECHNIQUES<br />
M. Turell1, R. Tubbs2 , C. Biscotti3 , Y. Sun2, Y. Saunthararajah4, P.<br />
Triozzi 5, A. Singh1 (turellm2@ccf.org)<br />
1. Cole Eye Institute; 2. Department of Molecular Pathology; 3.<br />
Department of Anatomic Pathology; 4. Hematologic Oncology & Blood<br />
Disorders; 5. Solid Tumor Oncology, Cleveland Clinic Foundation,<br />
Cleveland, OH<br />
Purpose. Tumor monosomy 3 confers a poor prognosis in patients<br />
with uveal melanoma. A critical review of the literature pertaining to<br />
techniques and procedures used for fluorescence in situ hybridization<br />
(FISH) detection of monosomy 3 was performed in order to compare<br />
practice patterns across oncology centers worldwide.<br />
Methods. A PubMed literature search was conducted for studies related<br />
to FISH-based uveal melanoma prognostication published between<br />
January 1, 1997 and January 1, 2011.<br />
Results. A total of 29 publications were relevant to this review.<br />
Significant variability was found in both clinical features (tumor size<br />
and location) and the specific FISH techniques that have been used to<br />
assess monosomy 3 status in uveal melanoma. In particular, parameters<br />
including tissue sampling Methods (fresh tissue [n=14], fine-needle<br />
aspiration biopsy [n=6], and paraffin-embedded tissue [n=9]), selection<br />
of FISH probes (centromeric [n=25], locus-specific probes [n=6], whole<br />
chromosome paints [n=2], and unspecified [n=2]), number of cells<br />
counted (range: 40-500), and cut-point (range 5-60%) used to determine<br />
monosomy 3 status varied widely.<br />
Conclusions. FISH to detect monosomy 3 in uveal melanoma has not<br />
been performed in a standardized manner. This likely affects reported<br />
Results and limits Conclusions regarding clinical utility.<br />
Financial disclosure. This work was supported by a Falk Trust grant and a Research to Prevent<br />
Blindness Challenge Grant, Department of Ophthalmology, Cleveland Clinic Lerner College of<br />
Medicine.<br />
116
First authors<br />
Abramson, David H.<br />
Al-Jamal, Rana’a<br />
Ambrosini, Grazia<br />
Arora, Amit K.<br />
Asencio-Duran, Mónica<br />
Ausburger, James<br />
Bagnatori Braga, Marcela<br />
Ballalai, Priscilla L.<br />
Behnam, Babak<br />
Berry, J.L.<br />
Bianciotto, Carlos<br />
Biewald, Eva M.<br />
Biscotti, C.V.<br />
Bita Esmaeli<br />
Blasi, Maria A.<br />
Bonanomi, Maria Teresa B.C.<br />
Bornfeld, Norbert<br />
Bosaleh, Andrea<br />
Bosscha, M.I.<br />
Brennan, Rachel C.<br />
Brodie, Scott E.<br />
Bronkhorst, I.H.G.<br />
Callejo, Sonia A.<br />
Carvajal, Richard D.<br />
Cebulla, Colleen M.<br />
Chantada, Guillermo<br />
Chévez-Barrios, Patricia<br />
Chintagumpala, M.<br />
Cobrinik, David<br />
Cohen, Victoria M.L.<br />
Colicchio, Daniel<br />
Corrêa, Zélia M.<br />
Croxatto, J. Oscar<br />
Damato, Bertil E.<br />
De Potter, Patrick<br />
Decatur, Christina L.<br />
Demirci, Hakan<br />
Desjardins, Laurence<br />
Dimaras, Helen<br />
Donato Macedo, Carla R.<br />
