By JAMA Ophthalmol (July 2025)

We read with interest the recent cohort study by Cai et al¹ on the association between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION). With literature reporting increased associations between semaglutide and NAION,^2–4 we believe it imperative to investigate this association further. A limitation of the Cai et al study is the inclusion only of individuals with type 2 diabetes (T2D). Furthermore, given the low incidence of NAION (2.3-10 cases/100 000 people),⁵ a cohort study design can yield a low number of case patients, affecting statistical efficiency. This limitation was observed in the Cai et al study, which included 1185 case patients with NAION in the sensitive definition and 541 in the specific definition from the MarketScan Commercial Claims and Encounters (CCAE) database. We used a case-control design to explore the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) exposure and NAION, based on the presence or absence of primary indications (T2D and obesity⁶) for GLP-1RAs.

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