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Randomized Controlled Trial
. 2025 Jun 12;96(7):647-654.
doi: 10.1136/jnnp-2024-334801.

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

Floriana De Angelis  1   2 , James R Cameron  3 , Arman Eshaghi  4 , Richard Parker  5 , Peter Connick  3 , Jonathan Stutters  4 , Domenico Plantone  4   6 , Anisha Doshi  4 , Nevin John  4   7 , Thomas Williams  4 , Alberto Calvi  4   8 , David MacManus  4 , Frederik Barkhof  4   2   9 , Siddharthan Chandran  3 , Christopher J Weir  5 , Ahmed Toosy  4 , Jeremy Chataway  4   2 ; MS-SMART trial investigators
Collaborators, Affiliations
Randomized Controlled Trial

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

Floriana De Angelis et al. J Neurol Neurosurg Psychiatry. .

Abstract

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.

Keywords: IMAGE ANALYSIS; MULTIPLE SCLEROSIS; RANDOMISED TRIALS.

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Conflict of interest statement

Competing interests: FDA has received speaker honoraria and/or congress fees or served in advisor boards from/for Neurology Academy, Coloplast, Janssen, Merck, Novartis, Roche, Sanofi and is a local principal investigator for commercial and academic trials included CHARIOT-MS, ALITHIOS (Novartis), O’HAND (Roche); she had received a research grant from the Multiple Sclerosis Society of Great Britain and Northern Ireland and funding from National Brain Appeal (Small Acorns fund). AE received research grants from the Medical Research Council (MRC), National Institute for Health and Social Care Research (NIHR), Innovate UK, Biogen, Merck, and Roche; he has served as an advisory board member of Merck Serono and Bristol Myers Squib. He is the founder and equity stake holder in Queen Square Analytics Limited, he serves on the editorial board of Neurology. NJ is a local principal investigator on commercial MS studies funded by Novartis, Roche and Sanofi. He has received speaker’s honoraria from Merck and congress sponsorship covering registration and travel from Novartis. TW reports research funding from the MS-STAT2 trial grant; and honoraria for educational talks from Novartis and Merck. FB serves on the editorial boards of Brain, European Radiology, Journal of Neurology, Neurosurgery & Psychiatry, Neurology, Multiple Sclerosis and Neuroradiology, and serves as consultant for Bayer Schering Pharma, Sanofi- Aventis, Biogen- Idec, TEVA Pharmaceuticals, Genzyme, Merck- Serono, Novartis, Roche, Synthon, Jansen Research and Lundbeck. AT has received speaker honoraria from Merck, Biomedia, Sereno Symposia International Foundation, Bayer and At the Limits and meeting expenses from Merck, Biogen Idec and Novartis and is an associate editor for Frontiers in Neurology—Neuro-ophthalmology section and on the editorial board for Neurology and Multiple Sclerosis Journal. JC has received support in the last 3 years from the Health Technology Assessment (HTA) Programme (National Institute for Health Research, NIHR), the UK MS Society, the US National MS Society and the Rosetrees Trust. He has been a local principal investigator for a trial in MS funded by MS Canada. A local principal investigator for commercial trials funded by Ionis and Roche; and has taken part in advisory boards/consultancy for Biogen, Janssen, Lucid, Merck, NervGen, Novartis and Roche. JRC, RP, PC, JS, DP, AD, AC, DMM, SC, CJW have no competing interests.

Figures

Figure 1
Figure 1. Study profile. Total number of MS-SMART trial participants randomised at UCL= 176 (172 consented the OCT substudy). Total number of participants randomised at Edinburgh = 93 (88 consented the OCT substudy). *For n=11 subjects excluded due to poor OCT imaging quality possible underlying retinal abnormalities were not systematically recorded. GCIPL, ganglion cell-inner plexiform layer; NON, no history of optic neuritis; OCT, optical coherence tomography; ON, optic neuritis; pRNFL, peripapillary retinal nerve fibre layer; UCL, University College London.
Figure 2
Figure 2. . Annualised rates of change for pRNFL and GCIPL. Mixed effect models are analysed at the eye level adjusted for history of optic neuritis. The bars represent annual mean changes in thickness (µm). Error bars represent confidence intervals. Eye are grouped as: overall group (including all eyes regardless history of optic neuritis); ON group (only eyes with history of optic neuritis), NON group (only eyes without history of optic neuritis). GCIPL, ganglion cell-inner plexiform layer; NON, no history of optic neuritis; ON, optic neuritis; pRNFL, peripapillary retinal nerve fibre layer.
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