Diagnosis and classification of optic neuritis
Axel Petzold 1, Clare L Fraser 2, Mathias Abegg 3, Raed Alroughani 4, Daniah Alshowaeir 5, Regina Alvarenga 6, Cécile Andris 7, Nasrin Asgari 8, Yael Barnett 9, Roberto Battistella 10, Raed Behbehani 11, Thomas Berger 12, Mukharram M Bikbov 13, Damien Biotti 14, Valerie Biousse 15, Antonella Boschi 16, Milan Brazdil 17, Andrei Brezhnev 18, Peter A Calabresi 19, Monique Cordonnier 20, Fiona Costello 21, Franz M Cruz 22, Leonardo Provetti Cunha 23, Smail Daoudi 24, Romain Deschamps 25, Jerome de Seze 26, Ricarda Diem 27, Masoud Etemadifar 28, Jose Flores-Rivera 29, Pedro Fonseca 30, Jette Frederiksen 31, Elliot Frohman 32, Teresa Frohman 32, Caroline Froment Tilikete 33, Kazuo Fujihara 34, Alberto Gálvez 35, Riadh Gouider 36, Fernando Gracia 37, Nikolaos Grigoriadis 38, José M Guajardo 39, Mario Habek 40, Marko Hawlina 41, Elena H Martínez-Lapiscina 42, Juzar Hooker 43, Jyh Yung Hor 44, William Howlett 45, Yumin Huang-Link 46, Zhannat Idrissova 47, Zsolt Illes 48, Jasna Jancic 49, Panitha Jindahra 50, Dimitrios Karussis 51, Emilia Kerty 52, Ho Jin Kim 53, Wolf Lagrèze 54, Letizia Leocani 55, Netta Levin 56, Petra Liskova 57, Yaou Liu 58, Youssoufa Maiga 59, Romain Marignier 60, Chris McGuigan 61, Dália Meira 62, Harold Merle 63, Mário L R Monteiro 64, Anand Moodley 65, Frederico Moura 66, Silvia Muñoz 67, Sharik Mustafa 68, Ichiro Nakashima 69, Susana Noval 70, Carlos Oehninger 71, Olufunmilola Ogun 72, Afekhide Omoti 73, Lekha Pandit 74, Friedemann Paul 75, Gema Rebolleda 76, Stephen Reddel 77, Konrad Rejdak 78, Robert Rejdak 79, Alfonso J Rodriguez-Morales 80, Marie-Bénédicte Rougier 81, Maria Jose Sa 82, Bernardo Sanchez-Dalmau 83, Deanna Saylor 84, Ismail Shatriah 85, Aksel Siva 86, Hadas Stiebel-Kalish 87, Gabriella Szatmary 88, Linh Ta 89, Silvia Tenembaum 90, Huy Tran 91, Yevgen Trufanov 92, Vincent van Pesch 93, An-Guor Wang 94, Mike P Wattjes 95, Ernest Willoughby 96, Magd Zakaria 97, Jasmin Zvornicanin 98, Laura Balcer 99,
Affiliations
Affiliations
- 1The National Hospital for Neurology and Neurosurgery, University College London, London, UK; Moorfields Eye Hospital, London, UK; Neuro-ophthalmology Expert Centre, Amsterdam University Medical Center, Amsterdam, Netherlands. Electronic address: a.petzold@ucl.ac.uk.
- 2Department of Ophthalmology, University of Sydney, Sydney, NSW, Australia.
- 3Department of Ophthalmology, University of Bern, Bern, Switzerland.
- 4Division of Neurology, Department of Medicine, Al-Amiri Hospital, Kuwait City, Kuwait.
- 5Department of Ophthalmology, King Saud University, Riyadh, Saudi Arabia.
- 6Department of Neurology, Universidade Federal do Estado do Rio de Janeiro (UNIRIO), Rio de Janeiro, Brazil.
- 7Department of Ophthalmology, University Hospital Liege, University of Liège, Liège, Belgium.
- 8Department of Neurology, Slagelse and Institute of Regional Health Research, and Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
- 9Department of Neuroradiology, St Vincent's Hospital, Sydney, NSW, Australia.
