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.