Department of Optometry and Vision Sciences, Melbourne School of Health Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia; Department of Surgery (Ophthalmology), Melbourne Medical School, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
Department of Optometry and Vision Sciences, Melbourne School of Health Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia.
Genet Med. 2022 Mar;24(3):521-534. doi: 10.1016/j.gim.2021.10.013. Epub 2021 Nov 30.
This study aimed to systematically review and summarize gene therapy treatment for monogenic retinal and optic nerve diseases.
This review was prospectively registered (CRD42021229812). A comprehensive literature search was performed in Ovid MEDLINE, Ovid Embase, Cochrane Central, and clinical trial registries (February 2021). Clinical studies describing DNA-based gene therapy treatments for monogenic posterior ocular diseases were eligible for inclusion. Risk of bias evaluation was performed. Data synthesis was undertaken applying Synthesis Without Meta-analysis guidelines.
This study identified 47 full-text publications, 50 conference abstracts, and 54 clinical trial registry entries describing DNA-based ocular gene therapy treatments for 16 different genetic variants. Study summaries and visual representations of safety and efficacy outcomes are presented for 20 unique full-text publications in RPE65-mediated retinal dystrophies, choroideremia, Leber hereditary optic neuropathy, rod-cone dystrophy, achromatopsia, and X-linked retinoschisis. The most common adverse events were related to lid/ocular surface/cornea abnormalities in subretinal gene therapy trials and anterior uveitis in intravitreal gene therapy trials.
There is a high degree of variability in ocular monogenic gene therapy trials with respect to study design, statistical methodology, and reporting of safety and efficacy outcomes. This review improves the accessibility and transparency in interpreting gene therapy trials to date.
本研究旨在系统地回顾和总结基因治疗治疗单基因视网膜和视神经疾病的方法。
本研究前瞻性注册（CRD42021229812）。在 Ovid MEDLINE、Ovid Embase、Cochrane 中心和临床试验注册库中进行了全面的文献检索（2021 年 2 月）。符合纳入标准的是描述单基因后眼部疾病 DNA 基因治疗的临床研究。对偏倚风险进行评估。采用无荟萃分析指南进行数据综合。
本研究确定了 47 篇全文出版物、50 篇会议摘要和 54 篇临床试验注册条目，描述了针对 16 种不同遗传变异的 DNA 眼部基因治疗。对 20 篇独特的全文出版物中 RPE65 介导的视网膜营养不良、脉络膜视网膜病变、Leber 遗传性视神经病变、杆状圆锥细胞营养不良、色盲和 X 连锁性视网膜劈裂的安全性和疗效结果进行了总结和可视化表示。最常见的不良事件与视网膜下基因治疗试验中的眼睑/眼表面/角膜异常和玻璃体内基因治疗试验中的前葡萄膜炎有关。
在眼部单基因基因治疗试验中，研究设计、统计方法和安全性及疗效结果的报告存在高度的可变性。本综述提高了迄今为止对基因治疗试验的解释的可访问性和透明度。
