Genetic susceptibility and causal pathway analysis of eye disorders coexisting in multiple sclerosis.

Introduction: The comorbidity of optic neuritis with multiple sclerosis has been well recognized. However, the causal association between multiple sclerosis and optic neuritis, as well as other eye disorders, remains incompletely understood. To address these gaps, we investigated the genetically relationship between multiple sclerosis and eye disorders, and explored potential drugs. Methods: In order to elucidate the genetic susceptibility and causal links between multiple sclerosis and eye disorders, we performed two-sample Mendelian randomization analyses to examine the causality between multiple sclerosis and eye disorders. Additionally, causal single-nucleotide polymorphisms were annotated and searched for expression quantitative trait loci data. Pathway enrichment analysis was performed to identify the possible mechanisms responsible for the eye disorders coexisting with multiple sclerosis. Potential therapeutic chemicals were also explored using the Cytoscape. Results: Mendelian randomization analysis revealed that multiple sclerosis increased the incidence of optic neuritis while reducing the likelihood of concurrent of cataract and macular degeneration. Gene Ontology enrichment analysis implicated that lymphocyte proliferation, activation and antigen processing as potential contributors to the pathogenesis of eye disorders coexisting with multiple sclerosis. Furthermore, pharmaceutical agents traditionally employed for allograft rejection exhibited promising therapeutic potential for the eye disorders coexisting with multiple sclerosis. Discussion: Multiple sclerosis genetically contributes to the development of optic neuritis while mitigating the concurrent occurrence of cataract and macular degeneration. Further research is needed to validate these findings and explore additional mechanisms underlying the comorbidity of multiple sclerosis and eye disorders.

Clinical and radiographic features of a cohort of adult and pediatric subjects in the Pacific Northwest with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a newly described clinical entity comprised of isolated or recurrent attacks of optic neuritis, transverse myelitis, acute disseminated encephalomyelitis (ADEM), encephalitis, or seronegative NMOSD. Prior studies report that 30-80 % of children and adults with MOGAD go on to have relapses though there are no reliable predictors. The objectives of this study were to (1) describe the demographic, clinical, and radiographic patterns of MOGAD at our center and (2) identify possible predictors of relapsing disease. METHODS: Single-center retrospective cohort study of pediatric and adult subjects with MOGAD evaluated at least once at our center between January 1, 2017 and September 30, 2022. Eligible subjects had a history of positive MOG-IgG and consistent clinical syndrome comprised of an initial attack of optic neuritis (ON), transverse myelitis (TM), ADEM, cerebral cortical encephalitis, seronegative neuromyelitis optica (simultaneous ON and TM), isolated brainstem or cerebellar syndrome, or other (not fitting into another group). Relapsing subjects or those remaining monophasic at 12 months were included in the analyses of predictors of relapsing disease. Covariates included age, sex, race/ethnicity, and index event phenotype. Unadjusted and adjusted risk ratios were calculated for pediatric and adult subjects. RESULTS: We describe the demographic, clinical, and radiographic characteristics of 58 subjects with MOGAD. Covariates from 48 subjects were analyzed for predictors of relapsing disease. In adults, Hispanics and non-White non-Hispanics were at increased risk of relapsing disease compared to non-Hispanic Whites [Adjusted RR 1.52 (95 % CI: 1.01, 2.30)]. There were no significant associations in the pediatric group. CONCLUSION: This study is the first to describe a cohort of MOGAD in the Pacific Northwest. Our findings highlight racial and ethnic differences in risk of relapsing MOGAD in adults. Further studies on racial and ethnic differences in MOGAD are needed to confirm these findings.

Risk of central nervous system demyelinating attack or optic neuritis recurrence after pediatric optic neuritis in Korea.

PURPOSE: To investigate the rate of development of symptomatic central nervous system (CNS) demyelinating attacks or recurrent optic neuritis (ON) after the first episode of ON and its risk factors for Korean pediatric patients. METHODS: This multicenter retrospective cohort study included the patients under 18 years of age (n=132) diagnosed with ON without previous or simultaneous CNS demyelinating diseases. We obtained the clinical data including the results of neuro-ophthalmological examinations, magnetic resonance images (MRIs), antibody assays, and laboratory tests. We investigated the chronological course of demyelinating disease with respect to the occurrence of neurological symptoms and/or signs, and calculated the 5-year cumulative probability of CNS demyelinating disease or ON recurrence.  RESULTS: During the follow-up period (63.1±46.7 months), 18 patients had experienced other CNS demyelinating attacks, and the 5-year cumulative probability was 14.0±3.6%. Involvement of the extraorbital optic nerve or optic chiasm and asymptomatic lesions on the brain or spinal MRI at initial presentation were significant predictors for CNS demyelinating attack after the first ON. The 5-year cumulative probability of CNS demyelinating attack was 44.4 ± 24.8% in the AQP4-IgG group, 26.2±11.4% in the MOG-IgG group, and 8.7±5.9% in the double-negative group (P=0.416). Thirty-two patients had experienced a recurrence of ON, and the 5-year cumulative probability was 24.6±4.0%. In the AQP4-IgG group, the 5-year cumulative probability was 83.3±15.2%, which was significantly higher than in the other groups (P<0.001). CONCLUSIONS: A careful and multidisciplinary approach including brain/spinal imaging and antibody assay can help predict further demyelinating attacks in pediatric ON patients.

