In vivo investigation of the modulation of retinal atrophy by ocrelizumab in multiple sclerosis: a prospective study

Background: Optical coherence tomography (OCT) is a high-resolution imaging technique enabling accurate quantification of discrete retinal layers. There is increasing evidence supporting retinal layer- and particularly ganglion cell + inner plexiform layer (GCIPL)- thickness as a reliable outcome measure in trials assessing neuroprotection in multiple sclerosis (MS). Objectives: To elucidate whether, and the extent to which, ocrelizumab modulates retinal atrophy in MS, relative to MS patients on alternative disease-modifying therapies (DMTs), MS patients on no treatment, and healthy controls (HCs). Methods: Patients with relapsing remitting MS (RRMS) due to commence ocrelizumab were followed prospectively with serial OCT assessments. Additional cohorts of RRMS patients on the high-potency DMTs rituximab or natalizumab, RRMS patients on the low-potency DMT glatiramer acetate (GA), progressive MS (PMS) patients on no DMT, and HCs were enrolled through a combination of prospective and retrospective recruitment. Participants with diabetes mellitus, uncontrolled hypertension, or glaucoma, and eyes with optic neuritis ≤6 months prior to baseline OCT assessment were excluded. Statistical analyses were performed using linear mixed effects regression models, adjusting for age, sex, race, and optic neuritis history. Results: Two hundred and nine patients with MS (ocrelizumab n=33; rituximab n=31; natalizumab n=66; GA n=47; PMS on no DMT n=32) and 41 HCs were included in the analyses. Median duration of follow-up was 2.1 years (interquartile range 1.6-3.0 years). During the overall period of follow-up, RRMS patients on ocrelizumab exhibited stable GCIPL thicknesses relative to RRMS patients on GA, RRMS patients on rituximab, and PMS patients on no DMT, who demonstrated 0.32 μm/year (95% confidence interval [CI] 0.12 to 0.51 μm/year; p = 0.001), 0.38 μm/year (95% CI 0.16 to 0.59 μm/year; p=0.001) and 0.34 μm/year (95% CI 0.13 to 0.56 μm/year; p = 0.001) faster rates of GCIPL atrophy, respectively. Rates of GCIPL thickness change were similar among ocrelizumab-treated patients compared to natalizumab-treated patients (difference: -0.18 μm/year; 95% CI -0.37 to 0.004 μm/year; p = 0.06) and HCs (difference: -0.13 μm/year; 95% CI -0.33 to 0.07 μm/year; p = 0.20). Conclusions: Ocrelizumab modulates retinal atrophy in RRMS, exerting a neuroprotective effect that is similar to that observed among RRMS patients on natalizumab.