Background: Optic neuritis (ON) is an important clinical manifestation of neuromyelitis optic spectrum disease (NMOSD). Myelin oligodendrocyte glycoprotein (MOG) antibody-related and aquaporin 4 (AQP4) antibody-related ON show different disease patterns. The aim of this study was to explore the differences in structure and function of the visual pathway in patients with ON associated with MOG and AQP4 antibodies. Methods: In this prospective study, we recruited 52 subjects at Beijing Tiantan Hospital, including 11 with MOG Ig+ ON (MOG-ON), 13 with AQP4 Ig+ ON (AQP4-ON), and 28 healthy controls (HCs). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of optic radiation (OR), primary visual cortex volume (V1), brain volume, and visual acuity (VA) were compared among groups. A multiple linear regression was used to explore associations between VA and predicted factors. In addition, we used optical coherence tomography (OCT) to examine thickness of the peripapillary retinal nerve fiber layer (pRNFL) and retinal ganglion cell complex (GCC) in a separate cohort consisting of 15 patients with ON (8 MOG-ON and 7 AQP4-ON) and 28 HCs. Results: Diffusion tensor imaging showed that the FA of OR was lower than controls in patients with AQP4-ON (p = 0.001) but not those with MOG-ON (p = 0.329) and was significantly different between the latter two groups (p = 0.005), while V1 was similar in patients with MOG-ON and AQP4-ON (p = 0.122), but was lower than controls in AQP4-ON (p = 0.002) but not those with MOG-ON (p = 0.210). The VA outcomes were better in MOG-ON than AQP4-ON, and linear regression analysis revealed that VA in MOG-ON and AQP4-ON was both predicted by the FA of OR (standard β = -0.467 and -0.521, p = 0.036 and 0.034). Both patients of MOG-ON and AQP4-ON showed neuroaxonal damage in the form of pRNFL and GCC thinning but showed no statistically significant difference (p = 0.556, 0.817). Conclusion: The structural integrity of OR in patients with MOG-ON, which is different from the imaging manifestations of AQP4-ON, may be a reason for the better visual outcomes of patients with MOG-ON.

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