Optic Neuritis and Cranial Neuropathies Diagnosis Rates before Coronavirus Disease 2019, in the Initial Pandemic Phase, and Post-Vaccine Introduction.

PURPOSE: To compare rates of diagnosis of neuro-ophthalmic conditions across the Coronavirus Disease 2019 (COVID-19) pandemic with pre-pandemic levels. DESIGN: Multicenter, retrospective, observational study. PARTICIPANTS: Patients seen for eye care between March 11, 2019, and December 31, 2021. METHODS: A multicenter electronic health record database, Sight Outcomes Research Collaborative (SOURCE), was queried for new diagnoses of neuro-ophthalmic conditions (cranial nerve [CN] III, IV, VI, and VII palsy; diplopia; and optic neuritis) and new diagnoses of other ophthalmic conditions from January 1, 2016, to December 31, 2021. Data were divided into 3 periods (pre-COVID, pre-COVID vaccine, and after introduction of COVID vaccine), with a 3-year look-back period. Logistic regressions were used to compare diagnosis rates across periods. Two-sample z-test was used to compare the log odds ratio (OR) of the diagnosis in each period with emergent ocular conditions: retinal detachment (RD) and acute angle-closure glaucoma (AACG). MAIN OUTCOME MEASURES: Diagnosis rate of neuro-ophthalmic conditions in each study period. RESULTS: A total of 323 261 unique patients (median age 59 years [interquartile range, 43-70], 58% female, 68% White) across 5 academic centers were included, with 180 009 patients seen in the pre-COVID period, 149 835 patients seen in the pre-COVID vaccine period, and 164 778 patients seen in the COVID vaccine period. Diagnosis rates of CN VII palsy, diplopia, glaucoma, and cataract decreased from the pre-COVID period to the pre-vaccine period. However, the optic neuritis diagnoses increased, in contrast to a decrease in RD diagnoses (P = 0.021). By comparing the diagnosis rates before and after widespread vaccination, all eye conditions evaluated were diagnosed at higher rates in the COVID vaccination period compared with pre-COVID and pre-vaccine periods. The log OR of neuro-ophthalmic diagnosis rates across every period comparison were largely similar to emergency conditions (RD and AACG, P > 0.05). However, the log OR of cataract and glaucoma diagnoses were different to RD or AACG (P < 0.05) in each period comparison. CONCLUSIONS: Neuro-ophthalmic diagnoses had a similar reduction in diagnosis rates as emergent eye conditions in the first part of the pandemic, except optic neuritis. After widespread COVID-19 vaccination, all ophthalmic diagnosis rates increased compared with pre-pandemic rates, and the increase in neuro-ophthalmic diagnosis rates did not exceed the increase in RD and AACG diagnosis rates. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Increased Risk of Optic Neuritis in Patients With Fibromyalgia: Nationwide Population-Based Cohort Study in South Korea.

PURPOSE: To estimate the risk of incidence of optic neuritis and identify the high-risk group among patients with fibromyalgia (FM). DESIGN: Population-based cohort study. METHODS: A nationwide, population-based study was conducted using data from the Korean National Health Claims database from 2012 to 2021. This study included all the patients with FM from the entire South Korean population aged 20-79 years (FM group). Moreover, those with pain but not diagnosed with FM were considered as the non-FM group. A cohort was established by classifying it into the FM and non-FM groups during the recruitment period. A log-rank analysis was used to compare the risk of optic neuritis incidence between the FM group and non-FM group. Cox proportional hazards regression analysis was performed to calculate the adjusted hazard ratio (HR). The cohort was analyzed by stratifying according to age and sex. RESULTS: The FM and non-FM groups included 479,892 and 479,892 participants, respectively. The incidence rate of optic neuritis was 35.65/100,000 person-years in the FM group; the HR was significantly higher in the FM group than in the non-FM group (HR 2.11, 95% CI 1.84-2.41; P < .001). The mean interval between the onset of FM and incident optic neuritis was 2.4 ± 1.8 years. The risk increased significantly in men aged 60-79 years (HR 3.37, 95% CI 2.54-4.48) and in women aged 20-39 years (HR 2.07, 95% CI 1.38-3.22). CONCLUSION: We quantified the risk of optic neuritis through a long-term follow-up, which could contribute to understanding the pathophysiology and estimating the general health care burden associated with FM in a practical setting. Great attention should be paid to its risk in older men and younger women.