- 10Department of Neuro-Ophthalmology, University of São Paulo, São Paulo, Brazil.
- 11Neuro-Ophthalmology Unit, Ibn Sina Hospital, Kuwait City, Kuwait.
- 12Department of Neurology, Medical University of Vienna, Vienna, Austria.
- 13Ufa Eye Research Institute, Ufa, Russia.
- 14Unité de Neurologie Inflammatoire B4, CHU Pierre-Paul Riquet/Purpan, Toulouse, France.
- 15Neuro-Ophthalmology Unit, Emory Eye Center, Emory University, Atlanta, GA, USA.
- 16Department of Head and Neck, Université Catholique de Louvain, Brussels, Belgium; Department of Ophthalmology, Cliniques Universitaires Saint Luc, Brusseles, Belgium.
- 17Department of Neurology, Masaryk University, Brno, Czech Republic; St Anne's University Hospital, Brno, Czech Republic.
- 18Department of Ophthalmology, Kursk State Medical University, Kursk, Russia.
- 19The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- 20Department of Ophthalmology, Université Libre de Bruxelles, Bruxelles, Belgium.
- 21Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
- 22College of Medicine, University of the Philippines-Philippine General Hospital, Manila, Philippines.
- 23Surgery Department of Juiz de Fora Medical School, Federal University of Juiz de Fora, Juiz de Fora, Brazil.
- 24Department of Neurology, University Mouloud Mammeri de Ttizi Ouzou, Ttizi Ouzou, Algeria.
- 25Department of Neurology, Hospital Foundation Adolphe de Rothschild, Paris, France.
- 26Department of Neurology, Hopitaux Universitaires Strasbourg, Strasbourg, France.
- 27Department of Neurology, University Clinic Heidelberg, Heidelberg, Germany.
- 28Department of Neurosurgery, Isfahan University of Medical Sciences, Isfahan, Iran.
- 29Universidad Nacional Autónoma de México, Instituto Nacional de Neurología y Neurocirugía, Centro Médico ABC, Mexico City, Mexico.
- 30Department of Ophthalmology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra, Portugal.
- 31Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark.
- 32Department of Neurology, Laboratory of Neuroimmunology, Stanford University School of Medicine, Palo Alto, CA, USA.
- 33Lyon Neurosciences Research Center, Lyon I University, Lyon France; Neuro-Ophthalmology Unit, Hospices Civils de Lyon, Lyon, France.
- 34Department of Multiple Sclerosis Therapeutics, Fukushima Medical University School of Medicine, Koriyama, Japan.
- 35Department of Ophthalmology, University of Alberta, AB, Canada.
- 36Department of Neurology, Razi University Hospital, University of Tunis El Manar, Tunis, Tunisia.
- 37Department of Neurology, Hospital Santo Tomás, Panama City, Panama; Instituto Conmemorativo Gorgas de Estudios de la Salud, Universidad Interamericana de Panama, Panama City, Panama.
- 38Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
- 39Servicio de Oftalmología, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile.
- 40Department of Neurology, University of Zagreb School of Medicine, Zagreb, Croatia; Department of Neurology, University Hospital Center Zagreb, Zagreb, Croatia.
- 41Eye Hospital, University Medical Centre, Ljubljana, Slovenia.
- 42Department of Neurology, Hospital Clinic of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
- 43Aga Khan University Hospital, Nairobi, Kenya.
- 44Department of Neurology, Penang General Hospital, Penang, Malaysia.
- 45Department of Neurology, Kilimanjaro Christian Medical Center (KCMC), Moshi, Tanzania.
- 46Department of Neurology, Linköping University Hospital, Linköping, Sweden.
- 47Department of Neurology, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan.
- 48Department of Neurology, Odense University Hospital, Odense, Denmark.
- 49Clinic of Neurology and Psychiatry for Children and Youth, Faculty of Medicine University of Belgrade, Belgrade, Serbia.
- 50Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
- 51Multiple Sclerosis Center, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
- 52Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
- 53Department of Neurology, National Cancer Center, Goyang, South Korea.
