PG 2403 IV - (A) (E) Apoint - by Governer.pmd

ARVO 2013 Annual Meeting Abstracts by Scientific Section/Group - Cornea 121 Ocular Fibrosis: Myofibroblast to Therapeutics Minisymposium Sunday, May 05, 2013 10:30 AM-12:15 PM TCC 303 Minisymposium Program #/Board # Range: 388-392 Organizing Section: Cornea Contributing Section(s): Anatomy/Pathology, Glaucoma, Lens, Retina Program Number: 388 Presentation Time: 10:30 AM - 10:50 AM Fibrosis - Keeping an Eye on the Myofibroblast Boris Hinz. University of Toronto, Toronto, ON, Canada. Commercial Relationships: Boris Hinz, None Program Number: 389 Presentation Time: 10:50 AM - 11:05 AM Fibrosis in Glaucoma: Role in Pathologenesis and Surgical Failure Colm J. O'Brien. Ophthalmology, Mater Misericordiae Univ Hospital, Dublin, Ireland. Commercial Relationships: Colm J. O'Brien, None Program Number: 390 Presentation Time: 11:05 AM - 11:20 AM Prevention of Keratocyte-Myofibroblast Conversion by Targeting the Matrix-Cytokine System Shizuya Saika. Ophthalmology, Wakayama Medical University, Wakayama, Japan. Commercial Relationships: Shizuya Saika, None Program Number: 391 Presentation Time: 11:20 AM - 11:35 AM Fibrosis in the lens: Regulation of TGFß-induced lens Epithelial to Mesenchymal Transition (EMT) leading to cataract Frank J. Lovicu. Anatomy & Histology - F13, University of Sydney, Sydney, NSW, Australia. Commercial Relationships: Frank J. Lovicu, None Program Number: 392 Presentation Time: 11:35 AM - 11:50 AM Regulation of Retinal and Subretinal Fibrosis David R. Hinton. Pathology, Keck School of Medicine USC, Los Angeles, CA. Commercial Relationships: David R. Hinton, RPT (I), RPT (P)

126 Contact Lens I Sunday, May 05, 2013 10:30 AM-12:15 PM Exhibit Hall Poster Session Program #/Board # Range: 487-523/B0124-B0160 Organizing Section: Cornea Program Number: 487 Poster Board Number: B0124 Presentation Time: 10:30 AM - 12:15 PM Evaluation of Surface Water Characteristics of Novel Daily Disposable Contact Lenses Using Refractive Index Shifts after Wear Jeffery Schafer, Robert B. Steffen. Bausch & Lomb, Rochester, NY. Purpose: Several novel daily disposable contact lenses have been introduced with unique water characteristics. Nesofilcon A lenses are described as having 78% water, the same water content as the cornea throughout the lens matrix. Delefilcon A lenses are described as

having a surface water content of 80% and a bulk water content of 33%. The delefilcon A high water content at the surface is reported to be the result of a surface modification using a copolymer of polyamidoamine and poly(acrylamide-acrylic acid) which is highly anionic (negative charge). During wear, these high water materials are exposed to air and tear components that may change the properties of the lenses. The objective of this study was to investigate surface water characteristics using refractive index shifts after wear with delfilcon A lenses compared to nesofilcon A and etafilcon A lenses. Methods: Twenty subjects wore each of the three lens types in a randomly determined order for 15 minutes. The worn lenses for each subject were measured for surface refractive index on the Metricon M-2010 Prism Coupler. To establish baseline refractive index values, unworn lenses of each type were also measured for refractive index directly from the package. Results: The mean changes in refractive index (unworn - worn) were 0.006 for nesofilcon A lenses, 0.012 for etafilcon A lenses and 0.093 for delefilcon A lenses. With the highly accurate measurement capability of the Metricon instrument, (routine refractive index accuracy of ± 0.00053 and standard deviation from 0.0008 to 0.0046), the difference between unworn and worn average values were statistically significant for each lens, p80% water, to 1.43, typical of a 33% water, following just 15 minutes of wear due to a change in the water content at the surface. There was no change in refractive index at the surface following lens wear for either the 78% water nesofilcon A lenses or the 58% water etafilcon A lenses. Commercial Relationships: Jeffery Schafer, Bausch & Lomb (E); Robert B. Steffen, Bausch + Lomb (E) Program Number: 488 Poster Board Number: B0125 Presentation Time: 10:30 AM - 12:15 PM Effect of Protein Adsorption on Dewetting and Corneal cell adhesion on Contact Lenses Saad Bhamla, Claire M. Elkins, David Bergsman, Gerald G. Fuller. Chemical Engineering, Stanford University, Stanford, CA. Purpose: We discuss the influence of lysozyme adsorption on contact lenses using two different experimental approaches dewetting on lenses and adhesion of corneal cells to a contact lens substrate. Methods: Dewetting is studied by stretching a contact lens flat on an elevation stage built on a miniature Langmuir trough. By raising the stage, the lens surface captures a sessile droplet coated with DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) at surface pressure of the eye (20-25 mN/m). Liquid is slowly drained and dewetting dynamics captured using a CCD camera. Corneal cell adhesion is studied using an apparatus developed in the Fuller lab. A contact lens is descended upon a cultured monolayer of live epithelial cells. After a waiting period, the contact lens is sheared laterally relative to the bottom plate, subjecting the cells to a controlled strain while a force transducer measures the applied stress. Our rheometer-based design allows precise control over the strain down to 0.001 strain units, as well as highly sensitive measurement of the applied stress. The entire apparatus is mounted on a DIC microscope, allowing live cell imaging. Results: Two commercial lenses are tested for both experimental

