The Correlative Study Between Aquaporin-4 Antibodies And Retinal Nerve Fiber Layer And Macular Injury In Neuromyelitis Optica Spectrum Disorders

ObjectiveTo compare the features of peripapillary retinal nerve fibre layer thickness(p RNFLT),cube macular volume(CMV)and cube average macular thickness(CAMT)among 4 groups of patients,i.e.optic neuritis with aquaporin-4 antibodies seropositive(AQP4ab+ON),neuromyelitis optica(NMO),optic neuritis with aquaporin-4 antibodies seronegative(AQP4ab-ON),and optic neuritis with myelin oligodendrocyte glycoprotein antibodies seropositive(MOGab+ON),by using optical coherence tomography(OCT).To explore the clinical factors that influence average p RNFLT,CMV and CAMT.Methods121 patients with ON and 21 healthy controls were recruited for this study.Two groups were unrelated by blood,and matched in age and sex.The patients with ON were divided into three groups: 40 patients with AQP4ab+ON,40 patients with NMO,41 patients with AQP4ab-ON.The AQP4ab-ON group were subdivided into 14 patients with MOGab+ON group and 6 patients with MOGab-ON group.Subgroup analyses were performed.All subjects were evaluated for their p RNFLT,CMV and CAMT by using OCT.Results1.Clinical characteristics:1)Demographic characteristics: the AQP4ab+ON,NMO and AQP4ab-ON groups were predominantly found in young and middle-aged women,respectively.The mean onset age in AQP4ab+ON group(40.48 ±15.13 years)was older than that in NMO group(33.45 ±16.50 years)and AQP4ab-ON group(33.29 ±16.24 years).The difference in the three groups was not statistically significant(P=0.269).2)The best corrected visual acuity in peak and remission stages of the diseases: NMO group > AQP4ab+ON group > AQP4ab-ON group(P<0.05).3)The frequency of ON attacks: NMO group > AQP4ab+ON group > AQP4ab-ON group(P=0.02).4)The disease course: NMO group [average 50.50 months(5.67-180.83 months)] > AQP4ab+ON [average 14.03 months(5.67-277.30 months)] group >AQP4ab-ON group [average 7.80 months(5.50-140.07 months)](P=0.000).2.Frequency of aquaporin-4 antibodies seropositive: 100%(40/40)in AQP4ab+ON group,80%(32/40)in NMO group,and 0%(0/41)in AQP4ab-ON group.3.Frequency of myelin oligodendrocyte glycoprotein antibodies seropositive: 0%(0/6)in AQP4ab+ON group,0%(0/10)in NMO group,and 70%(14/20)in AQP4ab-ON group.4.Frequency of other autoantibodies and connective tissue diseases: 52.5%(21/40)in AQP4ab+ON group,50.0%(20/40)in NMO group,and 17.1%(7/14)in AQP4ab-ON group.In the AQP4ab+ON group,two patients had comorbid Hashimoto's thyroiditis,and three patients had comorbid Sjogren's syndrome.In the NMO group,three patients had comorbid Hashimoto's thyroiditis.In the AQP4ab-ON group,one patient had comorbid anticardiophospholipid antibodies syndrome.Compared with AQP4ab-ON group,the AQP4ab+ON group and NMO group were more likely to have autoantibodies,and the differences were statistically significant(P=0.001,0.002).5.The imaging characteristics: the positive rate of the involved optic nerves(long T2 signals)on nuclear magnetic resonance imaging(MRI)was 90.0%(36/40)in AQP4ab+ON group,92.5%(37/40)in NMO group,and 78.0%(32/41)in AQP4ab-ON group(P=0.121).The positive rate of optic nerve enhancement on MRI was 45.0%(18/40)in AQP4ab+ON group,47.5%(19/40)in NMO group,and 43.9%(18/41)in AQP4ab-ON group(P=0.946).6.OCT in the three groups of ON eyes:1)Compared with HCs group,the CMV,CAMT,the average p RNFLT and the p RNFLT in the superior,inferior,nasal and temporal quadrants of AQP4ab+ON group,and NMO group and AQP4ab-ON group were significantly reduced(P < 0.0083).2)Compared with AQP4ab-ON group,the CMV,CAMT,the average p RNFLT and p RNFLT in the superior,inferior and nasal quadrants of the AQP4ab+ON group and NMO group were significantly reduced except for the temporal quadrants(P < 0.0083).3)Compared with the AQP4ab+ON