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Chen JJ, Pineles SL, Repka MX, et al. MOG-IgG Among Participants in the Pediatric Optic Neuritis Prospective Outcomes Study. JAMA Ophthalmol. 2021;139(5):583–585. doi:10.1001/jamaophthalmol.2021.0349
Myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG)–associated disorder (MOGAD) is a recently described entity that is distinct from multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG–positive neuromyelitis optica spectrum disorder.1-3 A small cohort from the Pediatric Optic Neuritis Prospective Outcomes Study4 underwent MOG-IgG testing and we compared those whose results were MOG-IgG positive with those whose results were negative.
The study, protocol, and Health Insurance Portability and Accountability Act–compliant informed consent forms were approved by each site’s institutional review board. Each patient’s parent or guardian provided written informed consent. Children also provided written consent when applicable as determined by the local institutional review board. Parents of 13 of 44 study participants who underwent MOG-IgG testing also provided written consent to provide their child’s serum to the Neuroimmunology Research Laboratory at the Mayo Clinic, Rochester, Minnesota, to measure AQP4-IgG and MOG-IgG with Clinical Laboratory Improvement Amendments–certified fluorescence-activated cell sorting cell-based assays. We compared demographic and clinical characteristics at enrollment and visual outcomes after 6 months for MOG-IgG–positive participants and MOG-IgG–negative participants. Analyses were conducted using SAS version 9.4 (SAS Institute).
Among 13 participants with MOG-IgG testing and 31 without MOG-IgG testing, the mean (SD) age was 10.9 (3.1) and 10.0 (3.6) years, respectively. Bilateral disease was found in 7 patients (54%) with MOG-IgG testing vs 9 patients (29%) without. Mean (SD) visual acuity (VA) from all eyes at enrollment was 0.83 (0.72) logMAR (Snellen equivalent of 20/140) for patients with testing vs 1.02 (0.69) logMAR (Snellen equivalent of 20/200) for those without.
MOG-IgG was positive in 7 of 13 children (54%; 95% CI, 25-81) (Table). Six of 7 MOG-IgG–positive participants and 3 of 6 MOG-IgG–negative participants were male (Table). Mean (SD) age was 10.3 (3.7) years for participants who were MOG-IgG positive and 11.5 (2.3) years for those who were MOG-IgG negative. Both eyes were affected in 4 of 7 MOG-IgG–positive participants and in 2 of 6 MOG-IgG–negative participants.
At presentation, the 10 MOG-IgG–positive eyes with optic neuritis (ON) had a median (range) VA of 1.7 (0-1.7) logMAR (Snellen equivalent of worse than 20/800), with 6 MOG-IgG–positive eyes worse than 20/800, for which a logMAR of 1.7 was assigned (Table). The 8 MOG-IgG–negative eyes with ON had a median (range) VA of 0.4 (−0.1 to 0.8) logMAR (Snellen equivalent of 20/50), with none having VA worse than 20/800. After 6 months, the median (range) VA for MOG-IgG–positive eyes with ON was 0.1 (−0.1 to 0.6) logMAR (Snellen equivalent of 20/25), while the median (range) VA for MOG-IgG–negative eyes with ON was 0 (−0.2 to 1.4) logMAR (Snellen equivalent of 20/20).
None of the participants who were MOG-IgG positive had periventricular white matter lesions or met the 2017 McDonald diagnostic criteria for MS. None were positive for AQP4-IgG.
Of the 13 participants tested in this prospective observational study on pediatric ON,4 7 (54%) tested positive for MOG-IgG. Our results are consistent with prior studies that suggest that more than 30% of children with demyelinating disease will be positive for MOG-IgG, with higher rates in association with pediatric ON and acute disseminated encephalomyelitis because of MOG-IgG predilection for these types of attacks.3,5 This varies from adults where MOG-IgG is positive in approximately 5% of individuals with demyelinating disease.3
In this small cohort, MOG-IgG–positive individuals with ON tended to have bilateral disease at presentation and present with severe VA loss. Despite the severity of VA loss at presentation, individuals who were MOG-IgG positive generally had substantial recovery, similar to previous reports.1,3,5,6 The present study also supports the lack of predominance of MOGAD among female individuals that has been demonstrated in previous studies.1-3,5
One limitation in this study was that not all participants underwent MOG-IgG testing. While demographic characteristics and severity of VA loss were similar between the 2 groups, individuals with bilateral disease were more often tested for MOG-IgG, which may have produced some bias in the analyzed subgroup.
In summary, the Pediatric Optic Neuritis Prospective Outcomes Study found MOGAD to be commonly associated with pediatric ON. Therefore, MOG-IgG testing may be considered for pediatric patients with new-onset ON to help guide prognosis and treatment.3 Diagnosing MOGAD in these individuals is important, because patients with MOGAD do not typically develop MS and because treatments differ between MOGAD and MS.
Accepted for Publication: February 2, 2021.
Published Online: March 25, 2021. doi:10.1001/jamaophthalmol.2021.0349
Corresponding Author: Stacy L. Pineles, MD, Jaeb Center for Health Research, 15310 Amberly Dr, Ste 350, Tampa, FL 33647 (firstname.lastname@example.org).
Author Contributions: Mr Henderson had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: All authors.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: Chen, Repka, Pittock, Henderson, Liu.
Statistical analysis: Pittock, Henderson.
Administrative, technical, or material support: Repka.
Supervision: Pineles, Repka, Pittock, Liu.
Conflict of Interest Disclosures: Dr Pittock reports grants from Grifols and the Autoimmune Encephalitis Alliance; honoraria and travel expenses from MedImmune, Inc and Alexion Pharmaceuticals, Inc; consulting fees from Astellas; personal fees from Genentech Sage Therapeutics, and Prime Therapeutics, UCB, Inc, and Hoffman/LaRoche AG; and consulting compensation from Euroimmun outside the submitted work; and has patents 8,889,102 for neuromyelitis optica autoantibodies as a marker for neoplasia and 9,891,219B2 for methods for treating neuromyelitis optica by administration of eculizumab to an individual that is aquaporin-4-IgG autoantibody positive; and pending patents for GFAP-IgG, Septin-5-IgG, MAP1B-IgG, Kelch-like protein 11, and PDE10A. No other disclosures were reported.
Funding/Support: This research was supported by grants EY011751, EY018810, and EY023198 from the National Eye Institute.
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Additional Information: The members of the Pediatric Eye Disease Investigator Group (PEDIG) are listed in reference 4.