Emerging data has identified a potential association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and nonarteritic anterior ischemic optic neuropathy (NAION), a typically sudden, painless, and irreversible cause of optic nerve-mediated vision loss. This review synthesizes the current clinical, epidemiologic, and potential mechanism linking GLP-1RA-based therapies to NAION risk, informing balanced risk assessment and interdisciplinary clinical decision-making. A structured PubMed search was performed using terms including "GLP-1 receptor agonist," "semaglutide," "liraglutide," "tirzepatide," and "nonarteritic anterior ischemic optic neuropathy," in addition to NAION risk factors, including disc-at-risk anatomy, type 2 diabetes, obstructive sleep apnea, hypertension, hyperlipidemia, renal disease, and ischemic heart disease. A small cup-to-disc ratio ("disc-at-risk") was found to be the most robust anatomical predictor of NAION. Systemic microvascular disease (diabetes, hypertension, hyperlipidemia) and conditions such as obstructive sleep apnea and end-stage renal disease were also linked to increased susceptibility to optic nerve head ischemia. Although data across electronic health records, national registries, and pharmacovigilance analyses suggest a very low absolute incidence of NAION, the use of GLP-1RAs demonstrates a statistically significant association with NAION development, yielding relative risk estimates between 1.2 and 4.3. At this time, the potential association between GLP-1RA therapy and NAION should be interpreted as a safety signal rather than a contraindication. Screening for disc-at-risk anatomy, consideration of prior NAION history, and patient counseling regarding acute visual symptoms may be warranted prior to initiation of therapy. As evidence evolves, collaboration between endocrinologists and ophthalmologists will be essential to support safe and effective patient care.