group,the average p RNFLT and the p RNFLT in the superior,inferior,nasal and temporal quadrants of the NMO group were not reduced significantly(P > 0.0083).7.OCT between the MOGab+ON group and MOGab-ON group ON eyes:1)Compared with HCs group,MOGab+ON group except nasal quadrants,the p RNFLT in the superior,inferior,and temporal quadrants,the average p RNFLT and CMV and CAMT were significantly decreased(P < 0.05).2)Compared with MOGab+ON group,the p RNFLT in the superior quadrants of MOGab-ON group was decreased(P < 0.05),while among the two groups in gender,age of onset,course of disease and frequency of ON attacks were no significant(P > 0.05).8.OCT between the AQP4ab+ON group and MOGab+ON group ON eyes:Compared with MOGab+ON group,AQP4ab+ON group except temporal quadrants,the p RNFLT in the superior,inferior and nasal quadrants,the average p RNFLT,CMV and CAMT were significantly decreased(P < 0.01),while among the two groups in gender and frequency of ON attacks were no significant(P > 0.05).9.The single factor analysis showed that the seropositive AQP4 antibodies,ON duration,and frequency of ON attacks had impact on the decrease of average p RNFLT,and that seropositive AQP4 antibodies had impact on the decrease of CMV and CAMT,the differences were statistically significant(P < 0.05).By ordinal logistic regression analysis:1)The seropositive AQP4 antibodies and the frequency of ON attacks were independent risk factors for the decrease of average p RNFLT,among which the seropositive AQP4 antibodies(OR=3.475 > 1),the frequency of ON attacks(OR=1.584 > 1)were positively correlated with the decrease of average p RNFLT.The risk ratio of the decrease of average p RNFLT in seropositive AQP4 antibodies ON was 3.475 times than that in seronegative AQP4 antibodies ON(P < 0.05).2)The seropositive AQP4 antibodies was an independent risk factor for the decrease of CMV,and the seropositive AQP4 antibodies(OR=3.704 > 1)was positively correlated with the decrease of CMV.The risk ratio of the decrease of CMV in seropositive AQP4 antibodies ON was 3.704 times than that in seronegative AQP4 antibodies ON(P < 0.05).3)The seropositive AQP4 antibodies was an independent risk factor for the decrease of CAMT,and the seropositive AQP4 antibodies(OR=3.604 > 1)was positively correlated with the decrease of CAMT.The risk ratio of the decrease of CAMT in seropositive AQP4 antibodies ON was 3.604 times than that in seronegative AQP4 antibodies ON(P < 0.05).Conclusion1.AQP4ab+ON and NMO induced similar structural injury in the peripapillary retinal nerve fibre layer and macular.The average p RNFLT,CMV and CAMT in the two types of ON showed more damage than those in AQP4ab-ON and healthy persons.The AQP4ab+ON and NMO preferentially involved the superior,inferior and nasal quadrants of p RNFL,which could be associated with pretty levels of anti-aquaporin-4 antibodies.2.In contrast to healthy persons,the p RNFLT,CMV and CAMT in patients with MOGab+ON decreased significantly,but less severe than in patients with AQP4ab+ON and NMO.And contrast to MOGab-ON,the p RNFLT,CMV and CAMT in patients with MOGab+ON were not reduced significantly.These results may further indicate that different pathogenic mechanisms may exist for MOG antibodies and AQP4 antibodies.3.To explore the effect of different clinical factors on the average p RNFLT,CMV and CAMT.By using ordinal logistic regression analysis: the seropositive AQP4 antibodies and frequency of ON attacks is positively correlated with the decrease of average p RNFLT.The seropositive AQP4 antibodies is positively correlated with the decrease of CMV.And the seropositive AQP4 antibodies is positively correlated with the decrease of CAMT.It is confirmed that AQP4 antibodies have a major effect on the peripapillary retinal nerve fiber layer and macular structural damage.