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

Ophthalmology. 2018 Oct;125(10):1628-1637. doi: 10.1016/j.ophtha.2018.03.041. Epub 2018 Apr 30.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Antibodies, Anti-Idiotypic / blood
  • Aquaporin 4 / immunology*
  • Autoantibodies / blood*
  • Cross-Sectional Studies
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • Immunoglobulin G / immunology
  • Male
  • Middle Aged
  • Myelin-Oligodendrocyte Glycoprotein / immunology*
  • Optic Neuritis / blood
  • Optic Neuritis / diagnosis
  • Optic Neuritis / immunology*
  • Prognosis
  • Recurrence
  • Retrospective Studies
  • Tomography, Optical Coherence
  • Visual Acuity*
  • Young Adult


  • Antibodies, Anti-Idiotypic
  • Aquaporin 4
  • Autoantibodies
  • Immunoglobulin G
  • Myelin-Oligodendrocyte Glycoprotein