Retinal ganglion cell loss is associated with future disability worsening in early relapsing–remitting multiple sclerosis

Background and purpose Thinning of the retinal combined ganglion cell and inner plexiform layer (GCIP) as measured by optical coherence tomography (OCT) is a common finding in patients with multiple sclerosis. This study aimed to investigate whether a single retinal OCT analysis allows prediction of future disease activity after a first demyelinating event. Methods This observational cohort study included 201 patients with recently diagnosed clinically isolated syndrome or relapsing–remitting multiple sclerosis from two German tertiary referral centers. Individuals underwent neurological examination, magnetic resonance imaging, and OCT at baseline and at yearly follow‐up visits. Results Patients were included at a median disease duration of 2.0 months. During a median follow‐up of 59 (interquartile range = 43–71) months, 82% of patients had ongoing disease activity as demonstrated by failing the no evidence of disease activity 3 (NEDA‐3) criteria, and 19% presented with confirmed disability worsening. A GCIP threshold of ≤77 μm at baseline identified patients with a high risk for NEDA‐3 failure (hazard ratio [HR] = 1.7, 95% confidence interval [CI] = 1.1–2.8, p = 0.04), and GCIP measures of ≤69 μm predicted disability worsening (HR = 2.2, 95% CI = 1.2–4.3, p = 0.01). Higher rates of annualized GCIP loss increased the risk for disability worsening (HR = 2.5 per 1 μm/year increase of GCIP loss, p = 0.03). Conclusions Ganglion cell thickness as measured by OCT after the initial manifestation of multiple sclerosis may allow early risk stratification as to future disease activity and progression. In this well‐defined study cohort of 201 patients with recently diagnosed multiple sclerosis, ganglion cell loss as measured by optical coherence tomography was associated with disability worsening and ongoing inflammatory disease activity during a follow‐up of up to 9 years. Optical coherence tomography may allow risk stratification and might have implications for the clinical management of patients with early multiple sclerosis.