1. Corneal Complications Following Topical Nonsteroidal Anti-inflammatory Drug Use Martel, S., Akin M., Shih CY., Udell IJ North Shore Long Island Jewish Health Systems April 2010 The authors have no financial interest in the subject matter of this presentation

2. Purpose and Background To examine the systemic and local risk factors associated with corneal complications after topical Non-Steroidal Anti-Inflammatory Drug (NSAID) use To examine the systemic and local risk factors associated with corneal complications after topical Non-Steroidal Anti-Inflammatory Drug (NSAID) use To examine corneal complications after NSAID use in a cohort of patients presenting subsequent to the removal of generic diclofenac from the market To examine corneal complications after NSAID use in a cohort of patients presenting subsequent to the removal of generic diclofenac from the market To our knowledge there is little data published examining the systemic and local risk factors that may predispose patients to corneal complications after NSAID use To our knowledge there is little data published examining the systemic and local risk factors that may predispose patients to corneal complications after NSAID use

3. Methods This was a retrospective review of all patients referred to the North Shore-Long Island Jewish Health Systems for corneal complications following topical NSAID use from 1998-2009 This was a retrospective review of all patients referred to the North Shore-Long Island Jewish Health Systems for corneal complications following topical NSAID use from 1998-2009 All cases were reviewed; any questionable cases where factors besides NSAIDs use could have contributed to complications were eliminated All cases were reviewed; any questionable cases where factors besides NSAIDs use could have contributed to complications were eliminated 36 patients were included in the study 36 patients were included in the study 23 of the 36 cases were subsequent to the removal of diclofenac DSOS from the market 23 of the 36 cases were subsequent to the removal of diclofenac DSOS from the market

4. Results Mean age was 73 Mean age was 73 The mean duration of topical NSAID use was 60 days (range 6-360 days) The mean duration of topical NSAID use was 60 days (range 6-360 days) 29/36 patients used NSAID drops for >2 weeks 29/36 patients used NSAID drops for >2 weeks Average dosage used 4 times a day dosing (range 1-8 drops a day) Average dosage used 4 times a day dosing (range 1-8 drops a day) Indications for NSAID use included post- cataract surgery (79%) and dry eye (21%) Indications for NSAID use included post- cataract surgery (79%) and dry eye (21%)

5. Table 1: Types of NSAID used NSAID TypeNumber of Patients Nevanac ®10 Acular ®10 Xibrom ®5 Diclofenac DSOS*6 Voltaren ®5 * Removed from the market 1999

8. Serologic Testing of Patients for Factors Predisposing Patients to Corneal Melt Factors tested include: ANA, RF, SS-A, SS-B, ESR 9 had positive blood work for autoimmune factors, 6 negative. 21 patients still need to be tested 4/15 had known autoimmune disease, 5/15 reported no symptoms but had positive bloodwork

9. Bromfenac: Post-Phaco 6 Weeks Patient had history of periorbital radiation

10. 2 wks after phacoemulsification Patient treated for persistent epithelial defect using NSAID’s for 1 month The patient had no rheumatologic symptoms, but +RF, +ANA, & elevated ESR

11. Bilateral descemetocele after 7 days of QID Ketorolac preservative free 62 y.o. patient with “Dry Eye” (+ RF and + ANA)

12. Conclusion Corneal complications with NSAID use continue to be seen despite the removal of generic diclofenac from the market Corneal complications with NSAID use continue to be seen despite the removal of generic diclofenac from the market Risks factors include: graft vs host disease, radiation, pseudophakic bullous keratopathy, dry eye symptoms related to autoimmune processes Risks factors include: graft vs host disease, radiation, pseudophakic bullous keratopathy, dry eye symptoms related to autoimmune processes Patients with Dry Eye Syndrome without clinically manifesting autoimmune disease may be still be predisposed to corneal melts if they have positive serologic markers (ANA, RF, SS-A, SS-B) Patients with Dry Eye Syndrome without clinically manifesting autoimmune disease may be still be predisposed to corneal melts if they have positive serologic markers (ANA, RF, SS-A, SS-B) Patients with risk factors should be monitored frequently to prevent corneal complications and to allow prompt discontinuation of the drug if necessary Patients with risk factors should be monitored frequently to prevent corneal complications and to allow prompt discontinuation of the drug if necessary