Semaglutide-associated NAION: a proposed ‘two-hit’ model involving buried optic disc drusen and sustained hypohydration

Semaglutide-associated non-arteritic anterior ischaemic optic neuropathy (NAION) mechanisms are unclear. We report a 28-year-old man with type 2 diabetes who developed right NAION 4–5 months after starting semaglutide. Multimodal imaging confirmed NAION and bilateral buried optic disc drusen. The affected eye was short, whereas the fellow eye was highly myopic and longer. Serial bioimpedance showed a 1.9 L decline in total body water over 7 weeks, with preserved fat mass and stable extracellular-to-total-body-water (ECW/TBW) ratio. We propose a hypothesis-generating ‘two-hit’ model in which anatomical susceptibility and sustained hypohydration together precipitate NAION. Heightened clinical awareness may be warranted and prospective studies are required.