The 100 Most-Cited Articles on Optic Neuritis: Trends of Subtypes, Authorship, and Time

Background: Optic neuritis (ON) is an optic nerve inflammation that may lead to different degrees of vision loss. In recent decades, ON research facilitated a better understanding of the disease and its subtypes. This bibliometric analysis aimed to detect the 100 most-cited medical articles related to ON in the last 50 years (1972-2021) and describe publication trends arising from the list. Methods: The Scopus database was used to locate and screen the 100 most influential ON papers based on the number of citations per article. Each entry was reviewed for the first author (name, gender, institution, and country), year of publication, journal, number of citations, ON subtype, and study design. The mean impact factor (IF) of each journal was calculated. Results: The median number of citations was 265 (range 182-2,396). Observational studies on neuromyelitis optica-associated ON were the most common (27%), and the most influential decade was 2002-2011 (54 papers). Seventy-nine percent of articles were published in neurology journals, and a positive correlation between the mean number of citations per article and the journal mean IF was observed ( r = 0.62, P < 0.001). Between 2009 and 2021, female authors led more ON studies (52%), and more publications originated outside the USA (68%), compared with previous years. Conclusions: This analysis summarizes the impact and shifting trends of ON research in the last decades.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD The 100 Most-Cited Articles on Optic Neuritis: Trends of Subtypes, Authorship, and Time Elishai Assayag, MD, Yishay Weill, MD, Daniel Rappoport, MD Background: Optic neuritis (ON) is an optic nerve inflammation that may lead to different degrees of vision loss. In recent decades, ON research facilitated a better understanding of the disease and its subtypes. This bibliometric analysis aimed to detect the 100 most-cited medical articles related to ON in the last 50 years (1972–2021) and describe publication trends arising from the list. Methods: The Scopus database was used to locate and screen the 100 most influential ON papers based on the number of citations per article. Each entry was reviewed for the first author (name, gender, institution, and country), year of publication, journal, number of citations, ON subtype, and study design. The mean impact factor (IF) of each journal was calculated. Results: The median number of citations was 265 (range 182–2,396). Observational studies on neuromyelitis opticaassociated ON were the most common (27%), and the most influential decade was 2002–2011 (54 papers). Seventynine percent of articles were published in neurology journals, and a positive correlation between the mean number of citations per article and the journal mean IF was observed (r = 0.62, P , 0.001). Between 2009 and 2021, female authors led more ON studies (52%), and more publications originated outside the USA (68%), compared with previous years. Conclusions: This analysis summarizes the impact and shifting trends of ON research in the last decades. Journal of Neuro-Ophthalmology 2023;43:307–316 doi: 10.1097/WNO.0000000000001859 © 2023 by North American Neuro-Ophthalmology Society dom has reported an incidence rate of 3.7 per 100,000 person-years.4 In the last decades, the understanding of ON and its distinct subtypes has dramatically progressed. The Optic Neuritis Treatment Trial (ONTT), followed by the discovery of the pathophysiologic role of aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) autoantibodies, facilitated this evolvement.5–7 In clinical practice, ON is often classified into a typical or atypical presentation and, more specifically, into the 3 main phenotypic subtypes: idiopathic/ multiple sclerosis-associated ON (MS-ON),8 neuromyelitis optica-associated ON (NMO-ON),9 and MOG-associated disease (MOGAD).10 This categorization has naturally led to new trends in research and literature. Previous bibliometric evaluations have portrayed the most influential papers on various ophthalmic and neurologic diseases.11–14 These analyses revealed major publication trends (timing, impact, authorship, etc.) over selected periods of time and provided insights that may aid researchers in conducting future studies. To the best of our knowledge, a bibliometric analysis of ON citation classics was never performed. This study aimed to analyze the top 100 most-cited medical articles on ON (T100-ON) in the last 50 years (1972–2021) and describe evident publication trends. METHODS O ptic neuritis (ON) is an optic nerve inflammation that can manifest as an isolated derangement or as part of a broader neurologic, infectious, or inflammatory condition.1 Depending on the underlining pathology, patients with ON may present with different severities