©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 permission to reproduce any abstract, contact the ARVO Office at [email protected].

ARVO 2013 Annual Meeting Abstracts by Scientific Section/Group - Cornea approaches. In the absence of DPPC, clean contact lenses were highly hydrophilic and resisted dewetting, whereas when soaked overnight in 1 mg/ml lysozyme showed substantial dewetting. Standard deviation across 4 samples was about 10%. In the presence of DPPC, dewetting is stabilized on the lysozyme adsorbed contact lens surface. For clean lenses, a 200% step-strain produces a low force response indicating no attachment of cells to the lens substrate. Whereas for contact lens soaked overnight in 1 mg/ml lysozyme solution, a higher maximum force is exhibited, indicating relatively greater cell adhesion to the contact lens. This stress relaxes quickly to a new equilibrium value, likely due to the re-organization and relaxation of the adhered corneal cells. Conclusions: Our findings show that adsorbed lysozyme decreases the hydrophilicity of the lens surface leading to dewetting. Deposition of lysozyme also makes the lens surface more attractive to cell adhesion.

Fig1: Normalized wet area as a function of time with standard deviation of 4 samples, for pure and lysozyme adsorbed contact lenses.

Fig2: Step-strain data for uncoated and lysozyme coated contact lens with corneal epithelial cells. Commercial Relationships: Saad Bhamla, None; Claire M. Elkins, None; David Bergsman, None; Gerald G. Fuller, None Program Number: 489 Poster Board Number: B0126 Presentation Time: 10:30 AM - 12:15 PM Secretory Phospholipase A2 Type IIA Levels across the Wear Cycle: Response to Lens Age or Indication of CL Intolerance Walter L. Nash, Alan Landers, Manal M. Gabriel, Jennifer D. Lane, Michael S. Foster. Vision Care, Alcon, Duluth, GA. Purpose: To evaluate the difference in day one versus day twentyeight levels of secretory phospholipase A2 Type IIA (sPLA2IIA) in the tear envelope of symptomatic (decline in comfort over wear cycle) and asymptomatic subjects. Methods: Lenses were collected from subjects aseptically and stored at below -20 degrees C. Subjects wore the same non-ionic silicone hydrogel lens material and used the same lens care regimen. Lenses were equilibrated to ambient temperature and rinsed in 2 mL of

