Author’s Disclosure Block: Reut Shor, none; Andrew Mihalache, none; Atefeh Noori, none; Renana Shor, none; Radha Kohly, none; Marko Popovic, none; Rajeev Muni, none

Abstract Body
Purpose: To determine whether glucagon-like peptide-1 receptor agonist (GLP-1RA) use is associated with increased risk of developing neovascular age-related macular degeneration (nAMD) among patients with type 2 diabetes mellitus (T2DM). Study Design: Population-based, retrospective cohort study Methods: This study was conducted in Ontario, Canada, and utilized comprehensive administrative health and demographic data collected by the Institute for Clinical Evaluative Sciences (ICES) in the context of a universal public health care system. Inclusioncriteriawere patients aged66 years or olderwith adiagnosisof T2DM anda minimum follow-up period of12months post-initial T2DM diagnosis. We excluded patients with incomplete OHIP or ODB data or patients exposed to GLP-1RA for less than 6 months. To evaluate the risk of a new diagnosis of nAMD in patients exposed to GLP-1RA compared to unexposed Cox proportional hazards model was applied. Results: Over a four-year period from January 2020 to November 2023, a cohort of 1,069,140 patients aged 66 years and older with T2DM was identified. Of these, there were 72,755 patients who were exposed to GLP-1RA for at least 6 months and 996,385 unexposed. In an unadjusted (univariable) and adjusted (multivariable) Cox proportional hazards model, there were greater hazard ratios of developing nAMD in those exposed to GLP-1RA (HR=2.04, 95% CI=1.68 to 2.47 and HR=4.90, 95% CI=2.64 to 9.11 respectively). A sensitivity analysis for duration of exposure to GLP-1RA revealed that shorter durations of exposure were associated with higher risks. Conclusion: In this large population-based analysis, there was a higher hazard rate for developing nAMD with the use of GLP-1RAs among those with T2DM. This study underscores the need for heightened surveillance and further investigation into the long-term ocular adverse events of GLP-1RA therapy to better inform clinical practice and patient management.