MIN-YEN HSUJAMES CHENG-CHUNG WEI2026-10-162026-10-162026-09-01Pure ID: 14988089Pure UUID: b1f2bc74-6181-4732-a1a6-617efb3e294e10.1016/j.ophtha.2026.04.027https://www.scopus.com/pages/publications/105041204900https://scholars.csmu.edu.tw/handle/123456789/28330Purpose To investigate the effect of nonsteroidal anti-inflammatory drug (NSAID) use and the risk of age-related macular degeneration (AMD). Design Retrospective cohort study using a de-identified multicenter electronic medical records database. Participants This study included patients who received prescriptions for NSAIDs and individuals who did not to assess for the effects of NSAID prescriptions on future AMD risk. Methods Data from the TriNetX database between January 1, 2015, and December 31, 2024, were used to identify patients who were prescribed NSAIDs with no prior history of AMD. The NSAID patient cohort was propensity score–matched in a 1:1 ratio with a control group of randomly selected patients without a history of NSAID use, based on age, sex, race, and selected comorbidities of interest, including smoking and other common adult comorbidities that potentially could affect future AMD risk. Main Outcome Measures Cumulative incidence and hazard ratio (HR) of AMD. Results Six hundred thirty-four thousand seven hundred ninety-four patients who were prescribed NSAIDs (mean ± standard deviation age, 59.93 ± 11.95 years) and 634 794 patients who were not prescribed NSAIDs (mean ± standard deviation age, 59.68 ± 12.15 years) were recruited. Among NSAID users, decreased risk of AMD development was seen at 6 months (HR, 0.31; 95% confidence interval [CI], 0.27–0.36), 1 year (HR, 0.36; 95% CI, 0.33–0.39), 3 years (HR, 0.42; 95% CI, 0.40–0.44), and 5 years (HR, 0.48; 95% CI, 0.47–0.50) after the index date compared with nonusers. A protective effect against AMD development was observed (HR, 0.58; 95% CI, 0.56–0.59) among NSAID users compared with nonusers. A protective effect against AMD development was observed among patients who were prescribed aspirin (HR, 0.72; 95% CI, 0.69–0.75) and those prescribed nonselective cyclooxygenase-2 inhibitors (HR, 0.41; 95% CI, 0.36–0.46) compared with their respective nonusers. A decreased risk of AMD was observed for both nonexudative (HR, 0.56; 95% CI, 0.55–0.58) and exudative (HR, 0.62; 95% CI, 0.59–0.65) AMD subtypes after index NSAID prescription compared with nonusers. Conclusions A protective effect against future AMD development was suggested among patients prescribed NSAIDs compared with nonusers. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.9enjournal article