Dos Santos Soares, Juliana<br />
Dunkel, Ira J.<br />
Eberhart, Charles<br />
Elizalde, Javier<br />
Esmaeli, Bita<br />
Fandiño, Adriana C.<br />
Francis, Jasmine H.<br />
Freistühler, Michael<br />
Frenkel, Shahar<br />
Furuta, Minoru<br />
Gallie, Brenda L.<br />
Gentile, Carolina M.<br />
Ghassemi, Fariba<br />
Giblin, Michael E.<br />
Glasson, William<br />
Gombos, Dan S.<br />
Graaf, P. de<br />
Gragoudas, Evangelos S.<br />
Grossniklaus, Hans E.<br />
Hadjistilianou, T.<br />
Page/s<br />
16, 30, 41, 62, 75<br />
34, 58, 93, 107<br />
94, 108<br />
92, 94, 102, 109<br />
29, 38, 95, 114<br />
91<br />
32, 52<br />
61, 64, 69, 95, 79, 115<br />
33, 56<br />
33, 53<br />
61, 70<br />
92, 104<br />
91, 99<br />
61, 67<br />
91, 96<br />
32, 48<br />
91, 97<br />
33, 55<br />
29, 36<br />
16, 24, 29, 37<br />
32, 50<br />
15, 21<br />
61, 71<br />
92, 101<br />
15, 18<br />
16, 92<br />
29, 30, 40, 62, 75<br />
31, 47<br />
16, 24<br />
61, 63, 70, 79<br />
32, 51<br />
15, 18, 63, 77, 91, 99<br />
61, 68<br />
63, 78, 91, 98<br />
61, 64, 71, 80<br />
31, 34, 46, 59<br />
63, 64, 65, 82, 85, 92, 95, 103, 114<br />
29<br />
29, 35<br />
30, 32, 39, 48<br />
32, 52<br />
31, 45<br />
15, 19, 65, 85<br />
61, 62, 73<br />
61, 64<br />
30, 41, 63, 76<br />
32, 50<br />
94, 110<br />
15, 20, 61, 64, 70, 80<br />
62, 72<br />
16, 23, 29, 36<br />
63, 77, 91, 96<br />
32, 49<br />
64, 81<br />
91, 96<br />
30, 33, 40, 55, 62, 75<br />
29, 35<br />
93, 104<br />
15, 19, 33, 55, 95, 114<br />
30, 31, 33, 42, 57<br />
AUTHOR INDEX<br />
118<br />
First authors<br />
Halaban, Ruth<br />
Hammouch, Fatima<br />
Harbour, J. William<br />
Hashimoto, Camila H.<br />
Heegaard, Steffen<br />
Heufelder, J.<br />
Holdt, M.<br />
Horgan, Noel<br />
Houston, Samuel K.<br />
Hovland, Peter<br />
Hungerford, John<br />
Hurwitz, Richard L.<br />
Irarrazaval, Arturo<br />
Islamov, Z.<br />
Jager, M.J.<br />
Jhanwar, Suresh C.<br />
Kakkassery, V.<br />
Kaneko, Akihiro<br />
Kashiwagi, Hiroya<br />
Kaushik, Megha<br />
Kenawy, Nihal<br />
Kilic, Emine<br />
Kim, Ivana K.<br />
Kiratli, Hayyam<br />
Kivelä, Tero<br />
Kleinerman, Ruth A.<br />
Klufas, Michael A.<br />
Krema, Hatem<br />
Krohn, J.<br />
Lally, Sara E.<br />
Laurent, Viviana<br />
Leahey, A.<br />
Leal, Carlos A.<br />
Lee, Christopher Seungkyu<br />
Lee, Sung Chul<br />
Lee, Susan<br />
Levy-Gabriel, Christine<br />
Li, Helen K.<br />
Liu, David T.L.<br />
Lumbroso-Le Rouic, Livia<br />
Madic, Jordan<br />
Malbran, Enrique S.<br />
Manquez, Maria E.<br />
Marback, Eduardo F.<br />
Marinkovic, M.<br />
Marr, Brian P.<br />
Materin, Miguel A.<br />
Mazzini, Cinzia<br />
McKenzie, John D<br />
McWhae, John<br />
Mehta, Sonul<br />
Metz, C.<br />
Midena, Edoardo<br />
Moll, A.C.<br />
Moreno-Páramo, Daniel<br />
Mosci, Carlo<br />
Moulin, Alexander P.<br />
Mruthyunjaya, Prithvi<br />
Munier, Francis L.<br />
Murray, Timothy G.<br />
Page/s<br />
16<br />
95, 113<br />
16, 22, 64, 79, 91, 92, 100<br />
62, 75<br />
61, 62, 68<br />
94, 111<br />
33, 54<br />
93, 105<br />