Prevalence of serum MOG antibody and AQP4 antibody in optic neuritis after SARS-CoV-2 infection.

Purpose: To evaluate the prevalence of serum myelin oligodendrocyte glycoprotein antibody (MOG-Ab) and aquaporin-4 antibody (AQP4-Ab) in optic neuritis (ON) patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by cell-based indirect immunofluorescence assay (CBA). Methods: In this prospective case series study, 35 patients clinically diagnosed as ON and laboratory-confirmed SARS-CoV-2 infection from 8 December 2022 to 8 February 2023 were included. All patients' clinical and laboratory data were collected and analyzed. Results: The mean age of the 35 patients (46 eyes) was 38.2 years (ranging from 6 to 69 years), and 17 cases were female patients. Thirty-three and two cases showed positive SARS-CoV-2 RNA test results before or shortly after ON onset, respectively. ON occurred unilaterally in 24 cases and bilaterally in 11 cases. Ophthalmic examination revealed swollen optic disc in 37 eyes, normal optic disc in 6 eyes, and temporally or wholly paled optic disc in 3 eyes. CBA revealed seropositive MOG-Ab in 10 cases and AQP4-Ab in 2 cases, respectively, of which 2 AQP4-Ab-seropositive cases and 1 MOG-Ab-seropositive case had a past medical history of ON. Most ON patients showed a rapid and dramatic response to pulse steroid therapy. The median of BCVA at the onset and at the last follow-up was 20/500 (ranging from light perception to 20/20) and 20/67 (ranging from counting fingers to 20/20), respectively. Conclusion: Serum MOG-Ab and AQP4-Ab were detected in 28.6% (10/35) and 5.7% (2/35) ON cases after SARS-CoV-2 infection. SARS-CoV-2 infection may trigger an onset or a relapse of ON, as well as the production of MOG-Ab.

Systematic review exploring the clinical features of optic neuritis after SARS-CoV infection and vaccination.

BACKGROUND: This study aims to characterise the symptoms and clinical features of optic neuritis (ON) following SARS-CoV-2 infection and vaccination. METHOD: A literature search was conducted in four databases (PubMed, Medline, Embase and Google Scholar) to identify relevant case reports and case series. The records were screened and articles adhering to the inclusion criteria were critically appraised. RESULTS: Sixty-eight studies were found to be eligible for inclusion, including 34 reporting ON following SARS-CoV-2 infection and an equal number reporting cases postvaccination. In total 93 patients and 125 eyes were included. The infection cohort included 42 patients and 56 eyes, 51.2% were female and 33.3% experienced bilateral ON. The mean visual acuity was 1.64 log of minimum angle of resolution (LogMAR), while pain was present in 77.8%. Oligoclonal bands were present in 3 patients, myelin oligodendrocyte glycoprotein (MOG) antibodies in 18 patients and AQP-4 antibodies in 4 patients. The vaccination cohort included 51 patients and 69 eyes. 60.8% were female and 35.3% had a bilateral ON. The mean visual acuity was 0.93 LogMAR. Oligoclonal bands were present in 46.7%, MOG antibodies in nine patients and AQP-4 antibodies in three patients. CONCLUSION: Patients with ON post-SARS-CoV infection were more likely to experience severe visual impairment than in cases following vaccination. Further research is required to outline the clinical features of ON after COVID-19 infection and vaccination, and establish causality.

Glial autoantibody prevalence in Chinese optic neuritis with onset after age 45: clinical factors for diagnosis.

