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目的:评价基因治疗Leber遗传性视神经病变(LHON)的安全性及临床效果。方法:采用多中心前瞻性非随机对照临床试验研究设计，于2017年12月至2018年2月在十堰市太和医院眼科中心招募线粒体DNA 11778位点突变的LHON患者40例80眼，以视力较差眼或右眼(双眼视力相等时)行玻璃体腔内注射重组腺相关病毒2-还原型辅酶Ⅰ脱氢酶4(rAAV2-n ND4)，对侧眼作为未注射眼，并依此分为注射眼组和未注射眼组，每组40眼。分别于术前和术后1、3、6、12个月采用两用对数视力表测量患者最佳矫正视力(BCVA)；采用非接触眼压计测量眼压；采用裂隙灯显微镜观察眼前节表现；采用CR-2免扩瞳眼底照相机检查眼底情况。对注射眼组与未注射眼组基因治疗前后视力、眼压变化及并发症发生情况进行比较。评估治疗有效率，以BCVA提高≥0.3 LogMAR为有效。n 结果:40例患者中23例患者视力提高≥0.3 LogMAR，有效率为57.5%，其中注射眼组视力提高6眼，未注射眼组视力提高4眼，双眼同时提高者13例。未注射眼组和注射眼组治疗后12个月BCVA分别为(1.51±0.62)LogMAR和(1.62±0.58)LogMAR，较治疗前的(1.75±0.46)LogMAR和(1.83±0.47)LogMAR明显提高，差异均有统计学意义(均n P<0.01)。2个组BCVA总体比较差异无统计学意义(n F组别＝0.084，n P＝0.772)；2个组治疗前后眼压总体比较差异均无统计学意义(n F组别＝0.557，n P＝0.575；n F时间＝2.314，n P＝0.106)。所有患者治疗后及随访期间均未发生严重并发症。n 结论:rAAV2-n ND4基因玻璃体腔内注射治疗LHON安全、有效，基因药物的单眼玻璃体腔内注射可以改善患者双眼视力。n “,”Objective:To evaluate the safety and clinical effect of gene therapy for Leber hereditary optic neuropathy (LHON).Methods:A multi-center prospective non-randomized controlled trial was conducted.Eighty eyes of 40 LHON patients with mitochondrial DNA 11778 mutation were enrolled in Taihe Hospital from December 2017 to February 2018.Intravitreal injection of recombinant adeno associated virus 2-NADH dehydrogenase 4 (rAAV2-n ND4) was carried out in the unilateral eye with worse visual acuity or the right eye (if the visual acuity of both eyes was equal) of each subject as the treated group and the fellow eyes as the untreated group.The best corrected visual acuity (BCVA) was detected using a standard logarithmic chart and intraocular pressure (IOP) was measured with a non-contact tonometer before treatment and 1, 3, 6, 12 months after treatment.The manifestations of the ocular anterior segment and fundus were examined by slit lamp microscopy and color photography.The changes of visual acuity and IOP before and after gene therapy were compared, and complications were evaluated between the treated group and the untreated group.The effective rate defined as visual acuity improved ≥0.3 LogMAR at the end of follow-up was assessed.This study adhered to the Declaration of Helsinki and the study protocol was approved by an Ethics Committee of Taihe Hospital (No.201807). Written informed consent was obtained from each subject prior to any medical examination and treatment.n Results:The visual acuity improved 6 eyes in the treated group and 4 eyes in the untreated group, and 13 patients showed bilateral improvement.The visual acuity improvement ≥0.3 LogMAR in 23 patients with the effective rate 57.5%.The BCVA was (1.51±0.62) LogMAR and (1.62±0.58) LogMAR at the end of following-up in the untreated group and treated group, respectively, which were significantly higher than (1.75±0.46) LogMAR and (1.83±0.47) LogMAR before treatment (both at n P<0.01), and no significant difference was found in BCVA between the two groups (n Fgroup=0.084, n P=0.772). There was no significant difference in IOP between the two groups before and after treatment (n Fgroup=0.557, n P=0.575; n Ftime=2.314, n P=0.106). No serious complications were found in all subjects during following-up.n Conclusions:rAAV2-n ND4 gene therapy is safe and effective for LHON, and binocular vision can be improved by monocular intravitreal injection of rAAV2-n ND4 gene.n