Investigating the impact of age on neurodegeneration after optic neuritis in multiple sclerosis using optical coherence tomography

BACKGROUND: While disability progression in multiple sclerosis (MS) is age-dependent, the exact timing of neuroaxonal degeneration throughout the patient lifespan remains unclear. OBJECTIVES: To investigate the influence of age on retinal neurodegeneration after the first unilateral episode of optic neuritis (ON). METHODS: We measured peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell inner plexiform layer (mGCIPL) absolute thickness and intereye differences (IEDs) in 61 MS patients with a single unilateral ON 6–24 months prior (MS-ON) and 61 MS patients without ON history (MS-NON). Participants were 1:1 matched based on age, sex, and Expanded Disability Status Scale (EDSS). Statistical significance was evaluated using mixed linear effects models. RESULTS: Age and ON status of eyes significantly interacted in predicting absolute pRNFL and mGCIPL thickness (pRNFL: B = 0.28, 95% confidence interval (CI) = [0.03, 0.54], p = 0.03, mGCIPL: B = 0.24, 95% CI = [0.01, 0.46], p = 0.04). DISCUSSION: Our data show evidence of increased relapse-associated neuroaxonal damage in older individuals. This suggests less neuronal resilience following attacks and implicates age-effects beyond insidious progression. The growing population of older people with MS (pwMS) may be at increased risk of neurodegeneration and permanent disability worsening after acute MS attacks. Longitudinal studies should confirm this.