Purpose: As glial autoantibody testing is not yet available in some areas of the world, an alternative approach is to use clinical indicators to predict which subtypes of middle-aged and elderly-onset optic neuritis (ON) have manifested. Method: This study was a single-center hospital-based retrospective cohort study. Middle-aged and elderly-onset ON patients (age > 45 years) who had experienced the first episode of ON were included in this cohort. Single- and multi-parametric diagnostic factors for middle-aged and elderly-onset myelin oligodendrocyte glycoprotein immunoglobulin-associated ON (MOG-ON) and aquaporin-4 immunoglobulin-related ON (AQP4-ON) were calculated. Results: From January 2016 to January 2020, there were 81 patients with middle-aged and elderly-onset ON, including 32 (39.5%) AQP4-ON cases, 19 (23.5%) MOG-ON cases, and 30 (37.0%) Seronegative-ON cases. Bilateral involvement (47.4%, P = 0.025) was most common in the MOG-ON group. The presence of other concomitant autoimmune antibodies (65.6%, P = 0.014) and prior neurological history (37.5%, P = 0.001) were more common in the AQP4-ON group. The MOG-ON group had the best follow-up best-corrected visual acuity (BCVA) (89.5% ≤ 1.0 LogMAR, P = 0.001). The most sensitive diagnostic factors for middle-aged and elderly-onset MOG-ON were 'follow-up VA ≤ 0.1 logMAR' (sensitivity 0.89), 'bilateral involvement or follow-up VA ≤ 0.1 logMAR' (sensitivity 0.95), 'bilateral involvement or without neurological history' (sensitivity 1.00), and 'follow-up VA ≤ 0.1 logMAR or without neurological history' (sensitivity 1.00), and the most specific factor was 'bilateral involvement' (specificity 0.81). The most sensitive diagnostic factors for middle-aged and elderly-onset AQP4-ON were 'unilateral involvement' (sensitivity 0.88), 'unilateral involvement or neurological history' (sensitivity 0.91), and 'unilateral involvement or other autoimmune antibodies' (sensitivity 1.00), and the most specific factor was neurological history (specificity 0.98). Conclusion: Based on our cohort study of middle-aged and elderly-onset ON, MOG-ON is less prevalent than AQP4-ON and Seronegative-ON. Using multiple combined parameters improves the sensitivity and negative predictive value for diagnosing middle-aged and elderly-onset MOG-ON and AQP4-ON. These combined parameters can help physicians identify and treat middle-aged and elderly-onset ON early when glial autoantibody status is not available.

Clinical risk factors for recurrence of myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a CNS demyelinating disease that targets myelin oligodendrocyte glycoprotein and recurs in approximately 50% of patients after the initial episode. Multiple relapses may have adverse consequences, but the factors influencing relapse are unclear. This study analyzed the clinical risk factors for relapse in patients with MOGAD. METHODS: Twenty-four MOGAD patients diagnosed at the Department of Neurology, First Hospital of Shanxi Medical University from March 2018 to November 2020 were retrospectively analyzed in this study. The patients were divided into a monophasic course and a relapsing course according to their disease process. The patients' epidemiological characteristics, clinical symptoms, laboratory tests, imaging features, and regression were summarized. Comparisons were made between the monophasic and relapsing course to identify the possible factors associated with the clinical features and recurrence. RESULTS: At a mean follow-up of 15 months (range: 8 to 24 months), seventeen of the 24 patients (70.8%) had monophasic disease, and 7 (29.2%) had relapsing disease. Among the 24 patients, 17 patients (70.9%) had low Myelin oligodendrocyte glycoprotein antibody (MOG-IgG) serum titers (<1:100), and 7 patients (29.1%) had high MOG-IgG serum titers (≥1:100). Compared to the monophasic course group, patients in the relapsing course group had higher serum antibody titers (71.4% vs. 11.7%, P = 0.035). Onset phenotypes included encephalitis (50%), myelitis (45.8%), and optic neuritis (45.8%), with 66.7% of patients starting with a single phenotype and 33.3% starting with two or more phenotypes. Optic neuritis was more common in the relapsing course group (85.7%) than the monophasic course group (29.4%) (P = 0.023). There was no significant difference between the two groups in the proportion of myelitis and encephalitis. A previous history or background of immunological disease was present in 33.3% of patients, with a significantly higher proportion in the relapsing course group than in the monophasic course group (71.4% vs. 17.6%, P = 0.021). Regarding ancillary examinations, the relapsing course group was more likely to have CSF leukocytes higher than 50/mm3 than the monophasic course group (60% vs. 0, P = 0.045), while there was no difference in the number and site distribution of the lesions on MRI. CONCLUSIONS: Our study suggests that the most common clinical manifestations of MOGAD are diminished visual acuity, limb/facial numbness, and ocular/orbital pain. The onset phenotype consisting of optic neuritis, a history of immune disease, high antibody titers (≥1:100), and high cerebrospinal fluid leukocytes (above 50/mm3) suggests a high likelihood of MOGAD recurrence.

Pregnancy prevalence and outcomes after optic neuritis in South Korea.

