Clinical Characteristics And Prognosis Of Myelin Oligodendrocyte Glycoprotein Antibody-positive Optic Neuritis

Background and objective:Optic neuritis(ON)is a disorder characterized by inflammatory demyelination of the optic nerve and predominantly affects young adults.The aquaporin-4 antibody(AQP4-Ab)is a marker for the diagnosis and prognosis of ON.Additionally,recent findings have suggested the potential value of the myelin oligodendrocyte glycoprotein antibody(MOG-Ab)to differentiate between ON phenotypes,further expanding the possibility of utilizing this technique for the diagnosis of this disease.To date,the clinical characteristics and prognosis of MOG-ON and their relation to age of onset is still unclear in China.? To investigate clinical characteristics and prognosis of pediatric optic neuritis(PON)in patients seropositive for myelin oligodendrocyte glycoprotein antibody(MOG-Ab)in China.?To describe different clinical characteristics and prognosis of optic neuritis(ON)in male patients with seropositive aquaporin-4 antibody(AQP4-Ab)or myelin oligodendrocyte glycoprotein antibody(MOG-Ab)in China.? To investigate the clinical characteristics and outcomes of myelin oligodendrocyte glycoprotein antibody-positive optic neuritis(MOG-ON)in patients with varying ages of onset in China.Methods:Retrospective case-control study.?Children displaying initial onset of optic neuritis(ON)were recruited from the Neuro-ophthalmology Department in the Chinese People's Liberation Army General Hospital from January 2016 to August 2017.They were assigned into three groups based on antibody status:MOG-Ab-seropositive ON(MOG-ON),aquaporin-4 antibody-seropositive ON(AQP4-ON)and double seronegative ON(seronegative-ON).? Males with ON were recruited from the Neuro-ophthalmology Department of the Chinese People's Liberation Army,General Hospital from January 2016 to February 2018.They were assigned to two groups based on antibodies status:MOG-Ab-seropositive ON(MOG-ON)and aquaporin-4 Ab-seropositive ON(AQP4-ON).?Patients displaying symptoms of MOG-ON were recruited from the Neuro-ophthalmology Department in the Chinese People's Liberation Army General Hospital from January 2016 to May 2018.They were assigned to one of three subgroups based on age of onset:pediatric(<18 years),young(18?46 years),and middle-aged(>46 years)MOG-ON.The patients underwent examinations including best corrected visual acuity(BCVA),fundus color photography,optical coherence tomography(OCT)and magnetic resonance imaging(MRI).The patients were tested for serum levels of antibodies for aquaporin 4 and MOG with a cell-based assay.Statistical analyses of patients' clinical features,neuroimaging features and prognosis were conducted.Results:?Totally 48 patients were assessed,including 25 MOG-ON(52.1%),7 AQP4-ON(14.6%),and 16 seronegative-ON(33.3%).The MOG-ON and seronegative-ON cohorts had equal ratios of female/male,but the AQP4-ON cohort was predominantly females(100%).The MOG-ON patients were significantly younger at onset compared to the AQP4-ON group.Of the MOG-ON eyes,97.6%had good recovery of visual acuity(?0.5)compared to 33.3%of AQP4-ON eyes(p<0.001).However,there was no significant difference compared to the seronegative-ON eyes(82.6%,P=0.052).Two children in the MOG-ON group ended up being diagnosed with acute disseminated encephalomyelitis,while only one patient in the AQP4-ON group developed neuromyelitis optica during follow-up.MOG-ON patients had thicker peripapillary retinal nerve fiber layers overall and in the superior and inferior quadrants than in AQP4-ON patients(P=0.005,P=0.002,and P=0.024,respectively).In addition,the macular ganglion cell-inner plexiform in MOG-ON eyes became significantly thicker than in AQP4-ON eyes(P=0.029).Orbital MRI revealed a larger proportion of MOG-ON patients had intracranial optic nerve involvement than seronegative-ON patients(51.2%vs.17.4%,P=0.009).?76 male patients were assessed,including 44 MOG-ON(57.9%)and 32 AQP4-ON(42.1%).The MOG-ON patients were significantly younger at onset compared to the AQP4-ON group(p<0.001).Frequencies of optic disc swelling,presence of abnormal autoimmune antibodies and elevated levels of CSF IgG were significantly higher in the AQP4-ON group than the MOG-ON group(P=0.040,P=0.016 and P=0.10,respectively).At the final visit,85.3%of MOG-ON eyes had increased visual acuity(?0.5)compared to 35.1%of AQP4-ON eyes(p<0.001).The ratio of this steroid-dependent condition is higher in MOG-ON patients than the AQP4-ON group(p<0.001).The ratio of conversion to NMO is higher in the AQP4-ON group than the MOG-ON group,with more AQP4-ON patients developing NMO by the follow-up(P=0.012).MOG-ON patients had thicker average peripapillary retinal nerve fiber layers and macular ganglion cell-inner plexiform than AQP4-ON patients(P=0.008 and P=0.012,respectively).Orbital MRI revealed more AQP4-ON patients had chiasmal involvement than MOG-ON patients(p<0.001).? 110 patients(188 eyes)were assessed,including 58 pediatric(52.7%),34 young(30.9%),and 18 middle-aged(16.4%)patients.Of the pediatric patients,93.9%had good recovery of visual acuity(?0.5)compared with 79.7%of young patients and 66.7%of middle-aged patients(p<0.001).The annual relapse rate was lower in the pediatric group than young and middle-aged groups(0.32±0.50 vs 0.73±0.87 vs 0.49±1.08,P=0.036).Six children(10.3%)were diagnosed with acute disseminated encephalomyelitis,while seven young patients(20.6%)were diagnosed with aquaporin-4 antibody seronegative neuromyelitis optica spectrum disorder upon follow-up.The average peripapillary RNFL and macular GCIPL thicknesses were not statistically different between subgroups(P=0.996,P=0.608).Overall,MRIs of the optic nerve showed perineural enhancement in 52.0%of patients and longitudinal extensive involvement in 87.7%.MRIs also revealed a greater proportion of pediatric patients with intracranial optic nerve involvement than in the other two subgroups(45.4%vs.21.2%vs.36.7%,P=0.014).Conclusion:? MOG-ON was the most common PON subtype in China.MOG-ON had different clinical features including earlier age of onset,equal female/male ratio,better recovery of visual acuity,and thicker peripapillary retinal nerve fiber and macular ganglion cell-inner plexiform layers.MOG-Abs may be a potential biomarker for determining visual prognosis with PON.?Male MOG-ON patients had different clinical features including earlier age of onset,higher optic disc swelling ratio,better visual acuity recovery,thicker peripapillary retinal nerve fiber and macular ganglion cell-inner plexiform layers,and less chiasmal involvement than male AQP4-ON patients.Serum antibody may be a potential biomarker for determining visual prognosis in male ON.?The clinical characteristics of MOG-ON are diverse.The pediatric patients are more common and some patients have demyelinating lesions in the brain.Pediatric patients had different clinical features,including better recovery of visual acuity,lower annual relapse rate,and more intracranial optic nerve involvement than young and middle-aged patients.Additionally,age of onset may be a potential predictor for determining visual prognosis with MOG-ON.