Glucagon-like Peptide-1 Receptor Agonists and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy

BACKGROUND AND OBJECTIVES: Recent observational studies have reported conflicting evidence regarding an association between glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly semaglutide, and nonarteritic anterior ischemic optic neuropathy (NAION). We aimed to synthesize the pooled evidence assessing the association between GLP-1RA use and NAION risk. METHODS: Embase, Medline, and Cochrane CENTRAL databases were searched from inception to April 5, 2025. Observational studies and randomized controlled trials comparing NAION risk in GLP-1RA users with non-GLP-1RA users were included. Title/abstract and full-text screening were conducted in duplicate by 2 independent reviewers. Discrepancies were resolved through discussion or adjudication by a third reviewer. Risk of bias was assessed using the Risk of Bias In Nonrandomized Studies of Interventions (ROBINS-I) tool, and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation framework. Pooled relative risks (RRs) were estimated using Bayesian random-effects models, incorporating half-normal, between-study, and weakly informative priors. The RR with 95% credible interval (CrI) was computed to analyze the development of NAION associated with GLP-1RA exposure. RESULTS: : 98.8%, P(incidence >0.00001): 100%). Leave-one-out sensitivity analyses consistently supported these findings. DISCUSSION: Low-to-moderate certainty evidence indicates that semaglutide significantly increases risk of NAION relative to non-GLP-1RAs, particularly among patients with diabetes. These findings warrant further investigation and should inform clinical risk-benefit discussions.