Cornea - ARVO

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ARVO 2013 Annual Meeting Abstracts by Scientific Section/Group - CorneaRepresentative histopathology findings in 3-snip punctoplastyspecimens. (B) Densely fibrotic collagenous scar tissue with no orminimal residual inflammation.Magnification 200XCommercial Relationships: Gary J. Lelli, None; Alexander D.Port, None; Yao-Tseng Chen, NoneProgram Number: 6031 Poster Board Number: A0094Presentation Time: 10:30 AM - 12:15 PMHyperosmolar dryness stress on 3D HCE model: a new tool forpre-clinical assessment of tear substitutesBarbara De Servi 1 , Celine Olmiere 2 , Marisa Meloni 1 . 1 VitroScreen,Milan, Italy; 2 Laboratoires Thea, Clermont-Ferrand, France.Purpose: Dryness stress model has already been established in 3Dhuman corneal epithelium cell culture (3D HCE). In order to bettermimic Tear Dysfunction Syndrome, a new stress model includingboth physical dryness stress and hyper-osmolarity has beendevelopped in 3D HCE. Relevance and predictability of this modelwere verified with reference tear substitutes.Methods: The 3D HCE tissues were transferred in controlledconditions (R.H.
ARVO 2013 Annual Meeting Abstracts by Scientific Section/Group - Corneasevere dry eye disease (including Graft vs Host Disease) in a doublemasked,vehicle-controlled, physician-sponsored Phase 2 clinicaltrial. The study’s hypothesis is that Tβ4, in its role as a modulator ofcorneal surface healing and inflammation, may be able to promotehealing of the corneal surface allowing for more conventionalmodalities to take over and maintain a smooth and regular ocularsurface.Methods: Nine patients with severe dry eye (18 eyes) were treatedwith Tβ4 drops (0.1%) or vehicle control six times daily over aperiod of 28 days. They were evaluated upon entering the study aftera two week washout period as follows: Study Day 1 (randomizationand first day of treatment), 7, 14, 21, 28 (End of Treatment), and 56(follow-up). Dry eye sign and symptom assessments, such as oculardiscomfort (using the OSDI questionnaire) and corneal fluoresceinstaining (using the NEI workshop grading system), were evaluated atvarious time points throughout the study.Results: Statistically significant differences in sign and symptomassessments, such as ocular discomfort and corneal fluoresceinstaining, were seen at various time points throughout the study. Ofparticular note at Day 56, the follow-up period, were the differencesbetween Tβ4 and vehicle control. The Tβ4-treated group (12 eyes)had a 35.1% reduction of ocular discomfort compared to vehiclecontrol (6 eyes) (p=0.0141), and a 59.1% reduction of total cornealfluorescein staining compared to vehicle control (p=0.0108). Otherimprovements seen in the Tβ4-treated patients included tear filmbreakup time and increased tear volume production.Conclusions: Tβ4 eye drops were found to be safe and well-toleratedand met key efficacy objectives with statistically significant sign andsymptom improvements, compared to vehicle control, at various timeintervals, including 28 days post-treatment. These positive resultssuggest that further clinical trials are warranted and should aim toassess Tβ4’s efficacy and optimal dosing regimens in the setting ofsevere dry eye disease.Commercial Relationships: Gabriel Sosne, RegeneRxBiopharmaceuticals (C); Steven P. Dunn, None; David Crockford,None; Chaesik Kim, None; Elizabeth Dixon, NoneClinical Trial: NCT01393132Program Number: 6034 Poster Board Number: A0097Presentation Time: 10:30 AM - 12:15 PMBiomarkers in the tear fluid during chemical ocular injury in therabbit modelXxxx Xxxxxx. Xxxxxx, Xxxxxx, MD.Purpose: Analysis of biomarkers in the tear fluid enables continuousfollow-up during ocular pathologies. The sight threatening sulfurmustard (SM) induced ocular injury presents specific clinicalsymptoms for each injury stage. While the partially healed acutephase is characterized by erosions and severe inflammation, thepermanent delayed pathology that is developed only in part of theeyes, is clinically expressed by epithelial defects andneovascularization (NV). The mechanisms underlying this injury arestill in research and treatment is not sufficient. Aiming to