Background: In multiple sclerosis (MS), inner retinal thinning measured by optical coherence tomography (OCT) is related to lesional and gray matter changes of the brain.

Objective: To evaluate the association between OCT markers and progression independent of relapse activity (PIRA).

Methods: Analysis within the Swiss MS Cohort Study, in patients with ≥ 1 OCT. Mean thicknesses of: peripapillary retinal nerve fiber- (pRNFL), macular ganglion cell-inner plexiform- (mGCIPL), and inner nuclear layers (mINL) were assessed, excluding asymmetric eyes. PIRA was investigated during ≥ 4 years before the OCT. The associations of retinal layers with PIRA rates were estimated in linear regression adjusted for disease duration, age at onset, sex, body mass index, treatment and annualized relapse rate. In a sensitivity analysis, we investigated the associations between retinal layers and PIRMA rates (PIRA without activity on magnetic resonance imaging).

Results: One hundred seventy one pwMS were included (median age: 51 years(y), Expanded Disability Status Scale: 2.5, pRNFL:94 µm, mGCIPL:67.2 µm, mINL:35.4 µm, observation time:8.1y). Sixty-seven patients (39%) showed PIRA. Mean pRNFL and mGCIPL thickness decreased respectively by - 2.28 µm (95% CI [- 4.32;- 0.24], p = 0.029) and - 1.70 µm (95% CI [- 2.97;- 0.42], p = 0.010) for each PIRA event per decade, while mINL (beta = - 0.33, CI: [- 0.75;0.1] p = 0.133) did not show significant associations with PIRA. In the sensitivity analysis, all three OCT measures were associated with PIRMA (pRNFL: beta = - 3.70, 95% CI [- 6.23; - 1.17], p = 0.005; mGCIPL: beta = - 2.49, 95% CI [- 4.12; - 0.87], p = 0.003), mINL: beta = - 0.58, 95% CI [- 1.11; - 0.05], p = 0.031).

Conclusions: Our findings underline the role of retinal thinning measured by OCT as sensitive marker of progression in pwMS.