PREVALENCE OF DRY EYE IN PLANNED PENETRATING OR ENDOTHELIAL KERATOPLASTY John D. Sheppard, M.D., M.M.Sc. President, Virginia Eye Consultants, Norfolk, Virginia Professor of Ophthalmology, Microbiology & Molecular Biology Clinical Director, Thomas R. Lee Lab for Ocular Pharmacology Medical Director, Lions Eye Bank of Eastern Virginia Ophthalmology Residency Research Director

Prevalence of Dry Eye in Planned Penetrating or Endothelial Keratoplasty: Poster #15668 Abstract Topic: Ocular Surface Disease Keywords: Dry eye, Endothelial keratoplasty, Penetrating keratoplasty, Complications of Surgery Purpose: To identify the prevalence of Dry Eye in patients undergoing either penetrating keratoplasty (PKP) or endothelial keratoplasty (DSEK) in a large academic referral practice. Methods: 220 consecutive keratoplasty patients were analyzed retrospectively over a 2 year period. Data included indication for keratoplasty, age, complaints specific to dry eye, superficial punctate keratopathy (SPK) consistent with dry eye, and ipsilateral and contralateral osmolarity. 120 PKP patients and 100 DSEK patients were accumulated. Most common indications for PKP were Keratoconus (64), Corneal Scar (25) and Pseudophakic Bullous Keratopathy or PBK (21). Most common indications for DSEK were Pseudophakic Fuchs Dystrophy (84), PBK (12), and Phakic Fuchs Dystrophy (4). Results: 54 of 120 (45%) PKP patients and 89 of 100 (89%) DSEK patients had a preoperative dry eye. 16/64 (25%) of Keratoconus, 22/25 (88%) of Corneal Scar, and 18/21 (86%) of PBK patients anticipating PKP surgery had a dry eye. 73/84 (87%) of Pseudophakic Fuchs Dystrophy, 9/12 (75%) of PBK, and 3/4 (75%) of Phakic Fuchs Dystrophy patients anticipating DSEK surgery had a dry eye. Osmolarity above 307 mOsm/L correlated with dry eye SPK and/or symptoms in 96% of PKP patients and 93% of DSEK patients. Conclusion: Although dry eye is common in patients undergoing corneal transplantation, this data is the first comprehensive analysis addressing pre-operative prevalence. Keratoplasty candidates should be carefully screened for dry eye and appropriate therapeutic measures should be instituted prior to keratoplasty surgery.

Dry Eye Prevalence: Surgery Candidates Cataract Surgery 1 77% Penetrating Keratoplasty 2 45% Endothelial Keratoplasty 2 89% Lasik 3 27% Glaucoma Surgery 4 78% Blepharoplasty 5 26% 1 Trattler, ASCRS CME Supplement, Sheppard, WCC, Azuma, BMC Research Notes, Leung, Journal of Glaucoma, Prischmann, JAMA Facial Plastic Surgery, 2013

Surgical Complications of Dry Eye Irregular Astigmatism Delayed epithelial healing Increased infection risk Inaccurate Biometry creating post-cataract refractive error Post-Lasik regression Post-Lasik neurotrophic keratopathy Increased risk of allograft rejection Increased risk of glaucoma filtering procedure failure Increased risk of post-blepharoplasty dry eye pain Cataract surgery adds 1 Delphi Panel severity step Lasik surgery adds 2 Delphi Panel severity steps

Severity Level 1234 SymptomsMild to moderateModerate to severeSevereExtremely severe Conjunctival Signs Mild to moderateStaining Scarring Corneal StainingMild punctate staining Marked punctate staining; central staining; filamentary keratitis Severe staining; corneal erosions Other Signs Tear film; decreased vision (blurring) Treatment Options Patient education Environmental modification Preserved tears Control allergy non-preserved tears Gels, ointments Cyclosporine A Topical steroids Secretagogues Nutritional support Oral tetracyclines Punctal plugs (once inflammation is controlled) Systemic anti- inflammatory therapy Oral cyclosporine Acetylcysteine Moisture goggles Surgery (punctal cautery) If no improvement, add level 2 treatments If no improvement, add level 3 treatments If no improvement, add level 4 treatments Surgery Impacts Dry Eye Plan pre-op and post-op care accordingly Cataract Surgery adds 1 severity step LASIK adds 2 severity steps Behrens A, et al. Cornea. 2006;25:

Most Neurodestructive Procedures: Procedure Penetrating Keratoplasty Lasik, Corneal Inlay Secondary AC IOL Cataract with LRIs LRIs DSEK Cataract, RLE or ICL SMILE Cord Length 25 mm 21 mm 6 mm 4 mm 2 mm