phosphate buffered saline for 5 minutes with agitation. The rinsate was subjected to a sandwich ELISA using a monoclonal antibody specific for sPLA2IIA. The plate was washed and an Acetylcholinesterase (ACHe); Fab’conjugate was added to the plate which selectively binds to a different epitope on the sPLA2IIA molecule. Finally, the enzymatic activity of ACHe was measured by adding a reagent containing the ACHe substrate and reading the plate at a wavelength of 420 nm by spectrophotometry. Results: Symptomatic and asymptomatic subjects exhibited similar levels of sPLA2IIA at day 1 as on day 28; with symptomatic subjects exhibiting 17.2±6.2 and 17.8±8.9 ng/lens sPLA2IIA, respectively, and asymptomatic subjects exhibiting 21.7±5.6 and 24.6±9.2 ng/lens sPLA2IIA, respectively. Comparing the amount sPLA2IIA in the tear envelope between symptomatic and asymptomatic subjects on both day 1 and day 28 showed no statistical differences using nonparametric Mann-Whitney analysis. Conclusions: sPLA2IIA hydrolyzes fatty acids generating free arachidonic acid and lysophospholipids, the precursors of proinflammatory lipid mediators. Studies have reported elevated levels of sPLA2IIA in the tears of intolerant contact lens wearers. This study demonstrates no changes in the level of sPLA2IIA in the tear envelope over the course of the wear cycle in symptomatic or asymptomatic lens wearers. Our findings, suggest that the mechanism driving comfort at the time of lens replacement may not be the same as the mechanism driving contact lens intolerance as described in the literature. Commercial Relationships: Walter L. Nash, ALCON, a Novartis Company (E); Alan Landers, Alcon (E); Manal M. Gabriel, Alcon, A Novartis company (E); Jennifer D. Lane, Alcon Laboratories (E), Novartis (E); Michael S. Foster, Alcon, a Novartis Company (E) Program Number: 490 Poster Board Number: B0127 Presentation Time: 10:30 AM - 12:15 PM Characterization of contact lenses through oxygen permeability, equilibrium water content, and silicone content Scott Curtin, Michelle Seitz, Meng Ouyang, Katarina Tomic, Meredith Wiseman, Hanny Vanwersch. DSM, Berkeley, CA. Purpose: In an effort to contribute to the growing knowledge base of materials properties of silicone hydrogel (“SiHy”) contact lenses and improve material design for formulation, DSM has evaluated three principal material parameters that affect oxygen permeability (Dk); amount of silicone component present, intrinsic permeability of silicone component, and connectivity of silicone-containing phase Methods: The coulometric oxygen permeability (Dk) and equilibrium water content (EWC) of commercial SiHy contact lenses were measured at DSM using methods described in ISO 183694:2006 and ANSI Z80.20-2010. A modified Mocon MH 2/21 was used to measure the oxygen permeability for 5 contact lenses using CIBA Vision O2 Optix for the Q value. The silicon and fluorine contents of dried commercial lenses were measured by X-ray fluorescence to approximately ± 0.5 wt%. Results: CIBA Vision Air Optix 108±3.3 (110), CIBA Vision Dailies Total One 131±4.3 (140), Acuvue Oasys 105±1.6 (105), Acuvue Trueye 114±2.1 (110), Coopervision Biofinity 128±6.1(128) with manufacturer-claimed values in parentheses and all lenses besides CIBA Vision lenses were reported using polarographic method . A wet blot gravimetric method was used to measure EWC for six lenses with measured values closely matching reported values. CIBA Vision Air Optix 32.7±0.5% (33%), CIBA Vision Dailies Total One 29.9±0.8% (33%), Acuvue Oasys 37.3±0% (38%), Acuvue Trueye 44.5±0.4% (46%), Coopervision Biofinity 46.3±0.8% (48%), and CIBA Vision O2 Optix 30.5±0.5% (33%). Additionally, the atomic silicon and fluorine contents of the dried lenses were measured with

©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 permission to reproduce any abstract, contact the ARVO Office at [email protected].

