TY - JOUR
T1 - Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Autoantibody Status Predict Outcome of Recurrent Optic Neuritis
AU - Jitprapaikulsan, Jiraporn
AU - Chen, John J.
AU - Flanagan, Eoin P.
AU - Tobin, W. Oliver
AU - Fryer, Jim P.
AU - Weinshenker, Brian G.
AU - McKeon, Andrew
AU - Lennon, Vanda A.
AU - Leavitt, Jacqueline A.
AU - Tillema, Jan Mendelt
AU - Lucchinetti, Claudia
AU - Keegan, B. Mark
AU - Kantarci, Orhun
AU - Khanna, Cheryl
AU - Jenkins, Sarah M.
AU - Spears, Grant M.
AU - Sagan, Jessica
AU - Pittock, Sean J.
N1 - Funding Information:
Supported by the Department of Laboratory Medicine and Pathology and the Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota; the National Institutes of Health, Bethesda, Maryland (grant no.: R01NS065829); and in part by Research to Prevent Blindness, Inc., New York, New York (an unrestricted grant to the Department of Ophthalmology, Mayo Clinic). The funders had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Publisher Copyright:
© 2018 American Academy of Ophthalmology
PY - 2018/10
Y1 - 2018/10
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ophtha.2018.03.041
DO - 10.1016/j.ophtha.2018.03.041
M3 - Article
C2 - 29716788
AN - SCOPUS:85046171735
VL - 125
SP - 1628
EP - 1637
JO - Ophthalmology
JF - Ophthalmology
SN - 0161-6420
IS - 10
ER -