Department of Ophthalmology, University Hospital Bonn, Bonn, Germany.
Department of Ophthalmology, Justus-Liebig-University, Giessen, Germany.
Ophthalmic Res. 2023;66(1):727-748. doi: 10.1159/000529777. Epub 2023 Mar 6.
The aim of this study was to evaluate the current management of RPE65 biallelic mutation-associated inherited retinal degeneration (RPE65-IRD) in Europe since market authorization of voretigene neparvovec (VN, LuxturnaTM) in 2018. By July 2022, over 200 patients have been treated outside the USA, of whom about 90% in Europe. We conducted among all centers of the European Vision Institute Clinical Research Network www.evicr.net and health care providers (HCPs) of the European Reference Network dedicated to Rare Eye Diseases (ERN-EYE) the second multinational survey on management of IRDs in Europe elaborated by www.evicr.net with a special focus on RPE65-IRD.
An electronic survey questionnaire with 48 questions specifically addressing RPE65-IRD (2019 survey 35) was developed and sent by June 2021 to 95 www.evicr.net centers and 40 ERN-EYE HCPs and affiliated members. Of note, 11 centers are members of both networks. Statistical analysis was performed with Excel and R.
The overall response rate was 44% (55/124); 26 centers follow RPE65 biallelic mutation-associated IRD patients. By June 2021, 8/26 centers have treated 57 RPE65-IRD cases (1-19/center, median 6) and 43 planned for treatment (range 0-10/center, median 6). The overall age range was 3-52 years, and on average 22% of the patients did not (yet) qualify for treatment (range 2-60%/center, median 15%). Main reasons were too advanced (range 0-100, median 75%) or mild disease (range 0-100, median 0). Eighty-three percent of centers (10/12) that follow RPE65 mutation-associated IRD patients treated with VN participate in the PERCEIVE registry (EUPAS31153, www.encepp.eu. Quality of life and full-field stimulus test improvements had the highest scores of the survey-reported outcome parameters in VN treatment follow-up.
This second multinational survey on management of RPE65-IRD by www.evicr.net centers and ERN-EYE HCPs in Europe indicates that RPE65-IRD might be diagnosed more reliably in 2021 compared to 2019. By June 2021, 8/26 centers reported detailed results including VN treatment. Main reasons for non-treatment were too advanced or mild disease, followed by absence of 2 class 4 or 5 mutations on both alleles or because of a too young age. Patient satisfaction with treatment was estimated to be high by 50% of the centers.
本研究旨在评估自 2018 年 voretigene neparvovec（VN，LuxturnaTM）获得市场批准以来，欧洲 RPE65 双等位基因突变相关遗传性视网膜变性（RPE65-IRD）的治疗现状。截至 2022 年 7 月，已有超过 200 名患者在未经美国批准的情况下接受了治疗，其中约 90%在欧洲。我们对所有欧洲视觉研究所临床研究网络 www.evicr.net 的中心和专门针对罕见眼病的欧洲参考网络（ERN-EYE）的医疗保健提供者（HCPs）进行了调查，这是由 www.evicr.net 进行的第二次关于欧洲 IRD 管理的多国调查，特别关注 RPE65-IRD。
我们开发了一份包含 48 个问题的电子调查问卷，专门针对 RPE65-IRD（2019 年调查为 35 个问题），并于 2021 年 6 月发送给 95 个 www.evicr.net 中心和 40 个 ERN-EYE HCPs 和附属成员。值得注意的是，有 11 个中心同时是这两个网络的成员。使用 Excel 和 R 进行统计分析。
总体回复率为 44%（55/124）；26 个中心对 RPE65 双等位基因突变相关 IRD 患者进行了随访。截至 2021 年 6 月，26 个中心中的 8 个已经治疗了 57 例 RPE65-IRD 病例（1-19/中心，中位数 6），并计划对 43 例进行治疗（范围为 0-10/中心，中位数 6）。患者的总体年龄范围为 3-52 岁，平均有 22%的患者尚未符合治疗条件（范围为 2-60%/中心，中位数为 15%）。主要原因是疾病太晚期（范围为 0-100，中位数为 75%）或病情较轻（范围为 0-100，中位数为 0）。10/12 个（10/12）治疗过接受 VN 治疗的 RPE65 突变相关 IRD 患者的中心参与了 PERCEIVE 登记处（EUPAS31153，www.encepp.eu）。在 VN 治疗随访中，生活质量和全视野刺激测试改善的评分最高。
由 www.evicr.net 中心和 ERN-EYE HCPs 进行的第二次关于欧洲 RPE65-IRD 管理的多国调查表明，与 2019 年相比，RPE65-IRD 的诊断可能更为可靠。截至 2021 年 6 月，已有 26 个中心中的 8 个报告了详细的治疗结果，包括 VN 治疗。不治疗的主要原因是疾病太晚期或太轻，其次是两个等位基因上都没有 2 个 4 类或 5 类突变，或者因为年龄太小。50%的中心估计患者对治疗的满意度较高。
