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VISION<br />
<strong>PAN</strong>-<strong>AMERICA</strong><br />
Miriam García-Fernández; Begoña Baamonde Arbaiza<br />
Volumen X No.1 Marzo 2011<br />
TRATAMIENTO PARA LINFOMAS INTRAOCULARES TREATMENT FOR<br />
INTRAOCULAR LYMPHOMAS<br />
Dr. Gian Paolo Giuliari<br />
NEW VITAL DYES TO STAIN INTRAOCULAR MEMBRANES AND TISSUES DURING VITRECTOMY<br />
Mauricio Maia MD PhD; Eduardo B. Rodrigues MD;<br />
Michel Eid Farah MD PhD; André Maia MD; Acácio Lima<br />
PhD; Octaviano Magalhães Jr MD; Eduardo Dib MD<br />
OZURDEX ® , A NOVEL DEXAMETHASONE DELIVERY SYSTEM, FOR TREATMENT OF<br />
MACULAR EDEMA FOLLOWING RETINAL VEIN OCCLUSION<br />
Rubens Belfort Jr. MD PhD; Cristina Muccioli MD; Susan S Lee MS; Michael R. Robinson MD<br />
INCIDENCIA DE DESPRENDIMIENTO DE RETINA EN PACIENTES ALTOS MIOPES<br />
POSTOPERADOS DE IMPLANTE DE LIO FÁQUICO ARTISAN/ARTIFLEX<br />
Luis Fernando Rosales Rodriguez MD; Luis Oswaldo Izquierdo Villavicencio MD; Maria Alejandra Henríquez MD<br />
QUERATITIS POR ACANTHAMOEBA. A PROPÓSITO DE UN CASO ACANTHAMOEBA<br />
KERATITIS: A CASE REPORT<br />
MULTILAYERED FOLDED DEHYDRATED AMNIOTIC MEMBRANE GRAFT FOR SCLERAL<br />
DELLE MANAGEMENT FOLDED DEHYDRATED AMT FOR SCLERAL DELLE<br />
Jay C. Bradley MD<br />
TRULY UNILATERAL KERATOCONUS ASSOCIATED WITH ORBITAL FIBROSIS<br />
Alejandro Navas MD; Armando González-Gomar MD; Zoraida Espinosa MD; José Luis<br />
Tovilla-Canales MD; Tito Ramírez-Luquín MD; Enrique O. Graue-Hernández MD<br />
ISSN 2219-4665
4 :<br />
<strong>PAN</strong>-<strong>AMERICA</strong>
Special thanks to Ana Carolina<br />
Vieira, Enrique Graue Hernandez,<br />
Mapy Padilla, and Cristian Luco<br />
for assistance in translation.<br />
CREATIVE LATIN MEDIA, LLC.<br />
2901 Clint Moore, P.M.B 117 Boca Raton, FL 33496<br />
Tel.: (561) 495 4728 Fax: (561) 865 1934<br />
E-mail: editorial@clatinmedia.com info@clatinmedia.com<br />
Cristián Luco, MD<br />
Santiago, Chile<br />
Associate Editor<br />
Eduardo Alfonso, MD<br />
Miami, Florida USA<br />
Eduardo Arenas, MD<br />
Bogotá, Colombia<br />
J. Fernando Arévalo, MD<br />
Caracas, Venezuela<br />
José A. Roca Fernández, MD<br />
Lima, Perú<br />
Denise de Freitas, MD<br />
São Paulo, Brazil<br />
Marian Macsai, MD<br />
Chicago, Illinois USA<br />
David E. Pelayes, MD PhD<br />
Buenos Aires, Argentina<br />
Mark J. Mannis, MD<br />
University <strong>of</strong> California, Davis<br />
Sacramento, California<br />
Editor-in-Chief<br />
Teresa J. Bradshaw<br />
Arlington, Texas<br />
Managing Editor<br />
EDITORIAL BOARD<br />
Terri L. Grassi<br />
Arlington, Texas<br />
Production Editor<br />
Alfredo Sadun, MD<br />
Los Angeles, California USA<br />
Allan Slomovic, MD<br />
Toronto, Ontario, Canada<br />
Luciene Barbosa de Sousa, MD<br />
São Paulo, Brazil<br />
Lihteh Wu, MD<br />
San José, Costa Rica<br />
Paulo Dantas, MD<br />
São Paulo, Brazil<br />
Chun Cheng Lin Yang, MD MSc<br />
San José, Costa Rica<br />
OFFICERS<br />
Cristián Luco MD<br />
Santiago, Chile<br />
President, <strong>Pan</strong>-<strong>American</strong> <strong>Association</strong> <strong>of</strong> Ophthalmology<br />
Nelson R. Marques<br />
São Paulo, Brazil<br />
Chairman <strong>of</strong> the Board,<br />
<strong>Pan</strong>-<strong>American</strong> Ophthalmological Foundation<br />
Advanced Medical Optics Inc.<br />
Alcon Inc.<br />
Allergan Inc.<br />
Bausch & Lomb Inc.<br />
Carl Zeiss Meditec Inc.<br />
PRODUCTION STAFF<br />
Director <strong>of</strong> Printed Matters CLM<br />
Eliana Barbosa<br />
Graphic Design CLM<br />
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Databases and Distribution CLM<br />
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telemarketing@clatinmedia.com<br />
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PAOF INDUSTRY SPONSORS<br />
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Santen Inc.<br />
Prepress Creative Latin Media. Printed in Printer Colombiana - Colombia<br />
Marzo 2011<br />
<strong>PAN</strong>-<strong>AMERICA</strong>
MENSAJE DEL PRESIDENTE / MESSAGE FROM THE PRESIDENT<br />
2 <strong>PAN</strong>-<strong>AMERICA</strong><br />
Del Editor:<br />
Editorial<br />
Mark J. Mannis, MD<br />
Editor en Jefe Vision <strong>Pan</strong>-America<br />
Con el 2011 comienza una nueva era para Vision <strong>Pan</strong>-America (VPA). Originalmente<br />
establecida como una comunicación científica de la PAAO hace una década,<br />
nuestra publicación ha crecido para convertirse en una revista pequeña pero de<br />
muy alta calidad de revisión por pares con una circulación y distribución mayor<br />
a muchas de las revistas de subespecialidad en lengua inglesa. Con artículos en<br />
inglés, español, portugués y en francés, VPA brinda a autores latinoamericanos,<br />
norteamericanos, del Caribe y Canadá una excelente oportunidad para que compartan<br />
su trabajo con una población de lectura muy amplia. Hemos sido beneficiados<br />
por un gran apoyo de la Fundación Oftalmológica <strong>Pan</strong>-<strong>American</strong>a, la industria y la<br />
PAAO. Tenemos un cuerpo editorial pro-activo y dedicado, y quienes inclusive han<br />
contribuido regularmente con artículos, además hemos incluido a un grupo de revisores<br />
justos y considerados para asegurarnos de publicar trabajos con calidad.<br />
Por primera vez verán que tenemos un número ISSN, mismo que se puede ver<br />
en la portada de esta edición. Nuestra junta directiva trabaja sin cesar para asegurarnos<br />
que al final de este año, VPA esté totalmente indexada y por ende logre la<br />
exposición al mundo entero.<br />
Esperamos que todos ustedes consideren contribuir con su mejor producción<br />
científica; ya sea una revisión clínica, una serie o reporte de casos interesantes,<br />
descripción de nuevas tecnologías diagnósticas, farmacológicas o<br />
quirúrgicas, o bien reportes de ciencias básicas para su publicación en VPA. Por<br />
favor, tomen un momento para revisar las instrucciones para los autores incluidas<br />
al final de esta edición y escojan a VPA como el vehículo para transmitir su<br />
trabajo a toda América.<br />
Mark J. Mannis<br />
Editor en Jefe<br />
Vision <strong>Pan</strong>-America
From the Editor<br />
With 2011, we begin a new era for Vision <strong>Pan</strong>-<br />
America (VPA). Established a decade ago as a scientific<br />
newsletter for the PAAO, our publication has<br />
grown into a small but very high quality peer-reviewed<br />
journal with a circulation larger than many <strong>of</strong> the English<br />
language subspecialty journals. With articles in<br />
English, Spanish, Portuguese and French, VPA provides<br />
a wonderful opportunity for Latin <strong>American</strong>, U.S.,<br />
Caribbean, and Canadian authors to submit their work<br />
to a broad readership. We have benefited from strong<br />
support from the <strong>Pan</strong>-<strong>American</strong> Ophthalmological<br />
Foundation, the ophthalmic industry, as well as the<br />
PAAO <strong>of</strong>fice. We have had a dedicated and pro-active<br />
Editorial Board who, themselves, have regularly contributed<br />
articles to the journal, and we have enlisted<br />
fair-minded and thoughtful reviewers who ensure that<br />
we publish quality work.<br />
We now have an ISSN number—seen for the first<br />
time on the cover <strong>of</strong> this issue. And our Board is working<br />
hard to ensure that by the end <strong>of</strong> this year, VPA<br />
will be fully indexed, opening exposure <strong>of</strong> the journal<br />
to the entire world.<br />
We hope that you will all consider contributing<br />
your best scientific work—whether it is a clinical<br />
review; case series; reports <strong>of</strong> interesting cases;<br />
descriptions <strong>of</strong> new diagnostic, pharmacologic or<br />
surgical technologies; or basic science reports—for<br />
publication in VPA. Please take a moment to look at<br />
the Instructions to Authors at the end <strong>of</strong> this issue<br />
and choose VPA as the vehicle for letting the Americas<br />
know about your work.<br />
Mark J. Mannis<br />
Editor-in-Chief<br />
Vision <strong>Pan</strong>-America<br />
Do Editor<br />
Com 2011, iniciamos uma nova era para a Vision<br />
<strong>Pan</strong>-America (VPA). Criada há uma década como um<br />
folheto científico informativo, tornou-se uma pequena<br />
revista, porém de altíssima qualidade, revisada pelos<br />
próprios pares e com maior circulação do que muitos<br />
journals publicados na língua inglesa dedicados a<br />
subespecialidades. Com artigos em Inglês, Espanhol,<br />
Português e Francês, VPA proporciona uma oportunidade<br />
maravilhosa a autores da América Latina, EUA,<br />
Caribe e Canadá de submeter seus trabalhos a um<br />
amplo público leitor. Temos nos beneficiado de grande<br />
apoio da Fundação <strong>Pan</strong>-<strong>American</strong>a de Oftalmologia,<br />
da indústria <strong>of</strong>tálmica, assim como da PAAO. Temos<br />
um Conselho Editorial dedicado e pró-ativo que<br />
tem contribuído com artigos próprios regularmente e<br />
contamos com revisores cuidadosos e justos que garantem<br />
a publicação de trabalhos de qualidade.<br />
Temos agora um número de ISSN – encontrado<br />
pela primeira vez na capa desta edição. E nosso Conselho<br />
está trabalhando para garantir que até o final<br />
deste ano, a VPA esteja totalmente indexada, ampliando<br />
a exposição da revista para todo o mundo.<br />
Esperamos que todos vocês considerem publicar<br />
seus melhores trabalhos científicos na VPA – seja ele<br />
uma revisão clínica, série de casos, relato de casos<br />
interessantes, descrição de novas tecnologias para<br />
diagnóstico, farmacologia ou cirurgia, ou pesquisas<br />
de ciências básicas.<br />
Por favor, leiam as Instruções para Autores ao final<br />
desta edição e escolham a VPA como o veículo para<br />
mostrar às Américas o seu trabalho.<br />
Mark J. Mannis<br />
Editor Chefe<br />
Vision <strong>Pan</strong>-America<br />
Marzo 2011<br />
<strong>PAN</strong>-<strong>AMERICA</strong> 3
MENSAJE DEL PRESIDENTE / MESSAGE FROM THE PRESIDENT<br />
4 <strong>PAN</strong>-<strong>AMERICA</strong><br />
Editorial<br />
Cristián Luco, MD<br />
Presidente PAAO 2009-2011<br />
Unidos en la Educación: Un mensaje del Presidente<br />
Europa unida. América desunida. Hay diferencias<br />
sociales, culturales, étnicas y económicas, pero tenemos<br />
en gran parte de nuestra región idiomas comunes,<br />
antecesores europeos comunes, creencias religiosas<br />
comunes y aún así somos desunidos. Tenemos grandes<br />
amigos, familias que vienen de igual tronco, uniones<br />
familiares, todas características que saltan las fronteras,<br />
pero seguimos desunidos.<br />
La PAAO es la unión de todos los <strong>of</strong>talmólogos desde<br />
el Polo Norte hasta el Mar de Drake. Somos la mejor<br />
sociedad <strong>of</strong>talmológica supranacional en América. Somos<br />
los <strong>of</strong>talmólogos los que estamos más unidos sin<br />
diferencias de credos, intereses comerciales, colores,<br />
etc. En nuestros congresos somos todos iguales, todos<br />
con los mismos derechos, como las Naciones Unidas<br />
de la <strong>of</strong>talmología. Los cursos y simposios son integrados<br />
por colegas de todos los países y juntos llegan a<br />
conclusiones válidas. Aunque el español, el inglés, el<br />
portugués y ahora el francés son el idioma de la PAAO,<br />
el simple sistema de tener diapositivas en inglés soluciona<br />
muchos problemas. En casos especiales se debe<br />
recurrir a traducción simultánea que es muy onerosa<br />
para los organizadores de algún evento.<br />
El idioma inglés, original de Inglaterra, derivó a Estados<br />
Unidos y a algunas islas del Caribe. Hoy día es<br />
el idioma universal de las comunicaciones científicas,<br />
así como alguna vez fue el latín y en el siglo XIX el<br />
francés. Hablamos y escribimos el inglés no por ser<br />
la lengua de dos o tres países, sino por ser la lengua<br />
franca universal. No distinguimos país alguno al usar<br />
ese idioma, sólo lo usamos como medio de comunicación<br />
global. Así, y sin sentirnos dependientes, usamos<br />
la sigla PAAO para referirnos a nuestra asociación y<br />
no confundirnos con la Asia Pacific <strong>Association</strong> <strong>of</strong><br />
Ophthalmology (APAO).<br />
Pero más allá de las formas, debemos trabajar para<br />
unir aún más a los <strong>of</strong>talmólogos de las Américas. Debemos<br />
hablar más en común, debemos hablar más de<br />
igual a igual; igual grado de conocimiento, igual grado<br />
de destreza. La destreza es un don, pero el conocimiento<br />
se puede adquirir.<br />
La educación de los residentes debe ser una preocupación<br />
fundamental de la PAAO. Los residentes son<br />
nuestro futuro. Esta frase parece muy “cliché”, pero es<br />
una obligación imperativa de los cuerpos docentes y<br />
la PAAO como entidad supranacional tiene un rol que<br />
jugar. La educación tiene información y formación. La<br />
formación depende de cada departamento docente en<br />
cada universidad en cada país y tiene características<br />
propias de cada lugar. La información no tiene fronteras<br />
ni geografía ni ideologías. La información es libre,<br />
está en el aire, no es secreta, está al alcance de todos.<br />
Solamente se debe encausar esta información en un<br />
currículo adecuado. El ICO ya está trabajando en un<br />
currículo de <strong>of</strong>talmología y la PAAO debería hacer lo<br />
mismo en paralelo. Hay algunos currículos para residentes<br />
de <strong>of</strong>talmología ya aprobados en nuestra región<br />
y sería necesario trabajar en ellos para uniformarlos.<br />
Conseguir que el “Currículo de la PAAO para residentes<br />
en <strong>of</strong>talmología” sea una información consensuada entre<br />
los departamentos de <strong>of</strong>talmología de los países de<br />
la PAAO sería un paso muy importante para igualar al<br />
menos la información entre nuestros residentes y sería<br />
el primer paso para que la enseñanza de la <strong>of</strong>talmología<br />
sea igual en toda la región.<br />
Dr. Cristián Luco<br />
Presidente, PAAO
United in Education: A Message from the President<br />
Europe united. America divided. Although there are<br />
social, cultural, ethnic, and economic differences across<br />
the Americas, in a large part <strong>of</strong> our region we share common<br />
languages, common European ancestors, and common<br />
religious beliefs. Even so, we are divided. We have<br />
great friends, families that come from the same roots,<br />
family connections, all <strong>of</strong> the characteristics that cross<br />
borders, but we continue to be divided.<br />
The PAAO represents the unification <strong>of</strong> all ophthalmologists<br />
from the North Pole to the Drake Passage. We<br />
are the finest supranational ophthalmologic society in<br />
America. We are the most united ophthalmologists despite<br />
our different creeds, commercial interests, colors,<br />
etc. In our meetings, we are all equal, each with the same<br />
rights-- the “United Nations <strong>of</strong> ophthalmology.” Within<br />
our classes and symposia, colleagues from all countries<br />
are integrated and together draw valid conclusions.<br />
Although Spanish, English, Portuguese, and now French<br />
are the languages <strong>of</strong> the PAAO, the simple system <strong>of</strong> having<br />
slides in English solves many problems. In special<br />
cases, one must resort to simultaneous translation which<br />
can be quite onerous for the organizers <strong>of</strong> an event.<br />
The English language, originating in England, was<br />
brought to the United States and some Caribbean Islands.<br />
Today it is the universal language <strong>of</strong> scientific<br />
communication, just as Latin was once, and later French<br />
in the nineteenth century. We speak and write in English<br />
not because it is the language <strong>of</strong> two or three countries,<br />
but instead because it is the universal lingua franca <strong>of</strong><br />
science. We do not distinguish any country using that<br />
language; we simply use it as a medium for global communication.<br />
And so, we use the acronym PAAO to refer<br />
to our association and to not confuse ourselves with the<br />
Asia Pacific <strong>Association</strong> <strong>of</strong> Ophthalmology (APAO) by<br />
using the Spanish acronym.<br />
But beyond form and language, we should work to<br />
further unite the ophthalmologists <strong>of</strong> the Americas. We<br />
should speak more as one, more as equal to equal with<br />
the same degree <strong>of</strong> both knowledge and skill. Skill is a<br />
gift, but knowledge must be acquired. For this reason,<br />
resident education should be a fundamental preoccupation<br />
<strong>of</strong> the PAAO. Our residents are our future. The phrase<br />
seems very much a “cliché”, but it is a necessary obligation<br />
<strong>of</strong> the teaching institutions as well as the PAAO, as a<br />
multinational entity. Education includes information and<br />
training. Training depends on every department’s faculty<br />
in every university in every country and, thus, bears the<br />
distinct characteristics <strong>of</strong> each place. Information, however,<br />
does not have borders or geography or ideology. Information<br />
is free; it is in the air; it is not secret; it is within<br />
everyone’s reach. This information can only be provided<br />
in an adequate curriculum that is relevant to all the Americas.<br />
The International Council <strong>of</strong> Ophthalmology (ICO)<br />
is already working on an ophthalmology curriculum,<br />
and the PAAO should do the same in parallel. There are<br />
curricula for ophthalmology residents already approved<br />
in our region, and it will be necessary to work to make<br />
these uniform. Fashioning the “PAAO Curriculum for<br />
Ophthalmology Residents” as a consensus among the<br />
departments <strong>of</strong> ophthalmology from the PAAO countries<br />
will be an important step to at least match the information<br />
between our residents, and it would be the first step<br />
in ensuring that the teaching <strong>of</strong> ophthalmology is uniform<br />
throughout the entire region.<br />
Cristián Luco MD<br />
PAAO President<br />
Marzo 2011<br />
<strong>PAN</strong>-<strong>AMERICA</strong> 5
REVIEW<br />
Tratamiento para linfomas intraoculares<br />
Treatment for intraocular lymphomas<br />
1, 2<br />
Dr. Gian Paolo Giuliari<br />
1 . Centro de Cirugía Oftalmológica (CECOF). Caracas-Venezuela.<br />
2 . Hospital Domingo Luciani. Departamento de Oftalmología. Caracas-Venezuela<br />
El autor no reporta ningún confl icto de interés<br />
No funding support to disclose/no proprietary or fi nancial interest to disclose<br />
Abstract<br />
Primary central nervous system lymphoma is a rare<br />
primary brain tumor, accounting for 1% to 3% <strong>of</strong> all<br />
central nervous system malignancies, which may affect<br />
the eye in up to a quarter <strong>of</strong> the cases. Failure to diagnose<br />
and treat the ocular component increases morbidity<br />
