Retinal asymmetry in multiple sclerosis

UK Biobank Eye and Vision Consortium

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Abstract

The diagnosis of multiple sclerosis is based on a combination of clinical and paraclinical tests. The potential contribution of retinal optical coherence tomography (OCT) has been recognized. We tested the feasibility of OCT measures of retinal asymmetry as a diagnostic test for multiple sclerosis at the community level. In this community-based study of 72 120 subjects, we examined the diagnostic potential of the inter-eye difference of inner retinal OCT data for multiple sclerosis using the UK Biobank data collected at 22 sites between 2007 and 2010. OCT reporting and quality control guidelines were followed. The inter-eye percentage difference (IEPD) and inter-eye absolute difference (IEAD) were calculated for the macular retinal nerve fibre layer (RNFL), ganglion cell inner plexiform layer (GCIPL) complex and ganglion cell complex. Area under the receiver operating characteristic curve (AUROC) comparisons were followed by univariate and multivariable comparisons accounting for a large range of diseases and co-morbidities. Cut-off levels were optimized by ROC and the Youden index. The prevalence of multiple sclerosis was 0.0023 [95% confidence interval (CI) 0.00229-0.00231]. Overall the discriminatory power of diagnosing multiple sclerosis with the IEPD AUROC curve (0.71, 95% CI 0.67-0.76) and IEAD (0.71, 95% CI 0.67-0.75) for the macular GCIPL complex were significantly higher if compared to the macular ganglion cell complex IEPD AUROC curve (0.64, 95% CI 0.59-0.69, P = 0.0017); IEAD AUROC curve (0.63, 95% CI 0.58-0.68, P < 0.0001) and macular RNFL IEPD AUROC curve (0.59, 95% CI 0.54-0.63, P < 0.0001); IEAD AUROC curve (0.55, 95% CI 0.50-0.59, P < 0.0001). Screening sensitivity levels for the macular GCIPL complex IEPD (4% cut-off) were 51.7% and for the IEAD (4 μm cut-off) 43.5%. Specificity levels were 82.8% and 86.8%, respectively. The number of co-morbidities was important. There was a stepwise decrease of the AUROC curve from 0.72 in control subjects to 0.66 in more than nine co-morbidities or presence of neuromyelitis optica spectrum disease. In the multivariable analyses greater age, diabetes mellitus, other eye disease and a non-white ethnic background were relevant confounders. For most interactions, the effect sizes were large (partial ω2 > 0.14) with narrow confidence intervals. In conclusion, the OCT macular GCIPL complex IEPD and IEAD may be considered as supportive measurements for multiple sclerosis diagnostic criteria in a young patient without relevant co-morbidity. The metric does not allow separation of multiple sclerosis from neuromyelitis optica. Retinal OCT imaging is accurate, rapid, non-invasive, widely available and may therefore help to reduce need for invasive and more costly procedures. To be viable, higher sensitivity and specificity levels are needed.

Original languageEnglish
Pages (from-to)224-235
Number of pages12
JournalBrain
Volume144
Issue number1
Early online date30 Nov 2020
DOIs
Publication statusPublished - 01 Jan 2021

Bibliographical note

Funding Information:
This analysis was supported by the Eranda Foundation via the International Glaucoma Association, UCL ORS & GRS programmes. A.P., N.G.S., P.T.K., P.J.F, and P.J.P. received salary support from the NIHR BRC at Moorfields Eye Hospital. The authors acknowledge a proportion of our financial support from the UK Department of Health through an award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Biomedical Research Centre for Ophthalmology. P.T.K. is supported in part by the Helen Hamlyn Trust. P.J.F. received support from the Richard Desmond Charitable Trust, via Fight for Sight, London. P.A.K. is supported by a Clinician Scientist award (CS-2014-14-023) from the National Institute for Health Research. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. The UK Biobank Eye and Vision Consortium is supported by grants from Moorfields Eye Charity, The NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology and the Alcon Research Institute. The NIHR BRC at Moorfields Eye Hospital supported A.P., N.G.S., P.A.K., P.T.K., P.J.F., and P.J.P. This analysis was supported by the Eranda Foundation via the International Glaucoma Association, UCL ORS and GRS programmes. P.J.F. received support from the Richard Desmond Charitable Trust, via Fight for Sight, London.

Publisher Copyright:
© 2020 The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • Biomarkers
  • Demyelination
  • Imaging
  • Multiple sclerosis
  • Optic neuritis

ASJC Scopus subject areas

  • Clinical Neurology

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