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Cornea - ARVO

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<strong>ARVO</strong> 2013 Annual Meeting Abstracts by Scientific Section/Group - <strong>Cornea</strong>existing dry eye questionnaires.Methods: A total of 50 subjects, 30 symptomatic and 20asymptomatic, as determined using the Ocular Surface Disease Index(OSDI) were enrolled. All subjects completed 5 different dry eyequestionnaires (SPEED, OSDI, DEQ, McMonnies and SESoD) in arandom order on two separate visits. Clinical measurements wereobtained on the first visit. Concordance correlation coefficient wasused to determine repeatability, Principal Component, Factor andRasch analyses were used to determine dimensionality, and thecomparison of SPEED scores to dry eye diagnosis defined by theOSDI (primarily using receiver-operator characteristic (ROC) curveanalysis) was used to determine validity.Results: The SPEED questionnaire was found to be uni-dimensionalusing Rasch analysis. Three principal components (dryness, burning,soreness/fatigue) were identified and SPEED scores between visitCCC was 0.923 (upper and lower 95% CI 0.868 to 0.955). The areaunder the ROC was 0.928. The only clinical measures that correlated“well” with SPEED scores were corneal staining (p < 0.05),meibomian gland score (MGS) (p < 0.05) and meibomian glandsyielding liquid secretion score (MGYLS) (p < 0.05).Conclusions: These results indicate that the SPEED questionnaire isa valid and repeatable instrument for measurement of dry eyesymptoms. The correlation of the SPEED score with clinicalmeasures of meibomian gland function suggests potential additionalclinical value for the diagnosis and/or management of meibomiangland dysfunction.Commercial Relationships: Nancy J. Keir, TearScience (F), Alcon(F), Alcon (R), Allergan (F), Johnson & Johnson (F), CooperVision(F), Visioneering, Inc. (F); William Ngo, None; Ping Situ, None;Donald R. Korb, TearScience (F); Caroline A. Blackie,TearScience (E); Trefford L. Simpson, NoneSupport: TearScienceProgram Number: 6029 Poster Board Number: A0092Presentation Time: 10:30 AM - 12:15 PMInhibition of Matrix Metalloproteinases by Mapracorat, a NovelSelective Glucocorticoid Receptor Agonist (SEGRA), in Human<strong>Cornea</strong>l Epithelial CellsThomas R. Vollmer, Karen L. Harrington, Jin-Zhong Zhang, MaryRichardson, Megan E. Cavet. Preclinical Pharmacology, Bausch +Lomb, Rochester, NY.Purpose: Dry eye disease is known to involve an increase in multiplematrix metalloproteinases (MMPs), particularly MMP-9, at the ocularsurface. Increased MMP-9 levels are associated with cornealepithelial barrier dysfunction that causes ocular irritation and visualdysfunction in dry eye disease. The aim of this study was todetermine the effect of mapracorat on MMP levels in human cornealepithelial cells (HCEpiC) exposed to hyperosmolarity and IL-1β.Methods: HCEpiC were challenged with 1 ng/ml IL-1β or 480mOsm hyperosmolar media (by the addition of sucrose) in thepresence of mapracorat or dexamethasone, both at 6 doses (1 - 300nM). After 24 h, culture medium was collected and evaluated forMMP release [MMP-1 MMP-2, MMP-3, MMP-9, MMP-10, MMP-12, and MMP-13] by Luminex. Dose response data were fitted to a 4parameter logistic equation to determine IC50 and efficacy.Results: IL-1β increased levels of all measured MMPs in theconditioned medium, while hyperosmolarity increased release of 4out of the 7 measured MMPs (MMP-1, 3, 9 and 13). Both IL-1β-(MMP-1, 2, 3, 9, 10, 12 and 13) and hyperosmolarity-induced(MMP-1, 3, 9, and 13) levels of MMPs were inhibited by mapracorat.Calculated IC50 values for inhibition of IL-1β and hyperosmolarityinducedMMPs for mapracorat were below 10 nM and were notstatistically significant from dexamethasone IC50 values. Mapracoratwas fully efficacious (>80% for the majority of MMPs) at reducingIL-1β and hyperosmolarity-induced cytokine release and nostatistically significant differences were identified when comparingMMP levels with those following dexamethasone treatment.Conclusions: Mapracorat potently reduced IL-1β andhyperosmolarity-induced MMP release to a similar extent asdexamethasone in HCEpiC. These data, together with mapracorat’sability to potently inhibit pro-inflammatory cytokines, and propensityfor an improved side effect profile as compared to traditional steroidswarrant investigation of this novel drug as a clinically effectivetreatment for dry eye disease.Commercial Relationships: Thomas R. Vollmer, Bausch + Lomb(E); Karen L. Harrington, Bausch + Lomb (E); Jin-Zhong Zhang,Bausch & Lomb, Inc (E); Mary Richardson, Bausch and Lomb (E);Megan E. Cavet, Bausch + Lomb (E)Program Number: 6030 Poster Board Number: A0093Presentation Time: 10:30 AM - 12:15 PMHistopathologic changes in punctal stenosisGary J. Lelli 1 , Alexander D. Port 3 , Yao-Tseng Chen 2 .1 Ophthalmology, Weill Cornell Medical College, New York, NY;2 Pathology and Laboratory Medicine, Weill Cornell Medical College,New York, NY; 3 Weill Cornell Medical College, New York, NY.Purpose: To describe the pathologic changes in punctal stenosis byreporting the histopathologic findings in a series of punctoplastyspecimens.Methods: Observational retrospective chart review. Electronic healthrecords of all patients having punctoplasty over a two-year period atan academic oculoplastic practice were examined. All patients whoserecords included pathology reports were entered into a database.Results: 24 patients, representing 30 eyes, had pathology records inthe EHR. Patients were 75% female, and had an average age of 65(19-88). Associated conditions included blepharitis (71%), dry eyesyndrome or Meibomian gland dysfunction (63%).Histopathologicexamination demonstrated chronic inflammation in 11 eyes (36.7%),fibrosis in 7 eyes (23.3%), chronic inflammation and fibrosis in 4eyes (13.3%), squamous metaplasia in 3 eyes (10%), normalconjunctival mucosa in 3 eyes (10%), and Acintomyces Israeliicanaliculitis in 2 eyes (6.7%).Conclusions: Nearly all histopathologic specimens revealed findingsconsistent with inflammation, fibrosis, or both. These findingsprovide evidence to support the hypothesis that the many etiologiccauses of punctal stenosis are linked by a common pathophysiologicmechanism involving inflammation.Representative histopathology findings in 3-snip punctoplastyspecimens. (A) Chronic inflammation with mainly lymphocyticinfiltrates in the conjunctival epithelium and underlying tissue.Magnification 400X©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 <strong>ARVO</strong> Office at arvo@arvo.org.

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