• Jiraporn Jitprapaikulsan, John J Chen, Eoin P Flanagan, W Oliver Tobin, Jim P Fryer, Brian G Weinshenker, Andrew McKeon, Vanda A Lennon, Jacqueline A Leavitt, Jan-Mendelt Tillema, Claudia Lucchinetti, B Mark Keegan, Orhun Kantarci, Cheryl Khanna, Sarah M Jenkins, Grant M Spears, Jessica Sagan, and Sean J Pittock.
• Department of Neurology, Mayo Clinic, Rochester, Minnesota; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
• Ophthalmology. 2018 Oct 1; 125 (10): 1628-1637.

PurposeTo determine the aquaporin-4 and myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG) serostatus and visual outcomes in patients with recurrent optic neuritis (rON) initially seeking treatment.DesignCross-sectional cohort study.ParticipantsThe study identified patients by searching the Mayo Clinic computerized central diagnostic index (January 2000-March 2017). The 246 eligible patients fulfilled the following criteria: (1) initially seeking treatment for at least 2 consecutive episodes of optic neuritis (ON) and (2) serum available for testing.MethodsSerum was tested for aquaporin-4 IgG and MOG IgG1 using an in-house validated flow cytometric assay using live HEK293 cells transfected with M1 aquaporin-4 or full-length MOG.Main Outcomes MeasuresAquaporin-4 IgG and MOG IgG1 serostatus, clinical characteristics, and visual outcomes.ResultsAmong 246 patients with rON at presentation, glial autoantibodies were detected in 32% (aquaporin-4 IgG, 19%; MOG IgG1, 13%); 186 patients had rON only and 60 patients had rON with subsequent additional inflammatory demyelinating attacks (rON-plus group). The rON-only cohort comprised the following: double seronegative (idiopathic), 110 patients (59%); MOG IgG1 positive, 27 patients (15%; 4 with chronic relapsing inflammatory optic neuropathy); multiple sclerosis (MS), 25 patients (13%); and aquaporin-4 IgG positive, 24 patients (13%). The rON-plus cohort comprised the following: aquaporin-4 IgG positive, 23 patients (38%); MS, 22 patients (37%); double seronegative, 11 patients (18%); and MOG IgG1 positive, 4 patients (7%). The annualized relapse rate for the rON-only group was 1.2 for MOG IgG1-positive patients, 0.7 for double-seronegative patients, 0.6 for aquaporin-4 IgG-positive patients, and 0.4 for MS patients (P = 0.005). The median visual acuity (VA) of patients with the worst rON-only attack at nadir were hand movements in aquaporin-4 IgG-positive patients, between counting fingers and hand movements in MOG IgG1-positive patients, 20/800 in idiopathic patients, and 20/100 in MS patients (P = 0.02). The median VA at last follow-up for affected eyes of the rON-only cohort were counting fingers for aquaporin-4 IgG-positive patients, 20/40 for idiopathic patients, 20/25 for MS patients and MOG IgG1-positive patients (P = 0.006). At 5 years after ON onset, 59% of aquaporin-4 IgG-positive patients, 22% of idiopathic patients, 12% of MOG IgG1-positive patients, and 8% of MS patients were estimated to have severe visual loss.ConclusionsGlial autoantibodies (MOG IgG1 or aquaporin-4 IgG) are found in one third of all patients with rON. Aquaporin-4 IgG seropositivity predicts a worse visual outcome than MOG IgG1 seropositivity, double seronegativity, or MS diagnosis. Myelin oligodendrocyte glycoprotein IgG1 is associated with a greater relapse rate but better visual outcomes.Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

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