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. 2020 Oct:45:102403.
doi: 10.1016/j.msard.2020.102403. Epub 2020 Jul 17.

Validation of inter-eye difference thresholds in optical coherence tomography for identification of optic neuritis in multiple sclerosis

Gabriel Bsteh  1 , Harald Hegen  2 , Patrick Altmann  3 , Michael Auer  2 , Klaus Berek  2 , Anne Zinganell  2 , Franziska Di Pauli  2 , Paulus Rommer  3 , Florian Deisenhammer  2 , Fritz Leutmezer  3 , Thomas Berger  3
Affiliations
Free article

Validation of inter-eye difference thresholds in optical coherence tomography for identification of optic neuritis in multiple sclerosis

Gabriel Bsteh et al. Mult Scler Relat Disord. 2020 Oct.
Free article

Abstract

Objective: To examine and validate thresholds for inter-eye differences in peripapillary retinal nerve fibre (pRNFL) and ganglion cell + inner plexiform layer (GCIPL) thicknesses for identifying unilateral optic neuritis in MS.

Methods: In this two-centre, cross-sectional study, optical coherence tomography was performed in 340 patients with clinically isolated syndrome (CIS) and MS. Cut-off values of inter-eye difference for identification of eyes with a history of unilateral ON were evaluated by receiver-operating characteristics analysis.

Results: For pRNFL ≥5 µm, sensitivity was 69% and specificity 68%, while for GCIPL ≥4 µm sensitivity was 67% and specificity 78%. The areas under the curve (AUC) were 0.72 (95% confidence interval: 0.64 - 0.79) for pRNFL and 0.78 (95%CI: 0.72 - 0.85) for GCIPL, indicating GCIPL as the superior model (p<0.001). When analysing only CIS patients, GCIPL inter-eye difference ≥4 µm also remained significant, while pRNFL inter-eye difference did not.

Interpretations: Inter-eye differences of ≥4 μm for GCIPL and to a lesser degree ≥5 μm for RNFL are robust thresholds for identifying unilateral optic nerve lesions. These thresholds could be used to demonstrate previous symptomatic and possibly asymptomatic ON and might be included into a new version of the diagnostic criteria.

Keywords: Biomarker; Inter-eye difference; Multiple sclerosis; Optic neuritis; Optical coherence tomography.

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Conflict of interest statement

Declaration of Competing Interest Gabriel Bsteh: has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene, Merck, Novartis, Sanofi-Genzyme and Teva, and received honoraria for consulting Biogen, Roche and Teva. Harald Hegen: has participated in meetings sponsored by, received speaker honoraria or travel funding from Bayer, Biogen, Merck, Novartis, Roche, Sanofi-Genzyme, Siemens and Teva, and received honoraria for consulting Biogen and Teva. Patrick Altmann: has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Merck, Roche, Sanofi-Genzyme and Teva, and received honoraria for consulting from Biogen. He received a research grant from Quanterix International and was awarded a combined sponsorship from Biogen, Merck, Sanofi-Genzyme, Roche, and Teva for a clinical study. Michael Auer: received speaker honoraria and/or travel grants from Biogen, Merck, Novartis and Sanofi Genzyme. Klaus Berek: has participated in meetings sponsored by and received travel funding from Roche. Anne Zinganell: has participated in meetings sponsored by, received speaking honoraria or travel funding from Biogen, Merck, Sanofi-Genzyme and Teva. Franziska Di Pauli: has participated in meetings sponsored by, received honoraria (lectures, advisory boards, consultations) or travel funding from Bayer, Biogen, Celgene, Merck, Novartis, Sanofi-Genzyme, Roche and Teva. Paulus Rommer: has received honoraria for consultancy/speaking from AbbVie, Allmiral, Alexion, Biogen, Merck, Novartis, Roche, Sandoz, Sanofi Genzyme, has received research grants from Amicus, Biogen, Merck, Roche. Florian Deisenhammer: has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Almirall, Alexion, Biogen, Celgene, Genzyme-Sanofi, Merck, Novartis, Roche, and Teva. His-institution has received research grants from Biogen and Genzyme Sanofi. He is section editor of the MSARD Journal (Multiple Sclerosis and Related Disorders). Fritz Leutmezer: has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Bayer, Biogen, Celgene, MedDay, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. Thomas Berger: has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for MS: Allergan, Bayer, Biogen, Bionorica, Celgene, MedDay, Merck, Novartis, Octapharma, Roche, Sanofi-Genzyme, Teva. His-institution has received financial support in the past 12 months by unrestricted research grants (Bayer, Biogen, Merck, Novartis, Sanofi Aventis, Teva) and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, Merck, Novartis, Octapharma, Roche, Sanofi-Genzyme, Teva.

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