水通道蛋白-4抗体阳性视神经脊髓炎谱系疾病患者光相干断层扫描血管成像特征及相关因素分析

The characteristics of optical coherence tomography angiography in aquaporin-4 antibody positive neuromyelitis optica spectrum disorders

目的观察水通道蛋白-4(AQP-4)抗体阳性视神经脊髓炎谱系疾病(NMOSD)患者光相干断层扫描血管成像(OCTA)特征,分析其相关因素。方法病例对照研究。2015年9月至2017年8月在复旦大学附属眼耳鼻喉科医院眼科检查确诊的AQP-4抗体阳性NMOSD患者48例96只眼及同期年龄性别与之匹配的健康志愿者20名40只眼(正常对照组)纳入研究。均为双眼入组。根据视神经炎(ON)发作次数将NMOSD患者分为0 ON组、1 ON组、2 ON组、3+ON组,分别为30、22、31、13只眼。0 ON组为无ON发作史;1 ON组、2 ON组、3+ON组分别为ON发作1、2、≥3次。受检眼均行最佳矫正视力(BCVA)、视野、OCTA检查。BCVA检查采用国际标准Snellen视力表进行,并将结果转换成最小分辨角对数视力记录。采用Humphery视野计测量受检眼视野平均缺损值(MD)。采用OCTA仪对受检眼视盘区4.5 mm×4.5 mm和黄斑区6.0 mm×6.0 mm范围进行扫描,测量放射状视盘周围毛细血管(RPC)血流密度、黄斑旁中心凹视网膜浅层毛细血管丛血流密度(SVD)以及视盘旁神经纤维层(pRNFL)、黄斑旁中心凹神经节细胞-内丛状层(GCIPL)厚度。采用广义估计方程分析4组受检眼之间BCVA、视野MD、pRNFL与GCIPL厚度、RPC血流密度、SVD的差异,以及视网膜灌注与视网膜结构、视功能的关系。结果与正常对照组比较,0 ON组患眼RPC血管密度、SVD明显降低,差异有统计学意义(Waldχ^(2)=7.190、10.134,P<0.01);两组受检眼之间BCVA和pRNFL、GCIPL厚度比较,差异均无统计学意义(Waldχ^(2)=2.308、1.020、2.558,P>0.05)。与0 ON组比较,1 ON组、2 ON组、3+ON组患眼BCVA、视野MD、RPC血流密度、SVD和pRNFL、GCIPL厚度均明显降低,差异有统计学意义(Waldχ^(2)=12.390、11.346、38.860、18.040、45.418、26.608,P<0.01);1 ON组、2 ON组、3+ON组患眼之间上述各项指标比较,差异无统计学意义(P>0.05)。相关性分析结果显示,RPC血流密度与pRNFL厚度(β=0.372,标准误=0.018,P<0.001)、SVD与GCIPL厚度(β=0.115,标准误=0.204,P<0.001)密切相关。BCVA、视野MD与RPC血流密度密切相关(BCVA:β=0.025,标准误=0.005,P=0.000;视野MD:β=0.737,标准误=0.185,P=0.000)。结论NMOSD患眼ON发作前RPC血流密度、SVD下降;ON发作后,视功能、视网膜结构和灌注进一步受损,但损伤程度与ON发作次数无明显相关性。NMOSD患眼RPC血流密度与视功能密切相关。

Objective To investigate the alteration of retinal perfusion in aquaporin-4 antibody(AQP4-ab)positive neuromyelitis optica spectrum disorders(NMOSD)patients by optical coherence tomography angiography(OCTA).Methods A case-control study.Forty-eight AQP4-ab positive NMOSD patients(96 eyes)and 20 age and gender matched healthy controls(40 eyes)were recruited from September 2015 to August 2017 at the Eye&ENT Hospital of Fudan University.Patients of both eyes were included in the groups.The patients were further divided into 4 subgroups(0 ON,1 ON,2 ON,3+ON group)according to the number of episodes of ON(0,1,2,or 3+)with respect to 30、22、31、13 eyes.0 ON group had no history of ON episodes;1 ON group,2 ON group,and 3+ON group had ON episodes 1,2,≥3 times,respectively.All patients underwent complete ophthalmological examinations including BCVA,visual field and OCTA examination.The BCVA was recorded for each eye using metric notation from the Snellen chart,and then converted to the logarithm of the minimum angle of resolution.The central visual field was assessed using a Humphrey Field Analyzer 750 and the mean deviation(MD)was determined.OCTA scans of the optic disc(4.5 mm×4.5 mm)and macula(6 mm×6 mm)were acquired.Radial peripapillary capillary(RPC)vessel density,superficial capillary plexus vessel density(SVD),the thickness of ganglion cell and inner plexiform layer(GCIPL)and peripapillary retinal nerve fiber layer(pRNFL)were determined.The generalized estimating equations was performed to compare the difference of BCVA,MD,pRNFL thickness,GCIPL thickness,RPC vessel density and SVD among the groups and the correlations between retinal perfusion and retinal structure,visual function were analyzed.Results The RPC vessel density and SVD were significant lower in the 0 ON group compared with healthy group(Waldχ^(2)=7.190,10.134;P<0.01),however,the BCVA,pRNFL and GCIPL thickness were not significant difference between the two groups(Waldχ^(2)=2.308,1.020,2.558;P>0.05).The BCVA,visual field MD,RPC vessel density,SVD,pRNFL and GCIPL were significant lower in 1 ON,2 ON and 3+ON groups compared with healthy group and 0 ON group(Waldχ^(2)=12.390,11.346,38.860,18.040,45.418,26.608;P<0.001),but the parameters had no significant difference among the three groups(P>0.05).The RPC vessel density was significantly correlated with pRNFL thickness(β=0.372,standard error=0.018,P<0.001),and the SVD was significantly correlated with GCIPL thickness(β=0.115,standard error=0.204,P<0.001).The MD and BCVA was significantly correlated with peripapillary vessel density after adjustment for other variables(BCVA:β=0.025,standard error=0.005,P=0.000;visual field MD:β=0.737,standard error=0.185,P=0.000).Conclusions Subclinical primary retinal vasculopathy may occur in NMOSD prior to ON attack,the ON attack may further impair visual function,retinal structure and perfusion,however,the extent of injure is not relevant with the increase of ON attack.The peripapillary vessel density might be a sensitive predictor of visual outcomes in NMOSD patients.