University Eye Hospital, Center for Ophthalmology, University of Tübingen, Tübingen, Germany; Center for Rare Eye Diseases, University of Tübingen, Tübingen, Germany.
The Vision Center, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California.
Ophthalmology. 2023 Jul;130(7):764-770. doi: 10.1016/j.ophtha.2023.02.015. Epub 2023 Feb 21.
To analyze demographic and ophthalmic data in patients with and without chorioretinal atrophy after voretigene neparvovec-rzyl (VN) to identify possible causes for this phenomenon.
Retrospective cohort study with longitudinal follow-up.
A total of 71 eyes of 38 patients aged 2 to 44 years with RPE65-mediated retinal dystrophy treated with VN across 2 large gene therapy centers in the United States and Germany.
Patients treated with VN who developed atrophy were compared with those who did not.
Gender, age, surgical center, spherical equivalent refraction, best-corrected visual acuity (BCVA), baseline full-field scotopic threshold testing (FST), and posttreatment change in FST.
A total of 20 eyes of 12 patients developed atrophy after treatment with VN (28% of all eyes). There was no significant difference in gender, age, surgical center, or spherical equivalent refraction between the atrophy group and the no atrophy group. However, patients between school age and young adulthood were predominantly affected, whereas the youngest and the oldest patients did not develop atrophy. Baseline BCVA was better in patients who developed atrophy than those who did not (P = 0.006). The postoperative improvement in FST at 1 month was significantly higher in the atrophy group than in the no atrophy group (P = 0.0005), and this difference remained statistically significant at 1 year (P = 0.0001). There was no correlation to baseline FST, to inflammation, or to which eye was treated first.
The degree of FST improvement after VN appears to be strongly correlated with the development of VN-related chorioretinal atrophy. This finding raises the possibility that atrophy may develop as a toxic or metabolic sequela of vector-mediated RPE65 expression. In light of the expanding number of retinal gene therapy clinical trials, this complication warrants further study because it may not be limited to VN.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
分析接受 voretigene neparvovec-rzyl（VN）治疗后出现和不出现脉络膜视网膜萎缩的患者的人口统计学和眼科数据，以确定这种现象的可能原因。
回顾性队列研究，具有纵向随访。
美国和德国的 2 个大型基因治疗中心共对 38 名 2 至 44 岁的 RPE65 介导的视网膜营养不良患者的 71 只眼进行了 VN 治疗。
比较接受 VN 治疗后发生萎缩的患者与未发生萎缩的患者。
性别、年龄、手术中心、球镜等效折射、最佳矫正视力（BCVA）、基线全视野暗适应阈值测试（FST）以及治疗后 FST 的变化。
共有 20 只眼（12 名患者）在接受 VN 治疗后发生萎缩（所有眼中的 28%）。萎缩组与无萎缩组在性别、年龄、手术中心或球镜等效折射方面无显著差异。然而，在校龄和成年早期的患者中，主要受到影响，而最小和最大的患者没有发生萎缩。发生萎缩的患者的基线 BCVA 优于未发生萎缩的患者（P=0.006）。治疗后 1 个月，萎缩组的 FST 改善程度明显高于无萎缩组（P=0.0005），并且在 1 年内仍具有统计学意义（P=0.0001）。与基线 FST、炎症或治疗的哪只眼无关。
VN 后 FST 的改善程度似乎与 VN 相关的脉络膜视网膜萎缩的发展密切相关。这一发现提示，萎缩可能是由于载体介导的 RPE65 表达的毒性或代谢后果而发展。鉴于越来越多的视网膜基因治疗临床试验，这种并发症需要进一步研究，因为它可能不仅限于 VN。
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