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Cited by 98Multiple Sclerosis Research StudiesGlaucoma and retinal disordersDrug-Induced Ocular Toxicity

Optical coherence tomography in multiple sclerosis: a 3-year prospective multicenter study

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Paul, Friedemann, Calabresi, Peter A., Barkhof, Frederik, Green, Ari J., Kardon, Randy, Sastre‐Garriga, Jaume, Schippling, Sven, Vermersch, Patrick +7 more·2021·Annals of Clinical and Translational Neurology
DOI 10.1002/acn3.51473PMC PMC8670323
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Abstract

Objective: To evaluate changes over 3 years in the thickness of inner retinal layers including the peripapillary retinal nerve fiber layer (pRNFL), and combined macular ganglion cell and inner plexiform layers (mGCIPL), in individuals with relapsing‐remitting multiple sclerosis (RRMS) versus healthy controls; to determine whether optical coherence tomography (OCT) is sufficiently sensitive and reproducible to detect small degrees of neuroaxonal loss over time that correlate with changes in brain volume and disability progression as measured by the Expanded Disability Status Scale (EDSS). Methods: Individuals with RRMS from 28 centers ( n = 333) were matched with 64 healthy participants. OCT scans were performed on Heidelberg Spectralis machines (at baseline; 1 month; 6 months; 6‐monthly thereafter). Results: OCT measurements were highly reproducible between baseline and 1 month (intraclass correlation coefficient >0.98). Significant inner retinal layer thinning was observed in individuals with multiple sclerosis (MS) compared with controls regardless of previous MS‐associated optic neuritis––group differences (95% CI) over 3 years: pRNFL: −1.86 (−2.54, −1.17) µ m; mGCIPL: −2.03 (−2.78, −1.28) µ m (both p < 0.0001; effect sizes 0.39 and 0.34). Greater inner retinal layer atrophy was observed in individuals diagnosed with RRMS <3 years versus >5 years (pRNFL: p < 0.05; mGCIPL: p < 0.01). Brain volume decreased by 1.3% in individuals with MS over 3 years compared to 0.5% in control subjects (effect size 0.76). mGCIPL atrophy correlated with brain atrophy ( p < 0.0001). There was no correlation of OCT data with disability progression. Interpretation: OCT has potential to estimate rates of neurodegeneration in the retina and brain. The effect size for OCT, smaller than for magnetic resonance imaging based on Heidelberg Spectralis data acquired in this study, was increased in early disease.

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  • OCT is emerging as a robust prognostic biomarker in MS and was also suggested to be applicable for treatment decisions and differential diagnosis.

    “Further, OCT is emerging as a robust prognostic biomarker in MS and was also suggested to be applicable for treatment decisions and differential diagnosis.”

    From Applying the 2024-revised McDonald criteria for multiple sclerosis using conventional diagnostic tools: a single-centre prospective cohort study in Germany (2026) · cites this paper as [39]

    The Conclusion reports highly reproducible OCT measurements and describes their potential for monitoring MS progression, supporting the claim that OCT is an emerging biomarker. The Introduction suggests OCT could assess treatment effects, but neither it nor the Conclusion proposes using OCT to make treatment decisions or for differential diagnosis. The paper also frames OCT’s clinical role as a potential rather than an established robust prognostic tool. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Paul, F., Calabresi, P. A., Barkhof, F., Green, A. J., Kardon, R., Sastre‐Garriga, J., Schippling, S., Vermersch, P., Saidha, S., Gerendas, B. S., Schmidt‐Erfurth, U., Agoropoulou, C., Zhang, Y., Seifer, G., & Petzold, A.
Affiliations
  • Max Delbrück Center (DE)
  • Johns Hopkins University (US)
  • Amsterdam University Medical Centers (NL)
  • University of California, San Francisco (US)
  • University of Iowa (US)
  • Universitat Autònoma de Barcelona (ES)
  • University Hospital Zurich (CH)
  • Inserm (FR)
  • Medical University of Vienna (AT)
  • Department of Ophthalmology Medical University of Vienna Vienna Austria
  • Novartis (Switzerland) (CH)
  • Novartis (United States) (US)
  • Moorfields Eye Hospital NHS Foundation Trust (GB)
Corresponding author
Paul, Friedemann
ORCID
Venue
Annals of Clinical and Translational Neurology
Publisher
Wiley
Published
2021-11-18
Volume
8
Issue
12
Pages
2235-2251
ISSN
2328-9503 (ISSN-L)
DOI
10.1002/acn3.51473
PMC
PMC8670323
OpenAlex
W3212182683
Cited by
98
References
0
Citations by year
2026: 17 · 2025: 25 · 2024: 21 · 2023: 24 · 2022: 10
FWCI
9.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Annals of Clinical and Translational Neurology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
  • Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by-nc-nd)
  • Pure Amsterdam UMC (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
Novartis Pharma
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
  • Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
Keywords
relapsing-remitting multiple sclerosis, optical coherence tomography, peripapillary retinal nerve fiber layer, brain atrophy, disability progression, optic neuritis, neurodegeneration, measurement reproducibility, Expanded Disability Status Scale
MeSH terms
Adult, Atrophy, Brain, Female, Humans, Male, Middle Aged, Prospective Studies, Retina, Multiple Sclerosis, Relapsing-Remitting, Tomography, Optical Coherence

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