Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Autoantibody Status Predict Outcome of Recurrent Optic Neuritis

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, Sean J. Pittock

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Purpose: To 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. Design: Cross-sectional cohort study. Participants: The 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. Methods: Serum 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 Measures: Aquaporin-4 IgG and MOG IgG1 serostatus, clinical characteristics, and visual outcomes. Results: Among 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. Conclusions: Glial 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.

Original languageEnglish (US)
Pages (from-to)1628-1637
Number of pages10
JournalOphthalmology
Volume125
Issue number10
DOIs
StatePublished - Oct 2018

ASJC Scopus subject areas

  • Ophthalmology

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