and mortality. Ninety-eight percent <strong>of</strong> the cases <strong>of</strong><br />
intraocular lymphomas are non-Hodgkin’s B-cell. They<br />
may affect both the vitreous and the retina, while secondary<br />
invasion from a nodal lymphoma usually affects<br />
the uvea. Both forms frequently masquerade as intraocular<br />
inflammation. Systemic chemotherapy, alone or<br />
in combination with radiotherapy has been used for the<br />
treatment <strong>of</strong> these malignancies. However, when ocular<br />
involvement is present, due to the limited penetration<br />
through the blood-retina barrier <strong>of</strong> most <strong>of</strong> these drugs,<br />
adjuvant therapies should be employed. Ocular radiation<br />
have been administered in the past, however, due<br />
the high rate <strong>of</strong> recurrences, as well as the commonly<br />
seen side effects prompted additional modalities <strong>of</strong><br />
treatment such intravitreal methotrexate and rituximab.<br />
Keywords: Ocular malignancy, Ocular lymphoma,<br />
Central nervous system lymphoma, reticulum cell<br />
sarcoma, Non-Hodgkin’s B cell lymphomas, Masquerade<br />
syndrome, Methotrexate and Rituximab.<br />
Resumen<br />
Los linfomas primarios del sistema nervioso central<br />
(SNC) son una causa poco común de tumores cerebrales,<br />
constituyendo sólo del 1 al 3% de todas las neoplasias<br />
del SNC, pudiendo afectar al ojo en un cuarto de<br />
los casos. La falla en el diagnóstico y el tratamiento del<br />
componente ocular incrementa la morbilidad y mortalidad<br />
de estos pacientes.<br />
En el 98% de los casos de linfoma intraocular se<br />
trata de un linfoma no Hodgkin de células B. Pueden<br />
afectar tanto el vítreo como la retina, mientras que una<br />
6 <strong>PAN</strong>-<strong>AMERICA</strong><br />
Correspondencias:<br />
Av. Francisco de Miranda, Edifi cio CAVENDES<br />
Piso 6, Ofi cina 606, Los Palos Grandes<br />
Caracas-Venezuela, 1060<br />
Email: gpgiuliari@gmail.com<br />
Teléfono: (58) (0212) 2852433<br />
Fax: (58) (0212) 2850047<br />
invasión secundaria a partir de un linfoma nodal puede afectar la úvea. Ambas formas<br />
pueden enmascararse como una inflamación intraocular. Quimioterapia sistémica,<br />
solo o en combinación con radioterapia ha sido el tratamiento de elección. Sin embargo,<br />
si existe un componente ocular, debido a la limitación en la penetración de<br />
estos medicamentos a través de la barrera hemato-retiniana, terapia co-adyuvante<br />
debe ser considerada. La radiación de los tejidos oculares ha sido empleada en el<br />
pasado, no obstante, debido a la alta tasa de recurrencias y a los frecuentes efectos<br />
secundarios se han estudiado otras opciones de tratamiento como la inyección intravítrea<br />
de metrotexate y rituximab.<br />
Palabras clave: Malignidad ocular, linfoma ocular, linfoma del sistema nervioso<br />
central, sarcoma de células reticulares, linfomas de células B no Hodgkin,<br />
síndromes de enmascaramiento, metrotexate, rituximab.<br />
Introducción<br />
Los linfomas primarios del sistema nervioso central (SNC) son una causa poco<br />
común de tumores cerebrales, constituyendo sólo del 1 al 3% de todas las neoplasias<br />
del SNC. 1-3<br />
El 98% de los linfomas primarios del SNC son linfomas no Hodgkin de células<br />
B, la mayoría de los cuales tienen su origen en un centro germinal. 4 Usualmente se<br />
desarrollan en el cerebro, médula espinal, leptomeninges o en el ojo, de donde se<br />
pueden diseminar a través de todo el SNC. 5-7<br />
Epidemiología<br />
Los linfomas primarios del SNC afectan principalmente a pacientes en la<br />
sexta y séptima década de la vida, aunque también se han reportado casos en<br />
niños. 8-9 Recientemente se ha visto una tendencia a presentarse más temprano,<br />
en especial en pacientes con deficiencias del sistema inmunológico, como es el<br />
caso de pacientes transplantados, o en pacientes con síndrome de inmunodeficiencia<br />
adquirida (SIDA). 1,10,11<br />
Manifestaciones clínicas<br />
Los linfomas primarios del SNC pueden presentarse aislados (confinados dentro<br />
de las estructuras del ojo), o presentar síntomas tanto oculares como del SNC. 12<br />
El compromiso ocular se puede presentar hasta en 1/4 de los pacientes. 12 Por este<br />
motivo, en casos de linfomas intraoculares se debe llevar a cabo una búsqueda extensa<br />
de un posible compromiso del SNC, en un esfuerzo de reducir la morbilidad y<br />
mortalidad asociada en estos pacientes. 13,14
En casos en los que hay compromiso ocular, las<br />
manifestaciones clínicas varían dependiendo del punto<br />
de infiltración de las células linfoides. Las estructuras<br />
mayormente afectadas son el vítreo, la retina, el espacio<br />
debajo del epitelio pigmentario y la cabeza del nervio<br />
óptico. Cuando la retina es afectada, generalmente pueden<br />
presentarse infiltrados amarillo-cremoso subretinales<br />
los cuales pueden producir desprendimientos<br />
localizados del epitelio pigmentario. 4 (Figura 1)<br />
Cuando el linfoma intraocular es consecuencia de<br />
una invasión secundaria a partir de un centro nodal,<br />
generalmente la estructura mayormente afectada es<br />
la úvea. En estos pacientes, además de los síntomas<br />
oculares, generalmente se presentan con una afectación<br />
sistémica, con cuadros febriles, linfoadenopatías y<br />
pérdida de peso, lo cual facilita el diagnóstico. 1-3<br />
Los síntomas intraoculares más comúnmente asociados<br />
con linfomas intraoculares son la disminución<br />
de la agudeza visual y la presencia de flotadores, los<br />
cuales son secundarios al compromiso del vítreo. 7,16,-17<br />
Diagnóstico<br />
Para poder hacer el diagnóstico de linfoma intraocular<br />
o del SNC lo más importante es tenerlo presente<br />
dentro del grupo de diagnósticos diferenciales. El uso de<br />
estudios ancilares como la ultransonografía, en los que<br />
se puede observar engrosamiento coroido-escleral con<br />
abundante debris en el vítreo (Figura 2), al igual que puntos<br />
hiperfluorescentes en defectos de ventana, vasculitis<br />
y edema macular cistoideo en la angiografía con fluoresceína<br />
pueden facilitar el diagnóstico. 18,19 (Figura 3)<br />
El diagnóstico definitivo requiere la identificación<br />
directa de las células malignas provenientes de fluidos<br />
y/o tejidos del ojo o del SNC. Estas células usualmente<br />
se presentan como células grandes y pleomórficas con<br />
hiperpigmentación del núcleo con nucleolos prominentes<br />
(Figura 4). La visualización de las células malignas<br />
se puede realizar principalmente mediante: (1) una<br />
punción lumbar con la extracción del fluido cerebroespinal;<br />
(2) una biopsia cerebral; y (3) una biopsia del<br />
vítreo mediante una vitrectomía. 20,21<br />
A su vez, diferentes métodos y técnicas se han desarrollado<br />
para facilitar el diagnóstico. Uno de ellos es<br />
la determinación de los niveles vítreos de interleuquina<br />
10 (IL-10) e interleuquina 6 (IL-6). 22 Se ha encontrado<br />
que en pacientes con inflamación ocular de origen<br />
linfoide existe un incremento en el ratio de IL-10:IL-6,<br />
mientras que en otras enfermedades inflamatorias hay<br />
un incremento de la IL-6. No obstante, se han encontrado<br />
niveles elevados de IL-10 en pacientes con uveítis<br />
no neoplásicas. 23 Otro método recientemente utilizado<br />
es el uso de re-arreglo genético de la cadena pesada de<br />
inmunoglobulinas (IgH). Generalmente los linfomas de<br />
Marzo 2011<br />
Figura 1. Montaje de fondo ocular en el cual se aprecian infi ltrados amarillocremoso<br />
subretinales secundario a la infi ltración de las células linfoides. (Cortesía<br />
del Massachusetts Eye Research and Surgery Institution)<br />
células B se presentan con un re-arreglo monoclonal de la IgH, pudiendo estar o no<br />
acompañados de un re-arreglo de la cadena liviana. Técnicas de análisis de Southern<br />
Blotting o por reacción de reacción en cadena de polimerasa (PCR) han mostrado<br />
beneficios en el diagnóstico. 24<br />
Tratamiento y pronóstico<br />
La quimioterapia sistémica con o sin radioterapia asociada ha sido el tratamiento<br />
de elección para los linfomas del SNC. La radiación cerebral con 50 gray (Gy), con un<br />
incremento de 10-Gy sobre la localización del tumor, ha mostrado índices de hasta un<br />
90% de éxito en el tratamiento de linfomas no Hodgkin extranodales. 25 Sin embargo,<br />
estudios recientes en el tratamiento de linfomas primarios del SNC han demostrado<br />
que la radiación como terapia única para el tratamiento de estos tumores, no sólo<br />
presenta un índice bajo de cura, sino una tasa alta de recurrencias, y una tasa alta de<br />
mortalidad en los primeros 5 años del diagnóstico; por lo que su uso en este tipo de<br />
neoplasias ha disminuido, principalmente en pacientes inmunocompetentes. 26,27<br />
El uso de protocolos con ciclosfosfamida, doxorubicin, vincristine y prednisona<br />
oral, no han demostrado un beneficio significativo con respecto al uso exclusivo de<br />
radioterapia. 28-30 Esto se debe principalmente a la dificultad de la mayoría de estos<br />
agentes de penetrar adecuadamente la barrera hemato-cerebral. Por esta razón, combinaciones<br />
entre medicamentos sistémicos y locales son necesarias para obtener<br />
remisión de la enfermedad.<br />
La radiación orbital con 30-Gy ha sido un tratamiento efectivo en el manejo de<br />
pacientes con compromiso intraocular. No obstante, pueden presentarse con significativos<br />
efectos secundarios, como retinopatía secundaria a la radiación, cataratas,<br />
neuropatía óptica y síndrome de ojo seco, además que si la enfermedad ocular recurre,<br />
no se puede repetir la radiación. 2,3,31<br />
<strong>PAN</strong>-<strong>AMERICA</strong> 7
REVIEW<br />
8 <strong>PAN</strong>-<strong>AMERICA</strong><br />
Debido a estas limitantes en el tratamiento con radiación<br />
orbital, nuevos esfuerzos han sido empleados,<br />
con el uso de agentes quimioterapéuticos. 32,33<br />
Varios estudios han demostrado la eficacia y seguridad<br />
de inyecciones intravítreas de metrotexate en el<br />
tratamiento de neoplasias linfoides intraoculares. 33,34<br />
Estos reportes, han demostrado una dramática<br />
desaparición de las células malignas del vítreo de estos<br />
pacientes luego de repetidas administraciones; en<br />
muchos casos correlacionados con una disminución<br />
de los niveles altos iniciales de IL-10. Smith y colaboradores<br />
33 describieron un protocolo para estos pacientes<br />
en los que se administra una fase de inducción<br />
con inyecciones de metrotexate intravítreo bisemanal<br />
por un periodo de un mes con dosis de 400 μg en 0.1<br />
ml. Subsecuentemente hay una fase de mantenimiento<br />
en la que se administran inyecciones mensuales<br />
por un año. Dentro de las complicaciones más frecuentemente<br />
encontradas en pacientes tratados con<br />
metrotexate intravítreo se encuentran el desarrollo de<br />
cataratas en más del 70% de los casos y el desarrollo<br />
de una epiteliopatía corneal en el 58%, la cual se resuelve<br />
luego de alargar los intervalos de tratamiento. 33<br />
Hemorragia vítrea, maculopatía y end<strong>of</strong>talmitis estéril<br />
son complicaciones menos frecuentes. 33-35<br />
Otro medicamento recientemente utilizado de manera<br />
local para el tratamiento de los linfomas con compromiso<br />
intraocular es el rituximab, un anticuerpo monoclonal<br />
quimérico ratón/humano dirigido contra las<br />
células B CD20 positivas, lo cual lo hace muy eficiente<br />
como tratamiento para estos linfomas, debido a que la<br />
gran mayoría de los linfomas primarios del SNC son<br />
linfomas no Hodgkin de células B que expresan tanto<br />
CD19 como CD20. 4,36-41<br />
El rituximab tiene una penetración limitada a través<br />
de las barreras hemato-cerebral y hemato-retinianas,<br />
con lo que se previene el acceso de anticuerpos<br />
al SNC y al ojo. 42 Reportes de casos sugieren<br />
que el uso de rituximab intratecal e intraocular en el<br />
tratamiento de linfomas del SNC con compromiso<br />
ocular es seguro y efectivo. 43-45<br />
A pesar que la mayoría de estos pacientes presentan<br />
una buena respuesta al tratamiento inicial, las<br />
recurrencias son frecuentes. La sobrevida de pacientes<br />
con linfoma intraocular fue calculada en 26 meses por<br />
Freeman y colaboradores, 16 mientras que para aquellos<br />
pacientes con compromiso del SNC es solo de 13.5<br />
meses. 12 Char y colaboradores demostraron que la terapia<br />
agresiva con la combinación de quimioterapia intratecal<br />
asociada con radioterapia de la órbita y el cerebro<br />
pueden mejorar la sobrevida de estos pacientes. 13 El<br />
tratamiento del componente ocular, aunque es de vital<br />
importancia para el manejo de estos pacientes, no mejora<br />
la sobrevida final. 46<br />
Figura 2. Ultransonografía de un paciente con linfoma<br />
intraocular de células B no Hodgkin que muestra<br />
engrosamiento coroido-escleral con abundante<br />
debris en el vítreo (Cortesía del Massachusetts Eye<br />
Research and Surgery Institution)<br />
Figura 3. Angiografía de la retina con fl uoresceína<br />
en fase tardía, en un paciente con linfoma intraocular<br />
mostrando múltiples puntos hiperfl uorescentes<br />
en defectos de ventana. (Cortesía del Massachusetts<br />
Eye Research and Surgery Institution)<br />
Figura 4. Espécimen vítreo citocentrifugado que<br />
muestra las células pleomórfi cas con tinción para<br />
el marcador CD20 de células B. (Cortesía del<br />
Massachusetts Eye Research and Surgery Institution)
Conclusiones<br />
Los linfomas primarios del SNC son un tipo de<br />
neoplasia insidiosa, agresiva y poco común que<br />
puede presentarse en muchos casos como procesos<br />
inflamatorios intraoculares. En la mayoría de los casos<br />
son linfomas no Hodgkin de células B, pudiendo<br />
comprometer al ojo hasta en 1/4 de los pacientes. 12<br />
El retraso en el diagnóstico y tratamiento precoz del<br />
componente intraocular incrementa la morbilidad y<br />
mortalidad de estos pacientes.<br />
Las estructuras oculares más frecuentemente<br />
afectadas son el vítreo, la retina, el espacio debajo del<br />
epitelio pigmentario y la cabeza del nervio óptico. Los<br />
síntomas oculares y las manifestaciones clínicas dependerán<br />
de cuales son las estructuras afectadas. 1-3<br />
El uso de agentes quimioterapéuticos como terapia<br />
única, o en combinación con radiación, han<br />
sido empleados comúnmente en el tratamiento de los<br />
linfomas del SNC. Sin embargo, si hay evidencia de<br />
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<strong>PAN</strong>-<strong>AMERICA</strong> 9
REVIEW<br />
New Vital Dyes to Stain Intraocular<br />
Membranes and Tissues during Vitrectomy<br />
Authors: Mauricio Maia MD PhD; Eduardo B. Rodrigues MD;<br />
Michel Eid Farah MD PhD; André Maia MD; Acácio Lima PhD;<br />
Octaviano Magalhães Jr MD; Eduardo Dib MD<br />
Vision Institute, Department <strong>of</strong> Ophthalmology, Federal University <strong>of</strong> São Paulo, São Paulo, Brazil<br />
ACKNOWLEDGMENTS /DISCLOSURE:<br />
Funding / Support:<br />
- Fundação de Amparo a Pesquisa do Estado de Sao Paulo – FAPESP<br />
- <strong>Pan</strong>-<strong>American</strong> <strong>Association</strong> <strong>of</strong> Ophthalmology (PAAO)/<strong>Pan</strong>-<strong>American</strong> Ophthalmological Foundation (PAOF)<br />
Abstract<br />
Purpose: To present the current state-<strong>of</strong>-the-art information<br />
regarding the properties, indications, surgical<br />
techniques, and toxic effects <strong>of</strong> current and past applications<br />
<strong>of</strong> vital dyes in chromovitrectomy.<br />
Design: Critical analysis and surgical perspective <strong>of</strong><br />
the literature, recent studies and personal contributions.<br />
Methods: Review, interpretation, and comments<br />
regarding the most relevant experimental as well as<br />
clinical studies including the authors’ clinical and laboratory<br />
research.<br />
Results: The evolution <strong>of</strong> vitreoretinal surgical techniques<br />
has been worldwide reported. Chromovitrectomy<br />
plays an important hole in these innovations and<br />
is very useful to improve the surgical results. There is<br />
a consensus that application <strong>of</strong> vital dyes facilitates the<br />
delicate removal <strong>of</strong> intraocular membranes during vitreoretinal<br />
surgery. Controversy still remains around various<br />
issues, mainly potential toxicity and safety. The dyes<br />
currently used for different steps in chromovitrectomy<br />
are: triamcinolone acetonide for vitreous identification;<br />
indocyanine green, infracyanine green, and brilliant<br />
blue for internal limiting membrane identification and<br />
trypan blue for epiretinal membrane identification. The<br />
indocyanine green may be toxic for the retinal pigment<br />
epithelium if subretinal migration occurs during the<br />
surgical procedure. Efforts to avoid subretinal migration<br />
<strong>of</strong> dyes are very important during macular hole surgery.<br />
The physiological osmolarity around 270-320mOsm as<br />
well as ideal concentrations <strong>of</strong> the vital dyes during vitreoretinal<br />
surgery are important subjects.<br />
Conclusions: The state-<strong>of</strong>-the-art staining-assisted<br />
procedures should be performed using concentrations<br />
and volumes as low as possible. Triamcinolone acetonide<br />
is the ideal dye for vitreous; indocyanine green,<br />
infracyanine green and brilliant blue are the ideal dyes<br />
for internal limiting membrane; trypan blue is the ideal<br />
dye for epiretinal membrane identification.<br />
10 <strong>PAN</strong>-<strong>AMERICA</strong><br />
Introduction<br />
Correspondence:<br />
Mauricio Maia MD PhD<br />
901 Otto Ribeiro<br />
Assis, SP Brazil 19800-320<br />
Email: retina@femanet.com.br<br />
Dyes may be designated “vital” when they are used to stain living tissues or cells.<br />
In ophthalmology, vital dyes have become very effective and useful surgical tools<br />
for ocular tissues identification. One especial surgical technique has been recently<br />
named chromovitrectomy, which concerns the use <strong>of</strong> vital dyes or crystals to improve<br />
the visualization <strong>of</strong> intraocular tissues during vitrectomy, thereby improving specific<br />
procedures such as internal limiting membrane (ILM) peeling. 1-10<br />
Chromovitrectomy – principles<br />
Chromovitrectomy has been introduced with the goal <strong>of</strong> avoiding ocular complications<br />
related to ILM peeling, poor removal <strong>of</strong> the vitreous and incomplete removal<br />
<strong>of</strong> the ERM. Since 2000, chromovitrectomy has become a popular approach among<br />
vitreoretinal specialists. 9<br />
Dyes have a variety <strong>of</strong> different chemical structures, which include a moiety responsible<br />
for the color, the so-called chromophore. 1-10 Although highly important in organic chemistry,<br />
Figure 1 - Intraoperative view from the posterior hyaloid detachment<br />
assisted by triamcinolone, showing that posterior hyaloid is detached<br />
from the optic nerve in a diabetic retinopathy eye.
