Centre for Ophthalmology, University Hospital Tübingen, Tübingen, Germany.
Centre for Ophthalmology, University Hospital Tübingen, Tübingen, Germany
Br J Ophthalmol. 2023 Sep;107(9):1331-1335. doi: 10.1136/bjophthalmol-2021-321023. Epub 2022 May 24.
BACKGROUND/AIMS: Voretigene neparvovec (VN) is the first and only subretinal gene therapy approved by the Food and Drug Administration and European Medicines Agency. Real-world application has started in 2018 in patients with vision impairment due to biallelic retinal pigment epithelium () mutation-associated inherited retinal degenerations. Herein, we evaluated the development of retinal atrophy within in a single-centre patient cohort treated with VN.
13 eyes of eight patients treated with VN were retrospectively analysed for areas of retinal atrophy over a period of 6-24 months following surgery. Ultrawide field images were used to measure the area of atrophy. Fundus autofluorescence imaging is presented as an instrument for early detection of signs of retinal atrophy in these patients.
Atrophic changes beyond the retinotomy site were observed in all eyes. Areas of atrophy developed within the area of detachment (bleb) in all eight patients and outside the bleb in three patients. Changes in autofluorescence preceded the development of retinal atrophy and were already evident 2 weeks after surgery in the majority of patients. The areas of atrophy increase with time and progression continued over year 1. Functional outcomes remained stable (VA, FST, visual field).
Subretinal injection of VN can lead to RPE atrophy with consequent photoreceptor loss in and outside of the bleb area. Fundus autofluorescence is an important tool to monitor atrophic changes in patients after gene therapy. Interestingly, while areas of atrophy also included central areas, the functional benefits of the treatment did not appear to be affected and remained stable.
背景/目的：Voretigene neparvovec（VN）是首个也是唯一一个获得美国食品和药物管理局及欧洲药品管理局批准的视网膜下基因治疗药物。自 2018 年以来，该药物已开始用于治疗因双等位基因视网膜色素上皮（RPE）突变相关遗传性视网膜变性而导致视力受损的患者。在此，我们评估了接受 VN 治疗的单中心患者队列中视网膜萎缩的发展情况。
对 8 例患者的 13 只眼进行回顾性分析，这些患者在手术后 6-24 个月内出现视网膜萎缩。使用超广角图像来测量萎缩区域。眼底自发荧光成像用于评估这些患者的视网膜萎缩早期迹象。
所有患者均观察到超出视网膜切开部位的萎缩性改变。在所有 8 例患者中，萎缩区域均在脱离（气肿）区域内发展，而在 3 例患者中，萎缩区域则在气肿外发展。荧光素眼底血管造影显示，在大多数患者中，萎缩的发生早于视网膜脱离，且在术后 2 周即已明显。萎缩区域随时间而增大，且在第 1 年内持续进展。功能结局保持稳定（VA、FST、视野）。
VN 的视网膜下注射可导致 RPE 萎缩，继而导致气肿区域内外的光感受器丧失。眼底自发荧光是监测基因治疗后患者萎缩性改变的重要工具。有趣的是，尽管萎缩区域也包括中央区域，但治疗的功能益处似乎并未受到影响，且保持稳定。