ARVO 2013 Annual Meeting Abstracts by Scientific Section/Group - Cornea X-ray Fluorescence. Conclusions: Dk of SiHy lenses can be understood in terms of three principal material parameters: the amount of silicone component present, the intrinsic permeability of silicone component, and the connectivity of silicone-containing phase. The volume fraction of the silicone phase is a more meaningful parameter than EWC in understanding Dk and it can be estimated using the EWC and atomic percentages of Si and F. A simple morphologically based permeability model can describe the Dk of commercial lenses. This gives a framework for how to achieve sufficient Dk while minimizing use of silicone materials by optimizing connectivity and intrinsic permeability of silicone phase. ©2012 DSM. All rights reserved. Commercial Relationships: Scott Curtin, None; Michelle Seitz, None; Meng Ouyang, None; Katarina Tomic, None; Meredith Wiseman, None; Hanny Vanwersch, None Program Number: 491 Poster Board Number: B0128 Presentation Time: 10:30 AM - 12:15 PM Effect of lens care system on silicone hydrogel contact lens wettability Cecile A. Maissa1, Michel Guillon1, Stephanie Wong1, Anna Lane1, Trisha Patel1, Renee J. Garofalo2. 1OTG Research & Consultancy, London, United Kingdom; 2Alcon, Fort Worth, TX. Purpose: The purpose of this study was to compare the effect of the repeated usage of two different care systems (one hydrogen peroxide cleaning and disinfecting system and one PHMB containing multipurpose system) with silicone hydrogel lenses worn on a daily wear basis for a three month period. A specific aspect of interest was the study of effects of the care systems on contact lens wettability. Methods: Seventy-four symptomatic contact lens wearers, currently wearing either ACUVUE® OASYS® (n=37) or PureVision (n=37), constituted the study population. The investigation was a two-arm prospective, bilateral study of three month duration to evaluate the potential beneficial effects of CLEAR CARE® compared with renu® freshTM. The subjects were randomized to use one of the two care systems. The effects on contact lens wettability were assessed with the Tearscope and reported in terms of Pre-lens Tear Film Non Invasive Break Up Time. Baseline assessments were carried out at the dispensing visit with new contact lenses. At the two and three month follow-up visits the contact lenses had been worn for at least six hours prior to the visits, and were at least 11 days old for ACUVUE® OASYS® and 25 days old for PureVision. Results: The results obtained showed that: i. Whereas no difference in contact lens wettability was observed at dispensing between the two lens care groups (Mean Median NIBUT: 4.5 vs. 4.2s, p=0.518) a significantly more stable pre-lens tear film was observed with CLEAR CARE® than with renu® freshTM at both the two (Mean Median NIBUT: 4.6 vs. 3.7s p=0.005) and three (Mean Median NIBUT: 5.8 vs. 4.2s p=0.028) month visits. ii. With CLEAR CARE® a significant improvement in contact lens wettability was recorded compared with their habitual contact lenses and care system at three months (Mean Median NIBUT 5.8 vs. 4.0s p0.05). However, storage of the lens in some MPSs showed more sustained wetting after 8 hours wear, with similar values at (A) and (B); for OL, ReNu and Complete; for DD and MS Biotrue, Express and Complete; and for PL ReNu, Express and Complete. The OSDI questionnaire showed less discomfort after 8 hours wear (at B) with storage in all the MPSs compared to the pack solution (p< 0.02). Conclusions: The effect of all MPS on the initial wetting of a SCL (compared to that with the pack solution) was limited. However, the ability to sustain wetting of a SCL over 8 hours of wear was better with Biotrue, Opti-Free Express and Complete. The wetting parameter of drying duration gave the closest objective measure to subjective responses to lens wear (Figure 1and 2). *Fagehi R, Tomlinson A, Manahilov V. ARVO 2011 E-abstract: 6524, 2011.

©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 permission to reproduce any abstract, contact the ARVO Office at [email protected].

ARVO 2013 Annual Meeting Abstracts by Scientific Section/Group - Cornea did not substantially change over the course of the 720 minutes of mechanical wear. Optical microscopy confirmed that the lenses still maintained a surface gel layer. Conclusions: A simple laboratory method for wearing contact lenses through mechanical agitation was developed and characterized. Even after 720 minutes of simulated wear, the lubricity and surface gel layers were maintained on the delefilcon A lenses. Brennan, AAO 2009. Dunn, et al., Tribology Letters, 2013.