the identification <strong>of</strong> chromophores in vital dyes relevant to<br />
chromovitrectomy has not been well studied yet. Such field<br />
<strong>of</strong> research is important because the chromophore could<br />
be separated from other parts <strong>of</strong> the molecule resulting in a<br />
safer vital dye for the retina. 1-10<br />
Triamcinolone acetonide<br />
The state-<strong>of</strong>-the-art staining agent for identification<br />
<strong>of</strong> the vitreous is the white steroid triamcinolone acetonide.<br />
2 Its crystals bind avidly to the vitreous gel and thereby<br />
enable the visualization <strong>of</strong> a clear contrast between the<br />
empty vitreous cavities (without vitreous) in comparison to<br />
areas where the vitreous fibers are still present. The surgical<br />
technique reported so far for triamcinolone acetonide application<br />
consists in a simple injection <strong>of</strong> 0.1-0.3 ml <strong>of</strong> the<br />
agent at a concentration <strong>of</strong> 40 mg/ml (4%) into the vitreous<br />
cavity directed toward the area to be visualized. In addition,<br />
this steroid injection during vitrectomy, for management<br />
<strong>of</strong> retinal detachment may prevent fibrin reaction and PVR<br />
postoperatively. 15 The steroid improves identification <strong>of</strong> the<br />
tissues by deposition <strong>of</strong> crystals, and this effect helps the<br />
achievement <strong>of</strong> a complete detachment and removal <strong>of</strong> the<br />
posterior hyaloid, improving the results <strong>of</strong> primary vitrectomy<br />
for retinal detachment management and also for diabetic<br />
retinopathy in young patients (Figure 1). 16,17<br />
The main side effects following 12 months <strong>of</strong> intraocular<br />
injection <strong>of</strong> 4mg <strong>of</strong> triamcinolone acetonide are: cataract<br />
around 30-40% <strong>of</strong> eyes and increase <strong>of</strong> intraocular pressure<br />
in 20-30% <strong>of</strong> eyes. 16 Cataract is more prevalent following<br />
12 months follow up and increase <strong>of</strong> intraocular pressure<br />
after 2-3 months follow-up. 16 However, it is supposed that<br />
these findings may be not true following its use at the intraoperative<br />
period because the steroid is removed from the<br />
Marzo 2010<br />
vitreous cavity at the end <strong>of</strong> chromovitrectomy and minimal amounts <strong>of</strong> the drug may be left<br />
at the vitreous cavity following this technique. 36 There is controversy regarding the possible<br />
decrease <strong>of</strong> macular hole closure rates following intraoperative triamcinolone use. 36<br />
Indocyanine green and infracyanine green<br />
ICG and infracyanine green may be considered the gold standard dyes for staining and<br />
visualizing the ILM by the majority <strong>of</strong> vitreoretinal surgeons worldwide for surgical therapy<br />
<strong>of</strong> MH, DME and even ERM. ICG may possess a great affinity for the matrix components<br />
<strong>of</strong> the ILM such as collagen type 4 or laminin. 2,18 ICG-guided chromovitrectomy initially<br />
gained worldwide popularity, and a large number <strong>of</strong> studies showed easier and less traumatic<br />
ICG-guided peeling with good clinical results in MH surgery. However, subsequent<br />
studies revealed the risk <strong>of</strong> ICG toxicity to the retina. For instance, clinical data showed that<br />
ICG could remain intravitreally or deposit persistently on the optic disc after MH surgery,<br />
or ICG could also diffuse to the subretinal space through the MH causing retinal pigment<br />
19, 20<br />
epithelium (RPE) damage (Figure 2).<br />
It has been postulated that the use <strong>of</strong> ICG at low concentrations in ILM peeling could be<br />
a safer alternative, since lower rates <strong>of</strong> RPE abnormalities have been observed with ICG at a<br />
concentration <strong>of</strong> 0.5mg/ml (0.05%) or less and osmolarity <strong>of</strong> around 290 mOsm. 21<br />
Infracyanine green is a dye that contains no iodine in its formulation either as free ion<br />
or as part <strong>of</strong> the dye moiety 2 . For this reason, infracyanine green is believed to have less<br />
potential for RPE toxicity, since iodine and its derivates may be toxic to the RPE. 14<br />
In summary, the presumed safer infracyanine green pr<strong>of</strong>ile may represent an alternative<br />
for ICG use during ILM peeling in chromovitrectomy due to the lack <strong>of</strong> sodium iodine in its<br />
formulation and physiological osmolarity. 2,14<br />
Indocyanine green toxicity<br />
Figure 2 - Aut<strong>of</strong>l uorescence<br />
and OCT images<br />
before macular hole<br />
surgery (upper left and<br />
lower left) and aut<strong>of</strong>l uorescence<br />
as well as OCT<br />
images after macular hole<br />
surgery and ILM peeling<br />
guided by 0.05% ICG<br />
staining (upper right and<br />
lower right). Note the<br />
absence <strong>of</strong> hyperaut<strong>of</strong>l<br />
uorescence image after<br />
surgery (upper right) and<br />
also the sealed hole by<br />
OCT (lower right). BCVA<br />
improved from 20/400<br />
(upper left and lower left)<br />
to 20/30 (upper right and<br />
lower right).<br />
The publications on retinal damage induced by ICG involve various hypotheses, and<br />
they may be divided in the following manner:<br />
Osmolarity <strong>of</strong> ICG solutions: Intravitreal ICG injections may change the osmolarity<br />
in the vitreous cavity, thereby damaging either the neurosensory retina or the<br />
RPE cells directly. 14,22,23,24<br />
<strong>PAN</strong>-<strong>AMERICA</strong> 11
REVIEW<br />
Figure 3 – Fundus phototographs after subretinal<br />
indocyanine green and trypan blue injection in rabbits.<br />
Source: Penha FM, Maia M, Eid Farah M et al.<br />
Effects <strong>of</strong> subretinal injections <strong>of</strong> indocyanine green,<br />
trypan blue, and glucose in rabbit eyes. Ophthalmology<br />
2007;114:899-908.<br />
Fundus photograph 1 hour after subretinal injection <strong>of</strong><br />
0.5% ICG using a 41-gauge cannula (upper left) (arrow<br />
and arrowhead). Fluorescein angiogram (upper<br />
right) 1 week after subretinal ICG injection (arrow) and<br />
subretinal BSS injection (arrowhead), showing atrophic<br />
changes in positions related to previous subretinal<br />
injection <strong>of</strong> ICG (arrow)<br />
Fundus photograph 1 hour after subretinal ICG and TB<br />
injection (middle left); Fluorescein angiogram shows a<br />
more substantial damage <strong>of</strong> RPE in positions related to<br />
previous subretinal ICG(arrow) (middle right) compared<br />
to subretinal TB (arrowhead). (middle right)<br />
Fundus photograph 1 week after subretinal ICG (arrow)<br />
and TB (arrowhead) injection (down left); Fluorescein<br />
angiogram shows a more substantial damage <strong>of</strong> RPE<br />
in positions related to previous subretinal ICG (arrow)<br />
(lower right), compared to subretinal TB (arrowhead)<br />
(lower right).<br />
Figure 4 - Surgical techniques <strong>of</strong> internal limiting membrane (ILM) peeling<br />
ILM peeling guided by ICG staining in macular hole surgery (upper left)<br />
ILM peeling guided by brilliant blue staining in a macular hole surgery (upper right)<br />
Technique <strong>of</strong> “double staining” using brilliant blue and triamcinolone acetonide injected<br />
over the retinal surface using a s<strong>of</strong>t tip cannula while the BSS infusion remained closed<br />
(lower left)<br />
ILM peeling guided by double staining technique after epiretinal membrane removal.<br />
Staining was performed with 0.2 ml <strong>of</strong> 40 mg/ml triamcinolone along with 0.2 ml <strong>of</strong><br />
0.25% brilliant blue (lower right)<br />
12 <strong>PAN</strong>-<strong>AMERICA</strong><br />
ICG molecule: Several investigations in various animal models have shown that<br />
ICG may be hazardous to the RPE or neuroretinal cells. Experiments showed that moderate<br />
to high doses (2.5 to 25 mg/ml or 0.25 to 2.5%) <strong>of</strong> intravitreal ICG are toxic<br />
to retinochoroidal cells, and impairment <strong>of</strong> retinal function was described even at low<br />
doses <strong>of</strong> ICG (0.025 mg/ml or 0.25%). (Figure 3). 24,25,26<br />
Ions: ICG molecule has around 5% iodine in its final solution and no sodium or<br />
calcium. 2,14,34 Nevertheless, it is suggested that removal <strong>of</strong> sodium from the saline<br />
solution used for diluting the dye may decrease the risk <strong>of</strong> RPE damage. 27<br />
ICG-potentiated light toxicity: It has been speculated that ICG injection into<br />
the vitreous cavity may absorb light and that this interaction may lead to photodynamic<br />
effect thereby inducing retinal damage. It was demonstrated that subretinal<br />
ICG injection plus light exposure in rabbits may result in functional retinal damage<br />
and RPE changes. 2,20,26,34<br />
Decomposition products <strong>of</strong> ICG solution: Once diluted in any solvent and<br />
exposed to light, ICG may undergo various chemical reactions by self-sensitized<br />
oxidation since it is chemically unstable; such phenomena may be also called<br />
decomposition. 29 It was demonstrated that independently <strong>of</strong> the light exposure,<br />
singlet oxygen (photodynamic type 2 reaction) is generated by ICG leading to<br />
dioxetanes by cycloaddition <strong>of</strong> singlet oxygen. 29 Furthermore, dioxetanes thermally<br />
decompose into several carbonyl compounds; the decomposition <strong>of</strong> ICG<br />
was blocked by sodium azide, a quencher <strong>of</strong> singlet oxygen. This supports the<br />
rationale for future use <strong>of</strong> quenchers in chromovitrectomy. 29<br />
Recently, it was reported that ICG may cause hipotony in 11% <strong>of</strong> eyes submitted to<br />
epiretinal membrane peeling and no fluid-air exchange; however, the intraocular pressure<br />
was normal in eyes that fluid-air exchange was used; the authors hypothesized that ICG in<br />
contact with the ciliar body may result in hipotony and suggest caution because postoperative<br />
ocular hypotony may occur in some cases <strong>of</strong> ICG-assisted macular surgery.<br />
Brilliant blue, trypan blue and patent blue<br />
In humans, brilliant blue caused adequate ILM staining in an iso-osmolar solution<br />
<strong>of</strong> 0.25 mg/ml (0.025%) with good clinical results and no signs <strong>of</strong> toxicity in multifocal<br />
ERG 2 . In brief, brilliant blue has become a good option for ICG and infracyanine<br />
green in chromovitrectomy due to its remarkable affinity for the ILM, although limited<br />
toxicity data in its application still warrant further investigations for confirmation <strong>of</strong><br />
these observations; however, we have recently demonstrated that subretinal migration
Figure 5 - Surgical techniques <strong>of</strong> epiretinal membrane<br />
(ERM) peeling<br />
ERM peeling using no dyes (upper left)<br />
ERM peeling using 0.2ml <strong>of</strong> 40 mg/ml triancinolone<br />
acetonide (upper right)<br />
ERM peeling using trypan blue (TB) (lower left)<br />
ERM peeling using TA and TB, called the “doublestaining”<br />
technique. Staining was performed with 0.2<br />
ml <strong>of</strong> 40 mg/ml triamcinolone along with 0.2 ml <strong>of</strong><br />
0.05% trypan blue (lower right).<br />
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21. Rodrigues EB, Meyer CH. Metaanalysis<br />
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24. Penha FM, Maia M, Eid Farah M,<br />
et al. Effects <strong>of</strong> subretinal injections <strong>of</strong><br />
indocyanine green, trypan blue, and<br />
glucose in rabbit eyes. Ophthalmology<br />
2007;114:899-908.<br />
25. Enaida H, Sakamoto T, Hisatomi T,<br />
Goto Y, Ishibashi T. Morphological and<br />
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26. Maia M, Kellner L, de Juan E Jr,<br />
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2004;24:80-91.<br />
27. Ho JD, Chen HC, Chen SN, Tsai<br />
RJ. Reduction <strong>of</strong> indocyanine greenassociated<br />
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28. Kadonosono K, Takeuchi S, Yabuki<br />
K, et al. Absorption <strong>of</strong> short wavelengths<br />
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29. Engel E, Schraml R, Maisch T, et<br />
al. Light-induced decomposition <strong>of</strong><br />
indocyanine green.Invest Ophthalmol<br />
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30. Koto T, Inoue M, Shinoda K, Ishida<br />
S, Tsubota K. Residual crystals <strong>of</strong> triamcinolone<br />
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Ophthalmol Scand 2007;85:913-4.<br />
31. Maia M, Penha FM, Farah ME, et<br />
al. Subretinal injection <strong>of</strong> preservativefree<br />
triamcinolone acetonide and supernatant<br />
vehicle in rabbits: an electron<br />
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32. Uno F, Malerbi F, Maia M, Farah<br />
ME, Maia A, Magalhães O Jr. Subretinal<br />
trypan blue migration during<br />
Marzo 2010<br />
<strong>of</strong> the dye may cause RPE atrophic changes and therefore, we strongly suggest avoidance<br />
<strong>of</strong> brilliant blue exposure to the RPE during chromovitrectomy. 35<br />
TB may not enable ILM visualization as well as ICG, but this blue dye remains an alternative<br />
dye for this purpose. 2 In order to enhance the TB staining property, this blue dye may<br />
be injected into the posterior pole after fluid air exchange or it may be mixed with glucose<br />
at 5 to 10% to thereby create a “heavy TB”, which is denser than BSS. 2,33 However, higher<br />
glucose concentrations should be avoided because glucose 50% has a highly toxic osmolarity<br />
<strong>of</strong> 2020 mOsm/L and should be avoided.2 In summary, current state-<strong>of</strong>-the-art TB<br />
usage recommends blue-dye application mainly for ERM-staining. 2,33 (Figure 5). For this<br />
reason, it has an affinity for epiretinal glial tissues such as the ERM, and therefore, we consider<br />
TB the best dye for staining the ERM. It is suggested to mix 0.3 ml <strong>of</strong> TB with 0.1 ml<br />
<strong>of</strong> glucose 10%, resulting in a 1 mg/ml (0.1%) solution and osmolarity <strong>of</strong> 300mOsm. 2,32,33<br />
Additionally, many authors have been reported the safety <strong>of</strong> trypan blue dye in prospective<br />
chromovitrectomy studies either for ERM or ILM peeling. 38,39<br />
Double staining technique<br />
The double-staining technique (Figures 4 and 5) is an elegant procedure that<br />
may facilitate the identification <strong>of</strong> the posterior hyaloid and epiretinal membrane as<br />
well as the posterior hyaloid and ILM. In this technique, the initial step consists in the<br />
injection <strong>of</strong> a dye with high affinity to the vitreous to enable vitreous removal, followed<br />
by a second injection <strong>of</strong> a dye such as infracyanine green, ICG, TB or brilliant blue to<br />
stain and peel pre-retinal membranes. 2 As an alternative technique, two dyes may be<br />
