Non-arteritic anterior ischemic optic neuropathy (NAION) is the most prevalent non-glaucomatous optic nerve disorder in patients aged >50 years and often leads to painless and sudden vision loss in the affected eye (Contreras et al., 2007). Although NAION is presumed to result from acute ischemia of the optic nerve head due to hypoperfusion of the short posterior ciliary arteries, its exact pathogenesis remains unclear. Moreover, no treatment has conclusively demonstrated efficacy (Atkins et al., 2010; Lantos et al., 2022). It is possible that the challenges mentioned above arose because certain risk factors were overlooked. These factors might precede or be caused by optic disc ischemia, subsequently affecting disease progression and the effectiveness of current treatments.

Proteomic analysis has emerged as a powerful tool for identifying disease-specific biomarkers and elucidating pathophysiological mechanisms in ocular diseases (Santos et al., 2023; Wu et al., 2022). Furthermore, increasing evidence suggests that pathological changes in the vitreous humor, a key extracellular environment surrounding the optic nerve, may offer novel insights into NAION progression (Parsa and Hoyt, 2015; Chan et al., 2023; Shen and MacIntosh, 2016; Li et al., 2024; Modarres et al., 2007). Although previous studies have analyzed the sera of NAION patients (Mesentier-Louro et al., 2021; Deramo et al., 2003; Kashani et al., 2024), the vitreous proteomic landscape of NAION remains largely unexplored.

In this study, we aimed to characterize the vitreous proteome in patients with NAION compared to controls with idiopathic epiretinal membranes (iERMs) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and to identify the potential mechanisms involved in the pathogenesis of NAION.