of visual impairment, eye pain, and additional symptoms.2 Significant variances were observed in the incidence and prevalence rates of ON, probably because of demographic and diagnostic aspects.3 A recent large cohort study from the United KingDepartment of Ophthalmology (EA, DR), Shaare Zedek Medical Center, affiliated with the Hebrew University-Hadassah Medical School, Jerusalem, Israel; and Department of Ophthalmology and Vision Sciences (YW), University of Toronto, Toronto, Canada. The authors report no conflicts of interest. Address correspondence to Elishai Assayag, MD, Department of Ophthalmology, Shaare Zedek Medical Center, 12 Shmuel Beit, Jerusalem 9103102, Israel; E-mail: [e-mail] Assayag et al: J Neuro-Ophthalmol 2023; 43: 307-316 Article Selection and Data Collection The institutional review board waived ethics approval for this study. The Scopus database was searched to acquire a list of medical publications on optic neuritis. Conducted on February 9, 2022, the search was limited to specific terms in the title field (“optic neuritis” OR “inflammatory optic neuropathy” OR “infectious optic neuropathy” OR “neuromyelitis optica” OR “MOG antibody-associated disease” OR “myelin oligodendrocyte glycoprotein antibody-associated disease”), and to the last 50 years in the publication date field (AND “1972/01/ 01 to 2021/12/31”). Results included full-length English articles and non-English articles with English abstracts. The results list was sorted by the number of citations (highest to lowest), and the first 100 titles formed the T100-ON list. Abstracts were individually reviewed by the first author to verify their relevance to ON. A similar search was performed on Google 307 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Scholar and Web of Science databases to rule out other highly cited papers. The following data were documented for each publication: name of first author/study group, gender of the first author, year of publication, journal, number of citations, country of origin (by the primary affiliation of the first author), ON subtype, and study design. In cases where an abstract was unavailable, the full-text article was accessed to obtain the information. Each paper was categorized into one of the ON subtypes according to the article’s main focus: MS-ON, NMO-ON, MOGAD, “nonspecific” (more than one subtype was studied), or “other” (paraneoplastic, infectious, etc). The list of study designs included the following options: clinical guidelines, review, basic science (molecular, animal models), observational (population-based, case series, retrospective or prospective cohort, cross-sectional), interventional (open-label, nonrandomized), and randomized controlled trial (RCT). In cases where the gender of the first author was not ascertained by the first name, an online search was performed to obtain a photo or relevant biographic data from institutional websites or social media. The impact factor (IF, Clarivate Journal Citation Reports) of each journal in the publication year of each item was documented, and all journals were ranked based on their mean IF. The official category of each journal (neurology, ophthalmology, etc.) was retrieved from Clarivate Master Journal List. Statistical Analysis Statistical analyses were performed using Microsoft Excel 2019 (Microsoft Corporation, Redmond, WA). Absolute and relative frequencies were used to describe categorical variables (number of publications, ON subtypes, and study designs). Quantitative variables were summarized as means and standard deviations. Correlations were assessed with a Pearson correlation coefficient. A P-value ,0.05 was considered significant. RESULTS Overview of Optic Neuritis Citation Classics Table 1 depicts the TOP100-ON list. The top 100 mostcited articles on ON in the last 50 years were published from 1972 to 2019. The mean and median number of citations per paper was 393 (SD = 400.7) and 265 (range 182–2,396), respectively. Articles were published in 26 medical journals. The first authors were from 14 countries. Twelve papers were published on behalf of a study group. The predominant ON subtype was NMO-ON (67 articles), which was the topic of the 5 most-cited articles (1,461–2,396 citations). Observational studies were the most prevalent among study designs (48 publications). 