injected initially before both peeling procedures.<br />
epiretinal membrane peeling. Retina.<br />
2006 Feb;26(2):237-9.<br />
33. Maia M, Penha F, Rodrigues EB,<br />
et al. Effects <strong>of</strong> subretinal injection <strong>of</strong><br />
patent blue and trypan blue in rabbits.<br />
Curr Eye Res. 2007 Apr;32(4):309-17.<br />
34. Costa E, Rodrigues EB, Farah ME,<br />
et al. Vital dyes and light sources for<br />
chromovitrectomy: comparative assessment<br />
<strong>of</strong> osmolarity, pH, and spectrophotometry.<br />
Invest Ophthalmol Vis<br />
Sci. 2009 Jan;50(1):385-91. Epub<br />
2008 Aug 8.<br />
35. Maia M; Farah ME; Rodrigues EB;<br />
Malerbi F. Subretinal brilliant blue<br />
G migration during internal limiting<br />
membrane peeling. British Journal <strong>of</strong><br />
Ophthalmology, v.93, p.330-331, 2009<br />
36. Farah ME, Maia M, Rodrigues.<br />
Dyes in ocular surgery: principles for<br />
use in chromovitrectomy. Am J Ophthalmol.<br />
2009;148(3):332-40<br />
37. Iwase T, Jo YJ, Tanaka N. Ocular<br />
hypotony after the use <strong>of</strong> indocyanine<br />
green for epiretinal membrane surgery.Cutan<br />
Ocul Toxicol. 2010<br />
Jun;29(2):130-6.<br />
38. Mackenzie SE, Gandorfer<br />
A, Rohleder M, Schumann R, et<br />
al.Ultrastructure and retinal imaging<br />
<strong>of</strong> internal limiting membrane: a clinicopathologic<br />
correlation <strong>of</strong> trypan blue<br />
stain in macular hole surgery. Retina.<br />
2010 Apr;30(4):655-61.<br />
39. Mackenzie SE, Gandorfer<br />
A, Rohleder M, Schumann R, et<br />
al.Ultrastructure and retinal imaging <strong>of</strong><br />
epiretinal membrane: a clinicopathologic<br />
correlation <strong>of</strong> trypan blue staining<br />
in epiretinal membrane surgery.Retina.<br />
2010 Apr;30(4):648-54<br />
<strong>PAN</strong>-<strong>AMERICA</strong> 13
CLINICAL SCIENCES<br />
Ozurdex ® , a Novel Dexamethasone Delivery<br />
System, for Treatment <strong>of</strong> Macular Edema<br />
Following Retinal Vein Occlusion<br />
Rubens Belfort Jr. MD PhD 1 ; Cristina Muccioli MD 1 ;<br />
Susan S Lee MS 2 ; Michael R. Robinson MD 2<br />
1 Deptartment <strong>of</strong> Ophthalmology, Paulista School <strong>of</strong> Medicine, Federal University <strong>of</strong> São Paulo, São Paulo, Brazil<br />
2 Department <strong>of</strong> Ophthalmic Clinical Research, Allergan, Inc.; Irvine, CA, USA<br />
Financial disclosures: Drs. Rubens Belfort and Cristina Muccioli are consultants<br />
to and have received research funding from Allergan, Inc. Mrs. Susan S. Lee and<br />
Dr. Michael R. Robinson are employees <strong>of</strong> Allergan, Inc.<br />
14 <strong>PAN</strong>-<strong>AMERICA</strong><br />
Resumen<br />
El tratamiento efectivo del edema macular representa<br />
un desafío principalmente debido a la limitada<br />
accesibilidad de fármaco vítreo para establecer y mantener<br />
niveles terapéuticos a largo plazo. El implante<br />
intravítreo de dexametasona (implante DEX; Ozurdex ® )<br />
es actualmente el único sistema de aplicación de fármaco<br />
ocular biodegradable aprobado por la Administración<br />
de Alimentos y Medicamentos de EE.UU. que<br />
proporciona liberación del fármaco a una tasa estable<br />
por hasta 6 meses en el vítreo. Estudios clínicos recientes<br />
indican que el implante DEX emerge como una<br />
opción terapéutica efectiva y segura para el tratamiento<br />
de edema macular secundario a diversas enfermedades<br />
subyacentes.<br />
Abstract<br />
Effective treatment <strong>of</strong> macular edema is challenging<br />
primarily because <strong>of</strong> the limited vitreous drug accessibility<br />
to establish and maintain long-term therapeutic<br />
levels. Dexamethasone intravitreal implant (DEX implant;<br />
Ozurdex®) is currently the only biodegradable<br />
ocular drug delivery system approved by the US Food<br />
and Drug Administration that provides sustained drug<br />
release at a stable rate for up to 6 months in the vitreous.<br />
Recent clinical studies indicate that DEX implant<br />
is emerging as an effective and safe therapeutic option<br />
for treatment <strong>of</strong> macular edema secondary to a variety<br />
<strong>of</strong> underlying diseases.<br />
Introduction<br />
Retinal vein occlusion is the second most common<br />
retinal vascular disease after diabetic retinopathy. In<br />
branch retinal vein occlusion (BRVO), the occlusion is<br />
typically at an arteriovenous intersection while in central<br />
retinal vein occlusion (CRVO), the occlusion is at or<br />
Address for Correspondence:<br />
Rubens Belfort Jr. MD PhD<br />
Department <strong>of</strong> Ophthalmology<br />
Federal University <strong>of</strong> Sao Paulo<br />
Rua Botucatu 822<br />
Sao Paulo, SP 04023-062, Brazil<br />
Phone: (55-11) 5085-2010<br />
Fax: (55-11) 5573-4002<br />
Email: clinbelf@uol.com.br<br />
proximal to the lamina cribrosa <strong>of</strong> the optic nerve, where<br />
the central retinal vein exits the eye. 1,2 As with diabetic<br />
retinopathy and uveitis involving the posterior segment,<br />
BRVO and CRVO are associated with macular edema,<br />
which is the primary cause <strong>of</strong> vision loss. 3-5 Macular<br />
edema is characterized by swelling <strong>of</strong> the macula due to<br />
breakdown <strong>of</strong> the blood–retinal barrier through a pathological<br />
process involving inflammatory cells, intercellular<br />
adhesion molecules, cytokines, and growth factors<br />
such as vascular endothelial growth factor (VEGF). 6-11<br />
Current strategies for the management <strong>of</strong> macular<br />
edema secondary to BRVO and CRVO are laser photocoagulation,<br />
vitrectomy, and pharmacotherapy with<br />
anti-VEGF agents and corticosteroids. 1,2 Laser therapy<br />
is the standard <strong>of</strong> care for treatment <strong>of</strong> macular edema<br />
secondary to BRVO and CRVO. Although laser therapy<br />
decreases macular edema, the improvements in visual<br />
acuity are either marginal and occurring slow (in BRVO<br />
patients) or absent (in CRVO patients). 12,13 Retrospective<br />
studies report that pars plana vitrectomy with internal<br />
limiting membrane peeling may improve visual acuity,<br />
warranting large scale, controlled clinical studies to establish<br />
the efficacy and safety. 14,15 Recently introduced<br />
anti-VEGF agents significantly improve visual acuity in<br />
patients with macular edema secondary to BRVO and<br />
CRVO. 16,17 To sustain the efficacy, however, anti-VEGF<br />
agents are to be administered every month, raising concerns<br />
about safety risks, patient compliance, logistical<br />
feasibility, and cost. 18,19<br />
Corticosteroids counteract many pathological processes<br />
that play a role in the development <strong>of</strong> macular<br />
edema, including prevention <strong>of</strong> leukocyte migration,<br />
inhibition <strong>of</strong> prostaglandin and pro-inflammatory cytokine<br />
synthesis, and reduction <strong>of</strong> fibrin deposition. 20<br />
Corticosteroids also inhibit the expression <strong>of</strong> VEGF as<br />
well as enhance the barrier function <strong>of</strong> tight junctions<br />
between vascular endothelial cells. 21,22
Challenges in Treatment <strong>of</strong> Macular Edema<br />
with Corticosteroids<br />
The efficacy <strong>of</strong> corticosteroids to treat macular<br />
edema is primarily dependent on their potency and<br />
long-term bioavailability to the back <strong>of</strong> the eye. Betamethasone<br />
and dexamethasone are the most potent<br />
corticosteroids, with an anti-inflammatory activity that<br />
is at least 5-fold greater than that <strong>of</strong> triamcinolone (Table<br />
1). 23,24 Unfortunately, oral, topical, peribulbar, and<br />
subconjunctival corticosteroid administrations may<br />
deliver sub therapeutic vitreous drug levels that can<br />
be associated with relatively high systemic corticosteroid<br />
concentrations and significant adverse events<br />
(Table 2). 25-29 Direct intravitreal corticosteroid injection,<br />
however, bypasses the blood–retinal barrier, leading to<br />
high local drug concentrations with few or no systemic<br />
adverse events. Yet, intravitreal administration is prone<br />
to rapid clearance <strong>of</strong> potent hydrophilic corticosteroids<br />
such as dexamethasone. 29 Instead, the crystalline form<br />
<strong>of</strong> a less potent but relatively more hydrophobic corticosteroid,<br />
triamcinolone acetonide (Kenalog ® -40,<br />
Bristol-<strong>My</strong>ers Squibb; Princeton, NJ, USA), has been<br />
used <strong>of</strong>f-label for treatment <strong>of</strong> macular edema. 30-32<br />
Triamcinolone acetonide preparations have a heterogeneous<br />
particle size—varying substantially from batch to<br />
batch—that is randomly solubilized in the vitreous over<br />
several months. 33 Although direct intravitreal injection<br />
<strong>of</strong> triamcinolone acetonide has gained some clinical<br />
success, it was associated with a high rate <strong>of</strong> elevated<br />
intraocular pressure (IOP) and cataract formation. 34-36<br />
Hence, new strategies providing more controlled and<br />
sustained drug release are needed to increase efficacy<br />
and improve safety.<br />
Drug Delivery Systems for the Posterior<br />
Segment<br />
In recent years, several intraocular drug delivery<br />
systems using implantable devices or injectable particles<br />
have been tested to achieve a more controlled<br />
drug release at a stable rate over a long period <strong>of</strong> time<br />
with a potentially lower rate <strong>of</strong> adverse events. Retisert ®<br />
(Bausch & Lomb, Rochester, NY, USA), Iluvien ® (Alimera<br />
Sciences, Alpharetta, GA, USA), and I-vation<br />
(SurModics, Inc., Eden Prairie, MN, USA) contain fluocinolone<br />
acetonide (Retisert ® and Iluvien ® ) or triamcinolone<br />
acetonide (I-vation) in a nonbiodegradable<br />
reservoir. 37-39 Retisert ® is approved for the treatment<br />
<strong>of</strong> chronic noninfectious uveitis affecting the posterior<br />
segment, while Iluvien ® and I-vation are under development<br />
for treatment <strong>of</strong> diabetic macular edema. 40,41<br />
Both Retisert ® and I-vation are inserted surgically,<br />
whereas Iluvien ® is injected into the vitreous using an<br />
applicator in an <strong>of</strong>fice setting. 42 All 3 implants, however,<br />
may need to be surgically removed once the drug release<br />
is complete because nonbiodegradable devices are<br />
not metabolized in vivo. In addition, there is an increa-<br />
fi gure 1<br />
(a)<br />
(b)<br />
Applicator<br />
Table 1. Relative Potency <strong>of</strong> Corticosteroids 23,24<br />
Corticosteroid<br />
Macula<br />
Implant<br />
Figure 1. DEX Implant with<br />
Approximate Ocular Location After<br />
Implantation (a) and Dexamethasone<br />
Posterior Segment Drug Delivery<br />
System applicator (b).<br />
Relative Potency to<br />
Cortisol<br />
Cortisol 1<br />
Cortisone 0.8<br />
Prednisolone 4<br />
Methylprednisolone 5<br />
Triamcinolone 5<br />
Fluocinolone 10-20<br />
Betamethasone 25-40<br />
Dexamethasone 30<br />
Table 2. Peak Vitreous and Serum Dexamethasone<br />
Concentrations (Cmax) After Varying Routes <strong>of</strong><br />
Administrations 25-29<br />
Route Dose (mg)<br />
Vitreous<br />
(C , ng/mL)<br />
max<br />
Serum<br />
(C , ng/mL)<br />
max<br />
Oral 7.5 5.2 61.6<br />
Topical 0.5 1.1 0.7<br />
Peribulbar 3.8 13 60<br />
Subconjunctival 1.9 72.5 32.4<br />
Intravitreal 0.4 100000 –<br />
Marzo 2010<br />
<strong>PAN</strong>-<strong>AMERICA</strong> 15
CLINICAL SCIENCES<br />
Figure 2.<br />
16 <strong>PAN</strong>-<strong>AMERICA</strong><br />
Before Implantation 3 weeks After Implantation<br />
Figure 2. Biodegradation <strong>of</strong> DEX Implant’s Copolymer<br />
Matrix. 46 Used with permission from S. Karger AG, Basel.<br />
Figure 3.<br />
(A) Intravitreal Gd-D TPA<br />
Injection (0.2 mg)<br />
(B) DEX Implant<br />
(0.7 mg)<br />
Figure 3. Temporal Kinetics <strong>of</strong><br />
Gd-DTPA and Dexamethasone in<br />
Vitreous. (A) Gd-DTPA, a small<br />
molecular weight MRI contrast<br />
agent with a similar molecular<br />
weight to dexamethasone (i.e. <<br />
1000 Daltons) was injected into the<br />
vitreous <strong>of</strong> 1 eye <strong>of</strong> an anesthetized<br />
rabbit. High resolution MRI was<br />
performed to image the drug depot<br />
in the vitreous (black arrow) over<br />
time. The contrast agent was<br />
completely cleared from the vitreous<br />
2.5 hours after direct injection<br />
(0.2 mg). 48 (B) In contrast, a DEX<br />
implant containing dexamethasone<br />
(0.7 mg) remained in monkey eyes<br />
for up to 6 months. 48 Gd-DTPA =<br />
gadopentetate-diethylenetriamine<br />
pentaacetic acid; MRI = magnetic<br />
resonance imaging.<br />
sed risk for such adverse events as retinal detachment,<br />
vitreous hemorrhage, and endophthalmitis while retrieving<br />
and reimplanting nonbiodegradable devices. 43<br />
Sustained-release dexamethasone intravitreal implant<br />
(DEX implant; Ozurdex ® ; Allergan, Inc.; Irvine, CA,<br />
USA) is the only biodegradable ocular drug delivery<br />
system approved by the US Food and Drug Administration<br />
(Figure 1a). DEX implant is indicated for the<br />
treatment <strong>of</strong> macular edema following RVO and for the<br />
treatment <strong>of</strong> non-infectious uveitis affecting the posterior<br />
segment <strong>of</strong> the eye. 44 DEX implant is inserted into<br />
the vitreous cavity by an applicator in an <strong>of</strong>fice setting<br />
(Figure 1b). 45 It contains dexamethasone within a biodegradable<br />
copolymer <strong>of</strong> lactic acid and glycolic acid<br />
(Novadur ® ; Allergan, Inc.) (Figure 2). 44,46 DEX implant<br />
releases drug in a biphasic fashion, with higher doses<br />
for up to 6 weeks followed by lower doses for up to<br />
6 months. 47 In sharp contrast to rapid clearance <strong>of</strong> directly<br />
injected gadopentetate-diethylenetriamine pentaacetic<br />
acid (Gd-DTPA; Magnevist ® , Bayer HealthCare<br />
Pharmaceuticals; Montville, NJ, USA) 48 —a magnetic<br />
resonance imaging (MRI) contrast agent with a similar<br />
molecular weight (570.0 Daltons) as dexamethasone<br />
(392.5 Daltons) that is used as a surrogate to study<br />
ocular pharmacokinetic <strong>of</strong> low molecular weight drugs<br />
such as corticosteroids 49-51 —DEX implant has been<br />
observed 6 months after implantation (Figure 3). 47 Inside<br />
the eye, the copolymer is metabolized into carbon<br />
dioxide and water. Sequential implants can be placed in<br />
an <strong>of</strong>fice setting without the need for surgical removal.<br />
Clinical Applications <strong>of</strong> DEX Implant<br />
A prospective, randomized, dose ranging, phase 2<br />
trial evaluated the safety and efficacy <strong>of</strong> DEX implant in<br />
patients with macular edema secondary to CRVO, BRVO,<br />
diabetic retinopathy, uveitis, or Irvine-Gass syndrome<br />
persisting for ≥ 90 days after laser or medical therapy. 52<br />
Participants (N = 315) were randomly assigned to observation<br />
or treatment with DEX implant at 2 doses, 0.35<br />
