Diagnosis and classification of optic neuritis
Open accessAbstract
There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.
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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 [17]
The Paraclinical criteria (p. 11) include OCT findings as evidence for diagnosing optic neuritis, supporting a diagnostic role. The available passages do not describe OCT as a robust prognostic biomarker in MS or suggest its use for treatment decisions; they also do not establish its use to distinguish among diagnoses. (LLM, conf=0.80)
Experimental — accuracy not yet measuredOptic neuropathy can be caused by other inflammatory causes, such as MOGAD and NMOSD, as well as infectious, vascular, metabolic, nutritional, drug-induced, genetic and toxic causes.
“Optic neuropathy can be caused by other inflammatory causes, such as MOGAD and NMOSD, as well as infectious, vascular, metabolic, nutritional, drug-induced, genetic and toxic causes. 38,76,77”
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 [38]
The Paraclinical criteria (p. 11) include AQP4 and MOG antibody positivity, and the Cases summary (p. 16) identifies NMO-associated and post-infectious optic neuritis. Our copy does not substantiate the remaining listed vascular, metabolic, nutritional, drug-induced, genetic, or toxic causes of optic neuropathy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredOptic nerve MRI with fat-saturation can better demonstrate symptomatic and asymptomatic T2 hyperintense optic nerve lesions than conventional brain MRIs.
“Optic nerve MRI with fat-saturation can better demonstrate symptomatic and asymptomatic T2hyperintense optic nerve lesions than conventional brain MRIs. 38”
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 [38]
The Paraclinical criteria (p. 11) say MRI can show increased intrinsic signal in a symptomatic optic nerve. Our copy does not specify fat-saturation or T2-hyperintense lesions, address asymptomatic optic nerve lesions, or compare optic nerve MRI with conventional brain MRI. (LLM, conf=0.83)
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Cites
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“15 Relapsing optic neuritis that is of autoimmune cause will require long-term immunomodulation or suppression.”
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- Authors
- Petzold, A., Fraser, C. L., Abegg, M., Alroughani, R., Alshowaeir, D., Alvarenga, R., Andris, C., Asgari, N., Barnett, Y., Battistella, R., Behbehani, R., Berger, T., Bikbov, M. M., Biotti, D., Biousse, V., Boschi, A., Brazdil, M., Brezhnev, A., Calabresi, P. A., Cordonnier, M., Costello, F., Cruz, F. M., Cunha, L. P., Daoudi, S., Deschamps, R., de Seze, J., Diem, R., Etemadifar, M., Flores-Rivera, J., Fonseca, P., Frederiksen, J., Frohman, E., Frohman, T., Tilikete, C. F., Fujihara, K., Gálvez, A., Gouider, R., Gracia, F., Grigoriadis, N., Guajardo, J. M., Habek, M., Hawlina, M., Martínez-Lapiscina, E. H., Hooker, J., Hor, J. Y., Howlett, W., Huang-Link, Y., Idrissova, Z., Illes, Z., Jancic, J., Jindahra, P., Karussis, D., Kerty, E., Kim, H. J., Lagrèze, W., Leocani, L., Levin, N., Liskova, P., Liu, Y., Maiga, Y., Marignier, R., McGuigan, C., Meira, D., Merle, H., Monteiro, M. L. R., Moodley, A., Moura, F., Muñoz, S., Mustafa, S., Nakashima, I., Noval, S., Oehninger, C., Ogun, O., Omoti, A., Pandit, L., Paul, F., Rebolleda, G., Reddel, S., Rejdak, K., Rejdak, R., Rodriguez-Morales, A. J., Rougier, M.-B., Sa, M. J., Sanchez-Dalmau, B., Saylor, D., Shatriah, I., Siva, A., Stiebel-Kalish, H., Szatmary, G., Ta, L., Tenembaum, S., Tran, H., Trufanov, Y., van Pesch, V., Wang, A.-G., Wattjes, M. P., Willoughby, E., Zakaria, M., Zvornicanin, J., Balcer, L., & Plant, G. T.
