BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, is increasingly used worldwide for its cardiometabolic benefits. However, it has recently been associated with nonarteritic anterior ischemic optic neuropathy (NAION). This report presents four clinical cases and explores a possible association. CASE PRESENTATION: Four male patients were diagnosed with NAION during semaglutide treatment, with treatment durations of less than one year in three cases. All presented with significant optic disc edema and intraretinal fluid on optical coherence tomography, along with crowded optic disc and small Bruch's membrane opening diameters (<
1.4 mm in three cases). One patient exhibited optic disc drusen. Visual field defects corresponded with ganglion cell layer atrophy on optical coherence tomography. Systemic risk factors varied
two patients had only obesity. CONCLUSIONS: Our observation suggests that individuals with small Bruch's membrane opening diameter may be at risk of developing NAION during semaglutide treatment.