- 54Eye Center, Medical Center, Medical Faculty, University of Freiburg, Germany.
- 55Vita-Salute San Raffaele University, Experimental Neurophysiology Unit, Institute of Experimental Neurology-INSPE, Scientific Institute San Raffaele, Milan, Italy.
- 56Department of Neurology, Hadassah Medical Center and Faculty of Medicine, Hebrew University, Jerusalem, Israel.
- 57Department of Paediatrics and Inherited Metabolic Disorders, and Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
- 58Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
- 59Department of Neurology, Gabriel Touré University Hospital, Bamako, Mali.
- 60Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et NeuroInflammation, and Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle, Hôpital Neurologique Pierre Wertheimer, Bron, France.
- 61School of Medicine, University College Dublin, Dublin, Ireland; Department of Neurology, St Vincent's University Hospital, Dublin, Ireland.
- 62Centro Hospitalar de Vila Nova de Gaia/Espinho, Portugal.
- 63Department of Ophthalmology, University Hospital of Martinique, Martinique, French West Indies, France.
- 64Division of Ophthalmology, University of São Paulo Medical School, São Paulo, Brazil.
- 65Department of Neurology, University of KwaZulu-Natal, Durban, South Africa.
- 66Department of Neuro-Ophthalmology, Instituto Paulista Da Visão, Higienópolis, Brazil.
- 67Department of Ophthalmology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
- 68Department of Neurology, Prime Healthcare Group, Dubai, United Arab Emirates.
- 69Department of Neurology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
- 70Department of Ophthalmology, Hospital Universitario La Paz, Madrid, Spain.
- 71Department of Neurology, School of Medicine UDELAR, Montevideo, Uruguay.
- 72Department of Ophthalmology, College of Medicine, University of Ibadan, Ibadan, Nigeria.
- 73Department of Ophthalmology, University of Benin, Benin City, Nigeria.
- 74Center for Advanced Neurological Research, Nitte University, Karnataka, India.
- 75Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité- Universiätsmedizin Berlin, Berlin, Germany.
- 76Department of Ophthalmology of Ramon y Cajal Hospital, and Alcala University Madrid, Madrid, Spain.
- 77Sydney Neurology, Sydney, NSW, Australia.
- 78Department of Neurology, Medical University of Lublin, Lublin, Poland.
- 79Department of General and Pediatric Ophthalmology Medical University of Lublin, Lublin, Poland.
- 80Grupo de Investigación Biomedicina, Faculty of Medicine, Fundacion Universitaria Autonoma de las Americas, Risaralda, Colombia.
- 81Department of Ophthalmology, University Hospital of Bordeaux, Bordeaux, France.
- 82Department of Neurology, Centro Hospitalar Universitário São João and Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal.
- 83Department of Ophthalmology, Hospital Clinic of Barcelona, Barcelona, Spain.
- 84Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- 85Department of Ophthalmology and Visual Science, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
- 86Department of Neurology, Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Istanbul, Türkiye.
- 87Neuro-Ophthalmology Unit at Rabin Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
- 88Department of Ophthalmology, University of Mississippi Medical Center, Jackson, MS, USA.
- 89Department of General Planning, Ho Chi Minh City Eye Hospital, Ho Chi Minh City, Vietnam.
- 90Department of Neurology, National Paediatric Hospital Dr Juan P Garrahan, Buenos Aires, Argentina.
- 91Department of Ophthalmology, Faculty of Medicine, Ho Chi Minh City University of Medicine and Pharmacy, and Hai Yen Vision Institute, Ho Chi Minh City, Vietnam.
- 92Department of Neurology and Reflexology, The Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine.
- 93Department of Neurology, Cliniques Universitaires Saint-Luc Brussels, Belgium; Neurochemistry Unit, Institute of Neuroscience, UCLouvain, Brussels, Belgium.
- 94Department of Ophthalmology, Taipei Veterans General Hospital, National Yang-Ming Chiao-Tung University School of Medicine, Taipei, Taiwan.
- 95Department of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Germany.
- 96Department of Neurology, Auckland City Hospital, Auckland, New Zealand.
