Audo Isabelle, Barale Pierre-Olivier, Devisme Céline, Mohand-Said Saddek, Meunier Isabelle, Smirnov Vasily M, Dhaenens Claire-Marie, Andrieu Camille, Zeitz Christina, Pagot Chloé, Barbier Pascaline, Tindel Malka, Chapon Perrine, Sahel Jose-Alain
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Centre de Référence Maladies Rares REFERET and INSERM-DGOS CIC 1423, F-75012 Paris, France.
Sorbonne Université, INSERM, CNRS, Institut de la Vision Paris France, Paris, France.
Eye (Lond). 2025 Jun;39(9):1758-1764. doi: 10.1038/s41433-025-03691-8. Epub 2025 Mar 14.
This retrospective real-world study evaluated the effectiveness and safety of subretinal voretigene neparvovec (VN) in French patients (six children, six adults) with inherited retinal dystrophies.
Data were collected from medical records for the year following bilateral treatment with subretinal VN. Functional vision was assessed using the Streetlab mobility course with obstacles. The main outcome was Percentage of Preferred Walking Speed (PPWS) 1 month after treatment (the average speed to navigate the obstacle course as a percentage of the speed to walk straight for 4 m without obstacles at 500 lux).
PPWS median relative improvement to month 1 was 63.9% (interquartile range 47.8%; 88.5%) at 2 lux. Gains were sustained to month 6, were comparable in children and adults, with similar patterns at 7.5 and 50 lux. Course completion time and the number of collisions improved at month 1 at 2 lux. Median full-field stimulus test (FST) improved at month 1 (-33.2 [interquartile range -33.7; -19.8] dB), with improvements sustained to month 24. Over the study, best corrected visual acuity (BCVA) appeared stable, and kinetic visual field had no discernible pattern. All patients experienced at least one ocular AE related to surgery, VN, or both. One serious AE occurred (retinal detachment in a child), and was considered related to surgery. Chorioretinal atrophies occurred in four adults and one child, with no impact on FST.
Functional vision, measured in the Streetlab mobility course, demonstrated rapid, sustainable improvements in lower light intensities. Safety data were in line with current knowledge for VN.
这项回顾性真实世界研究评估了视网膜下注射voretigene neparvovec（VN）在法国遗传性视网膜营养不良患者（6名儿童，6名成人）中的有效性和安全性。
收集双侧视网膜下注射VN治疗后一年的病历数据。使用带有障碍物的Streetlab移动课程评估功能性视力。主要结局是治疗后1个月的首选步行速度百分比（PPWS）（在500勒克斯光照下，通过障碍物路线的平均速度占无障碍直线行走4米速度的百分比）。
在2勒克斯光照下，至第1个月PPWS的中位数相对改善为63.9%（四分位间距47.8%；88.5%）。改善持续至第6个月，儿童和成人相当，在7.5勒克斯和50勒克斯时模式相似。在2勒克斯光照下，第1个月时路线完成时间和碰撞次数有所改善。全视野刺激试验（FST）中位数在第1个月时有所改善（-33.2[四分位间距-33.7；-19.8]分贝），改善持续至第24个月。在研究过程中，最佳矫正视力（BCVA）似乎稳定，动态视野无明显变化模式。所有患者至少经历了一次与手术、VN或两者相关的眼部不良事件。发生了1例严重不良事件（一名儿童视网膜脱离），被认为与手术有关。4名成人和1名儿童发生脉络膜视网膜萎缩，对FST无影响。
在Streetlab移动课程中测量的功能性视力在低光照强度下显示出快速、持续的改善。安全性数据与目前关于VN的认识一致。
