Optic neuritis (ON) represents the most common optic neuropathy in young adults; however, longitudinal data on visual recovery, particularly in autoimmune ON subtypes, remain limited. This study aimed to assess long-term visual outcomes in patients with severe ON without multiple sclerosis stratified by autoantibody status: aquaporin-4 (AQP4)-IgG positive, myelin oligodendrocyte glycoprotein (MOG)-IgG positive and double seronegative (DN).

A retrospective cohort analysis was conducted at a tertiary neurology center in southern India, including severe ON patients (best-corrected visual acuity [BCVA] ≤1.0 logMAR) between January 2016 and April 2024. Serological testing for AQP4 and MOG antibodies was performed via cell-based assays. Visual outcomes were categorized as “good recovery” (≥66.77% improvement in BCVA) and “complete recovery” (return to baseline BCVA).

Among 42 patients, 17 were AQP4-IgG positive, 10 MOG-IgG positive and 15 DN. The median BCVA at nadir was 1.7 logMAR. Compared with that in the MOG-IgG group, the likelihood of complete visual recovery was lower in both the AQP4-IgG (hazard ratio [HR]: 0.18; p = 0.16) and DN (HR: 0.56; p = 0.34) groups. For good recovery, the AQP4-IgG (HR: 0.16; p = 0.001) and DN (HR: 0.24; p = 0.001) groups had significantly lower HR. All MOG-IgG–positive patients achieved good recovery, compared with fewer than half in the other groups.

Antibody status predicted long-term visual outcomes in patients with isolated ON, with MOG-IgG conferring the best recovery, AQP4-IgG the worst and DN intermediate, underscoring the importance of early, antibody-guided management.