- 97Department of Neurology, Ain Shams University Hospitals, Cairo, Egypt.
- 98Department of Ophthalmology, University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina.
- 99Department of Neurology, Department of Population Health, and Department of Ophthalmology, New York University Grossman School of Medicine, New York, NY, USA.
- 100Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Faculty of Brain Sciences, London, UK.
Abstract
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.
Conflict of interest statement
Declaration of interests AP received grant support for remyelination trials in multiple sclerosis to the Amsterdam University Medical Centre, Department of Neurology, MS Centre (RESTORE trial), and UCL, London RECOVER trial; received grant fees from Fight for Sight (nimodipine in optic neuritis trial); received royalties or licenses from Up-to-Date (Wolters Kluwer) for a book chapter; received speaker fees for the Heidelberg Academy; participates on advisory board for SC Zeiss OCTA Angi-Network, and the SC Novartis OCTiMS study; holds leadership roles for governing board IMSVISUAL; was chairman of ERN-EYE Neuro-ophthalmology (until Oct, 2020); is board member of National Dutch Neuro-ophthalmology Association; received equipment from OCTA from Zeiss (Plex Elite); and received medical writing support from Novartis for a manuscript (https://doi.org/10.1002/acn3.51473). CF received consulting fees from Invex Therapeutics; received speaker honoraria from University of Dunedin; and holds leadership as Director of Royal Australian and New Zealand College of Ophthalmologists. VB received personal fees as consultant for Gensight and Neurophoenix. PC obtained grants from Annexon, Biogen, Genentech; received royalties from Cambridge Press for an OCT book; received consulting fees from Disarm Therapeutics, Nervgen, Biogen, Avidea; received honoraria from NY Academy of Sciences; and received equipment from Myelin Repair Foundation, Academic CME, Neuraly, and Landos. FC received speaker honoraria from Alexion, Accure Therapeutics, and the Sumiara Foundation. RDe obtained consulting fees from Alexion. JdS received consulting fees from Biogen, Teva, BMS Celegen, Roche, Novartis, Janssen, Merck, Alexion, CSL Behring; and honoraria from Biogen, Teva, BMS Celegen, Roche, Novartis, Janssen, Merck, Alexion, and CSL Behring. JFR received consulting fees from Roche, and Sanofi. EF holds honoraria from Alexion, Genzyme, Biogen, Novartis, and Janssen. TF holds honoraria from Alexion. CFT received honoraria from Novartis; and received support for attending meetings and travel from Novartis and Teva. KF obtained grants from Ministry of Education, Science and Technology of Japan as well as the Ministry of Health, Welfare and Labor of Japan; received consulting fees from Alexion Chugai-Roche Mitsubishi Tanabe, Novartis, Biogen, Eisai, Takeda, Teijin, Viela Bio, UCB, Merck, Japan Tobacco Pharma, and Abbvie; received honoraria from Alexion, Chugai-Roche, Mitsubishi Tanabe, Novartis, Biogen, Eisai, Takeda, Asahi Kasei Medical, Teijin, and Bayer; participated on a data safety monitoring board or advisory board from Alexion, Chugai, Mitsubishi Tanabe, Novartis, Biogen, Eisai, Takeda, Asahi Kasei Medical, Teijin, UCB, and Viela Bio; and received medical writing support from Oxford PharmaGenesis and Apothecom. RG acquired personal fees for participation on data safety monitoring boards, and served on the advisory boards for Biogen, Hikma, Merck, Roche, and Sanofi as well as receiving a grant from Roche. FG received grants or contracts from Roche (NMO epidemiologic studies) and Novartis (MS epidemiologic studies); received honoraria from for lectures from Roche, Novartis, Stendhal, and Merck; received support for attending meetings from the European Charcot Foundation, and ECTRIMS; and reports leadership of FOCEM (Foro Centroamericano y del Caribe de la Esclerosis Múltiple y otras enfermedades desmielinizantes del Sistema Nervioso Central) and Academia Panameña de Medicina y Cirugía (both unpaid). MHab obtained honoraria from Biogen, Sanofi