Due to improved phenotyping and genetic characterization, the field of ‘incurable’ and ‘blinding’ inherited retinal diseases (IRDs) has moved substantially forward. Decades of ascertainment of IRD patient data from Philadelphia and Toronto centers illustrate the progress from Mendelian genetic types to molecular diagnoses. Molecular genetics have been used not only to clarify diagnoses and to direct counseling but also to enable the first clinical trials of gene-based treatment in these diseases. An overview of the recent reports of gene augmentation clinical trials by subretinal injections is used to reflect on the reasons why there has been limited success in this early venture into therapy. These first-in human experiences have taught that there is a need for advancing the techniques of delivery of the gene products - not only for refining further subretinal trials, but also for evaluating intravitreal delivery. Candidate IRDs for intravitreal gene delivery are then suggested to illustrate some of the disorders that may be amenable to improvement of remaining central vision with the least photoreceptor trauma. A more detailed understanding of the human IRDs to be considered for therapy and the calculated potential for efficacy should be among the routine prerequisites for initiating a clinical trial.

由于表型分析和遗传特征的改进，“无法治愈”和“致盲”遗传性视网膜疾病（IRD）领域已取得了实质性进展。费城和多伦多中心数十年对 IRD 患者数据的确定说明了从孟德尔遗传类型到分子诊断的进展。分子遗传学不仅被用来澄清诊断和直接咨询，而且还使基于基因的治疗这些疾病的首次临床试验成为可能。对最近通过视网膜下注射进行基因增强临床试验的报告进行了概述，以反思这种早期治疗尝试取得有限成功的原因。这些首次人类经验告诉我们，需要推进基因产物的递送技术——不仅是为了完善进一步的视网膜下试验，而且是为了评估玻璃体内的递送。然后建议用于玻璃体内基因传递的候选 IRD 来说明一些可能适合以最少的光感受器创伤改善剩余中央视力的疾病。更详细地了解要考虑用于治疗的人类 IRD 以及计算出的疗效潜力应该是启动临床试验的常规先决条件之一。