LHON患者基因治疗后视功能恢复与视神经纤维层厚度关联分析  

Association between visual function and optic fiber layer thickness after gene therapy for Leber hereditary optic neuropathy

作　　者：元佳佳 张勇 陈长征[1] 杨雪莹 缪青梅 Kai Yoon Fan 李斌 Yuan Jiajia;Zhang Yong;Chen Changzheng;Yang Xueying;Miao Qingmei;Kai Yoon Fan;Li Bin(Department of Ophthalmology,People's Hospital of Wuhan University,Wuhan 430065,China;Department of Ophthalmology,Taihe Hospital,Hubei University of Medicine,Shiyan 442000,China;Wuhan Neurophth Biological Technology Co.,Ltd.,Wuhan 420200,China)

机构地区：[1]武汉大学人民医院眼科,武汉430065 [2]十堰市太和医院眼科,湖北医药学院附属医院,十堰442000 [3]武汉纽福斯生物科技有限公司,武汉420200

出　　处：《中华实验眼科杂志》2022年第10期908-913,共6页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金项目(82101115、81770969);武汉大学自主创新基金青年项目(2042021kf0094)。

摘　　要：目的探讨Leber遗传性视神经病变(LHON)患者接受基因治疗后视功能恢复与视网膜神经纤维层(RNFL)厚度变化之间的关联。方法采用多中心非随机单臂临床试验设计,于2017年12月至2018年12月在华中科技大学同济医学院附属同济医院、十堰市太和医院及武汉大学附属鄂州市中心医院纳入LHON患者159例,所有患眼均接受重组腺相关病毒2-还原型辅酶Ⅰ脱氢酶4(rAAV2-ND4)0.05μl玻璃体腔注射,于术前及术后1、3、6、12个月进行随访;采用标准对数视力表检查患眼最佳矫正视力(BCVA)(转换为LogMAR视力);采用Humphrey自动视野计测定患眼视野指数(VFI)和平均偏差(MD);采用Spectralis?HRA+OCT仪测量患眼视盘上方、下方、颞侧、鼻侧和平均RNFL厚度。以术后第12个月BCVA、视野和RNFL厚度作为治疗的主要结局。依据治疗后12个月BCVA改善情况将患者分为注射眼视力改善组81眼、注射眼视力未改善组62眼、未注射眼视力改善组65眼和未注射眼视力未改善组78眼;依据术后第12个月VFI改善情况将患者分为注射眼VFI改善组48眼、注射眼VFI未改善组71眼、未注射眼VFI改善组47眼和未注射眼VFI未改善组72眼,依据MD改善情况分为注射眼MD改善组52眼、注射眼MD未改善组67眼、未注射眼MD改善组47眼和未注射眼MD未改善组72眼。采用Pearson线性回归法分析各组患眼BCVA、VFI和MD恢复情况与RNFL厚度之间的关联。结果治疗后12个月,注射眼和未注射眼BCVA(LogMAR视力)分别为1.37±0.55和1.29±0.59,分别优于注射前的1.70±0.41和1.53±0.51,差异均有统计学意义(t=4.920、3.550,均P<0.001)。治疗后12个月注射眼VFI较治疗前明显改善,MD明显下降,差异均有统计学意义(均P<0.001);未注射眼VFI较治疗前明显提高,MD有所下降,差异均有统计学意义(均P<0.01)。治疗后RNFL厚度总体逐渐变薄。注射眼视力提高组BCVA与视网膜上方、下方、鼻侧、平均RNFL厚度均呈负Objective To investigate the association between the rehabilitation of visual function and retinal nerve fiber layer(RNFL)thickness in Leber hereditary optic neuropathy(LHON)patients receiving gene therapy for the disease.Methods A multi-center,non-randomized,single-arm clinical trial was conducted.A total of 159 LHON patients were enrolled in Tongji Hospital,Tongji Medical College,Huazhong University of Science&Technology,Taihe Hospital and Ezhou Central Hospital from December 2017 to December 2018.All of the patients were administered with a single unilateral intravitreal injection(0.05μl)of recombinant adeno-associated virus 2 carrying reduced nicotinamide adenine dinucleotide dehydrogenase subunit 4(rAAV2-ND4)and were followed up before and 1,3,6 and 12 months after treatment.The best corrected visual acuity(BCVA)converted to logarithm of the minimum angle of resolution(LogMAR)unit was assessed with a standard logarithmic visual acuity chart.Perimetry indicators including visual field index(VFI)and mean deviation(MD)were measured with Humphrey Field Analyzer.RNFL thickness in the superior,inferior,temporal,nasal optic disc and the average RNFL thickness were detected with Spectralis®HRA+OCT.The 12-month postoperative BCVA,visual field,and RNFL thickness were taken as the primary outcomes.According to the improvement of BCVA,VFI and MD at 12 months after therapy,there were 81 vision improved eyes with injection,62 vision unimproved eyes with injection,65 vision improved eyes without injection,and 78 vision unimproved eyes without injection,48 VFI improved eyes with injection,71 VFI unimproved eyes with injection,47 VFI improved eyes without injection,and 72 VFI unimproved eyes without injection,52 MD improved eyes with injection,67 MD unimproved eyes with injection,47 MD improved eyes without injection,and 72 MD unimproved eyes without injection.The correlations between BCVA,VFI,MD and RNFL thickness were evaluated by Pearson linear correlation analysis.This study adhered to the Declaration of Helsinki.The s

关 键 词：基因疗法 Leber遗传性视神经病变/治疗 视力 视野 视神经纤维层厚度 人 光相干断层扫描 重组腺相关病毒 还原型辅酶Ⅰ脱氢酶4 

分 类 号：R774.6[医药卫生—眼科]