308 Publication Years, Optic Neuritis Subtypes, and Study Designs Figure 1A presents a distribution of the T100-ON list by decades and ON subtypes. More than half of the papers (54) were published between 2002 and 2011, followed by publications from the last decade (2012–2021, 31 articles). In the last 20 years, studies on NMO-ON accounted for 74.1% of the most-cited articles on ON. Only 4 papers from the T100-ON list were on MOGAD, of which 3 were published between 2012 and 2021. Of the 15 research items that reported basic science studies, 14 investigated NMO-ON, and none were on MSON (Fig. 1B). All interventional studies and clinical guidelines in the T100-ON list were on NMO-ON. However, of the 10 detected RCTs, 8 were related to MS-ON, and only 2 were conducted on NMO-ON patients. Journals and Ranking The highest number of papers from the T100-ON list were published in Neurology (23, Table 2). Four articles were published in New England Journal of Medicine, the journal with the highest mean IF on the list (62.9). Most studies were published in neurology journals (79). The remainder of the research items were published in journals of general medicine/basic science (14), ophthalmology (5), and immunology (2). A positive and statistically significant correlation was detected between the mean number of citations per article and the journal mean IF (r = 0.62, P , 0.001). Gender Distribution and Countries of Origin In the first 50 publications (1972–2008), only 24% of the first authors were female. The female representation in senior authorship significantly improved in the second half of publications (2009–2021, 52% female first authors). The mean number of citations per article of female first authors was lower than that of male authors, although this difference did not reach statistical significance (n = 38, 345.1 citations vs n = 62, 423.0 citations, respectively, P = 0.34). Articles by female authors had a similar mean IF compared with male authors (9.3 vs 9.8, respectively, P = 0.40). The distribution of papers by countries of origin is detailed in Table 3. Most articles in the T100-ON list originated from institutions in the United States of America (USA, 47), followed by publications from the United Kingdom (UK, 19) and Germany (10). American articles accounted for 62% of the first half of publications (1972– 2008), whereas the relative contribution of other countries was higher in the latest 50 articles (68%, 2009–2021). DISCUSSION Citation counts are widely used to quantify the scientific impact of medical research, and several bibliometric indices are citation-based.15 Previous bibliometric assessments Assayag et al: J Neuro-Ophthalmol 2023; 43: 307-316 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 1. The 100 most-cited articles on optic neuritis (1972–2021) Rank 1st Author (Study Group) 1 Lennon P.V.A. 2 7 Wingerchuk D.M. Wingerchuk D.M. Wingerchuk D.M. Wingerchuk D.M. Beck R.W. (Optic Neuritis Study Group) Lucchinetti C.F. 8 9 Pittock S.J. Bettelli E. 10 Roemer S.F. 11 12 Beck R.W. (Optic Neuritis Study Group) Pittock S.J. 13 Cree B.A.C. 14 Beck R.W. (Optic Neuritis Study Group) Halliday A.M. Misu T. 3 4 5 6 15 16 17 19 Weinshenker B.G. Jarius S. (German NMO Study Group) Costello F. 20 Pittock S.J. 21 Bradl M. 22 Trip S.A. 23 Bennett J.L. 24 Brodsky M. (Optic Neuritis Study Group) 18 Title Year Journal Citations A serum autoantibody marker of neuromyelitis optica: Distinction from multiple sclerosis Revised diagnostic criteria for neuromyelitis optica 2004 Lancet 2,396 2006 Neurology 2,272 International consensus diagnostic criteria for neuromyelitis optica spectrum disorders The spectrum of neuromyelitis optica 2015 Neurology 2,099 2007 Lancet Neurology 1,641 The clinical course of neuromyelitis optica (Devic’s syndrome) A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis 1999 Neurology 1,461 1992 New England Journal of Medicine 982 A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica Brain abnormalities in neuromyelitis optica Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis The clinical profile of optic neuritis: experience of the optic neuritis treatment trial 2002 Brain 953 2006 2003 JAMA Neurology Journal of Experimental Medicine Brain 596 594 1991 Archives of Ophthalmology 560 Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression An open label study of the effects of rituximab in neuromyelitis optica The effect of corticosteroids for acute optic neuritis on the subsequent development of multiple sclerosis 2006 Archives of Neurology Neurology 554 1993 New England Journal of Medicine 528 Delayed visual evoked response in optic neuritis Loss of aquaporin 4 in lesions of neuromyelitis optica: Distinction from multiple sclerosis Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients Quantifying axonal loss after optic neuritis with optical coherence tomography Neuromyelitis optica and non-organ-specific autoimmunity Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis Intrathecal pathogenic anti-aquaporin-4 antibodies in early neuromyelitis optica Multiple sclerosis risk after optic neuritis: Final optic neuritis treatment trial follow-up 1972 2007 Lancet Brain 521 499 2006 Annals of Neurology Journal of Neuroinflammation 481 Annals of Neurology Archives of Neurology Annals of Neurology Annals of Neurology Annals of Neurology Archives of Neurology 457 Assayag et al: J Neuro-Ophthalmol 2023; 43: 