Commercial Relationships: Alan Tomlinson, Allergan (E), Allergan (R), Bausch and Lomb (C), TearLab (C), TearLab (I), Alcon, CibaVision (C), Pfizer (R), Pfizer (C); Raied Fagehi, None; Velitchko Manahilov, None Program Number: 493 Poster Board Number: B0130 Presentation Time: 10:30 AM - 12:15 PM Laboratory Model for Wear of Contact Lenses and Effects on Lens Lubricity of Surface Gel Layers W G. Sawyer1, Juan M. Uruena1, Thomas E. Angelini1, Alison C. Dunn1, John Pruitt2. 1Mechanical and Aerospace Eng, University of Florida, Gainesville, FL; 2Biocompatibility Projects, Alcon Vision Care Research, Johns Creek, GA. Purpose: Lubricity of contact lenses is recognized as an important contributor of comfort (Brennan 2009). Experiments aimed at quantifying the lubricity of lenses are traditionally measured on new lenses that have been removed from the package and either gently rinsed in a saline solution or tested in the packing solution directly (Dunn 2013). The purpose of this research is to establish a simple and scalable method to mechanically exercise contact lenses and simulate wear in a controlled laboratory environment, and then to perform lubricity measurements on the front curve surface of the lenses at varying time points of wear. Methods: Poly(HEMA) (60% pHEMA) hydrogels were molded inside of transparent acrylic containers to a thickness of approximately 3 mm. A series of poly(HEMA) spheres of 6 mm diameter were also molded and added to the hydrogel lined cup to a packing fraction of approximately 25%. A single contact lens (delefilcon A) was placed within the ensemble of hydrogel spheres and the container was filled with Phosphate Buffered Saline. The entire collection was shaken at 31 Hz for various time points. Image analysis was used to track the hydrogel spheres and to quantify the collision frequencies. Based on this analysis a mathematical model of mechanical energy and tribological severity was developed and compared to the tribological severity of 1,000 blinks per hour of wear. Prior to friction testing lenses were examined for evidence of wear and damage was quantified using scanning optical microscopy. Results: This delefilcon A lenses showed a characteristic friction coefficient of mu=0.02, with a standard deviation for each measurement of approximately mu = 0.005. The friction coefficients

Experimental Setup for Laboratory Wear Studies.

Plot of Friction Coefficient versus Simulated Wear Time. Commercial Relationships: W G. Sawyer, Alcon (F); Juan M. Uruena, Alcon (F); Thomas E. Angelini, alcon (F); Alison C. Dunn, Alcon (F); John Pruitt, Alcon (E) Program Number: 494 Poster Board Number: B0131 Presentation Time: 10:30 AM - 12:15 PM Assessment of the relationship between contact lens coefficient of friction and subject lens comfort Jami R. Kern1, Joseph M. Rappon2, Erich Bauman2, Ben Vaughn3. 1 Global Medical Affairs, R&D, Alcon, Fort Worth, TX; 2Vision Care R&D, Alcon, Fort Worth, TX; 3Biostatistics, Rho, Chapel Hill, NC. Purpose: To examine the relationship between subjective comfort and contact lens coefficient of friction among multiple soft contact lens materials. Methods: A meta-analysis of clinical data (n=157) exploring the association between comfort and contact lens lubricity was conducted on 5 soft contact lens materials (delefilcon A, lotrafilcon B, balafilcon A , balafilcon A2, etafilcon A+). Subjective data for insertion comfort, overall comfort and end of day comfort were obtained from a database of clinical trials that included studies conducted between 2004 and 2011. Trials were included in the analysis unless they met exclusion criteria, including; extended or

©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 permission to reproduce any abstract, contact the ARVO Office at [email protected].

ARVO 2013 Annual Meeting Abstracts by Scientific Section/Group - Cornea continuous lens wear, exclusively acute measures, multi-purpose lens care utilized, contra-lateral eye study design, small sample size (n< 30). The last on-eye treatment value for a lens was used and the association between reported comfort and the coefficient of friction, measured using the inclined plane method (Tucker et al), was assessed. Each comfort assessment (Insertion, Overall, End of Day) was analyzed separately in a mixed effect model with a fixed effect for the coefficient of friction and random effects for clinical trial and subject (for crossover studies). A serial gate-keeping approach was used to adjust for multiple comparisons. Results: There were 117 females included in the analysis (74.5%) and the average age of subjects was 32 years. An inverse relationship was found between coefficient of friction and comfort. Coefficient of friction was highly predictive of each measure of comfort (all p0.05). Dryness symptom scores showed non-significant increase from pre to post chamber for CLA (+1.10±0.53) but a significant (p=0.001) increase for CLB (+1.40±0.31). Blink rate significantly increased (p