To compare pregnancy rates and complications in women with and without a history of optic neuritis (ON). A nationwide, population-based, retrospective study using data from the Korean National Health Claims from January 2011, to December 2017 was done. ON cohort (ON group) consisting of women aged 18 to 50 with a history of ON and 1:3 age-matched controls (control group) were compared for pregnancy and delivery rates using logistic regression after adjusting for possible confounders. Pregnancy-ON cohort (pregnancy-ON group), women aged 18 to 55 with a history of ON and pregnancy, and 1:3 age at pregnancy matched controls (pregnancy-control group) were analyzed for pregnancy complications using logistic regression after adjusting for covariates. ON group (n = 2516) showed decreased odds ratio (OR) for pregnancy [Adjusted OR2: 0.716, 95% confidence interval (CI): 0.626-0.820] and delivery (adjusted OR2: 0.647, 95% CI: 0.554-0.756) compared to controls (n = 7548). Pregnancy-ON group (n = 550) showed increased risk of delayed fetal growth (adjusted OR2: 9.867, 95% CI: 1.224-79.564), pre-eclampsia (adjusted OR2: 8.327, 95% CI: 2.911-23.819), preterm delivery (adjusted OR2: 3.914, 95% CI: 2.667-5.742), pregnancy and postpartum infection (adjusted OR1: 1.671, 95% CI: 1.296-2.154), diabetes in pregnancy (adjusted OR2: 1.365, 95% CI: 1.062-1.754) compared to pregnancy-control group (n = 1650). Our population-based cohort study suggests that history of ON is associated with decreased pregnancy and delivery rates. It may be a risk factor for various pregnancy complications.

The prevalence and clinical phenotype of dual seropositive neuromyelitis optica spectrum disorders at a national reference center in South Asia.

BACKGROUND: Neuromyelitis Optica Spectrum Disorders (NMOSD) is an autoimmune syndrome that is frequently positive for Aquaporin 4 (AQP4) IgG or Myelin Oligodendrocyte Glycoproteins (MOG) IgG. However, dual positivity to both is rare. OBJECTIVE: To assess the prevalence of dual-positive NMOSD and outline its clinical phenotype. DESIGN/METHODS: This is a retrospective cross-sectional study conducted at a tertiary healthcare center in South Asia between August 2018 and November 2021. The serum and/or CSF samples of suspected cases of NMOSD were tested for both AQP4-IgG and MOG-IgG using an Indirect immunofluorescence test on transfected cells. RESULTS: During the study period, 1935 cases of NMOSD were tested for both antibodies- 65 patients (3.35%; 57 females and 8 males) tested positive for AQP4-IgG, 217 patients (11.21%; 122 females and 95 males) tested positive for MOG-IgG and 3 patients (0.15%; 2 females and 1 male) showed dual positivity. There was a strong female preponderance in all three groups (87.69%, 56.22%, and 66.66% respectively). This study identified 3 patients with dual positivity. The first patient (42 years, Male) presented with area postrema syndrome initially and subsequently relapsed by developing right-sided numbness of the temporal area and limbs during which he tested dual positive. The second patient (27 years, Female) presented with bilateral optic neuritis (left>right) initially and subsequently relapsed following an episode of a seizure with left-sided hemiplegia. The third patient (25 years, Female) initially presented with acute bilateral optic neuritis and later developed left-sided hemiplegia post-recovery at which point she tested dual positive. Management using methylprednisolone was ineffective for all three patients, however, plasmapheresis and/or periodic rituximab injections produced an excellent response. CONCLUSIONS: Our study reports that the prevalence of dual-positive NMOSD is 0.15% and its clinical phenotype is more similar to NMO rather than MOG- associated disease.

Clinical characteristics and prognosis of optic neuritis in Taiwan - a hospital-based cohort study.

BACKGROUND: Optic neuritis (ON) is an inflammatory disease of optic nerve. The distinct etiologies of ON significantly influence its clinical manifestation, neuroimaging findings, and visual outcomes. However, the clinical characteristics might be influenced by the racial differences. The purpose of this study is to investigate the clinical characteristics of various types of ON at a Taiwanese tertiary center. METHODS: This cohort study analyzed 163 patients who received treatment and continued following-up for ON between 2015 and 2022. We selected patients who had been tested for anti-aquaporin-4 antibody (AQP4-Ab) and anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab). The participants were classified into four groups on the basis of their etiologies, specifically (1) multiple sclerosis (MS)-related, (2) AQP4-Ab-positive, (3) MOG-Ab-positive, or (4) idiopathic ON. The researchers recorded the patients' clinical characteristics, treatment course, magnetic resonance imaging and optical coherence tomography (OCT) findings, and visual outcomes. RESULTS: MOG-Ab-positive group had higher percentages of disk swelling and pain with eye movement. Long optic nerve and perineural enhancement are the hallmarks of MOG-Ab-related ON. The ON relapse rate was higher in AQP4-Ab-positive group. Although members of AQP4-Ab-positive group received immediate steroid pulse therapy, these patients experienced the worst visual outcomes. Moreover, a thinner retinal nerve fiber layer (RNFL) was noted in AQP4-Ab-positive group. MS group had a higher incidence of extra-optic nerve lesions. Multivariate regression identified pretreatment visual acuity and RNFL thickness as the important factors affecting visual outcomes. CONCLUSIONS: This cohort study identified the clinical features of different types of ON. Patients with AQP4-Ab-positive ON had poorer visual outcomes, which may be attributed to multiple relapses and profound nerve damage, as revealed by OCT findings. Patients with MOG-Ab-positive ON displayed long optic nerve enhancement but had more favorable prognoses. Thus, antibody-based classification facilitates treatment and prognosis in ON.