307-316 2007 2005 2012 2006 2008 2009 2005 2009 2008 568 534 459 443 434 426 414 402 309 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution (Continued ) Rank 1st Author (Study Group) 25 Kitley J. 26 Saadoun S. 27 28 Trebst C. (German NMO Study Group) Hinson S.R. 29 Jacob A. 30 O’Riordan J.I. 31 Beck R.W. 32 Kim H.J., Paul (NMO International Clinical Consortium & Biorepository) Beck R.W. (Optic Neuritis Study Group) 33 34 Jarius S. 35 36 Papadopoulos M.C. Mandler R.N. 37 Kitley J. 38 Matiello M. 39 Mader S. 40 Jarius S. 41 Sellner J. 42 Mandler R.N. 43 44 Toosy A.T. Chihara N. 310 Title Year Journal Citations Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies a comparative study Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice Update on the diagnosis and treatment of neuromyelitis optica: Recommendations of the Neuromyelitis Optica Study Group (NEMOS) Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica Treatment of neuromyelitis optica with rituximab: Retrospective analysis of 25 patients Clinical, CSF, and MRI findings in Devic’s neuromyelitis optica 2014 JAMA Neurology 402 2010 Brain 391 2014 Journal of Neurology 385 2007 Neurology 381 2008 379 The 5-year risk of MS after optic neuritis: Experience of the Optic Neuritis Treatment Trial MRI characteristics of neuromyelitis optica spectrum disorder: An international update 1997 Archives of Neurology Journal of Neurology, Neurosurgery and Psychiatry Neurology 2015 Neurology 359 High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis experience of the optic neuritis: Treatment trial optic neuritis study group Antibody to aquaporin-4 in the long-term course of neuromyelitis optica Aquaporin 4 and neuromyelitis optica 2003 Archives of Ophthalmology 347 2008 Brain 338 2012 Lancet Neurology 338 Devic’s neuromyelitis optica: A prospective study of seven patients treated with prednisone and azathioprine Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype NMO-IgG predicts the outcome of recurrent optic neuritis Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders AQP4 antibodies in neuromyelitis optica: Diagnostic and pathogenetic relevance EFNS guidelines on diagnosis and management of neuromyelitis optica Devic’s neuromyelitis optica: A clinicopathological study of 8 patients Optic neuritis Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica 1998 Neurology 330 2012 Neurology 328 2008 Neurology 323 2011 Journal of Neuroinflammation 323 2010 Nature Reviews Neurology European Journal of Neurology Annals of Neurology Lancet Neurology Proceedings of the National Academy of Sciences of the United States of America 319 1996 2010 1993 2014 2011 362 362 303 302 301 290 Assayag et al: J Neuro-Ophthalmol 2023; 43: 307-316 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution (Continued ) Rank 1st Author (Study Group) 45 Jurynczyk M., 46 Pittock S.J. 47 48 Wingerchuk D.M. Kitley J. 49 Balcer L.J. 50 Jarius S. 51 Misu T. 52 Palace J. 53 Pittock S.J. 54 Ramanathan S. 55 Jacob A. 56 Waters P. 57 Hinson S.R. 58 Youl B.D. 59 60 Wingerchuk D.M. Syc S.B. 61 Ghezzi A. 62 Watanabe S. 63 Jarius S. 64 Kleiter I. 65 66 Beck R.W. (Optic Neuritis Study Group) Ratchford J.N. 67 Araki M. Title Year Journal Citations Clinical presentation and prognosis in MOG-antibody disease: A UK study Eculizumab in AQP4-IgG-positive relapsing neuromyelitis optica spectrum disorders: An open-label pilot study Neuromyelitis optica: Clinical predictors of a relapsing course and survival Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan Optic neuritis 2017 Brain 287 2013 Lancet Neurology 278 2003 Neurology 276 2012 Brain 276 2006 275 Mechanisms of disease: Aquaporin-4 antibodies in neuromyelitis optica Intractable hiccup and nausea with periaqueductal lesions in neuromyelitis optica Interferon beta treatment in neuromyelitis optica: Increase in relapses and aquaporin 4 antibody titers Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination 2008 New England Journal of Medicine Nature Clinical Practice Neurology Neurology 257 Treatment of neuromyelitis optica with mycophenolate mofetil: Retrospective analysis of 24 patients Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down- Regulating EAAT2 The pathophysiology of acute optic neuritis: An association of gadolinium leakage with clinical and electrophysiological deficits A secondary progressive clinical course is uncommon in neuromyelitis optica Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis Clinical characteristics, course and prognosis of relapsing Devic’s Neuromyelitis Optica Therapeutic efficacy of plasma exchange in NMO-IgGpositive patients with neuromyelitis optica Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: Results from 211 lumbar punctures Failure of natalizumab to prevent relapses in neuromyelitis optica Optic neuritis treatment trial: One-year follow-up results 2009 1991 Archives