Genzyme, Merck, Bayer, Novartis, Pliva-Teva, Roche, and Zentiva; received support for attending meetings from Biogen, Sanofi Genzyme, Merck, Bayer, Novartis, Pliva-Teva, and Roche; and participated on advisory board for Biogen, Sanofi Genzyme, Merck, Bayer, Novartis, Pliva-Teva, and Roche. ZIl obtained grants or contracts from Biogen and Alexion; received honoraria from Biogen, Novartis, Roche, Merck, and Alexion; received payment for expert testimony from Roche; received support for attending meetings and travel from Biogen and Sanofi; and participated on a data safety monitoring board or advisory board from Biogen, Novartis, Merck, Sanofi, Roche, and Alexion. HJK received grants or contracts from National Research Foundation of Korea, Aprilbio, and Eisai; received consulting fees from Aprilbio, Daewoong, HanAll BioPharma, MDimune, Roche, Sanofi Genzyme, Teva-Handok, UCB, and Viela Bio; and received honoraria from Alexion, Biogen, Celltrion, Eisai, GC Pharma, Merck Serono, Novartis, Sanofi Genzyme, and Teva-Handok. RM received consulting fees from UCB, Alexion, Merck, Viela Bio, Novartis, and Roche; and participated on an advisory board for Viela Bio and Roche. FP obtained research support from Alexion; received grants or contracts from German Ministry for Research Support Recipient Charité Education and Research (BMBF), Deutsche Forschungsgemeinschaft (DFG), Einstein Foundation, Guthy Jackson Charitable Foundation, EU FP7 Framework Program, Biogen, Genzyme, Merck, Serono, Novartis, Bayer, Roche, Parexel, and Almirall; received honoraria from the Guthy Jackson Foundation, Bayer, Biogen, Merck Serono, Sanofi Genzyme, Novartis, Viela Bio, Roche, UCB, Mitsubishi Tanabe, and Celgene; received support for attending meetings from Guthy Jackson Foundation, Bayer, Biogen, Merck Serono, Sanofi Genzyme, Novartis, Alexion, Viela Bio, Roche, UCB, Mitsubishi Tanabe, and Celgene; participated on an advisory board for Celgene, Roche, UCB, Merck; and reports leadership as academic editor for Plos One, and associate editor for Neurology, Neuroimmunology, and Neuroinflammation. MBR received support for attending meeting from Novartis. BSD received consulting fees from Chiesi; received honoraria from Chiesi and Sanofi; received support for attending meetings from Bausch + Lomb; participated on an advisory board for Chiesi; and has stock options from Accure Therapeutics. DS received grants or contracts from National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Mental Health (NIMH), American Academy of Neurology (AAN), National Institute of Aging (NIA), National Multiple Sclerosis Society (NMSS), and United States Department of State; and was a committee member for Multiple Sclerosis International Federation (MSIF) and American Neurological Association (ANA). AS received grants or contracts from the Turkish MS society, and Istanbul University Research Support Grants; received consulting fees from Roche, Merck Serono, Biogen, Gen Pharma of Türkiye, Sanofi Genzyme, and Novartis; received honoraria from Sanofi Genzyme, Novartis, Roche, and Teva; and received support for attending meetings from Sanofi Genzyme. VvP obtained grants or contracts from Biogen; received consulting fees from Biogen, Merck, Sanofi, BMS, Novartis, Janssen, Almirall, and Roche; received honoraria from Biogen, Merck, Sanofi, BMS, Novartis, Roche; and received support for attending meetings from Biogen, Roche, and Almirall. MPW received royalties from Springer Healthcare and Elsevier; received consulting fees from Biogen, Roche, Biologix, Novartis, BMS-Celgene, Imcyse, Merck Serono, Sanofi Aventis, IXICO, and Icometrix; received honoraria from Bayer, Biogen, Biologix, Genilac, Novartis, Medison, Merck Serono, Roche, Sanofi Aventis, and BMS-Celgene; and participated on a data safety monitoring board for VU University Medical Center. LB received consulting fees as editor for the Journal of Neuro-Ophthalmology. GTP is an Emeritus editor for Neuro-ophthalmology. All other authors declare no competing interests.
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