mg or 0.7 mg. At days 90 and 180, a significantly higher<br />
proportion <strong>of</strong> patients treated with DEX implant 0.7 mg<br />
had a ≥ 10-letter or a ≥ 15-letter improvement in BCVA<br />
than those in the observation group. While the improvement<br />
in BCVA was statistically similar in the observation<br />
group and the DEX implant 0.35 mg group, treatment<br />
with DEX implant at both doses (0.35 mg and 0.7 mg)<br />
significantly decreased central retinal thickness and fluorescein<br />
angiographic leakage at day 90 compared to the<br />
observation group. 52 Subset analyses demonstrated that<br />
the treatment effect with DEX implant 0.7 mg was similar<br />
across the underlying causes <strong>of</strong> persistent macular<br />
edema (Table 3). 52-54 The phase 2 study reported relatively<br />
few adverse events, including mild cases <strong>of</strong> IOP<br />
elevation. Overall, 3% <strong>of</strong> the observation patients, 12% <strong>of</strong><br />
the DEX implant 0.35 mg patients, and 17% <strong>of</strong> the DEX<br />
implant 0.7 mg patients had an incidence <strong>of</strong> a ≥ 10 mm
Table 3. Effi cacy <strong>of</strong> DEX Implant 0.70 mg in Improving BCVA<br />
Stratifi ed by the Underlying Cause <strong>of</strong> Macular Edema <strong>of</strong> Patients<br />
Who Participated in the Phase 2 Trial52-54 Patients with ≥ 10-Letter Improvement<br />
in BCVA at Day 90 (%)<br />
Underlying Disease Observation DEX Implant P<br />
Retinal vein occlusion<br />
(n = 34a )<br />
15.0 31.0 ND<br />
Infl ammatory diseaseb (n =14c )<br />
14.3 53.8 .029<br />
Diabetic retinopathy<br />
(n = 57)<br />
12.3 33.3 .007<br />
a n = 35 for DEX implant 0.70 mg.<br />
b Infl ammatory disease = uveitis or Irvine-Gass syndrome.<br />
c n = 13 for DEX implant 0.70 mg.<br />
ND = not determined.<br />
Hg increase in IOP from baseline. Most <strong>of</strong> these patients<br />
(> 65%) had only a single occurrence <strong>of</strong> an IOP increase<br />
<strong>of</strong> this magnitude or greater. 52<br />
Two identical, multicenter, masked, clinical studies<br />
randomly assigned 1267 patients with vision loss due<br />
to clinically detectable macular edema associated with<br />
CRVO or BRVO to either a sham procedure or treatment<br />
with DEX implant at the dose <strong>of</strong> 0.35 mg or 0.7 mg. 55<br />
Compared to eyes receiving sham treatment, a significantly<br />
greater proportion <strong>of</strong> eyes receiving either dose<br />
<strong>of</strong> DEX implant achieved a 15-letter improvement from<br />
baseline BCVA from day 30 to day 90 (11% vs 29%<br />
and 29% at peak on day 60; P < .001). A similar significant<br />
difference was also found between the sham<br />
group and the DEX implant 0.7 mg group at day 180<br />
after excluding patients who had the last study visit after<br />
180 days (Figure 4). The time to achieve 15 letters<br />
<strong>of</strong> improvement from baseline BCVA was also significantly<br />
shorter in patients treated with either dose <strong>of</strong> DEX<br />
implant compared to those receiving sham procedure<br />
(P < .001). When analyzed by the underlying cause<br />
<strong>of</strong> macular edema, eyes with CRVO did not respond to<br />
the therapy for as long as did the eyes with BRVO, and<br />
they were not improved without therapy, suggesting that<br />
CRVO is a more visually disabling disorder than BRVO. 55<br />
Treatment with either dose <strong>of</strong> DEX implant significantly<br />
decreased the mean central retinal thickness compared<br />
to sham treatment at day 90 (P < .001), but not at<br />
day 180. 55 Overall, DEX implants had favorable safety<br />
pr<strong>of</strong>iles and were associated with generally transient,<br />
moderate, and readily manageable adverse events. The<br />
proportion <strong>of</strong> patients experiencing an IOP elevation <strong>of</strong><br />
10 mm Hg or greater from baseline peaked at day 60<br />
and was less than 1% in the sham group and approximately<br />
15% in both DEX implant groups.55 Based on<br />
these pivotal trials, DEX implant 0.7 mg was approved<br />
in the United States and Europe for treatment <strong>of</strong> macular<br />
edema due to RVO. Subsequently, DEX implant 0.7 mg<br />
was approved in the United State for the treatment <strong>of</strong><br />
non-infectious uveitis affecting the posterior segment<br />
<strong>of</strong> the eye and in Brazil for treatment <strong>of</strong> macular edema<br />
due to RVO and uveitis.<br />
Ongoing clinical studies are evaluating the safety<br />
and efficacy <strong>of</strong> DEX implant for treating macular edema<br />
in uveitic and vitrectomized diabetic patients as monotherapy<br />
and in diabetic patients and those with choroidal<br />
neovascularization secondary to exudative age-related<br />
macular degeneration (AMD) as combination therapy<br />
with laser photocoagulation or ranibizumab, respectively.<br />
Preliminary findings indicate that DEX implant improves<br />
visual acuity in uveitic, vitrectomized diabetic,<br />
and diabetic patients and reduces the need for repeated<br />
ranibizumab injections in patients with AMD-induced<br />
choroidal neovascularization. 56-59<br />
Conclusions<br />
Percentage <strong>of</strong> Patients With > 15-Letter<br />
Improvement From Baseline BCVA at Day 180<br />
DEX implant significantly decreases central retinal<br />
thickness and improves BCVA in patients with macular<br />
edema caused by BRVO or CRVO. The current clinical<br />
experience indicates the potential <strong>of</strong> the DEX implant<br />
to emerge as a new treatment modality for improving<br />
vision <strong>of</strong> patients suffering from macular edema secondary<br />
to a variety <strong>of</strong> underlying diseases.<br />
Acknowledgment<br />
30<br />
25<br />
20<br />
15<br />
10<br />
5<br />
0<br />
a p =.017 compared to sham<br />
17.0<br />
Sham<br />
(n = 208)<br />
19<br />
DEX Implant 0.35 mg<br />
(n = 216)<br />
Editorial assistance in the preparation <strong>of</strong> this manuscript<br />
was provided by Hadi Moini PhD, <strong>of</strong> Pacific<br />
Communications, a wholly owned subsidiary <strong>of</strong> Allergan,<br />
Inc.<br />
Marzo 2010<br />
DEX Implant 0.70 mg<br />
(n = 229)<br />
Figure 4. Patients Achieving at Least 15 Letters <strong>of</strong><br />
Improvement From Baseline BCVA at Day 180 in Phase 3<br />
Trial <strong>of</strong> Patients With Retinal Vein Occlusion. 55 Patients who<br />
had the last study visit later than 180 days were excluded<br />
from this analysis.<br />
26 a<br />
<strong>PAN</strong>-<strong>AMERICA</strong> 17
CLINICAL SCIENCES<br />
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secondary to age-related macular<br />
degeneration. Presented at: 10th European<br />
Society <strong>of</strong> Retina Specialists (EUTORETINA)<br />
Congress; September 2-5, 2010; Paris, France.
Incidencia de desprendimiento de<br />
retina en pacientes altos miopes<br />
postoperados de implante de LIO<br />
fáquico Artisan/Artiflex<br />
Luis Fernando Rosales Rodriguez MD; Luis Oswaldo Izquierdo<br />
Villavicencio MD; Maria Alejandra Henríquez MD<br />
Ninguno de los autores tiene interés comercial en el presente trabajo<br />
Abstract<br />
Purpose: To described the incidence <strong>of</strong> retinal detachment<br />
(RD) in patients with preoperative high myopic<br />
value after five year <strong>of</strong> phakic intraocular lens (pIOL)<br />
was implant Artisan/Artiflex.<br />
Setting: Instituto de Ojos Oftalmosalud, Lima, Peru.<br />
Methods: This retrospective study included a review<br />
<strong>of</strong> 203 medical records (271 eyes) <strong>of</strong> patients<br />
with myopic refraction that underwent pIOL implantation<br />
by the same experimented surgeon between<br />
January 2004 to 2009, with a minimum postoperative<br />
follow-up <strong>of</strong> 1 year. The inclusion criteria were patients<br />
over 18 years old, a spherical equivalent (SE)<br />
over -6.00 Diopter (D) or with an axial length greater<br />
than 26mm, stable refraction for at least 2 years with<br />
best visual acuity (BVA) better than 20/100, without<br />
abnormalities in the anterior segment, and minimum<br />
endothelial cell count <strong>of</strong> 2,000 cells/mm3 .<br />
Results: The average age <strong>of</strong> patients was 28.5<br />
years (21-39 years). The women/men ratio was 1.7:<br />
1 (36% men, 64% women). The average preoperative<br />
SE was -12.39 D (-8.00 to -23.00). In 69.74%<br />
(203 patients) we implant pIOL in both eyes. 189 eyes<br />
(69.74%) and 82 eyes (30.26%) had Artisan and Artiflex<br />
implanted respectively. The incidence <strong>of</strong> RD after<br />
pIOL implantation was 1.1% (3/271 eyes) <strong>of</strong> them was<br />
after artisan lens implant.<br />
Conclusion: The pIOL implant is a safe and effective<br />
option <strong>of</strong> correction high myopia. The incidence <strong>of</strong><br />
RD was not different from the natural history <strong>of</strong> RD in<br />
myopic patients or high myopic patients with anterior<br />
segment surgery. Likewise, the prompt surgical management<br />
<strong>of</strong> this complication led to a satisfactory visual<br />
resolution in these patients.<br />
Resumen<br />
Correspondencias:<br />
Instituto de Ojos Oftalmosalud<br />
Avenida Javier Prado Este 1142,<br />
San Isidro, Lima, Perú<br />
Marzo 2010<br />
Propósito: Describir la incidencia del desprendimiento de retina (DR) en pacientes<br />
altos miopes evaluados a un año de seguimiento posterior al implante del lente<br />
intraocular fáquico (pIOL) Artisan/Artiflex.<br />
Lugar: Instituto de Ojos Oftalmosalud, Lima, Perú.<br />
Métodos: Estudio retrospectivo en el que se incluyeron 203 historias clínicas<br />
(271 ojos) de pacientes con alta miopía a los que se les implanto pIOL entre enero de<br />
2004 a 2009, por un solo cirujano experto, con un año de seguimiento post operatorio.<br />
Los criterios de inclusión fueron pacientes mayores de 18 años, con equivalente<br />
esférico (EE) superior a -6.00 dioptrías (D) o longitud axial mayor de 26 mm, con una<br />
refracción estable de 2 años previos, agudeza visual mejor corregida (AVCC) mejor<br />
de 20/100, sin anormalidades en el segmento anterior y con un contaje de células<br />
endoteliales mínimo de 2,000 cel/mm 3 .<br />
Resultados: La media de edad de los pacientes fue de 28.5 años (21 – 39 años).<br />
La relación mujer/hombre fue de 1.7:1 (36% hombres, 64% mujeres). La media de<br />
Equivalente esférico preoperatorio fue de -12.39 D (-8.00 a -23.00). En el 74.90%<br />
(203 pacientes) fue implantado pIOL en ambos ojos. A 189 ojos (69.74%) y 82 ojos<br />
(30.26%) les fue implantado el pIOL Artisan y Artiflex respectivamente. La incidencia<br />
de DR posterior a la implantación de pIOL fue 1.1% (3/271 ojos). Todos ellos presentados<br />
en pacientes a los que se les implantó el pIOL Artisan. (3 ojos).<br />
Conclusión: El implante de pIOL es una opción segura y efectiva para la corrección<br />
de alta miopía. La incidencia de DR no fue diferente frente a la historia natural<br />
del DR en pacientes miopes o en cirugías del segmento anterior. No obstante,<br />
el manejo precoz de dicha complicación lleva a una recuperación satisfactoria de<br />
su AV en estos pacientes.<br />
Introducción<br />
La alta miopía se define como un aumento de la longitud axial del globo ocular<br />
por encima de 2 mm con respecto a la longitud axial del ojo emétrope ( 23 mm) 1 o de<br />
un poder dióptrico superior de -6 dioptrías (d). La incidencia de desprendimiento de<br />
retina (DR) en pacientes miopes oscila entre 0.7 al 6%. Se estima que en pacientes<br />
miopes con más de -5.00d la incidencia es del 4.2% durante los primeros 60 años<br />
de su vida 2 , en comparación con pacientes emétropes cuya incidencia es de tan solo<br />
0.06% 2 . En los pacientes miopes que son sometidos a cirugías de catarata, la inci-<br />
<strong>PAN</strong>-<strong>AMERICA</strong> 19
CLINICAL SCIENCES<br />
20 <strong>PAN</strong>-<strong>AMERICA</strong><br />
Tabla 1. Características de cada paciente que presentó DR posterior al implante de pIOL.<br />
Paciente<br />
Característica<br />
dencia es entre del 1 al 2% 3 y en aquellos sometidos a<br />
implante de lentes intraoculares fáquicos (pIOL por sus<br />
siglas en inglés) esta incidencia no varía. 4<br />
Los pIOL evaluados en el presente estudio son:<br />
Artisan y Artiflex. El pIOL Artisan (Figura 1) es un lente<br />
rígido de polimetilmetacrilato (PMMA) que se ingresa<br />
a cámara anterior (CA) por una incisión corneoescleral<br />
de 6.5mm mientras el pIOL Artiflex (Figura 2) es<br />
un lente plegable que se ingresa a CA por una incisión<br />
corneoescleral de 3.00 mm cuyo material es de PMMA<br />
para la háptica y polysiloxane en la óptica3 .<br />
La zona óptica del lente Artisan está disponible<br />
en diámetros de 5 y 6 mm: sus rangos de poder varían<br />
de -2.00 d a -23.5 d (cuya óptica es de 5 mm) y de<br />
-2.00 d a -15.5 d (cuya óptica es de 6 mm). Su grosor<br />
1 2 3<br />
Edad (años) 26 20 36<br />
Sexo Femenino Femenino Femenino<br />
AVSC preoperatoria CD CD CD<br />
AVCC preoperatoria 20/30 20/40 20/40<br />
EE preoperatorio -7.00 -12.0 -9.00<br />
pIOL implantado Artisan Artisan Artisan<br />
Día postoperatorio de<br />
diagnóstico de DR<br />
Características del DR<br />
37 días 4 mes 5 mes<br />
DR superior (meridianos<br />
11 a 3 horas)<br />
DR superior (meridianos 11<br />
a 2 horas)<br />
DR total<br />
Involucro Macular No No Sí<br />
Tratamiento quirúrgico<br />
del DR<br />
Complicaciones Post<br />
cirugía de retina<br />
AVSC postoperatoria<br />
Retinopexia neumática,<br />
con vitrectomía.<br />
Con aplicación de láser<br />
al opérculo para sellar el<br />
desgarro retinal.<br />
Retinopexia neumática con<br />
C3F8 (Octafl uoropropano)<br />
con vitrectomía,<br />
Endoláser al opérculo para<br />
sellar el defecto.<br />
Ninguna Ninguna<br />
Retinopexia neumática con<br />
C3F8 (Octafl uoropropano) con<br />
vitrectomía,<br />
Endoláser para sellar múltiples<br />
puntos de desgarro en área<br />
temporal superior.<br />
A los 36 días presentó DR, se<br />
realizó vitrectomía con cerclaje<br />
escleral e implante de banda<br />
de silicona 360°, y retinopexia<br />
neumática con C3F8<br />
AVCC postoperatoria 20/40 20/40 20/60<br />
Seguimiento post<br />
cirugía de retina<br />
1 año (AVCC 20/40) 1 año (AVCC 20/40) 7 meses (20/60)<br />
en el eje óptico es 0.2 mm. En el caso del Artiflex sus<br />
rangos de poder varían de -2.00D a -15.00D 1 con óptica<br />
de 6 mm. Por otra parte, existen pIOL con poderes<br />
positivos, que han sido diseñados para pacientes áfacos,<br />
que en el presente estudio no se incluyeron 6 .<br />
El objetivo del presente estudio es evaluar la incidencia<br />
de DR en pacientes altos miopes, postoperados<br />
de implante de pIOL Artisan o Artiflex a un año<br />
de evaluación.<br />
Materiales y métodos<br />
Estudio retrospectivo de 203 pacientes miopes<br />
(271 ojos) a los cuales se les había sometido a cirugía<br />
de implante de pIOL, por el mismo cirujano con experiencia,<br />
entre enero de 2004 y enero de 2009, y con seguimiento<br />
postoperatorio mínimo a un año de cirugía.
