Previous studies have demonstrated that optic neuritis (ON) affects brain plasticity. However, whether ON affects the spinal cord remains unclear. We aimed to investigate the spinal cord changes in ON and their associations with disability.A total of 101 ON patients, and 41 healthy controls (HC) were retrospectively recruited. High-resolution imaging was conducted using a Magnetization Prepared Rapid Acquisition Gradient-Echo (MP-RAGE) sequence for T1-weighted images and an echo planar imaging (EPI) sequence for Diffusion Tensor Imaging (DTI) data collection. Additionally, patients' disability and cognitive impairment were evaluated using the Expanded Disability Status Scale (EDSS) and the Paced Auditory Serial Addition Test (PASAT), respectively. The quantitative spinal MRI was employed to examine the cross-sectional area (CSA) and diffusion indicators, with a specific focus on calculating the average values across the C2-C7 cervical spinal cord segments. CSA, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were compared between groups. Correlation analyses were performed between CSA, diffusion indicators, and clinical variables.No significant differences were found in CSA between ON patients and HCs. MD (p = 0.007) and RD (p = 0.018) were increased in ON patients compared with HCs, and AD was decreased in ON (p = 0.013). The AD values of the ON patients were significantly positively correlated with PASAT scores (r = 0.37, p < 0.001).This study provided imaging evidence for DTI abnormalities in patients with ON. Spinal cord DTI can improve our knowledge of the path physiology of ON, and clinical progression.Copyright © 2024 Elsevier B.V. All rights reserved.