Retinal Layer Thickness for Risk Stratification of Progression Independent of Relapse Activity in Relapsing‐Remitting Multiple Sclerosis

BACKGROUND: Identifying people with relapsing-remitting multiple sclerosis (pwRRMS) at risk of progression independent of relapse activity (PIRA) remains an unmet clinical need. Optical coherence tomography (OCT)-derived measures of retinal neuroaxonal damage may provide prognostic value. This study aimed to evaluate whether peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIP) thickness predict PIRA within a heterogenous group of pwRRMS. METHODS: We retrospectively screened pwRRMS with ≥ 2 years relapse-free follow-up from prospective observational cohort studies in Berlin (n = 74) and Munich (n = 146). PIRA was defined as disability worsening, determined by method-specific thresholds across multimodal assessments, sustained until end of follow-up. Analyses were restricted to non-optic neuritis eyes. Cox hazard models were used to assess the adjusted hazard (aHR) of PIRA with age-adjusted pRNFL or GCIP Z-scores. RESULTS: Out of 220 pwRRMS (age: 38.1 ± 9.9 years), 65 (29.5%) developed PIRA over a follow-up of 2.9 [IQR: 1.6-4.1] years. No associations between OCT measures and PIRA were found within the overall study population or Munich cohort. In the Berlin cohort, thinner pRNFL predicted PIRA (aHR [95% CI] = 1.41 [1.03-1.92], p = 0.032), while GCIP did not (aHR [95% CI] = 1.38 [0.90-2.10], p = 0.140). CONCLUSIONS: OCT measurements do not predict the hazard of PIRA within a heterogeneous group of pwRRMS. However, they have potential prognostic value in early disease stages. Clinical characteristics might influence the association and require further investigation.