Figura 1: Lente Artifl ex.<br />
Figura 2: Inyector del<br />
lente Artifl ex.<br />
Los criterios de inclusión fueron pacientes mayores de 18 años con un equivalente<br />
esférico (EE) > -6.00 d, o con una longitud axial > 26 mm, refracción estable<br />
por lo menos 2 años, agudeza visual mejor corregida (AVCC) menor de 20/100, sin<br />
anormalidades en el segmento anterior, recuento de células endoteliales > 2000 cel/<br />
mm3 . Se excluyó a pacientes con cirugía de retina previa.<br />
La evaluación pre y postimplantación de pIOL (se realizó a los 1, 15vo día y 1,3, y<br />
12 meses), incluyó AVSC, AVCC, refracción con y sin ciclopléjicos, examen <strong>of</strong>talmológico<br />
a la biomicroscopia y examen de fondo de ojo, con midriasis farmacológica,<br />
usando <strong>of</strong>talmoscopio indirecto con lupa de +20 D y + 90 D.<br />
Los equipos utilizados para el cálculo de la longitud axial y del poder dióptrico<br />
del lente fue el IOL Master (versión 3.01 de la marca Zeiss), utilizando una<br />
fórmula computarizada provista por el fabricante de los pIOL, el contaje de células<br />
endoteliales se realizó con el microscopio especular Topcon SP-2000P, y topografía<br />
corneal con el topógrafo córneal Keratron Scort optikon 2000.<br />
La cirugía fue realizada con incisión corneo-escleral superior (6.5 mm para el<br />
implante de pIOL Artisan y 3 mm para el Artiflex) e implante de pIOL con fijación<br />
iridiana. En el caso del Artiflex el implante del LIO se realizó a través de su inyector.<br />
El cierre de herida quirúrgica con Nylon 10-0 de la marca Johnson & Johnson en los<br />
casos de Artisan y con hidratación corneal en los casos de Artiflex.<br />
Resultados<br />
La edad media de los pacientes fue de 28.5 años (rango 21 - 39 años). La relación<br />
mujer/hombre fue 1.7:1 (36% a 64%) respectivamente, el EE preoperatorio promedio<br />
fue -18.3 (rango -8.00 a -23.00 d). La media de seguimiento fue de 14 meses (rango<br />
12 – 22 meses). En el 74.90% de los pacientes se les implantó pIOL en ambos ojos<br />
(203 pacientes), de los cuales fueron 189 Artisan (69.74%) y 82 Artiflex (30.26).<br />
La incidencia del DR posterior al implante de pIOL fue del 1.1%. (3 /271). La edad<br />
media de estos pacientes fue de 27.3 años (rango 20 a 36). El rango del EE preoperatorio<br />
fue entre -7 y – 12D. Se reportó DR en 3 ojos (1.1%), los cuales (100%)<br />
fueron sometidos a vitrectomía vía pars plana (VVPP), reportándose una recurrencia<br />
del DR en 1 paciente (33.33%), el cual fue sometido a una segunda intervención,<br />
recuperándose satisfactoriamente.<br />
Los pacientes que presentaron DR fueron intervenidos por un cirujano de retina<br />
y vítreo. Se utilizó anestesia peribulbar y se intervino con equipo de vitrector Dorc,<br />
con puertos de 20 gauge (g). Tabla 1 muestra las caracteristicas de cada paciente<br />
que presentó DR.<br />
Conclusión<br />
REFERENCIAS<br />
Marzo 2010<br />
La incidencia del DR no fue diferente a la historia<br />
natural del DR en pacientes miopes, ni operados de cirugía<br />
de catarata7 . Así mismo, el manejo quirúrgico del<br />
DR llevó a una resolución satisfactoria de la visión en<br />
dichos pacientes.<br />
Discusión<br />
Según nuestros resultados el implante de un pIOL<br />
tiene riesgo similar al descrito en la literatura en pacientes<br />
altos miopes sometidos a cirugía de catarata8 .<br />
Además, si bien es cierto que el riesgo de presentar<br />
un DR aumenta al momento de un evento quirúrgico<br />
en un paciente alto miope3 , también lo es que esta<br />
complicación se presenta en el postoperatorio mediato3<br />
. En todos los casos del presente estudio, el DR se<br />
presentó dentro de los primeros 6 meses postoperatorios,<br />
por lo que consideramos de suma importancia el<br />
seguimiento postoperatorio de estos pacientes a largo<br />
plazo, con evaluación de fondo de ojo dilatado por<br />
especialista de retina.<br />
Por lo tanto, y basados en el presente estudio, concluimos<br />
que la incidencia de DR en implante de pIOL<br />
es baja y que el implante de estos lentes es eficaz pero<br />
no exento de complicaciones.<br />
1. Kaufman, Paul, Alm Albert. Fisiología del Ojo, Decima<br />
edición, Mosby<br />
2. Törnquist R. Stenkula, Törnquist P. Retinal detachment,<br />
a study <strong>of</strong> population – based patient material in<br />
Sweden 1971 – 1981. i. Epidemiology., Acta Opthalmol<br />
(Copenh) 1987 Apr. 65 (2) 213-22<br />
3. Martínez–Castillo V, Boixadera A, Verdugo A, Elíes<br />
D, Coret A, García–Arumí. Rhegmatogenous retinal detachment<br />
in phakic eyes after posterior chamber phakic<br />
intraocular lens implantation for severe myopia. J. Ophthalmology,<br />
2005 apr 112 (4) 580-5.<br />
4. Navarro R, Gris O, Broc L, Corcóstegui B. Bilateral<br />
gigant retinal tear following posterior chamber phakic<br />
intraocular lens implantation. J Refract Surg. 2005 May<br />
– Jun; 21 (3): 298-300.<br />
5. Ruiz-Moreno JM, Montero JA, De La Vega C, Alió JL,<br />
Zapater P. Retinal detachment in myopic eyes after phakic<br />
intraocular lens implantation. J Refract Surg. 2006<br />
Mar; 22 (3): 247-52<br />
6. Budo C, Hessloehl JC, Izak M & Cols. Multicenter<br />
study <strong>of</strong> the artisan phakic intraocular lens. J Cataract<br />
Refract Surg. 2000 Aug; 26 (8): 1163-71.<br />
7. Maloney RK, Nguyen LH, John ME. Artisan phakic<br />
intraocular lens for myopia: short-tem results <strong>of</strong> a prospective,<br />
multicenter study. Ophthalmology, 2002 Sep;<br />
109 (9): 1631-41.<br />
8. Camille JR, Budo MD, The Artisan Lens, Highlights<br />
<strong>of</strong> Ophthalmology, 2004.<br />
<strong>PAN</strong>-<strong>AMERICA</strong> 21
CASE REPORT<br />
Queratitis por Acanthamoeba.<br />
A Propósito de un Caso<br />
Acanthamoeba Keratitis: A Case Report<br />
Miriam García-Fernández 1 ; Begoña Baamonde Arbaiza 2<br />
1 Licenciado en Medicina<br />
2 Doctor en Medicina<br />
Los autores certifi can que este trabajo no ha sido publicado ni está en vías de consideración para<br />
publicación en otra revista. Asimismo transfi eren los derechos de propiedad (copyright) del presente<br />
trabajo a Vision <strong>Pan</strong>-<strong>American</strong>a.<br />
Acanthamoeba Keratitis. A Case Report<br />
Case report: A 33 year-old male, with hyperemic<br />
painful eye and no improvement after antibiotic and<br />
corticoid topic therapy. By biomicroscopy: annular<br />
infiltrate with inferior de-epithelialization, and limbal<br />
inflammation. Due to the suspicion <strong>of</strong> Acanthamoeba<br />
keratitis, we started treatment with clorhexidine 0.02%,<br />
polimyxin B+neomicin+ gramicidin (Oftalmowell ® )<br />
and propamidine isethionate (Brolene ® ). A microbiological<br />
diagnosis confirmed the presence <strong>of</strong> Acanthamoebae,<br />
and diagnosis <strong>of</strong> Acanthamoeba keratitits was<br />
established. We observed a satisfactory evolution, with<br />
formation <strong>of</strong> a central corneal leukoma, followed by penetrating<br />
keratoplasty, with good results.<br />
Discussion: Clinical and microbiological early<br />
diagnoses are fundamental, since inappropirate<br />
treatment will lead to the development <strong>of</strong> cysts, and<br />
treatment resistance.<br />
Keywords: Acanthamoeba keratitis, early diagnosis,<br />
microbiological diagnosis.<br />
Queratitis por Acanthamoeba. A Propósito<br />
de un Caso<br />
Caso clínico: Varón de 33 años con ojo hiperémico,<br />
doloroso, sin mejoría tras tratamiento con antibióticos<br />
y corticoides tópicos. A la exploración biomicroscópica:<br />
infiltrado anular desepitelizado por la parte<br />
inferior, con limbitis. Ante la sospecha de queratitis por<br />
Acanthamoebae, se inició tratamiento con clorhexidina<br />
0.02%, polimixina B+neomicina+gramicidina<br />
(Oftalmowell ® ) e isetionato de propamidina (Brolene<br />
® ). El estudio microbiológico confirmó el crecimiento<br />
de Acanthamoebae, por lo que se estableció<br />
el diagnóstico de queratitis por Acanthamoeba. La<br />
evolución fue satisfactoria, con formación de leucoma<br />
corneal central, que llevó a queratoplastia penetrante,<br />
con buenos resultados.<br />
22 <strong>PAN</strong>-<strong>AMERICA</strong><br />
Correspondencias:<br />
Dra. Miriam García Fdez<br />
c/Dionisio Ridruejo, No. 5, 11º D<br />
Oviedo, CP 33007 Spain<br />
E-mail: migarci@hotmail.es<br />
Institución responsable<br />
Hospital Universitario Central de Asturias (H.U.C.A)<br />
Discusión: Un diagnóstico precoz, clínico y microbiológico es fundamental,<br />
pues un tratamiento inicial poco acorde dará lugar al enquistamiento y resistencia<br />
al tratamiento.<br />
Palabras clave: Queratitis por Acanthamoeba, diagnóstico precoz, diagnóstico<br />
microbiológico.<br />
Queratitis por Acanthamoeba. A Propósito de un Caso<br />
Introducción<br />
Figura 1.<br />
a) Infi ltrado<br />
anular inicial.<br />
B) Defecto<br />
epitelial<br />
centrocorneal<br />
inicial con<br />
limbitis<br />
importante.<br />
Las Acanthamoebae son protozoos ubicuos libres que se encuentran en aguas<br />
corrientes y en el suelo. Pueden existir como tr<strong>of</strong>ozoítos móviles o quistes latentes.
La mayoría de estas queratitis (70%) se asocian al uso<br />
de lentes de contacto.<br />
Es frecuente que el tratamiento se retrase debido a<br />
diagnósticos erróneos tales como queratitis por herpes<br />
simple o por hongos.<br />
Caso clínico<br />
Varón de 33 años, que acude al Servicio de Urgencias<br />
por ojo derecho hiperémico, doloroso, con irradiación<br />
a región periorbitaria, sin mejoría tras un mes de<br />
tratamiento con antibióticos y corticoides tópicos.<br />
Como antecedente personal destaca que es portador<br />
de lentes de contacto blandos desechables de un mes.<br />
A la exploración se observa un infiltrado anular desepitelizado<br />
por la parte inferior con limbitis importante, así<br />
como ausencia de tyndall (Figura 1). La exploración de<br />
polo posterior es normal. La agudeza visual (AV) es de<br />
percepción y proyección de luz. Ante la sospecha de<br />
queratitis por Acanthamoeba se toman muestras para<br />
cultivo y frotis y se inicia tratamiento con clorhexidina<br />
0.02% (CHX, Ashton Chemicals Ltd., Aylesbury, Reino<br />
Unido) 1 gota cada hora día y noche 48 horas y luego<br />
solo durante el día, así como una combinación de neomicina<br />
sulfato + gramicidina + polimixina B sulfato<br />
(Oftalmowell ® ) cada hora, ciclopléjico, flurbipr<strong>of</strong>eno<br />
(Froben ® ) e itraconazol (Canadiol ® ) oral, y se solicita<br />
isetionato de propamidina al 0,1% (Brolene ® ) como medicación<br />
extranjera, asociándolo al tratamiento en régimen<br />
horario a los 7 días.<br />
Los resultados de microbiología confirman el crecimiento<br />
de la ameba (Figura 2). Tras un mes de tratamiento<br />
antiamebiano, iniciamos corticoterapia sistémica<br />
y suspendemos Froben ® . A los 6 meses, el paciente se<br />
encuentra estable, con un ojo bastante tranquilo, úlcera<br />
completamente epitelizada con leucoma central y adelgazamiento<br />
corneal (Figura 3). Para entonces, ya mantenemos<br />
dosis de 1 gota/8 h de Brolene ® y CHX, así como<br />
corticoterapia sistémica a dosis bajas de 10 mg/ día. Se<br />
realiza microscopía confocal, que nos permite comprobar<br />
la ausencia de quistes. Un año después del inicio de la<br />
clínica, y ya sin tratamiento médico, dado la estabilidad<br />
del cuadro (persiste el leucoma y se observa una discreta<br />
opacificación capsular anterior y posterior del cristalino).<br />
Se decide incluir en lista de espera para queratoplastia<br />
penetrante. Ésta se practica a los 9 meses, sin complicaciones,<br />
siguiendo un tratamiento en el postoperatorio<br />
inmediato (Figura 4), con corticoides sistémicos, así<br />
como con antibioterapia, corticoterapia, midriáticos tópicos<br />
y Brolene ® 1 gota 3veces/día. En la actualidad, tras<br />
siete meses de la queratoplastia, presenta una evolución<br />
satisfactoria, con el injerto epitelizado y transparente.<br />
Discusión<br />
La queratitis por Acanthamoeba inicialmente, se caracteriza<br />
por queratopatía punteada, pseudodendritas,<br />
infiltrados epiteliales y subepiteliales difusos o focales<br />
Figura 2. A) Tr<strong>of</strong>ozoito de Acanthamoeba con vacuola<br />
digestiva en su interior. B) Quistes de Acanthamoeba<br />
con la típica pared poligonal. Se introdujeron las<br />
muestras en salino de Page hasta su cultivo en agar no<br />
nutriente y posterior cultivo monoxenico.<br />
e infiltrados perineurales (queratoneuritis radial). Más<br />
adelante, se observan ulceración, infiltrados anulares y<br />
uveítis anterior (a menudo con hipopion). La limbitis<br />
es común tanto en etapas tempranas como avanzadas.<br />
Pueden producirse abscesos, escleritis, glaucoma, catarata<br />
e infección microbiana secundaria con hipotonía.<br />
En los estadios finales, el epitelio aparece íntegro, sobre<br />
un leucoma denso y vascularizado, a menudo con<br />
sinequias anteriores. 1<br />
Entre los factores predisponentes se destacan los<br />
traumatismos corneales, el contacto con cuerpos extraños2<br />
o la exposición a aguas contaminadas (piscinas, por<br />
ejemplo); pero el factor de riesgo más importante para<br />
contraer esta infección es el uso de lentes de contacto.<br />
El diagnóstico se establece al ver las amebas en los<br />
frotis teñidos o cultivando los microorganismos obtenidos<br />
en los raspados corneales. Las amebas se ven en<br />
los frotis teñidos con Giemsa, ácido peryódico-Schiff<br />
(PAS), calc<strong>of</strong>lúor blanco o naranja de acridina. El agar<br />
sin nutrientes con una cepa de E. coli o E. aerogenes<br />
es el medio de cultivo preferido. 3 Para demostrar<br />
la presencia de los microorganismos, en especial de<br />
las formas quísticas, se recurre también al microscopio<br />
confocal in vivo. 4<br />
Marzo 2010<br />
<strong>PAN</strong>-<strong>AMERICA</strong> 23
CASE REPORT<br />
24 <strong>PAN</strong>-<strong>AMERICA</strong><br />
Figura 3. A) Leucoma residual corneal. B) Práctica completa resolución del defecto epitelial.<br />
Figura 4. Aspecto 9 días posqueratoplastia.<br />
La reacción en cadena de la polimerasa (PCR) detecta<br />
el ADN amebiano y también puede ser de utilidad. 5<br />
El diagnóstico precoz es el indicador pronóstico<br />
más importante del éxito del tratamiento. Las biguanidas<br />
y las diamidinas son los antiamebianos más<br />
eficaces y son quisticidas. Las diamidinas más usadas<br />
son el isetionato de propamidina (Brolene ® ) y la<br />
hexamidina al 0.1% (Desomedine ® ). Como biguanidas,<br />
polihexametileno biguanida (polihexamida) al<br />
0.02% (PHMB, Avecia HQ, Manchester, Reino Unido),<br />
y Clorhexidina al 0.02% (CHX, Ashton Chemicals Ltd.,<br />
Aylesbury, Reino Unido).<br />
La mayoría de estos fármacos sólo son eficaces<br />
frente a la forma libre del tr<strong>of</strong>ozoíto, con eficacia menor<br />
contra los quistes. 3,6 Otros antiamebianos pueden ser<br />
aminoglucósidos e imidazoles por vía tópica. El uso de<br />
corticoesteroides tópico es controvertido. 6<br />
La queratoplastia penetrante puede ser necesaria<br />
en caso de cicatrices corneales o astigmatismo corneal<br />
irregular. Es recomendable esperar hasta haber<br />
conseguido la inactivación de la enfermedad, pues el<br />
pronóstico del injerto es mejor. No obstante, el riesgo<br />
de recurrencias es muy alto. 1,3<br />
Como conclusión, destacar, que aunque la queratitis<br />
por Acanthamoeba es poco frecuente en nuestro<br />
medio, las consecuencias pueden ser devastadoras. Se<br />
asocian a un mal pronóstico: el diagnóstico tardío, un<br />
tratamiento antimicrobiano inadecuado, el empleo de<br />
corticoides tópicos antes del diagnóstico o la presencia<br />
de microorganismos resistentes. De ahí que sea importante<br />
un diagnóstico precoz, clínico y microbiológico,<br />
como se realizó en nuestro caso, pues un tratamiento<br />
inicial poco acorde da lugar al enquistamiento, el cual<br />
deriva, a su vez en resistencia y dificultades para erradicar<br />
la infección.<br />
Por otra parte, el conocimiento por parte de los<br />
usuarios de lentes de contacto de sistemas eficaces<br />
de desinfección, como el calor o el peróxido de hidrógeno<br />
en dos pasos y empleo de soluciones comerciales<br />
de suero fisiológico, 7 así como la evitación de<br />
situaciones de riesgo es fundamental en la prevención<br />
de esta enfermedad.<br />
REFERENCIAS<br />
1. Juan A. Durán de la Colina. Queratitis por Acanthamoeba.<br />
En: Complicaciones de las lentes de contacto.<br />
Madrid: Tecnimedia; 1998:263-274<br />
2. Abreu Reyes JA, Aguilar Estévez J, Rodríguez Martín<br />
FJ, Díaz Alemán VT, Abreu González R. Queratitis por<br />
acanthamoeba en paciente no portador de lentes de contacto.<br />
Arch Soc Canar Oftal 2003; 14:77-80<br />
3. Thomas J. Liesegang, Gregory L. Skuta. Enfermedades<br />
infecciosas del exterior del ojo. En: Enfermedades externas<br />
y córnea. <strong>American</strong> Academy <strong>of</strong> Ophthalmology.<br />
Barcelona: Elsevier; 2008:187-189<br />
4. Matsumoto Y, Dogru M, Sato EA, Katono Y, Uchino<br />
Y, Shimmura S et al. The application <strong>of</strong> in vivo confocal<br />
scanning laser microscopy in the management <strong>of</strong> Acanthamoeba<br />
keratitis. Mol Vis. 2007; 13:1319-26.<br />
5. Zamfi r O, Yera H, Bourcier T, Batellier L, Dupouy-Camet<br />
J, Tourte-Schaeffer C.Diagnosis <strong>of</strong> Acanthamoeba spp.<br />
keratitis with PCR. J Fr Ophtalmol. 2006; 29:1034-40<br />
6. Ueki N, Eguchi H, Oogi Y, Shiota H, Yamane S,<br />
Umazume H. Three cases <strong>of</strong> Acanthamoeba keratitis<br />
diagnosed and treated in the early stage. J Med Invest.<br />