of Neurology New England Journal of Medicine Journal of Neurology, Neurosurgery and Psychiatry Archives of Neurology Archives of Neurology Journal of Experimental Medicine Brain 2007 Neurology 236 2012 Brain 236 2004 Journal of Neurology Multiple Sclerosis 230 Journal of the Neurological Sciences Archives of Neurology Archives of Ophthalmology 223 2009 Neurology 218 2014 Neurology 218 Optical coherence tomography helps differentiate neuromyelitis optica and MS optic neuropathies Efficacy of the anti-IL-6 receptor antibody tocilizumab in neuromyelitis optica Assayag et al: J Neuro-Ophthalmol 2023; 43: 307-316 2005 2010 2019 2018 2008 2008 2007 2011 2012 1993 265 260 256 253 251 250 248 239 227 222 220 311 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution (Continued ) Rank 1st Author (Study Group) 68 Banwell B. 69 Kim S.-H. 70 Jarius S. 71 Pellkofer H.L. 72 Hinson S.R. 73 Uzawa A. 74 Costanzi C. 75 Varrin-Doyer M. 76 Min J.-H. 77 Lucchinetti C.F. 78 Popescu B.F.G. 79 80 Hickman S.J. Kim S.-H. 81 Rizzo J.F. 82 Tradtrantip L. 83 Kinoshita M. 84 85 Cree B.A.C. (NMOmentum study investigators) Hacohen Y. 86 Asgari N. 87 Paul F. 312 Title Year Journal Citations Neuromyelitis optica-IgG in childhood inflammatory demyelinating CNS disorders Repeated treatment with rituximab based on the assessment of peripheral circulating memory B cells in patients with relapsing neuromyelitis optica over 2 years Neuromyelitis optica: Clinical features, immunopathogenesis and treatment 2008 Neurology 214 2011 Archives of Neurology 214 2014 214 Long-term follow-up of patients with neuromyelitis optica after repeated therapy with rituximab Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes 2011 Clinical and Experimental Immunology Neurology Cytokine and chemokine profiles in neuromyelitis optica: Significance of interleukin-6 Azathioprine: Tolerability, efficacy, and predictors of benefit in neuromyelitis optica Aquaporin 4-specific T cells in neuromyelitis optica exhibit a Th17 bias and recognize Clostridium ABC transporter Development of extensive brain lesions following fingolimod (FTY720) treatment in a patient with neuromyelitis optica spectrum disorder The pathology of an autoimmune astrocytopathy: Lessons learned from neuromyelitis optica Neuromyelitis optica unique area postrema lesions: Nausea, vomiting, and pathogenic implications Management of acute optic neuritis A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder Risk of developing multiple sclerosis after uncomplicated optic neuritis: A long-term prospective study Anti-aquaporin-4 monoclonal antibody blocker therapy for neuromyelitis optica Neuromyelitis optica: Passive transfer to rats by human immunoglobulin 2012 213 213 2010 Proceedings of the National Academy of Sciences of the United States of America Multiple Sclerosis 212 2011 Neurology 209 2012 Annals of Neurology 206 2012 Multiple Sclerosis Journal 204 2014 Brain Pathology 204 2011 Neurology 202 2002 2013 Lancet JAMA Neurology 201 200 1988 Neurology 199 2012 198 196 Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N-MOmentum): a double-blind, randomised placebo-controlled phase 2/3 trial 2019 Annals of Neurology Biochemical and Biophysical Research Communications Lancet Disease course and treatment responses in children with relapsing myelin oligodendrocyte glycoprotein antibody–Associated disease A population-based study of neuromyelitis optica in Caucasians Antibody to aquaporin 4 in the diagnosis of neuromyelitis optica 2018 JAMA Neurology 195 2011 Neurology 194 2007 PLoS Medicine 193 2009 196 Assayag et al: J Neuro-Ophthalmol 2023; 43: 307-316 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution (Continued ) Rank 88 89 90 1st Author (Study Group) Pandit L. (NMO International Clinical Consortium & Biorepository) Mealy M.A. 91 Kleiter I. (German NMO Study Group) Miller D.H. 92 Gal R.L. 93 Vincent T. 94 Höftberger R. 95 Cross S.A. 96 Söderström M. 97 Ramanathan S. 98 Rizzo J.F. 99 Papeix C. 100 Kimbrough D.J. Title Year Journal Citations Demographic and clinical features of neuromyelitis optica: A review 2015 Multiple Sclerosis Journal 192 Epidemiology of neuromyelitis optica in the United States: A multicenter analysis Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses 2012 Archives of Neurology Annals of Neurology 191 Magnetic resonance imaging of the optic nerve in optic neuritis Visual function more than 10 years after optic neuritis: Experience of the optic neuritis treatment trial Functional Consequences of Neuromyelitis Optica-IgG Astrocyte Interactions on Blood–Brain Barrier Permeability and Granulocyte Recruitment Antibodies to MOG and AQP4 in adults with neuromyelitis optica and suspected limited forms of the disease Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG Optic neuritis: Prognosis for multiple sclerosis from MRI, CSF, and HLA findings Radiological