Study Design Retrospective clinical analysis Single surgeon 220 consecutive corneal transplant patients: 120 penetrating (PKP) patients 100 endothelial keratoplasty (DSEK) patients Dry eye definition: Complaints of dryness, irritation, visual fluctuations Superficial punctate keratopathy (SPK): Grade II or greater NEI Scale in two zones SPK separate from corneal micro-cystic edema (MCE)

Penetrating Keratoplasty Patients IndicationNumberPercent Keratoconus 64 53% Corneal Scar 25 21% Pseudophakic Bullous Keratopathy 21 18% Graft Failure 10 8% Total120100%

Endothelial Keratoplasty Patients IndicationNumberPercent Pseudophakic Fuchs Dystrophy 84 84% Pseudophakic Bullous Keratopathy 12 12% Phakic Fuchs Dystrophy 4 4% Total100100%

Dry Eye Prevalence: Procedure ProcedureNumberPercent PKP54/120 45% DSEK89/100 89% Overall143/220 65%

Dry Eye Prevalence: Indication IndicationNumberPercent Keratoconus 16/64 25% Corneal Scar 22/25 88% Pseudophakic Bullous Keratopathy 27/33 82% Pseudophakic Fuchs Dystrophy 76/84 87% Phakic Fuchs Dystrophy 3/4 75%

Dry Eye Prevalence: Age IndicationNumberPercent Keratoconus (young) 16/64 25% Scar, Fuchs & PBK (older)128/146 88% Pseudophakic Fuchs (young) 76/84 87% Phakic Fuchs Dystrophy (older) 3/4 75%

Osmolarity Correlation with Clinical Dry Eye Penetrating Keratoplasty 52/5496% Endothelial Keratoplasty 83/8993% Abnormal Osmolarity Definition: >307 mOsm/L in at least one eye >8mOsm/L difference between eyes

Conclusions: Dry eye is highly prevalent in patients anticipating corneal transplantation surgery. Dry eye is more prevalent in older transplant patients. Dry eye may lead to significant peri-operative complications. Corneal transplantation, particularly PKP, can significantly exacerbate dry eye. Keratoplasty patients should be screened for dry eye prior to surgery. Appropriate therapeutic measures should be undertaken to control dry eye prior to keratoplasty surgery whenever possible. Osmolarity correlates closely with clinical dry eye in this keratoplasty population.

Acknowledgments: Virginia Eye Foundation Virginia Eye Consultants Lions Medical Eye Bank of Eastern Virginia: A Vision Share Eye Bank

Professional Disclosures: Alcon: Research Grants, Speaker, Advisor Aldeyra Pharmaceuticals: Advisory Board, Clinical Research Allergan: Research Grants, Speaker, Advisory Board, Media Spokesman Bausch & Lomb, Ista, Valeant: Research Grants, Speaker, Advisory Boards Abbvie, Shire: Research, Advisor, Spokesman BioTissue: Advisory Board, Clinical Research Doctors Allergy Formula: Advisor, Investor EyeGate Research: Advisory Board, Research, Shareholder, Speaker EyeRx Research: Clinical Research, Stock Ownership Imprimis Pharma: Advisory Board Isis Pharmaceuticals: Research, Advisory Board Inspire/Merck Pharmaceuticals: Research, Speaker, Advisory Board Insite: Research Grants Kala Pharmaceuticals: Research, Advisory Board Lacrisciences: Shareholder, Advisor LayerBio: Advisor, Investor Lumenis: Speaker Lux Biosciences: Advisory, Research Grants Novartis/Ciba Vision: Speaker, Advisory Board NiCox: Advisory Board Omeros: Advisory Board OcuCure: Advisory Board, Shareholder OcuHub: Advisor, Investor Pfizer: Research, Speaker RPS: Advisory, Research, Investor Rtech: Clinical Investigator, Advisory Board Santen: Research, Speaker, Advisory Board Shire, SarCode Biosciences: Advisory Board, Shareholder, Research Grant Synedgen: Advisory Board Science Based Health: Research, Advisory, Media Spokesman Senju: Research Grants Srathspey Crowne: Investor Talia Technology: Speaker, Advisory Board Tear Lab: Advisory Board, Speaker, Shareholder Tear Science: Advisory Board, Speaker Topcon: Clinical Research Grant Vistakon: Advisory Board, Clinical Research Xoma, Servier: Clinical Investigator DOCTORS: Advisory Board, Shareholder