2009; 56:166-9<br />
7. López L, de Fernando S, Gaztelurrutia L, Vilar B,<br />
Pérez-Irezábal J, Barrón J. Queratitis por Acanthamoeba<br />
spp.: presentación de diez casos. Enferm Infecc Microbiol<br />
Clin. 2000; 18:229-33
Folded dehydrated AMT for scleral delle<br />
Marzo 2010<br />
Multilayered folded dehydrated amniotic<br />
membrane graft for scleral delle management<br />
Jay C. Bradley MD<br />
Department <strong>of</strong> Ophthalmology & Visual Sciences,<br />
Texas Tech University Health Sciences Center<br />
No funding or support was provided for this study.<br />
The author does not have any fi nancial or proprietary interests to disclose.<br />
Abstract<br />
Purpose: Report technique utilizing multilayered<br />
folded dehydrated amniotic membrane for refractory<br />
scleral delle management.<br />
Methods: A 3 x 2 centimeter dehydrated amniotic<br />
membrane was folded four times onto itself, with the<br />
basement membrane side on the exterior, to yield a 7.5<br />
x 10 millimeter graft. This was sutured into the delle<br />
using four 9-0 vicryl sutures. Once adequate fixation <strong>of</strong><br />
the multilayered folded graft was obtained, a primary<br />
conjunctival closure was performed using five 9-0 vicryl<br />
sutures. Total surgical time was fifteen minutes.<br />
Results: This technique was utilized on one patient<br />
with a refractory scleral delle after undergoing pterygium<br />
excision outside <strong>of</strong> my institution with bare sclera<br />
technique and intra-operative mitomycin C application.<br />
No post-operative complications or recurrence <strong>of</strong> the<br />
delle occurred after 9 months <strong>of</strong> followup.<br />
Conclusion: This technique provides an alternative<br />
efficient management <strong>of</strong> refractory scleral dellen while<br />
avoiding use <strong>of</strong> donor corneal or scleral tissue.<br />
Key words: multilayered, folded, dehydrated, amniotic<br />
membrane, scleral delle<br />
Introduction<br />
Scleral dellen occur due to various causes and<br />
are sometimes refractory to medical management. 1-4<br />
The association between sclera dellen and bare sclera<br />
pterygium excision with concomitant mitomycin C use<br />
is well known. 2-3 Techniques for surgical management<br />
<strong>of</strong> scleral dellen, which generally involve a lamellar<br />
tectonic graft with overlying amniotic membrane and/or<br />
conjunctival closure, have been previously described. 1,3<br />
A few prior reports describe the use <strong>of</strong> fresh frozen amniotic<br />
membrane but, if multiple layers were used, separate<br />
grafts were cut and placed in a stepwise fashion. 1,3-4<br />
Dissection and manipulation <strong>of</strong> fresh frozen amniotic<br />
membrane for multilayered closure can be tedious due<br />
to the thin nature <strong>of</strong> the graft and the tendency <strong>of</strong> the<br />
Corresponding author/reprint requests:<br />
Jay C. Bradley MD<br />
3601 4 th St, STOP 7217<br />
Lubbock, TX 79430-7217<br />
Offi ce: (806) 743-2020<br />
Fax: (806) 743-2671<br />
Email: jay.bradley@ttuhsc.edu<br />
Figure 1: Intra-operative anterior segment photographs demonstrating<br />
nasal scleral delle without perforation (upper, left), folded multilayered<br />
dehydrated amniotic membrane prior to suturing (upper, right) and<br />
after suturing (bottom, left), and immediate post-operative appearance<br />
after amniotic membrane graft and primary conjunctival closure<br />
(bottom, right).<br />
amniotic membrane to fold and inappropriately stick to itself or the ocular surface.<br />
Dehydrated amniotic membrane is also thin but can be easily folded and manipulated<br />
using forceps prior to wetting <strong>of</strong> the graft and is fixated in a single step. To the author’s<br />
knowledge, this report provides the first description <strong>of</strong> the use <strong>of</strong> folded multilayered<br />
dehydrated amniotic membrane with overlying conjunctival flap for the treatment <strong>of</strong><br />
an acute scleral delle.<br />
Case Report<br />
The patient was a 78 year-old Hispanic male who underwent pterygium excision<br />
using bare sclera technique and mitomycin C by a surgeon outside Texas Tech<br />
University Health Sciences Center. After the surgery, delayed ocular surface healing<br />
was encountered which was refractory to medical therapy (including topical steroids,<br />
non-preserved artificial tears, and lubricating ointments). Almost three months after<br />
the surgery, the patient was referred to my institution for evaluation and a sceral delle<br />
adjacent to the nasal limbus was found (Figure 1). The scleral wall was thinned to<br />
approximately 20% normal thickness (estimated using anterior segment optical co-<br />
<strong>PAN</strong>-<strong>AMERICA</strong> 25
CASE REPORT<br />
herence tomography) with a large overlying epithelial<br />
defect. The scleral bed surrounding the delle appeared<br />
avascular but no evidence <strong>of</strong> active melt or infection<br />
was noted. Since patient was refractory to prior medical<br />
management, surgical intervention was recommended.<br />
Methods/Results<br />
All necrotic material was removed to provide a<br />
smooth surface in the scleral delle. The scleral delle<br />
was measured and found to be 6 by 8 millimeters. A<br />
3 x 2 centimeter dehydrated amniotic membrane (AmbioDry<br />
2, IOP, Inc., Costa Mesa, California, USA) was<br />
used to fill the scleral delle and provide a substrate to<br />
allow revascularization and healing <strong>of</strong> the area postoperatively.<br />
The dry amniotic membrane was folded,<br />
using non-toothed forceps, four times onto itself, with<br />
the basement membrane side on the exterior, to yield<br />
a 7.5 x 10 millimeter graft. This was sutured into the<br />
delle using four 9-0 vicryl sutures. Once adequate fixation<br />
<strong>of</strong> the multilayered graft was obtained, a primary<br />
conjunctival closure was performed to close the defect<br />
overlying and adjacent to the scleral delle (Figure 1).<br />
This was performed using five 9-0 vicryl sutures being<br />
sure to eliminate any tension on the conjunctival closure.<br />
Total surgical time was fifteen minutes. Anterior segment<br />
optical coherence tomography was performed at 1<br />
and 6 weeks post-operatively (Figure 2). After 9 months<br />
<strong>of</strong> additional follow-up, no complication or recurrence<br />
<strong>of</strong> the sclera delle was experienced.<br />
Discussion<br />
Sceral dellen can complicate pterygium surgery<br />
especially when bare scleral technique and mitomycin<br />
C are utilized. 2-3 If perforation occurs or is imminent, a<br />
corneal or scleral graft with overlying amniotic membrane<br />
and/or conjunctival closure is likely the best option<br />
for surgical intervention.1 In cases with significant<br />
scleral thinning but without active melt or infection, my<br />
technique can be utilized effectively.<br />
This technique is simple to perform and can be performed<br />
under topical anesthesia. It does not require donor<br />
corneal or scleral tissue and can be performed more<br />
quickly than previously reported techniques. Folding <strong>of</strong><br />
a single dehydrated amniotic membrane was performed<br />
to obtain the multilayered graft, as opposed to numerous<br />
single layered grafts stacked on one another, and<br />
the resultant graft had many more layers than previously<br />
reported techniques. 1,3-4 The dehydrated amniotic membrane,<br />
prior to wetting, can be easily folded numerous<br />
times as desired using non-toothed forceps in a matter<br />
<strong>of</strong> seconds. This technique avoids some <strong>of</strong> the difficulty<br />
in manipulating fresh frozen amniotic membrane during<br />
multilayered closure and may decrease overall surgical<br />
time. By utilizing the folding technique, the amount <strong>of</strong><br />
26 <strong>PAN</strong>-<strong>AMERICA</strong><br />
Figure 2: 1 week post-operative anterior segment optical coherence tomography<br />
(AS-OCT) testing (left) showing scleral delle with multi-layered folded amniotic<br />
membrane graft with overlying conjunctival closure. A space between the<br />
amniotic membrane graft and overlying conjunctival closure was noted. 6<br />
week post-operative AS-OCT (right) showing thickening <strong>of</strong> scleral wall with<br />
incorporation <strong>of</strong> amniotic membrane graft. Resolution <strong>of</strong> space between amniotic<br />
membrane and overlying conjunctival closure was noted.<br />
graft material and associated costs are significantly decreased. Another advantage is<br />
that if this surgical intervention fails, a corneal or scleral graft can still be performed<br />
as previously described. 1<br />
Multilayered amniotic membrane has been reported for use in corneal ulcers, corneal<br />
perforations, and scleral dellen. 1,3-5 There is some debate whether the amniotic<br />
membrane dissolves over time or if it adds thickness to the stroma in these cases.<br />
This case illustrates that folded multilayered amniotic membrane can also be used<br />
for thinning associated to scleral dellen and that the amniotic membrane appears<br />
to act as a tectonic graft, thickening the scleral wall. I utilized a graft <strong>of</strong> 8 layers<br />
(approximately 320 micrometers) in thickness based on single layer thickness <strong>of</strong> 40<br />
microns. In the future, the optimal number <strong>of</strong> folds to use depending on the extent <strong>of</strong><br />
the scleral thinning will need to be determined. Although additional study is needed,<br />
multilayered folded dehydrated amniotic membrane appears to be a valid alternative<br />
to previously reported techniques in the management <strong>of</strong> sclera dellen.<br />
BIBLIOGRAFÍA<br />
1. Casas VE, Kheirkhah A, Blanco G, Tseng SC. Surgical approach for sclera ischemia and melt.<br />
Cornea. 2008;27(2):196:201.<br />
2. Tsai YY, Lin JM, Shy JD. Acute sclera thinning pterygium excision with intraoperative mitomycin<br />
C: a case report <strong>of</strong> sclera dellen after bare sclera technique and review <strong>of</strong> the literature. Cornea.<br />
2002;21(2):227-9.<br />
3. Sridhar MS, Bansal AK, Rao GN. Multilayered amniotic membrane transplantation for partial<br />
thickness sclera thinning following pterygium surgery. Eye. 2002;16:639-42.<br />
4. Hanada K, Shimazaki J, Shimmura S, Tsubota K. Multilayered amniotic transplantation for severe<br />
ulceration <strong>of</strong> the cornea and sclera. Am J Ophthalmol. 2001;131(3):324-31.<br />
5. Muller M, Meltendorf C, Mirshahi A, Kohnen T. Use <strong>of</strong> multilayer amniotic membrane as fi rst<br />
therapy for penetrating corneal ulcers. Klin Monbl Augenheilkd. 2009;226(8):640-4.
Truly Unilateral Keratoconus<br />
Associated with Orbital Fibrosis<br />
Alejandro Navas MD; Armando González-Gomar MD;<br />
Zoraida Espinosa MD; José Luis Tovilla-Canales MD;<br />
Tito Ramírez-Luquín MD; Enrique O. Graue-Hernández MD<br />
Affi liation: Department <strong>of</strong> Cornea and Refractive Surgery, Institute <strong>of</strong> Ophthalmology<br />
“Conde de Valenciana”, Mexico City, Mexico<br />
The authors have no proprietary interest in the materials presented herein.<br />
RESUMEN<br />
Objetivo: Reportar el caso de un paciente con queratocono<br />
unilateral verdadero en el ojo derecho asociado<br />
a fibrosis localizada en la órbita ipsilateral.<br />
Métodos: Hombre de 25 años de edad con agudeza<br />
visual progresiva en el ojo derecho con diagnóstico<br />
de queratocono unilateral y fibrosis orbitaria unilateral.<br />
El ojo derecho con una agudeza visual de 20/800 que<br />
mejoraba a 20/40 con una refracción de -7.50 -6.00<br />
x 175°, presentando signos clínicos de queratocono.<br />
Los movimientos oculares muestran limitaciones en la<br />
mirada hacia arriba en todas las posiciones. El ojo y<br />
órbita del lado izquierdo sin ninguna alteración con una<br />
agudeza visual de 20/20.<br />
Resultados: Se realizó tomografía computada,<br />
confirmando el diagnóstico de fibrosis orbitaria en la<br />
órbita derecha, las topografías corneales a través del<br />
tiempo mostraron progresión evidente del queratocono<br />
en el ojo derecho y estabilidad en el ojo izquierdo.<br />
Conclusiones: El queratocono unilateral verdadero<br />
es una condición rara. La asociación de queratocono<br />
unilateral con alteraciones unilaterales de párpados y<br />
órbita se ha descrito previamente. Sin embargo, según<br />
nuestro conocimiento, este es el primer reporte de fibrosis<br />
orbitaria asociado con queratocono.<br />
ABSTRACT<br />
Purpose: To report a case <strong>of</strong> a patient who presented<br />
with true unilateral keratoconus in his right eye associated<br />
to a localized fibrosis in his ipsilateral orbit.<br />
Methods: A 25-year old male with progressive visual<br />
acuity loss in the right eye was diagnosed with unilateral<br />
keratoconus and unilateral orbital fibrosis. Right<br />
eye visual acuity was 20/800 improving to 20/40 with a<br />
Corresponding authors and Reprints:<br />
Alejandro Navas MD<br />
Deparment <strong>of</strong> Cornea and Refractive Surgery<br />
Institute <strong>of</strong> Ophthalmology “Conde de Valenciana”<br />
Chimalpopoca #14, Col Obrera, Mexico City,<br />
DF 06800 Mexico<br />
e-mail: babesian@gmail.com<br />
refraction <strong>of</strong> -7.50 -6.00 x 175° and he presented with<br />
clinical signs <strong>of</strong> keratoconus. Eye movements showed<br />
limitations in the upper gaze <strong>of</strong> the right eye in all positions.<br />
The fellow eye and orbit were under normal limits<br />
and visual acuity was 20/20.<br />
Results: Computed Tomography scan confirmed<br />
the diagnosis <strong>of</strong> orbital fibrosis in the right orbit and<br />
corneal topographies during a time span showed evident<br />
keratoconus progression <strong>of</strong> the right eye and stability<br />
in the left eye.<br />
Conclusions: True unilateral keratoconus is a<br />
rare condition. <strong>Association</strong> <strong>of</strong> unilateral keratoconus<br />
with unilateral eyelid and orbital conditions has been<br />
previously reported. Nevertheless, to our knowledge,<br />
this is the first report <strong>of</strong> orbital fibrosis associated<br />
with keratoconus.<br />
Key words: Keratoconus; unilateral keratoconus;<br />
monocular keratoconus; orbital fibrosis; eye rubbing<br />
Keratoconus (KC) is usually a bilateral condition<br />
that affects the cornea, producing thinning and protrusion<br />
without inflammation. 1, 2 The asymmetry <strong>of</strong> the<br />
disease is well accepted, nonetheless, confirmed truly<br />
unilateral KC cases are rare and remote. 3, 4, 5, 6 KC has<br />
been associated with several ocular disorders 1, 2 as well<br />
as some eyelid and lacrimal system alterations, 7, 8, 9 but<br />
there are no previous associations with orbital fibrosis<br />
to the best <strong>of</strong> our knowledge.<br />
Congenital orbital fibrosis is a disease classified<br />
under the congenital fibrosis <strong>of</strong> extraocular muscles<br />
(CFEOM). CFEOM classification has still been useful,<br />
even though sometimes the clinical presentation can<br />
overlap the subtypes <strong>of</strong> CFEOM. 10, 11 Recently, some authors<br />
proposed to consider orbital fibrosis as a different<br />
clinical disease. 12, 13 We present a case <strong>of</strong> true unilateral<br />
keratoconus secondary to orbital fibrosis.<br />
Marzo 2010<br />
<strong>PAN</strong>-<strong>AMERICA</strong> 27
CASE REPORT<br />
Figure 2: Planar and contrast-enhanced CT<br />
scan images on coronal view showing a mass<br />
with thickening between the inferior and medial<br />
extraocular muscles, with increasing density<br />
corresponding to fi brotic tissue.<br />
28 <strong>PAN</strong>-<strong>AMERICA</strong><br />
CASE REPORT<br />
A 25 year-old male complained <strong>of</strong> progressive visual acuity loss in the right eye.<br />
He also noted changes in the cosmetic appearance <strong>of</strong> his right eyelid since childhood.<br />
Under examination, we found uncorrected distance visual acuity <strong>of</strong> 20/800 in<br />
his right eye with 20/20 in the left eye. The refraction was -7.50 -6.00 x 175° with<br />
scissoring reflex in the right eye and -0.50 -0.50 x 15° in the left eye, improving to<br />
a best spectacle corrected visual acuity <strong>of</strong> 20/40 and 20/15 respectively. Slit-lamp<br />
examination showed corneal thinning, Vogt’s striae as well as Munson’s and Rizzutti’s<br />
signs in the right eye. He presented a mild blepharoptosis and an inferior palpebral<br />
retraction. Interestingly, we found a limitation in the upper gaze <strong>of</strong> the right eye in all<br />
the eye movement positions (Fig. 1). We also performed a passive duction test that<br />
was positive upward and temporal in the right eye. The left eye slit-lamp examination<br />
was unremarkable. Computed Tomography (CT) scan, focused on the orbital region,<br />
showed thickening <strong>of</strong> the inferior and medial intraocular muscles and a mass with<br />
increased density both in the intraconal and extraconal areas that can correspond with<br />
fibrotic tissue (Fig. 2). We analyzed the Orbscan II (Bausch & Lomb, Rochester, NY)<br />
corneal topographies <strong>of</strong> the patient in both eyes finding throughout time, KC progression<br />
data in the right eye (Fig. 3) with no KC data and lack <strong>of</strong> progression in the left<br />
eye (Fig 4). We decided to treat the right eye with a rigid contact lens improving visual<br />
