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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., Competing Interests: 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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Cerebral small vessel disease (SVD) is a common accompaniment to aging. Magnetic resonance imaging (MRI) features of SVD include lacunar infarcts (LI) and white matter hyperintensity (WMH). Brain iron deposition is also a known marker of SVD that is associated with cognitive impairment and can be detected with susceptibility-weighted imaging (SWI) MRI technique. According to recent studies, the pulsation of cerebral blood flow can be one of the main factors of the development of pathological brain changes in elderly patients. The objective of this study was to investigate the relationship between the brain iron deposition, cerebral blood flow pulsation, and cognitive impairment in patients with SVD., Materials and Methods: For the study, 97 patients with diagnosed SVD were selected. The patients were divided into two groups based on the Montreal Cognitive Assessment (MoCA) test scores. All patients underwent MRI in the SWI sequence. Pulsatility index (PI) and resistivity index (RI) were recorded from the middle cerebral artery bilaterally using transcranial Doppler (TCD)., Results: The linear regression model showed that the pulsatility index (PI) and resistivity index (RI) were associated with cognitive impairment and brain iron deposition in basal ganglia. The most significant association was found between left globus pallidus severe hypointensity voxels count and left middle cerebral artery (MCA) RI (p = 0.009)., Conclusion: The results of the study provide information that TCD indicators may be associated with brain iron deposition and cognitive decline in patients with SVD. Our findings suggest that both brain iron deposition and cerebral hemodynamics abnormalities may play an important role in the pathophysiological mechanisms of SVD.