16, 26, 93, 106<br />
33, 56, 63, 78<br />
30, 42<br />
16, 26<br />
63, 76, 78, 92, 93, 107<br />
29, 32, 33, 35, 49, 54<br />
91, 96<br />
16, 22<br />
66, 88<br />
65, 84<br />
65, 83<br />
62, 73<br />
61, 70<br />
15<br />
15, 21<br />
61, 67<br />
62, 66, 75, 87, 92, 103<br />
31, 45<br />
31, 43<br />
61, 67<br />
92, 102<br />
64, 65, 82, 84<br />
16, 25<br />
29, 37<br />
32, 50<br />
65, 87<br />
65, 87<br />
34, 58<br />
33, 54<br />
62, 64, 72, 81<br />
61, 67<br />
29, 38<br />
15, 21<br />
91<br />
63, 64, 65, 80, 85<br />
62, 65, 75, 83<br />
61, 68<br />
31, 43<br />
15, 16, 23, 63, 77, 92<br />
65, 86, 92, 100<br />
32, 33, 52, 53<br />
63, 78<br />
63, 79<br />
92, 103<br />
63, 64, 81, 92, 93, 106<br />
32, 51<br />
64, 81<br />
95, 114<br />
63, 79<br />
62, 63, 65, 72, 78, 86<br />
30, 43<br />
17, 27, 31, 33, 44, 56
First authors<br />
Naseripour, Masood<br />
Novetsky-Friedman, D.<br />
Ohshima, Koh-ichi<br />
Oliver, Scott C. N.<br />
Owusu-Agyemang, Pascal<br />
Palioura, Sotiria<br />
Papastefanou, Vasilios P.<br />
Parrozzani, Raffaele<br />
Parulekar, M.<br />
Pe’er, Jacob<br />
Pelayes, David E.<br />
Piña, Yolanda<br />
Piperno-Neumann, S.<br />
Poulaki, Vasiliki<br />
Pulido, Jose S.<br />
Qaddoumi, Ibrahim<br />
Rashid, M.M.<br />
Reddy, M Ashwin<br />
Rosner, Mordechai<br />
Saakyan, S.V.<br />
Sagoo, Mandeep S.<br />
Sauerwein, Wolfgang<br />
Schaiquevich, Paula<br />
Schalenbourg, Ann<br />
Schefler, Amy C.<br />
Schoenfield, Lynn<br />
Scott, Oliver<br />
Shields, Carol L.<br />
Shields, Jerry A.<br />
Shigenobu Suzuki<br />
Singh, Arun D.<br />
Stoffelns, B.M.<br />
Sun, Xufang<br />
Takashi, Yamane<br />
Teixeira, Luiz F.<br />
Tsimpida, Maria<br />
Tsuji, Hideki<br />
Turell, M.E.<br />
Ushakova, Tatiana<br />
Vishnevskia-Dai, Vicktoria<br />
Wei, Wenbin<br />
Wells, Jill R<br />
Willerding, G.D.<br />
Wilson, David J.<br />
Wilson, Matthew W.<br />
Woodman, Scott E.<br />
Xu, Xiaoliang L.<br />
Yarovoy, A.A.<br />
Zeolite, Ignacio<br />
Zografos, Leonidas<br />
Page/s<br />
32, 49, 63, 64, 81, 94, 109<br />
31, 45<br />
65, 84<br />
15, 19, 65, 87, 94, 111<br />
34, 58<br />
31, 44<br />
63, 76, 91, 95, 97, 112<br />
91, 98<br />
16, 23, 29, 33, 36, 58<br />
62, 63, 73, 77<br />
91, 97<br />
17, 26, 34, 59<br />
92, 100<br />
92, 101<br />
66, 88, 94, 112<br />
29, 32, 37, 48<br />
92, 103<br />
30, 31, 32, 44, 51, 64, 81<br />
64, 80, 92, 102<br />
33, 54, 65, 84<br />
63, 64, 81, 94, 109<br />
33, 57, 61, 69, 94, 110<br />
30, 42<br />
64, 81<br />
62, 63, 76, 93, 106<br />
15, 20, 63, 78, 94, 109<br />
64, 80<br />
29, 30, 41, 62, 63, 65, 78, 83<br />
33, 57, 61, 62, 63, 71, 77<br />
31, 46<br />
15, 18, 63, 64, 78, 91, 92, 95, 102, 115<br />
94, 112<br />
94, 108<br />
33, 53<br />
29, 32, 38, 52, 63, 77<br />
64, 80, 92, 104<br />
61, 65, 83<br />
62, 66, 76, 88, 91, 95, 98, 116<br />
29, 39<br />
62, 73, 76<br />
94, 108<br />
95, 113<br />
93, 105<br />
15, 20, 62, 74<br />
16, 25, 30, 40<br />
16, 22, 95, 115<br />
16, 25<br />
94, 110<br />
95, 113<br />
93, 105<br />
119