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Abstract：
IRDs are one of the leading causes of visual loss in children and young adults. Mutations in over 271 genes lead to retinal dysfunction, degeneration and sight loss. Though no cure exists, gene augmentation therapy has brought hope to the field. This systematic review sought to assess the efficacy of available gene therapy treatments for IRDs. Databases and public resources were searched for randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs). Standard methodological procedures were used, including a risk-of-bias assessment. One RCT and five NRSIs were assessed, all for adeno-associated virus two (AAV2)-mediated treatment of RPE-specific 65 kDa (RPE65)-associated LCA (Leber congenital amaurosis). Five outcomes were reported for meta-analyses. Modest improvements in visual acuity, ambulatory navigation/mobility testing or central retinal thickness was observed. There was significant improvement in red and blue light full-field stimulus testing (FST) (red light risk ratio of 1.89, treated v control, p = 0.04; and blue light risk ratio of 2.01, treated v control, p = 0.001). Study design assessment using a ROBIN-I tool (Cochrane Library) showed risk-of-bias judgement to be \"low/moderate\", whilst there were \"some concerns\" for the RCT using a RoB-2 tool (Cochrane Library). Although comparison by meta-analysis is compromised by, amongst other issues, a variable amount of vector delivered in each trial, FST improvements demonstrate a proof-of-principle for treating IRDs with gene therapy.
摘要：
IRD是儿童和年轻人视力丧失的主要原因之一。超过271个基因的突变导致视网膜功能障碍,退化和视力丧失。虽然没有治愈方法，基因增强疗法为该领域带来了希望。本系统综述旨在评估可用的基因疗法治疗IRD的疗效。在数据库和公共资源中搜索随机对照试验（RCT）和非随机干预研究（NRSIs）。使用了标准的方法学程序，包括偏见风险评估。评估了一个RCT和五个NRSIs，全部用于两种腺相关病毒（AAV2）介导的RPE特异性65kDa（RPE65）相关LCA（Leber先天性黑蒙）的治疗。荟萃分析报告了五个结果。视敏度的适度改善，观察到动态导航/移动性测试或中央视网膜厚度。红光和蓝光全场刺激测试（FST）有显著改善（红光风险比为1.89，治疗v对照，p=0.04；蓝光风险比为2.01，治疗对照组，p=0.001)。使用ROBIN-I工具（CochraneLibrary）进行的研究设计评估显示，偏倚风险判断为“低/中等”，而使用RoB-2工具(CochraneLibrary)的RCT存在“一些担忧”。尽管通过荟萃分析进行比较会受到影响，除其他问题外，在每次试验中递送的不同数量的载体，FST的改善证明了用基因疗法治疗IRD的原理证明。