improve thetherapeutic strategies, we focused on finding biomarkers in the tearfluid that point out towards the pathological processes during theinjury.Methods: Rabbit eyes were exposed to SM vapor and a clinicalfollow-up was carried out up to 4 weeks. Tear fluid and cornealsamples were collected at different time points and MMP-2 andMMP-9 activities were measured by zymography and VEGF, IL-8,IL-6, TNFα and IL-1β levels were measured by ELISA.Results: Typical SM-induced ocular injury was developed, includingan acute phase that subsided within a week in all of the exposed eyes,followed by a permanent delayed pathology in 50%-80% of the eyes,beginning at 2w. In the tear fluid elevation in MMP-9 activity and IL-8 level was seen. While MMP-9 activity remained high throughoutthe follow-up period in all of the exposed eyes, IL-8 levelscorresponded with the severity of the clinical symptoms.Interestingly, relatively higher IL-8 levels in tear fluid were noticedin future neovascularized eyes before NV appearance, indicating arole in prediction of the delayed pathology. IL-8 level and MMP-9activity were elevated in the corneal tissue as well, indicating apossible source for these proteins in the tear fluid.Conclusions: Biomarkers in the tear fluid are a sensitive tool formonitoring pathological mechanisms during the dynamic course ofthe ocular injury. These biomarkers can rationalize novel therapeuticstrategies and serve as a tool for treatment evaluation. Moreover, IL-8level in the tear fluid at the early stages of the injury may beindicative for the future injury outcome and the need for a preventivetherapy.Commercial Relationships: Xxxx Xxxxxx, NoneProgram Number: 6035 Poster Board Number: A0098Presentation Time: 10:30 AM - 12:15 PMCharacterization of cultivated Human Oral Mucosal EpithelialCells (HOMEs) in an autologous culture mediumCamilla Gram, Dag Krohn-Hansen, Eli Gulliksen, Kristiane Haug,Jon K. Slettedal, Morten C. Moe, Liv Drolsum, Bjorn Nicolaissen,Aboulghassem Shahdadfar. Department of Ophthalmology, OsloUniversity Hospital Oslo, Norway, Center for Eye Research, Oslo,Norway.Purpose: The aim of this study is to culture human oral mucosal cells(HOMEs) for reconstruction of human ocular surface. In the presentstudy we characterize two different cell populations expanded inmedium supplemented with autologous serum.Methods: Small biopsy of human oral mucosal epithelium washarvested and after enzymatic treatment cultured in mediumsupplemented with autologous serum for 3 weeks at 37 degreesCelsius with 5% CO2 in a humidified atmosphere and the mediumwas changed every 3-4 days. Two different cell populations werethen isolated and analyzed by qRT-PCR, electron microscopy (EM)and immunohistochemistry.Results: In our study, two isolated populations (Pa and Pb) weresuccessfully proliferated in medium supplemented with autologousserum compared with fetal bovine serum (FBS) containing medium.The levels of markers associated with proliferation, stemness, celljunction, and functional ocular surface such as KI67, ABCG2, P63,SOX9, CK19, CK3, CX43, E-CAD, and OCLN were differentiallyexpressed in these two Pa and Pb populations, but in the Papopulation stemness and cell junction related markers were extremelyhigher expressed compared with the Pb population.Conclusions: The preliminary results of this study show thatexpanded human oral mucosal cells (HOMEs) in our culture systemgenerates a committed cell population that can potentially be used inreconstraction of human ocular surface.Commercial Relationships: Camilla Gram, None; Dag Krohn-Hansen, None; Eli Gulliksen, None; Kristiane Haug, None; Jon K.Slettedal, None; Morten C. Moe, None; Liv Drolsum, None; BjornNicolaissen, None; Aboulghassem Shahdadfar, NoneProgram Number: 6036 Poster Board Number: A0099Presentation Time: 10:30 AM - 12:15 PMEffects of lens care solutions on dynamic interfacial properties ofhuman tear lipidsTatyana F. Svitova, Meng C. Lin. Optometry School, Univ ofCalifornia, Berkeley, Berkeley, CA.©2013, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permissionto reproduce any abstract, contact the ARVO Office at arvo@arvo.org.
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