differentiation of optic neuritis with myelin oligodendrocyte glycoprotein antibodies, aquaporin-4 antibodies, and multiple sclerosis Optic neuritis and ischemic optic neuropathy: Overlapping clinical profiles Immunosuppressive therapy is more effective than interferon in neuromyelitis optica Treatment of neuromyelitis optica: Review and recommendations 1988 Neurology 188 2004 American Journal of Ophthalmology Journal of Immunology 188 2016 2008 191 188 2015 Multiple Sclerosis 188 2003 187 1998 Annals of Neurology Neurology 2016 Multiple Sclerosis 186 1991 Archives of Ophthalmology Multiple Sclerosis 182 2007 2012 Multiple Sclerosis and Related Disorders 186 182 182 AQP4, aquaporin-4; CNS, central nervous system; CSF, cerebrospinal fluid; EFNS, European Federation of Neurological Societies; HLA, human leukocyte antigen; MOG, myelin oligodendrocyte glycoprotein; MS, multiple sclerosis; NMO, neuromyelitis optica. based on citation classics identified noteworthy research trends in specific neurologic and neuro-ophthalmologic conditions, such as idiopathic intracranial hypertension12 and meningiomas.11 This study recognized the 100 mostcited medical articles on ON in the last 50 years. In the first 3 decades covered by this bibliographic analysis (1972–2001), MS-ON was the most significant subtype in frequently-cited articles. The ONTT, a landmark study in neuro-ophthalmology,5 and its follow-up analyses make up most of the T100-ON list until 2001. Nevertheless, after the final ONTT follow-up (2008), only one MS-ON paper gained enough citations to be included in the list. This can be reasoned by the natural history of the disease, which was well-described by the ONTT study group, and the good visual prognosis regardless of treatment (at 1 year, 95% have 20/40 or better visual acuity).3 Assayag et al: J Neuro-Ophthalmol 2023; 43: 307-316 The dominance of 2002–2011 in the TOP100-ON list may be attributed to NMO-related research. Until the early 2000s, NMO was well-recognized clinically, but no breakthrough was accomplished in its pathophysiological description, resulting in relatively few items on the T100-ON list (only 4 NMO-ON papers between 1972 and 2001). However, in a pivotal study from 2004 (2,396 citations, the highest number on the list), Lennon et al detected an NMO-specific IgG autoantibody,6 later shown to target AQP4 selectively. This extraordinary revelation gave rise to other high-impact NMO papers in the following years, dozens of which form the T100ON list, including the revised diagnostic criteria of the disorder. RCTs are considered the gold standard in evaluating novel treatment agents or regimens. However, after the ONTT and its subsequent observations, years passed until new high-impact RCTs related to ON appeared. In MS-ON, the lack of RCTs 313 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. The 100 most-cited articles on optic neuritis between 1972 and 2021 divided into subtypes and distributed by 10year intervals (A) and study designs (B). or other interventional studies after the ONTT is probably because of the favorable visual outcomes, as detailed above. A similar explanation can be offered regarding MOGAD, because only 6% of patients were reported to have a final visual acuity of 20/200 or worse in either eye after treatment with intravenous steroids during an attack.10 The visual prognosis of NMO-ON is much worse, with functional blindness occurring in the damaged eye of 20%– 30% of patients experiencing their first attack.16 Indeed, after discovering the anti-AQP4 autoantibody, efforts have been made to target it in open-label trials (10 of which are on the T100-ON list), examining the benefits of immunosuppressive drugs such as rituximab, mycophenolate mofetil, azathioprine, 314 natalizumab, tocilizumab, and others. Only recently (2019), 2 RCTs on NMO patients were published and are already included in the T100-ON list. Because the disease itself is relatively rare (0.5–10 persons per 100,000 population), and the recruitment of patients demands the cooperation of multiple centers in different countries, it seems reasonable that it took years to complete the RCTs. Four neurology journals (Neurology, JAMA Neurology, Annals of Neurology, Brain) published more than half (56%) of the T100-ON list. Apart from their broad scientific scope and high IF, those journals have various article types available for submission (original articles, editorials, reviews, brief communications, etc), a feature that authors find attractive. In Assayag et al: J Neuro-Ophthalmol 2023; 43: 307-316 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 2. Top 100 most-cited articles on optic neuritis distributed by journals Journal Neurology JAMA Neurology (formerly Archives of Neurology) Annals of Neurology Brain Multiple Sclerosis Lancet New England Journal of Medicine Lancet Neurology JAMA Ophthalmology (formerly Archives of Ophthalmology) Journal of Experimental Medicine Proceedings of the National Academy of Sciences of the USA Journal of Neuroinflammation Journal of Neurology Journal of Neurology, Neurosurgery and Psychiatry Multiple Sclerosis Journal Biochemical and Biophysical Research Communications PLoS Medicine Journal of Immunology Clinical and Experimental Immunology Brain Pathology European Journal of Neurology Journal of the Neurological Sciences Multiple Sclerosis and Related Disorders† Nature Clinical Practice Neurology Nature Reviews Neurology American Journal of Ophthalmology Papers Impact Factor* Citations (Total) 23 14 10 9 5 4 4 4 4 2 2 2 2 2 2 1 1 1 1 1 1 1 1 1 1 1 6.6 6.9 9.0 9.1 4.2 32.4 62.9 19.4 3.2 15.3 9.6 4.0 3.2 8.3 4.5 2.5 12.6 6.0 3.0 4.6 3.7 2.3 — 6.9 6.5 2.3 11,262 4,556 3,296 3,787 995 3,314 2,041 2,558 1,309 842 503 782 615 615 396 196 193 188 214 204 303 223 182 265 319 188 *Mean impact factor (IF) of each journal, based on publication years of the articles included in the T100-ON list. This value does not reflect the latest IF of journals. † The IF of this journal was not calculated in the relevant year. addition, because ON is potentially a clinical manifestation of severely disabling neurologic disorders, neurology journals are the most appropriate platform. Although influential ON articles are of great interest to ophthalmologists, only 5 papers from the T100-ON list were published in ophthalmic journals. This finding correlates with the small proportion of neuroophthalmology articles in leading general ophthalmic journals (3%–4%).17 Hence, practicing ophthalmologists and neuroophthalmology experts are advised to stay alert for updates in the relevant neurological literature. Designation as the first or last author is necessary for pursuing an academic medical career because these authors receive the highest credit for their contribution to a study. Unfortunately, gender disparity in senior authorship of medical articles and, more specifically, in neurology and ophthalmology papers has been well-documented18 and was also evident in this review. Data from these reports suggest that until the last 15– 20 years, despite a constantly increasing and more balanced sex distribution in medical schools, no more than 30% of first authors were women in many disciplines. Therefore, the academic promotion of many female physicians was perhaps delayed or even prevented for years. Nevertheless, an encouraging trend of higher female scholarly impact in the last decade was also noted, resembling the proportion of female first authors in the T100-ON list between 2009 and 2021 (52%). Assayag et al: J Neuro-Ophthalmol 2023; 43: 307-316 The American dominance in ON research (47% of all articles) was particularly evident in the earlier half of publications and corresponded to the high research productivity of the USA described in similar reviews.12,14 Apart from the American scientific community’s impressive size and excellent quality, it has been postulated that significant governmental research funds and favorable reviewing by journals enable the high representation of the USA in the medical literature.19 In addition, in the context of this study, American groups are responsible for the ONTT and the unraveling of AQP4 and MOG autoantibodies. Hence, the finding of 31/50 (62%) American papers until 2008 was not surprising. However, we observed an opposite distribution between US- and non-US-based studies (34/50 articles, 68%) in the second half of the list (2009– 2021). Germany played an essential role in this shift (9 publications), primarily thanks to the efforts of the German NMO study group.20 Furthermore, studies conducted in a SouthKorean national referral center for NMO patients yielded 4 articles between 2009 and 2021, included in the T100-ON list. This study has several limitations. First, some high-impact ON articles may have gone undetected by the search method because of the selected search terms or the search engine algorithm. Articles about MS, which often include ON analysis and outcomes, although ON was not their primary focus, are a 315 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Y. Weill. Drafting the manuscript: E. Assayag, Y. Weill, D. Rappoport; Revising the manuscript for intellectual content: E. Assayag, Y. Weill, D. Rappoport. Final approval of the completed manuscript: E. Assayag, Y. Weill, D. Rappoport. TABLE 3. Top 100 most-cited articles on optic neuritis distributed by countries Country USA UK Germany Japan South-Korea Australia Austria Canada France Denmark Sweden India Italy Spain Articles 1–50 (1972–2008) Articles 51–100 (2009–2021) Total 31 10 1 3 — — — 2 1 — 1 — 1 — 16 9 9 4 4 2 2 — 1 1 — 1 — 1 47 19 10 7 4 2 2 2 2 1 1 1 1 1 probable example of this limitation. We minimized this possibility by performing similar searches in other engines