Epidemiological and clinical characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease in a nationwide survey.

BACKGROUND: To our knowledge, no nationwide epidemiological study of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has been conducted. OBJECTIVE: We examined the epidemiology and clinical features of MOGAD in Japan. METHODS: We distributed questionnaires on the clinical characteristics of patients with MOGAD to neurology, pediatric-neurology, and neuro-ophthalmology facilities throughout Japan. RESULTS: In total, 887 patients were identified. The estimated number of total and newly diagnosed MOGAD patients was 1,695 [95% confidence interval (CI): 1483-1907] and 487 (95% CI: 414-560), respectively. The estimated prevalence and incidence were 1.34/100,000 (95% CI: 1.18-1.51) and 0.39/100,000 (95% CI: 0.32-0.44), respectively. The median age at onset was 28 years (range: 0-84 years). At onset, optic neuritis was present in approximately 40% of patients, irrespective of the onset age. Acute disseminated encephalomyelitis was more frequent in younger patients, whereas brainstem encephalitis, encephalitis, and myelitis were more frequent in elderly patients. Immunotherapy was highly effective. CONCLUSION: The prevalence and incidence rates of MOGAD in Japan are similar to those in other countries. Notable characteristics such as the preferential occurrence of acute disseminated encephalomyelitis in children exist; however, general characteristics including symptoms and treatment response are common irrespective of the onset age.

Clinical features and visual outcomes of pediatric optic neuritis in the Indian population: A prospective study.

Purpose: Optic neuritis, defined as inflammation of the optic nerve, is the most common optic neuropathy affecting adults. Various studies in Southeast Asia have shown that the clinical profile of optic neuritis might differ in these regions from that reported in the western literature. Through this study, we evaluate the clinical profile of pediatric optic neuritis (PON) in the Indian population. Methods: This was a hospital-based prospective observational study. Patients with optic neuritis younger than 16 years who attended the neuro-ophthalmology clinic from May 2016 to April 2017 were included in the study. Results: This study included 54 eyes of 38 patients. The mean age of presentation was 10.6 years. Unilateral disease (58%) was found to be more common, and a slight female preponderance (58%) was noted. The most common feature was visual loss (96.3%). Pupillary light reflex abnormality was seen in most patients. Fundus examination revealed disk edema (77.7%) to be the most common feature. Neuroimaging was performed in 34 patients, and multiple sclerosis was diagnosed in four patients. At 3 months follow-up after treatment, 89% of eyes had best correct visual acuity of 6/9 or better (P < 0.001). Conclusion: In our study, we found the clinical profile of PON to be similar to that seen in western studies as well as those done previously in the Indian population, although with a few differences.

Predictors of Glucocorticoid Use for Acute Optic Neuritis in the United States, 2005-2019.

PURPOSE: Acute optic neuritis (ON) is variably treated with glucocorticoids. We aimed to describe factors associated with glucocorticoid use. METHODS: In this retrospective, longitudinal cohort study of insured patients in the United States (2005-2019), adults 18-50 years old with one inpatient or ≥2 outpatient diagnoses of ON within 90 days were included. Glucocorticoid use was classified as none, any dose, and high-dose (>100 mg prednisone equivalent ≥1 days). The primary outcome was glucocorticoid receipt within 90 days of the first ON diagnosis. Multivariable logistic regression models assessed the relationship between glucocorticoid use and sociodemographics, comorbidities, clinician specialty, visit number, and year. RESULTS: Of 3026 people with ON, 65.8% were women (n = 1991), median age (interquartile range) was 38 years (31,44), and 68.6% were white (n = 2075). Glucocorticoids were received by 46% (n = 1385); 54.6% (n = 760/1385) of whom received high-dose. The odds of receiving glucocorticoids were higher among patients with multiple sclerosis (OR 1.61 [95%CI 1.28-2.04]; P < .001), MRI (OR 1.75 [95%CI 1.09-2.80]; P = .02), 3 (OR 1.80 [95%CI 1.46-2.22]; P < .001) or more (OR 4.08 [95%CI 3.37-4.95]; P < .001) outpatient ON visits, and in certain regions. Compared to ophthalmologists, patients diagnosed by neurologists (OR 1.36 [95%CI: 1.10-1.69], p = .005), emergency medicine (OR 3.97 [95%CI: 2.66-5.94]; P < .001) or inpatient clinicians (OR 2.94 [95%CI: 2.22-3.90]; P < .001) had higher odds of receiving glucocorticoids. Use increased 1.1% annually (P < .001). CONCLUSIONS: Demyelinating disease, care intensity, setting, region, and clinician type were associated with glucocorticoid use for ON. To optimize care, future studies should explore reasons for ON care variation, and patient/clinician preferences.

