Optimal intereye difference thresholds by optical coherence tomography in multiple sclerosis: An international study
Open accessAbstract
Objective: To determine the optimal thresholds for intereye differences in retinal nerve fiber and ganglion cell + inner plexiform layer thicknesses for identifying unilateral optic nerve lesions in multiple sclerosis. Current international diagnostic criteria for multiple sclerosis do not include the optic nerve as a lesion site despite frequent involvement. Optical coherence tomography detects retinal thinning associated with optic nerve lesions. Methods: In this multicenter international study at 11 sites, optical coherence tomography was measured for patients and healthy controls as part of the International Multiple Sclerosis Visual System Consortium. High‐ and low‐contrast acuity were also collected in a subset of participants. Presence of an optic nerve lesion for this study was defined as history of acute unilateral optic neuritis. Results: Among patients (n = 1,530), receiver operating characteristic curve analysis demonstrated an optimal peripapillary retinal nerve fiber layer intereye difference threshold of 5μm and ganglion cell + inner plexiform layer threshold of 4μm for identifying unilateral optic neuritis (n = 477). Greater intereye differences in acuities were associated with greater intereye retinal layer thickness differences ( p ≤ 0.001). Interpretation: Intereye differences of 5μm for retinal nerve fiber layer and 4μm for macular ganglion cell + inner plexiform layer are robust thresholds for identifying unilateral optic nerve lesions. These thresholds may be useful in establishing the presence of asymptomatic and symptomatic optic nerve lesions in multiple sclerosis and could be useful in a new version of the diagnostic criteria. Our findings lend further validation for utilizing the visual system in a multiple sclerosis clinical trial setting. Ann Neurol 2019;85:618–629
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The optimal inter-eye difference threshold for identifying PwMS with known prior unilateral ON was 5μm for pRNFL (AUC = 0.74) and 4μm for GCIPL (AUC = 0.77) across OCT devices.
“The optimal IED threshold for identifying PwMS with known prior unilateral ON for the pRNFL was 5µm (AUC = 0.74) and GCIPL was 4µm (AUC = 0.77) across OCT devices.”
From The use of optical coherence tomography and visual evoked potentials in the 2024 McDonald diagnostic criteria for multiple sclerosis (2025) · cites this paper as [52]
The available indexed passages identify the paper as a study of optimal intereye-difference thresholds, but do not report the claimed pRNFL and GCIPL thresholds or AUC values. Searches for unilateral optic neuritis, 5 μm, GCIPL, and AUC 0.74/0.77 found no passage that verifies those figures or the across-device qualifier. (LLM, conf=0.70)
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The OSCAR-IB Consensus Criteria for Retinal OCT Quality Assessment
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Vidal-Jordana, A., Rovira, A., Calderon, W., Arrambide, G., Castilló, J., Moncho, D., Rahnama, K., Collorone, S., Toosy, A. T., Ciccarelli, O., et al. (2024) · Neurology · doi:10.1212/wnl.0000000000207805 · Cited by 88 · see citing works
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- Authors
- Nolan‐Kenney, R. C., Liu, M., Akhand, O., Calabresi, P. A., Paul, F., Petzold, A., Balk, L., Brandt, A. U., Martínez‐Lapiscina, E. H., Saidha, S., Villoslada, P., Al‐Hassan, A. A., Behbehani, R., Frohman, E. M., Frohman, T., Havla, J., Hemmer, B., Jiang, H., Knier, B., Korn, T., Leocani, L., Papadopoulou, A., Pisa, M., Zimmermann, H., Galetta, S. L., Balcer, L. J., & on behalf of the International Multiple Sclerosis Visual System Consortium
- Affiliations
- Department of Population Health, Sackler Institute for Biomedical Sciences New York University School of Medicine New York NY
- New York University (US)
- NYU Langone Health (US)
- Johns Hopkins University (US)
- Max Delbrück Center (DE)
- Moorfields Eye Hospital (GB)
- University of California, Irvine (US)
- Hospital Clínic de Barcelona (ES)
- Dasman Diabetes Institute (KW)
- The University of Texas at Austin (US)
- Institut für Klinische Neuroimmunologie (DE)
- Munich Cluster for Systems Neurology (DE)
- University of Miami (US)
- Technical University of Munich (DE)
- Vita-Salute San Raffaele University (IT)
- University Hospital of Basel (CH)
- Humboldt-Universität zu Berlin (DE)
- Corresponding author
- Balcer, Laura J.
- ORCID
- Liu, Mengling
- Calabresi, Peter A.
- Paul, Friedemann
- Petzold, Axel
- Balk, Lisanne
- Brandt, Alexander U.
- Martínez‐Lapiscina, Elena H.
- Saidha, Shiv
- Villoslada, Pablo
- Behbehani, Raed
- Frohman, Elliot M.
- Havla, Joachim
- Hemmer, Bernhard
- Jiang, Hong
- Knier, Benjamin
- Korn, Thomas
- Leocani, Letizia
- Papadopoulou, Athina
- Pisa, Marco
- Zimmermann, Hanna
- Galetta, Steven L.
- Balcer, Laura J.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2019-04-10
- Volume
- 85
- Issue
- 5
- Pages
- 618-629
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2922294220
- Cited by
- 164
- References
- 1
- Citations by year
- 2026: 23 · 2025: 21 · 2024: 21 · 2023: 25 · 2022: 26 · 2021: 24 · 2020: 14 · 2019: 9
- FWCI
- 13.43
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Multiple Sclerosis Society (RG 4649A5/1)
- Federal Ministry of Education and Research (01ZZ1804[A‐H], 01ZZ1603[A‐D])
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
- Keywords
- multiple sclerosis, optic nerve lesions, optic neuritis, retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, optical coherence tomography, diagnostic criteria, visual function, visual acuity, retinal thinning
- MeSH terms
- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Multiple Sclerosis, Optic Nerve, Retinal Ganglion Cells, Visual Acuity, Cohort Studies, Internationality, Tomography, Optical Coherence, Retinal Neurons, Young Adult
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