and did not identify such papers. Second, the most-cited articles in a particular field are not necessarily the most applicable. For instance, several NMO guidelines appear in the T100-ON list, yet the international consensus from 2015 is the most updated and already has 2,099 citations, making the previous guidelines less relevant. Nevertheless, analysis of citation classics is an acceptable method to summarize the research on a specific subject. Finally, citation counts are naturally dynamic, and relatively recent publications not included in the list may soon gain many new citations. Still, we postulate that this citation-based analysis provides a valuable snapshot of the most important articles on inflammatory optic neuropathies in the last 50 years. In conclusion, this bibliometric study identified the mostcited literature items on optic neuritis and suggested several publication trends of this disease in the last 50 years. Neurology journals were the primary venue for most papers. After the high impact of the ONTT and its follow-up studies in earlier decades (1972–2001), NMO became the most studied ON subtype, owing to the detection of AQP4 autoantibodies. Once again, this demonstrates how dramatically the discovery of a single molecule can change the understanding of a disorder. As in other fields of medicine, an improvement in gender equity of authors was evident, along with a more balanced distribution of nations contributing to the topic. Researchers are advised to be aware of the described trends when considering the publication of a new ON study. STATEMENT OF AUTHORSHIP Conception and design: E. Assayag, D. Rappoport; Acquisition of data: E. Assayag; Analysis and interpretation of data: E. Assayag, 316 REFERENCES 1. Costello F. Inflammatory optic neuropathies. Contin Lifelong Learn Neurol. 2014;20:816–837. 2. Nakazawa M, Ishikawa H, Sakamoto T. Current understanding of the epidemiologic and clinical characteristics of optic neuritis. Jpn J Ophthalmol. 2021;65:439–447. 3. De Lott LB, Bennett JL, Costello F. The changing landscape of optic neuritis: a narrative review. J Neurol. 2022;269:111–124. 4. Braithwaite T, Subramanian A, Petzold A, et al. Trends in optic neuritis incidence and prevalence in the UK and association with systemic and neurologic disease. JAMA Neurol. 2020;77:1514– 1523. 5. Beck RW, Cleary PA, Anderson MM, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. N Engl J Med. 1992;326:581–588. 6. Lennon PVA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364:2106–2112. 7. Bettelli E, Pagany M, Weiner HL, Linington C, Sobel RA, Kuchroo VK. Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis. J Exp Med. 2003;197:1073–1081. 8. Beck RW, Sellers BJ, Cleary PA, et al. The clinical profile of optic neuritis: experience of the optic neuritis treatment trial. Arch Ophthalmol. 1991;109:1673–1678. 9. Papais-Alvarenga RM, Carellos SC, Alvarenga MP, Holander C, Bichara RP, Thuler LCS. Clinical course of optic neuritis in patients with relapsing neuromyelitis optica. Arch Ophthalmol. 2008;126:12–16. 10. Chen JJ, Flanagan EP, Jitprapaikulsan J, et al. Myelin oligodendrocyte glycoprotein antibody–positive optic neuritis: clinical characteristics, radiologic clues, and outcome. Am J Ophthalmol. 2018;195:8–15. 11. Almutairi O, Albakr A, Al-Habib A, Ajlan A. The top-100 mostcited articles on meningioma. World Neurosurg. 2017;107:1025–1032.e5. 12. Samanci Y, Samanci B, Sahin E. Bibliometric analysis of the top-cited articles on idiopathic intracranial hypertension. Neurol India. 2019;67:78. 13. Schargus M, Kromer R, Druchkiv V, Frings A. The top 100 papers in dry eye—a bibliometric analysis. Ocul Surf. 2018;16:180–190. 14. Koh BMQR, Banu R, Nusinovici S, Sabanayagam C. 100 mostcited articles on diabetic retinopathy. Br J Ophthalmol. 2021;105:1329–1336. 15. Wang M, Zhang J, Jiao S, Zhang T. Evaluating the impact of citations of articles based on knowledge flow patterns hidden in the citations. PLoS One. 2019;14:1–19. 16. Merle H, Olindo S, Bonnan M, et al. Natural history of the visual impairment of relapsing neuromyelitis optica. Ophthalmology. 2007;114:810–815. 17. Kumar A, Cheeseman R, Durnian JM. Subspecialization of the ophthalmic literature: a review of the publishing trends of the top general, clinical ophthalmic journals. Ophthalmology. 2011;118:1211–1214. 18. Jagsi R, Guancial EA, Worobey CC, et al. The “gender gap” in authorship of academic medical literature—a 35-year perspective. N Engl J Med. 2006;355:281–287. 19. Link AM. US and non-US submissions. An analysis of reviewer bias. J Am Med Assoc. 1998;280:246–247. 20. Trebst C, Jarius S, Berthele A, et al. Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the neuromyelitis optica study group (NEMOS). J Neurol. 2014;261:1– 16. Assayag et al: J Neuro-Ophthalmol 2023; 43: 307-316 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.