Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) exhibits phenotypic diversity and it varies by age. However, less is known about whether the manifestations of isolated MOG antibody-associated optic neuritis (iMOG-ON) vary across different age groups. We aimed to investigate the clinical and prognostic features of iMOG-ON in young and middle-aged adult patients.Patients with iMOG-ON were enrolled in the Department of Neurology, Beijing Tongren Hospital, Capital Medical University between January 2018 and October 2021. Medical records were reviewed to obtain clinical data and orbital MRI images of adult patients with iMOG-ON. Multivariate linear regression analysis was performed to investigate the associations between final best-corrected visual acuity (BCVA) in logMAR and clinical characteristics.Based on the age of onset, 70 patients were divided into 2 groups: 38 young (< 46 years; female/male = 0.76:1) and 32 middle-aged (≥ 46 years; female/male = 5.56:1) adults. There were statistical differences in both the female-to-male ratio and frequencies of contrast enhancement of the optic nerve sheaths and surrounding orbital tissues between both groups (p = 0.001, p = 0.004, respectively). The average follow-up periods were 28.04 ± 11.22 months. The median final BCVA was 0 (0 - 0.50) logMAR and 0.5 (0.3 - 1.0) logMAR in the young and middle-aged patients, respectively (p = 0.000). The multivariate linear regression analysis indicated significant positive relationships between final BCVA and age of onset (p = 0.038, 95 % CI: 0.020 - 0.728), sex (p = 0.030, 95 % CI: -0.793 - -0.042), BCVA at nadir (p = 0.000, 95 % CI: 0.164 - 0.386), and numbers of segments of optic nerve lesions (p = 0.009, 95 % CI: 0.068 - 0.450) with a coefficient of determination (R2) of 0.359 after adjusting for prior attacks of ON, time intervals between sudden-onset vision loss and administration of intravenous methylprednisolone, and corticosteroid dosages. The worst final BCVA was observed in afflicted eyes with lesions extending across three segments of the optic nerve.Compared to young adults with iMOG-ON, the middle-aged patients tended to have a female predominance, higher frequencies of perineural enhancement, and worse visual outcomes. In addition to age of onset, visual recovery may also be influenced by patient's sex, BCVA at nadir, and lengths of longitudinally expansive lesions of the optic nerve to a certain extent.Copyright © 2024. Published by Elsevier B.V.