Incidence of Optic Neuritis and the Associated Risk of Multiple Sclerosis for Service Members of U.S. Armed Forces.

INTRODUCTION: Optic neuritis (ON), an acute inflammation of the optic nerve resulting in eye pain and temporary vision loss, is one of the leading causes of vision-related hospital bed days in the U.S. Military and may be a harbinger of multiple sclerosis (MS). We developed a case identification algorithm to estimate incidence rates of ON and the conversion rate to MS based on a retrospective assessment of medical records of service members (SMs) of the U.S. Armed Force. MATERIALS AND METHODS: Electronic medical records (EMRs) from 2006 to 2018 in the Defense Medical Surveillance System were screened using the case identification algorithms for ON and MS diagnosis. The incidences rates of ON were calculated. The rates of conversion to MS was modeled using the Kaplan-Meier survival analysis. RESULTS: The overall incidence rate of ON was 8.1 per 100,000 from 2006 to 2018. Females had a rate (16.9 per 100,000) three times higher than males. Most (68%) of subsequent diagnoses of MS were made within 1 year after diagnosis of ON. The overall 5-year risk of progression to MS was 15% (11%-16% for 95% CI). The risk of conversion to MS in females was significantly higher than in males. CONCLUSIONS: We developed an efficient tool to explore the EMR database to estimate the burden of ON in the U.S. Military and the MS conversion based on a dynamic cohort. The estimated conversion rates to MS feeds into inform retention and fitness-for-duty policy in these SMs.

MOG antibody prevalence in adult optic neuritis and clinical predictive factors for diagnosis: A Chinese cohort study.

OBJECTIVE: Because AQP4/MOG antibody testing is not available in some parts of the world and there are often delays in obtaining results, it is particularly important to use clinical factors to predict the subtypes of adult optic neuritis (ON). METHODS: This was a single-center retrospective cohort study. RESULTS: The final analysis included 249 adult patients presenting with the first ON attack during January 2016 to January 2020. These included 109 (43.8%) AQP4-ON cases, 49 (19.7%) MOG-ON cases, and 91 (36.5%) Seronegative-ON cases. The proportion of optic disk swelling (ODS) and bilateral involvement in MOG-ON group was significantly higher than in the other two subgroups (P = 0.029, 0.001). The MOG-ON group had the best follow-up BCVA (P = 0.003). To predict adult AQP4-ON, unilateral involvement (sensitivity 0.88, NPV 0.77) was the most sensitivity predictors, while neurological history (specificity 0.96, PPV 0.65) and concomitant other autoimmune antibodies (specificity 0.76, PPV 0.65) were the most specific predictors. Using the parallel test 'unilateral or other autoimmune antibodies' increased sensitivity to 0.95, with an optimal NPV of 0.88. To predict adult MOG-ON, the most sensitive clinical characteristics were ODS (sensitivity 0.79, NPV 0.88), and follow-up VA ≤0.1logMAR (sensitivity 0.78, NPV 0.92), whereas the most specific values were prior neurological history or bilateral involvement, with specificities of 0.92 and 0.82, respectively. The sensitivity increased to 0.94, 0.97, and 0.97 when using the parallel clinical factors of 'bilateral or ODS or relapse', 'bilateral or ODS or follow-up VA ≤0.1logMAR', and 'ODS or follow-up VA ≤0.1logMAR', and the corresponding NPV (0.94, 0.97 vs 0.98). CONCLUSION: The proportion of MOG-ON (19.7%) was less than that of AQP4-ON and Seronegative-ON. Moreover, MOG-ON had a better prognosis and was more likely to be associated with ODS or bilateral involvement. The use of parallel clinical parameters improved the sensitivity for the diagnosis of adult MOG-ON and AQP4-ON.

Optic neuritis: A South African hospital-based prospective study protocol.