capacity to 20/25 and we strongly suggested for him to avoid eye rubbing.<br />
DISCUSSION<br />
Figure 1: All gaze positions showing right eye limitation in the upper gaze.<br />
We presented a case <strong>of</strong> true unilateral KC in a patient with orbital fibrosis on the<br />
right eye. The corneal topographic compilation during three years confirmed the progression<br />
<strong>of</strong> the disease in the right eye and inversely showed no significant change in<br />
the left eye. Some studies support that mechanical rubbing can affect the progression<br />
<strong>of</strong> KC. 14, 15 We intentionally inquired <strong>of</strong> our patient about eye rubbing and he admitted<br />
a positive eye rubbing history in both eyes and more importantly in the right eye.<br />
Also, it is important to comment that he is a right-handed patient, which could have<br />
contributed with more force and intensity to this mechanical factor.<br />
Prior to videokeratoscopy studies unilateral KC was believed to occur in higher<br />
incidences <strong>of</strong> 14.3% and up to 41%, 1 although at present, it is considered rare with<br />
ranges between 0.5 to 4%. 4 Conversely some authors challenged that the possibility
Figure 3: Right eye topographic<br />
maps showing evident signs <strong>of</strong><br />
progression in curvature, elevation<br />
and pachymetric maps during time:<br />
(A) three years ago, (B) one year ago<br />
and (C) most recent evaluation.<br />
Figure 4: Left eye topographic<br />
maps showing stability and lack <strong>of</strong><br />
keratoconus data during time: (A)<br />
three years ago, (B) one year ago and<br />
(C) most recent evaluation.<br />
<strong>of</strong> true monocular KC can exist and even created some diagnosis criteria. 5 In our case<br />
there is evidence <strong>of</strong> the presence <strong>of</strong> true unilateral or monocular KC during a significant<br />
time period that discards the involvement <strong>of</strong> the left eye.<br />
There are previous reports <strong>of</strong> unilateral or asymmetric KC associated with various<br />
clinical conditions that are associated with eye rubbing, 3, 7, 8, 9 notwithstanding, to our<br />
knowledge, there are no previous associations <strong>of</strong> KC with unilateral orbital fibrosis.<br />
Krachmer suggested that there are some factors that control the changes induced<br />
by eye rubbing such as corneal thickness and biomechanics, as well as<br />
orbital structure.16 In this case, the orbital involvement can provide a role in the<br />
eye rubbing effect. Orbital fibrosis is a rare disease usually classified as a type <strong>of</strong><br />
congenital fibrosis <strong>of</strong> the extraocular muscles, but recently some authors proposed<br />
to consider this entity as a different disease because it is unilateral, affects the orbit<br />
and not just the extraocular muscles, and apparently does not have a well established<br />
hereditary pattern. 12,13<br />
There is one report <strong>of</strong> congenital fibrosis <strong>of</strong> the inferior rectus developing high<br />
myopia in the ipsilateral eye in a child, 11 yet authors did not mention any keratoconic<br />
data. In our case, the patient’s relatives noticed his ocular affection since he<br />
was 2 or 3 years old, but KC did not become evident until adolescence. Thus, we<br />
recommend performing corneal topographic analysis in cases with orbital fibrosis<br />
and myopia or anisometropia.<br />
This case suggests that a chronic habit <strong>of</strong> abnormal rubbing can be part <strong>of</strong> the<br />
pathogenesis <strong>of</strong> KC, or that it can contribute to the progression, as reported in previous<br />
studies. 14, 15, 17 It is easier to deduce that eye rubbing is the shared factor in the<br />
BIBLIOGRAFÍA<br />
1. Krachmer JH, Feder RS,<br />
Belin MW. Keratoconus<br />
and related noninfl ammatory<br />
corneal thinning disorders.<br />
Surv Ophthalmol.<br />
1984;28:293-322.<br />
2. Rabinowitz YS. Keratoconus.<br />
Surv Ophthalmol.<br />
1998;42:297-319.<br />
3. Jafri B, Lichter H,<br />
Stulting RD. Asymmetric<br />
keratoconus attributed<br />
to eye rubbing. Cornea.<br />
2004;23:560-564.<br />
4. Li X, Rabinowitz YS,<br />
Rasheed K, et. al. Longitudinal<br />
study <strong>of</strong> the normal<br />
eyes in unilateral keratoconus<br />
patients. Ophthalmology.<br />
2004;111:440-446.<br />
5. Phillips AJ. Can true<br />
monocular keratoconus<br />
occur? Clin Exp Optom.<br />
2003;86:399-402.<br />
6. Zadnik K, Steger-May K,<br />
Fink BA, et. al. Between-eye<br />
asymmetry in keratoconus.<br />
Cornea. 2002;21:671-679.<br />
7. Ioannidis AS, Speedwell<br />
L, Nischal KK. Unilateral<br />
keratoconus in a child with<br />
chronic and persistent eye<br />
rubbing. Am J Ophthalmol.<br />
2005;139:356-357.<br />
8. Lindsay RG, Bruce AS,<br />
Gutteridge IF. Keratoconus<br />
associated with continual<br />
eye rubbing due to<br />
punctual agenesis. Cornea.<br />
2000;19:567-569.<br />
9. Diniz CM, Tzelikis PF,<br />
Rodrigues Júnior A, et. al.<br />
Unilateral keratoconus associated<br />
with continual eye<br />
rubbing due to nasolac-<br />
Marzo 2010<br />
presented case and other diseases associated with KC,<br />
such as Leber congenital amaurosis, Down syndrome,<br />
atopic disease, contact lens wear and floppy eyelid<br />
syndrome, 16 than to assume that all have a different associated<br />
factor that affects the cornea.<br />
In conclusion, this is a case <strong>of</strong> true unilateral KC<br />
secondary to mechanical trauma owed to orbital fibrosis.<br />
Further follow-up is recommended in order to<br />
rule out the possibility <strong>of</strong> keratoconus in the fellow eye,<br />
since KC can <strong>of</strong>ten present in a unilateral fashion with<br />
significant asymmetry for several years or even decades<br />
with development <strong>of</strong> keratoconus in the other eye<br />
in the future. 4 These kinds <strong>of</strong> cases accentuate the role<br />
<strong>of</strong> eye rubbing as an etiologic or exacerbating factor in<br />
patients with KC.<br />
rimal obstruction –case<br />
report. Arq Bras Oftalmol.<br />
2005;65:122-125.<br />
10. Shivaram SM, Engle<br />
EC, Petersen RA, et.al.<br />
Congenital fi brosis syndromes.<br />
Int Ophthalmol<br />
Clin. 2001;41:105-113.<br />
11. Bagheri A, Naghibozakerin<br />
J, Yazdani S. Management<br />
<strong>of</strong> congenital fi brosis<br />
<strong>of</strong> the inferior rectus muscle<br />
associated with high myopia:<br />
a case report. Strabismus.<br />
2007;15:157-163.<br />
12. Athanasiov PA, Prabhakaran<br />
VC, Selva D. Unilateral<br />
orbital fi brosis with blepharoptosis<br />
and enophthalmos.<br />
Ophthal Plas Reconstr Surg.<br />
2008;24:156-158.<br />
13. Mavrikakis I, Pegado<br />
V, Lyons C, et al. Congenital<br />
orbital fi brosis: a distinct<br />
clinical entity. Orbit.<br />
2009;28:43-49.<br />
14. McMonnies CW. Mechanisms<br />
<strong>of</strong> rubbing-related<br />
corneal trauma in keratoconus.<br />
Cornea. 2009;28:607-<br />
615.<br />
15. McMonnies CW. The<br />
evidentiary signifi cance <strong>of</strong><br />
case reports: eye rubbing<br />
and keratoconus. Optom Vis<br />
Sci. 2008;85:262-269.<br />
16. Krachmer JH. Eye rubbing<br />
can cause keratoconus.<br />
Cornea. 2004;23:539-540.<br />
17. Carlson AN. Keratoconus.<br />
Ophthalmology.<br />
2009;116:2036-2037.<br />
<strong>PAN</strong>-<strong>AMERICA</strong> 29
Marzo 2011<br />
30 <strong>PAN</strong>-<strong>AMERICA</strong><br />
New Publication<br />
Ha ssido<br />
sid ido pu publ publicada blic icad ada la eedi<br />
edición dici ción ón e een<br />
español de Of-<br />
talmogeriatría. Todos los que nos ddedicamos<br />
a la <strong>of</strong>-<br />
talmología clínica reconocemos qu que los viejos son el<br />
centro de nuestra actividad. Marce Marcela Cypel y Rubens<br />
Belfort Jr., de la Universidad Federal<br />
de São Paulo, han<br />
producido un texto de gran importa importancia y que tendrá<br />
gran valor para los <strong>of</strong>talmólogos de hhabla<br />
hispana. Este<br />
libro tiene un enfoque único, pues tra<br />
trata el diagnóstico y<br />
tratamiento de enfermedades que afectan todas las edades,<br />
desde el punto de vista geriátrico. Hace especial<br />
énfasis en el impacto que tienen varias entidades <strong>of</strong>talmológicas<br />
en la población de edad avanzada y como<br />
el factor etario afecta el manejo de la enfermedad. Con<br />
más de 40 autores de los centros más importantes de<br />
Brasil, los 27 capítulos del libro cubren una gran gama<br />
de alteraciones <strong>of</strong>talmológicas que afectan a la población<br />
de la tercera edad.<br />
Reviewed by Mark J. Mannis MD<br />
Oftalmogeriatría<br />
Marcela Cypel and Rubens Belfort Jr<br />
Creative Latin Media, LLC<br />
Boca Raton, FL<br />
440 pp. + Index<br />
Geriatric Ophthalmology<br />
The Spanish language edition <strong>of</strong> Oftalmogeriatría<br />
has now been published. All <strong>of</strong> us who practice<br />
ophthalmology clinically recognize that the elderly are<br />
at the very center <strong>of</strong> what we do. Marcela Cypel and Rubens<br />
Belfort Jr. from the Federal University <strong>of</strong> São Paulo<br />
have produced a very important text that will be <strong>of</strong> great<br />
value to Spanish and Portuguese speaking ophthalmologists.<br />
The unique approach <strong>of</strong> this book is that it treats<br />
the diagnosis and management <strong>of</strong> entities that affect<br />
all ages from the special viewpoint <strong>of</strong> the elderly. The<br />
book emphasizes the specific impact that the wide variety<br />
<strong>of</strong> eye diseases have on the aging population and<br />
how the age factor specifically affects disease management.<br />
With over 40 contributing authors from the major<br />
ophthalmology programs in Brazil, the 27 chapters in<br />
the book cover the broad range <strong>of</strong> ophthalmic disorders<br />
and their impact on the aging population.<br />
Reviewed by Mark J. Mannis MD
VISION<br />
<strong>PAN</strong>-<strong>AMERICA</strong><br />
Vision <strong>Pan</strong>-America is the <strong>of</strong>ficial publication <strong>of</strong> the <strong>Pan</strong>-<br />
<strong>American</strong> <strong>Association</strong> <strong>of</strong> Ophthalmology (PAAO). The publication<br />
is particularly interested in receiving manuscripts that are<br />
short state-<strong>of</strong>-the-art review papers that will be <strong>of</strong> interest to the<br />
practicing PAAO member ophthalmologist. In addition to review<br />
articles, the publication is interested in articles on new surgical<br />
techniques, medical therapies, and case reports that emphasize<br />
clinicopathologic correlations.<br />
Submission information<br />
Manuscripts should be submitted electronically to the Editor-in-Chief,<br />
Mark J. Mannis MD at mjmannis@ucdavis.edu or<br />
can be sent via mail to:<br />
All submissions must be provided in electronic form as well as<br />
written manuscript form if mailed. All submissions must be original<br />
publications that have not been published elsewhere. Submissions<br />
can be in Spanish, English, Portuguese or French. All papers should<br />
be preceded by an abstract in either English or Spanish.<br />
Submission Format<br />
Mark J. Mannis MD<br />
Department <strong>of</strong> Ophthalmology<br />
University <strong>of</strong> California, Davis<br />
4860 Y Street, Suite 2400<br />
Sacramento, CA 95817, U.S.A.<br />
Papers submitted should be no longer than 1500 words (six double<br />
–spaced type-written pages) plus references.<br />
References should be included as a list on a separate page at<br />
the end <strong>of</strong> the manuscript with cited references keyed to the text in<br />
the order <strong>of</strong> appearance.<br />
The following format should be used for referenced papers:<br />
Jones JS, Garcia TL, Perrero M. Diabetic retinopathy in Bolivia.<br />
Cornea, 1996; 26 (2): 341- 343.<br />
Smith DJ, Caldera MC, Chang N, Ferrer RJ. Managing Ocular<br />
Trauma. H<strong>of</strong>stra and Kennimore Publishers, London, 1989.<br />
Color figures are encouraged and should be submitted in PICT<br />
or JPEG format. Powerpoint format is not acceptable, and images<br />
embedded in word documents are not acceptable.<br />
The title page should include the following: (1) each author’s<br />
full name (i.e., first name, middle initial if used, and last name) and<br />
highest degree (i.e. MD, PhD); (2) city, state, and country in which<br />
work was carried out; (3) name and address <strong>of</strong> author to receive<br />
reprint requests; (4) statement about the authors’ proprietary or financial<br />
interest in a product or lack there<strong>of</strong>.<br />
Marzo 2010<br />
Instructions to Authors<br />
Vision <strong>Pan</strong>-America es la publicación <strong>of</strong>icial de la Asociación <strong>Pan</strong>americana<br />
de Oftalmología (PAAO). La publicación está particularmente<br />
interesada en recibir manuscritos que sean cortas revisiones de materias<br />
novedosas de interés para los <strong>of</strong>talmólogos miembros de la Asociación.<br />
Además de las revisiones, la publicación está interesada en artículos<br />
acerca de nuevas técnicas quirúrgicas, nuevas terapias médicas y casos<br />
de correlación clínico-patológica.<br />
Información de presentación<br />
Los manuscritos deben enviarse electrónicamente al jefe de redacción,<br />
Mark J. Mannis, MD a mjmannis@ucdavis.edu o puede enviarse<br />
vía correo a:<br />
Mark J. Mannis, MD,<br />
Departamento de Oftalmología<br />
Universidad de California, Davis<br />
4860 Y Street, Suite 2400<br />
Sacramento, CA 95817, U.S.A.<br />
Si se envía el trabajo por correo, este debe ir tanto impreso (a máquina,<br />
etc.) y en forma electrónica (CD, etc.). Todas las presentaciones<br />
deben ser publicaciones originales que no se hayan publicado en otra<br />
parte. Las presentaciones pueden ser escritas en idioma español, inglés,<br />
portugués o francés. Todos los trabajos deben tener un resumen en inglés<br />
y en español.<br />
Formato de presentación<br />
Los trabajos presentados no deben sobrepasar las 1500 palabras<br />
(seis páginas escritas a doble espacio) más las referencias.<br />
Las referencias deben ser incluidas como una lista en una página<br />
separada al final del manuscrito con referencias citadas codificadas al<br />
texto en el orden de aparición.<br />
El siguiente formato debe usarse para las referencias:<br />
Jones JS, García TL, Perrero M. Retinopatía Diabética en Bolivia. Córnea,<br />
1996; 26 (2): 341 - 343.<br />
Smith DJ, Caldera MC, Chang N, Ferrer RJ. Managing Trauma Ocular.<br />
H<strong>of</strong>stra y Publicadores de Kennimore, Londres, 1989.<br />
Se aceptan figuras de color y deben enviarse en PICT o formato de<br />
JPG. El formato de Powerpoint no es aceptable.<br />
La página del título debe incluir lo siguiente: (1) el nombre completo<br />
de cada autor (es decir, nombre(s) y apellido(s)) y el grado académico<br />
más alto (ej. MD PhD); (2) la ciudad, estado, y país en que el trabajo se<br />
llevó a cabo; (3) el nombre y dirección del autor para recibir pedidos de<br />
separata; (4) declaración de los autores si existe o no interés financiero<br />
en un producto citado o utilizado en el trabajo.<br />
<strong>PAN</strong>-<strong>AMERICA</strong> 31
Sponsored by<br />
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2011 Pre ARVO<br />
<strong>Pan</strong><strong>American</strong><br />
Research Day<br />
April 30, 2011<br />
Renaissance Fort Lauderdale Hotel<br />
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11:00 am - 12:30 pm<br />
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(light buffet<br />
will be served)<br />
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presiones-objetivo en más pacientes<br />
Investigadores de diversos estudios, (AGIS, Shirakashi, Shields)<br />
han comprobado que alcanzar y mantener la PIO entre 14 y 15 mmHg<br />
reduce la progresión de pérdida del campo visual 1,2,3.<br />
Lumigan ® alcanza la PIO-objetivo de 14/15 mmHg en un mayor número<br />
de pacientes:<br />
®<br />
vs. timolol 4 vs. latanoprost 6<br />
® dorzolamida/<br />
®<br />
vs.<br />
timolol 5<br />
Porcentaje de Pacientes que<br />
alcanzaron la PIO-Objetivo ≤14 21% 9% 17% 2% 19% 9%<br />
Porcentaje de Pacientes que<br />
alcanzaron la PIO-Objetivo ≤15 31% 16% 24% 9% 29% 14%<br />
Lumigan umigan ® (bimatoprost) Forma Forma farmacéutica farmacéutica y y pr presentación.<br />
pr esentación. esentación.Frascos esentación. cuenta-gotas conteniendo 5 ml de solución <strong>of</strong>talmológica estéril de bimatoprost a 0,03%. USO ADULTO.Composición.<br />
Composición.<br />
Composición. Cada ml contiene: 0,3 mg de bimatoprost. Vehículo: cloreto de sódio, fosfato de sódio<br />
hepta-hidratado, ácido cítrico mono-hidratado, ácido clorídrico y/o hidróxido de sódio, cloruro de benzalconio y agua purificada qsp. Indicaciones. Indicaciones. LUMIGAN ® (bimatoprost) es indicado para la reducción de la presión intra-ocular elevada en pacientes con glaucona o hipertensión<br />
ocular.Contraindicaciones.<br />
Contraindicaciones. LUMIGAN ® (bimatoprost) está contraindicado en pacientes con hipersensibilidad al bimatoprost o cualquier otro componente de la fórmula del producto. Pr Precauciones Pr Precauciones<br />
ecauciones y y Adver Advertencias.<br />
Adver tencias. Advertencias. Fueron relatados aumento gradual del crescimiento<br />
de las pestañas en el largo y espesura, y oscurecimiento de las pestañas (en 22% de los pacientes después 3 meses, y 36% después 6 meses de tratamiento), y, oscurecimiento de los párpados (en 1 a