- Affiliations
- Moorfields Eye Hospital (GB)
- The University of Sydney (AU)
- University of Bern (CH)
- Amiri Hospital (KW)
- King Saud University (SA)
- Universidade Federal do Estado do Rio de Janeiro (BR)
- University of Liège (BE)
- University of Southern Denmark (DK)
- St Vincent's Hospital Sydney (AU)
- Universidade de São Paulo (BR)
- Ibn Sina Hospital (KW)
- Medical University of Vienna (AT)
- Ufa Eye Research Institute (RU)
- Hôpital Purpan (FR)
- Cliniques Universitaires Saint-Luc (BE)
- Kursk State Medical University (RU)
- Johns Hopkins University (US)
- Université Libre de Bruxelles (BE)
- University of Calgary (CA)
- Philippine General Hospital (PH)
- Universidade Federal de Juiz de Fora (BR)
- Mouloud Mammeri University of Tizi-Ouzou (DZ)
- Fondation de Rothschild (FR)
- University Hospital Heidelberg (DE)
- Isfahan University of Medical Sciences (IR)
- Unidade Local de Saúde de Coimbra (PT)
- University of Copenhagen (DK)
- Stanford Medicine (US)
- Lyon 1 Université (FR)
- Fukushima Medical University (JP)
- Tunis El Manar University (TN)
- Instituto Conmemorativo Gorgas de Estudios de la Salud (PA)
- Aristotle University of Thessaloniki (GR)
- Clínica Alemana (CL)
- University Hospital Centre Zagreb (HR)
- Ljubljana University Medical Centre (SI)
- Aga Khan University Hospital Nairobi (KE)
- Kilimanjaro Christian Medical Centre (TZ)
- Kazakh National Medical University (KZ)
- Mahidol University (TH)
- Tel Aviv University (IL)
- National Cancer Center (KR)
- University of Freiburg (DE)
- Vita-Salute San Raffaele University (IT)
- Hebrew University of Jerusalem (IL)
- Capital Medical University (CN)
- Observatoire Français de la Sclérose en Plaques (FR)
- University College Dublin (IE)
- Centro Hospitalar de Vila Nova de Gaia (PT)
- Centre Hospitalier Universitaire de Martinique (MQ)
- University of KwaZulu-Natal (ZA)
- Bellvitge University Hospital (ES)
- Tohoku Medical and Pharmaceutical University (JP)
- Hospital Universitario La Paz (ES)
- University of Ibadan (NG)
- University of Benin (NG)
- Nitte University (IN)
- Max Delbrück Center (DE)
- Hospital Universitario Ramón y Cajal (ES)
- Medical University of Lublin (PL)
- Institución Universitaria Visión de las Américas (CO)
- Centre Hospitalier Universitaire de Bordeaux (FR)
- Universiti Sains Malaysia (MY)
- Garrahan Hospital (AR)
- University of Medicine and Pharmacy at Ho Chi Minh City (VN)
- Shupyk National Healthcare University of Ukraine (UA)
- National Yang Ming Chiao Tung University (TW)
- Medizinische Hochschule Hannover (DE)
- Auckland City Hospital (NZ)
- Ain Shams University Hospital (EG)
- New York University (US)
- UCL Queen Square Institute of Neurology (GB)
- Corresponding author
- Petzold, Axel
- ORCID
- Petzold, Axel
- Fraser, Clare L
- Abegg, Mathias
- Alroughani, Raed
- Alshowaeir, Daniah
- Alvarenga, Regina
- Asgari, Nasrin
- Barnett, Yael
- Behbehani, Raed
- Berger, Thomas
- Bikbov, Mukharram M
- Biotti, Damien
- Brezhnev, Andrei
- Calabresi, Peter A
- Costello, Fiona
- Cunha, Leonardo Provetti
- Deschamps, Romain
- Diem, Ricarda
- Etemadifar, Masoud
- Fonseca, Pedro
- Frederiksen, Jette
- Frohman, Elliot
- Tilikete, Caroline Froment
- Fujihara, Kazuo
- Gouider, Riadh
- Gracia, Fernando
- Grigoriadis, Nikolaos
- Guajardo, José M
- Habek, Mario
- Hawlina, Marko
- Hooker, Juzar
- Hor, Jyh Yung
- Idrissova, Zhannat
- Jindahra, Panitha
- Karussis, Dimitrios
- Kim, Ho Jin
- Lagrèze, Wolf
- Leocani, Letizia
- Liu, Yaou
- Maiga, Youssoufa
- Marignier, Romain
- Meira, Dália
- Merle, Harold
- Monteiro, Mário L R
- Moodley, Anand
- Moura, Frederico
- Muñoz, Silvia
- Nakashima, Ichiro
- Noval, Susana
- Pandit, Lekha
- Paul, Friedemann
- Reddel, Stephen
- Rejdak, Konrad
- Rodriguez-Morales, Alfonso J
- Rougier, Marie-Bénédicte
- Saylor, Deanna
- Shatriah, Ismail
- Tenembaum, Silvia
- Wang, An-Guor
- Wattjes, Mike P
- Zakaria, Magd
- Balcer, Laura
- Plant, Gordon T
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2022-12
- Volume
- 21
- Issue
- 12
- Pages
- 1120-1134
- ISSN
- 1474-4422 (ISSN-L)
- OpenAlex
- W4297231406
- Cited by
- 330
- References
- 3
- Citations by year
- 2026: 86 · 2025: 94 · 2024: 85 · 2023: 60 · 2022: 4 · 2014: 1
- FWCI
- 10.01
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc-nd)
- HAL (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- HAL (submittedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Digital Access to Libraries (submittedVersion, other-oa)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- UCL
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Keywords
- optic neuritis, diagnostic criteria, disease classification, multiple sclerosis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, antibody biomarkers, protein biomarkers, retinal imaging, neuroimaging, misdiagnosis, clinical course
- MeSH terms
- Autoantibodies, Humans, Multiple Sclerosis, Neuromyelitis Optica, Optic Neuritis, Retrospective Studies, Aquaporin 4
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