BACKGROUND: Optic neuritis is a relatively common disease with an estimated lifetime risk of 0.6 per 1000; the estimated prevalence is 1-5 per 100 000/year. It occurs because of inflammation of the optic nerve from a variety of causes. The diagnosis of the disorder is established clinically and current literature is predominantly based on white patients from high-income countries. Optic neuritis presents differently in black patients compared to white patients. This study aims to assess the presentation and outcome of optic neuritis patients in a South African setting. METHODS: This is a prospective, hospital-based cohort study that will enrol patients with optic neuritis presenting to either the neurology department at Chris Hani Baragwanath Academic Hospital or the ophthalmology department at St John Eye Hospital, both in Johannesburg, South Africa. The specific aetiologies, clinical presentation and radiological findings will be studied, and the patient's course over one year will be documented in three-monthly follow-up visits. A specific group of patients with Neuromyelitis Optica Spectrum Disorders (NMOSD) and Myelin Oligodendrocyte Glycoprotein Associated Disorders (MOGAD) optic neuritis will be followed up for 5 years at yearly intervals. DISCUSSION: This study represents one of the few cohort studies in Sub-Saharan Africa that seeks to investigate optic neuritis. Our hope is that it will lead to better insights regarding the presentation, course and outcome of this condition. We will also analyse the data with a view of developing a predictive model for good visual outcome.

Optic Neuritis in the Era of NMOSD and MOGAD: A Survey of Practice Patterns in Singapore.

PURPOSE: The Optic Neuritis Treatment Trial was a landmark study with implications worldwide. In the advent of antibody testing for neuromyelitis optica spectrum disease (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), emerging concepts, such as routine antibody testing and management, remain controversial, resulting mostly from studies in White populations. We evaluate the practice patterns of optic neuritis investigation and management by neuro-ophthalmologists and neurologists in Singapore. DESIGN: 21-question online survey consisting of 4 clinical vignettes. METHODS: The survey was sent to all Singapore Medical Council- registered ophthalmologists and neurologists who regularly manage patients with optic neuritis. RESULTS: Forty-two recipients (17 formally trained neuro-ophthalmol-ogists [100% response rate] and 25 neurologists) responded. Participants opted for routine testing of anti-aquaporin-4 antibodies (88.1% in mild optic neuritis and 97.6% in severe optic neuritis). Anti-MOG antibodies were frequently obtained (76.2% in mild and 88.1% in severe optic neuritis). Plasmapheresis was rapidly initiated (85.7%) in cases of nonresponse to intravenous steroids, even before obtaining anti-aquaporin-4 or anti-MOG serology results. In both NMOSD and MOGAD, oral mycophenolate mofetil was the preferred option if chronic immunosuppression was necessary. Steroids were given for a longer duration and tapered more gradually than in idiopathic optic neuritis cases. CONCLUSIONS: Serological testing for NMOSD and MOGAD is considered as a routine procedure in cases of optic neuritis in Singapore, possibly due to local epidemiological features of these conditions. Chronic oral immunosuppression is preferred for the long term, but further research is necessary to establish the efficacy and cost-effectiveness of these practices.

Clinico-epidemiologic characteristics of optic neuritis in a tertiary eye centre in Eastern India based on the status of serum aquaporin-4 antibody.

PURPOSE: To elucidate the clinico-epidemiologic characteristics of optic neuritis based on the status of serum aquaporin-4 antibody (AQP4-Ab) in patients with optic neuritis (ON). METHODS: Medical records of 106 patients with ON and a follow-up of 3 years were reviewed. For each patient, the following data were extracted: medical history, findings of the ocular examination, brain, orbital or spinal MRI, and serological tests for AQP4. The ON was classified as typical or atypical based on disc examination and improvement in vision after intravenous methylprednisolone (IVMP). The clinical findings (typical or atypical), disease course, and outcomes were analyzed according to the serostatus of the ON. RESULTS: 10 patients ((9.4%) were seropositive for AQP4-Ab; all had atypical ON. 96 patients (91%) were seronegative for AQP4-Ab: 36 atypical ON and 60 typical ON. Profound visual impairment at presentation was seen in all patients. However, at the end of the study period, seropositive and seronegative atypical ON had poor visual outcomes as compared to seronegative typical ON (P = 0.002). Five seropositive and four seronegative patients with atypical ON developed transverse myelitis. Bilateral disease with relapse was more in seropositive patients (80%); however, seronegative with atypical ON also had bilateral presentation and relapse in 42% and 41%, respectively. CONCLUSION: AQP4-Ab seropositive patients mostly present with atypical features such as bilateral recurrent ON, poor visual outcome, and increased incidence of transverse myelitis. However, atypical clinical features can also be seen in seronegative ON with a poor visual outcome and a recalcitrant course.