无脉络膜症诊断技术及基因治疗的新进展

New advances in diagnostic techniques and gene therapy for choroideremia

无脉络膜症(CHM)是一种X连锁隐性遗传性视网膜疾病,表现为光感受器、视网膜色素上皮和脉络膜的进行性退化。临床表现为缓慢进行性夜盲及视野缺损,目前尚无有效治疗方法。眼底检查技术的发展为临床提供了更多辅助诊断和随访观察的指标,二代测序技术的出现进一步提高了遗传性视网膜疾病的诊断率,逐渐加深了对CHM发病机制及自然病程的认识。CHM基因治疗的多项临床试验在十年内已经取得一定效果,在基因治疗的载体优化、治疗时间窗选择及试验不良事件的处理等方面均有重要进展。未来需要加深对CHM自然病程的认识,针对治疗时间窗采取个性化的治疗及终点评价指标。通过评估疾病严重程度的差异,针对不同阶段采取个性化治疗方案更有益于预后。

Choroideremia(CHM)is an X-linked recessive inherited retinal disease characterized by progressive degeneration of photoreceptors,retinal pigment epithelium and choroid.Clinical manifestations include slowly progressive night blindness and visual field defects,for which there is no effective treatment.The development of fundus examination technology has provided more indicators for clinical diagnosis and followup observation,and the emergence of next generation sequencing technology has further improved the diagnostic rate of inherited retinal diseases,gradually deepening the understanding of the pathogenesis and natural history of CHM.Numerous clinical trials of CHM gene therapy have been conducted over a decade,with important advances in vector optimization for gene therapy,treatment time window selection,and management of trial adverse events.In the future,there is a need to deepen the understanding of the natural course of CHM and to adopt personalized treatment and endpoint evaluation targets for the treatment time window.Assessing differences in disease severity and individualizing treatment plans for different stages is more beneficial to prognosis.