Optical coherence tomography in secondary progressive multiple sclerosis: cross-sectional and longitudinal exploratory analysis from the MS-SMART randomised controlled trial

Background: Optical coherence tomography (OCT) inner retinal metrics reflect neurodegeneration in multiple sclerosis (MS). We explored OCT measures as biomarkers of disease severity in secondary progressive MS (SPMS). Methods: We investigated people with SPMS from the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial OCT substudy, analysing brain MRIs, clinical assessments and OCT at baseline and 96 weeks. We measured peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thicknesses. Statistical analysis included correlations, multivariable linear regressions and mixed-effects models. Results: Of the 212 participants recruited at baseline, 192 attended at 96 weeks follow-up. Baseline pRNFL and GCIPL thickness correlated with Symbol Digit Modalities Test (SDMT) (respectively, r=0.33 (95% CI 0.20 to 0.47); r=0.39 (0.26 to 0.51)) and deep grey matter volume (respectively, r=0.21 (0.07 to 0.35); r=0.28 (0.14 to 0.41)).pRNFL was associated with Expanded Disability Status Scale (EDSS) score change (normalised beta (B)=-0.12 (-0.23 to -0.01)). Baseline pRNFL and GCIPL were associated with Timed 25-Foot Walk change (T25FW) (respectively, B=-0.14 (-0.25 to -0.03); B=-0.20 (-0.31 to -0.10)) and 96-week percentage brain volume change (respectively, B=0.14 (0.03 to 0.25); B=0.23 (0.12 to 0.34)). There were significant annualised thinning rates: pRNFL (-0.83 µm/year) and GCIPL (-0.37 µm/year). Conclusions: In our cohort of people with SPMS and long disease duration, OCT measures correlated with SDMT and deep grey matter volume at baseline; EDSS, T25FW and whole brain volume change at follow-up.