Short-Term Outcomes of Pediatric Patients With Mild Autosomal Recessive RPE65-Associated Retinal Dystrophy Treated With Voretigene Neparvovec.

IF 2.6 3区医学 Q2 OPHTHALMOLOGY

Translational Vision Science & Technology Pub Date : 2025-08-01 DOI:10.1167/tvst.14.8.8

David A Merle, Leen Hertens, Spyridon Dimopoulos, Susanne Kohl, Manon Van Haute, Elfride De Baere, Marieke De Bruyne, Barbara Janssens, Klaus Rüther, Cord Huchzermeyer, Pascale Mazzola, Fanny Nerinckx, Tobias Haack, Lasse Wolfram, Melanie Kempf, Laura Kühlewein, Krunoslav Stingl, Bart P Leroy, Katarina Stingl

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引用次数: 0

Abstract

Purpose: Voretigene neparvovec is approved for RPE65-associated inherited retinal degeneration (RPE65-IRD) in the United States and the European Union. According to current knowledge, early treatment benefits efficacy. However, consensus on treating mild cases is lacking due to ambiguity in balancing clinical benefits with potential side effects. Therefore, we present short-term outcomes of four pediatric patients with milder types of RPE65-IRD.

Methods: Two unrelated pediatric patients were unilaterally treated at the University Eye Hospital in Tübingen, Germany. Another two unrelated pediatric patients were bilaterally treated at Ghent University Hospital, Belgium. Examinations were performed before and until at least 6 months after treatment, including best-corrected visual acuity, slit-lamp examination, fundus photography, short-wavelength fundus autofluorescence, optical coherence tomography, 90° kinetic perimetry, dark-adapted chromatic perimetry, and full-field stimulus threshold measurements.

Results: Despite surgical challenges, treatment with voretigene neparvovec was successful in all four patients. All patients showed rod functional rescue with stable best-corrected visual acuity. Three patients suffered chorioretinal atrophy at the retinotomy site but none developed signs of fast-growing CRA. One case developed limited CRA in the bleb area, potentially related to inflammation in the subretinal space.

Conclusions: Treatment with voretigene neparvovec was safe and effective in patients with mild RPE65-IRD. Early treatment showed good functional outcomes. Also, treatment at stages without profound retinal degeneration might lower the risk of fast-growing CRA.

Translational relevance: This study aids clinical decision-making in unclear cases by demonstrating that early treatment with voretigene neparvovec in mild RPE65-IRD provides functional benefits while minimizing the risk of fast-growing chorioretinal atrophy.

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Voretigene Neparvovec治疗轻度常染色体隐性rpe65相关视网膜营养不良患儿的短期疗效

目的：Voretigene neparvovec在美国和欧盟被批准用于rpe65相关遗传性视网膜变性（RPE65-IRD）。根据目前的知识，早期治疗有利于疗效。然而，由于在平衡临床益处和潜在副作用方面存在歧义，对治疗轻度病例缺乏共识。因此，我们报告了4例轻度RPE65-IRD患儿的短期预后。方法：在德国宾根大学眼科医院对两名无亲缘关系的儿童患者进行单方治疗。另外两名无关的儿科患者在比利时根特大学医院接受了双边治疗。在治疗前和治疗后至少6个月进行检查，包括最佳矫正视力、裂隙灯检查、眼底摄影、短波眼底自身荧光、光学相干断层扫描、90°动力学视界、暗适应彩色视界和全场刺激阈值测量。结果：尽管手术难度很大，但所有4例患者均成功接受了voretigene neparvovec治疗。所有患者均显示棒功能恢复，最佳矫正视力稳定。3例患者在视网膜切除术部位出现了绒毛膜视网膜萎缩，但没有一例出现CRA快速增长的迹象。一例在水泡区出现有限的CRA，可能与视网膜下间隙的炎症有关。结论：voretigene neparvovec治疗轻度RPE65-IRD安全有效。早期治疗显示出良好的功能预后。此外，在没有严重视网膜变性的阶段进行治疗可能会降低快速增长的CRA的风险。翻译相关性：该研究通过证明早期使用voretigene neparvovec治疗轻度RPE65-IRD可提供功能益处，同时将快速生长的绒毛膜视网膜萎缩的风险降至最低，从而有助于在不明确病例中的临床决策。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Vision Science & Technology Engineering-Biomedical Engineering

CiteScore

5.70

自引率

3.30%

发文量

346

审稿时长

25 weeks

期刊介绍： Translational Vision Science & Technology (TVST), an official journal of the Association for Research in Vision and Ophthalmology (ARVO), an international organization whose purpose is to advance research worldwide into understanding the visual system and preventing, treating and curing its disorders, is an online, open access, peer-reviewed journal emphasizing multidisciplinary research that bridges the gap between basic research and clinical care. A highly qualified and diverse group of Associate Editors and Editorial Board Members is led by Editor-in-Chief Marco Zarbin, MD, PhD, FARVO. The journal covers a broad spectrum of work, including but not limited to: Applications of stem cell technology for regenerative medicine, Development of new animal models of human diseases, Tissue bioengineering, Chemical engineering to improve virus-based gene delivery, Nanotechnology for drug delivery, Design and synthesis of artificial extracellular matrices, Development of a true microsurgical operating environment, Refining data analysis algorithms to improve in vivo imaging technology, Results of Phase 1 clinical trials, Reverse translational ("bedside to bench") research. TVST seeks manuscripts from scientists and clinicians with diverse backgrounds ranging from basic chemistry to ophthalmic surgery that will advance or change the way we understand and/or treat vision-threatening diseases. TVST encourages the use of color, multimedia, hyperlinks, program code and other digital enhancements.