In cases of optic disc edema or a pale optic disc, distinguishing an episode of optic neuritis (ON) from that of non-arteritic anterior ischemic optic neuropathy (NAION) during a clinical examination is challenging. Optical coherence tomography angiography (OCTA) can reveal differences in peripapillary vascular network structures and provide biomarkers for differential diagnosis. A total of 23 eyes with NAION, 22 eyes with demyelinating ON (DON), and 27 eyes from healthy participants were imaged using OCTA to observe the radial peripapillary capillaries (RPCs). Optical coherence tomography was used to measure peripapillary retinal nerve fiber layer (RNFL) thickness and the macular ganglion cell complex (mGCC). Data for all patients were recorded at 2-3 weeks and more than 3 months after the symptom onset. A total of 23 affected eyes from 23 patients with NAION (average age 52.17 ± 7.92 years), 22 eyes from 22 patients with demyelinating optic neuritis (DON) (average age 47.88 ± 19.24 years), and 27 eyes from 27 healthy individuals (average age 46.43 ± 14.08 years) were included in the study. There were no significant differences in sex, age, and eye laterality between any two groups (F = 0.968, 0.475, 0.870; p > 0.05). Throughout the course of NAION and DON, the superior RPC, superior mGCC, and peripapillary RNFL decreased with time (p < 0.05). In contrast, the inferotemporal RPC and inferior mGCC did not decrease from the acute to chronic stage in NAION (t = 1.639, 0.834, p = 0.117, 0.413). Compared with the normal group, patients with NAION and DON exhibited a sharp reduction in the average RPC, RNFL, and GCC from the acute to the chronic stage (p < 0.05). Patients with DON exhibited a significant decrease in the inferotemporal RPC and inferior mGCC compared with the patients with NAION (p < 0.05). In contrast, there were no significant differences in the inferior mGCC at the chronic stage between the patients with NAION and those with ON (t = 2.547, p = 0.093). Various structural and microvascular changes were observed in patients with NAION and ON, indicating distinct features of the optic nerve during the different stages of NAION and ON. Peripapillary vascular density, measured using spectral domain OCT (SD-OCT), may be a biomarker to distinguish NAION from ON.
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