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Retinal asymmetry in multiple sclerosis

Retinal asymmetry in multiple sclerosis
Retinal asymmetry in multiple sclerosis

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.

Biomarkers, Demyelination, Imaging, Multiple sclerosis, Optic neuritis
0006-8950
224-235
Petzold, Axel
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Petzold, Axel
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Chua, Sharon Y.L.
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Khawaja, Anthony P.
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Reisman, Charles
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Dhillon, Baljean
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Aslam, Tariq
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Carare, Roxana O.
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Garway-Heath, David F.
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Gibson, Jane
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Gore, Dan
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Hysi, Pirro
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Self, Jay
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Stratton, Irene
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UK Biobank Eye and Vision Consortium (2021) Retinal asymmetry in multiple sclerosis. Brain, 144 (1), 224-235. (doi:10.1093/brain/awaa361).

Record type: Article

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.

This record has no associated files available for download.

More information

Published date: 1 January 2021
Keywords: Biomarkers, Demyelination, Imaging, Multiple sclerosis, Optic neuritis

Identifiers

Local EPrints ID: 449559
URI: http://eprints.soton.ac.uk/id/eprint/449559
ISSN: 0006-8950
PURE UUID: 45f8190a-51aa-4c20-8138-b997bbf66d61
ORCID for Roxana O. Carare: ORCID iD orcid.org/0000-0001-6458-3776
ORCID for Sarah Ennis: ORCID iD orcid.org/0000-0003-2648-0869
ORCID for Jane Gibson: ORCID iD orcid.org/0000-0002-0973-8285
ORCID for Andrew J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305
ORCID for Jay Self: ORCID iD orcid.org/0000-0002-1030-9963

Catalogue record

Date deposited: 08 Jun 2021 16:30
Last modified: 26 Nov 2021 02:50

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Contributors

Author: Axel Petzold
Author: Sharon Y.L. Chua
Author: Anthony P. Khawaja
Author: Pearse A. Keane
Author: Peng T. Khaw
Author: Charles Reisman
Author: Baljean Dhillon
Author: Nicholas G. Strouthidis
Author: Paul J. Foster
Author: Praveen Patel
Author: Denize Atan
Author: Tariq Aslam
Author: Sarah A. Barman
Author: Jenny H. Barrett
Author: Paul Bishop
Author: Catey Bunce
Author: Usha Chakravarthy
Author: Michelle Chan
Author: Sharon Y.L. Chua
Author: David P. Crabb
Author: Alexander Day
Author: Parul Desai
Author: Bal Dhillon
Author: Andrew D. Dick
Author: Cathy Egan
Author: Sarah Ennis ORCID iD
Author: Paul J. Foster
Author: Marcus Fruttiger
Author: John E.J. Gallacher
Author: David F. Garway-Heath
Author: Jane Gibson ORCID iD
Author: Dan Gore
Author: Jeremy A. Guggenheim
Author: Chris J. Hammond
Author: Alison Hardcastle
Author: Simon P. Harding
Author: Ruth E. Hogg
Author: Pirro Hysi
Author: Pearse A. Keane
Author: Sir Peng T. Khaw
Author: Anthony P. Khawaja
Author: Gerassimos Lascaratos
Author: Tom MacGillivray
Author: Sarah MacKie
Author: Michelle McGaughey
Author: James E. Morgan
Author: Jay Self ORCID iD
Author: Irene Stratton
Corporate Author: UK Biobank Eye and Vision Consortium

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