目的:分析有和没有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。
方法:纵向随访的回顾性队列研究。
方法:在美国和德国的两个大型基因治疗中心,用VN治疗38例2-44岁的RPE65介导的视网膜营养不良患者的71只眼。
方法:将发生萎缩的VN治疗患者与未发生萎缩的患者进行比较。
方法:性别,年龄,手术中心,球面等效折射,BCVA,基线FST,和全场暗场阈值测试(FST)的治疗后变化。
结果:12例患者的20只眼在接受VN治疗后出现萎缩(占所有眼的28%)。性别差异无统计学意义,年龄,手术中心,或在萎缩组和无萎缩组之间的球面等效折射。然而,在学龄期和成年期之间的患者主要受到影响,而年龄最小和年龄最大的患者没有出现萎缩。发生萎缩的患者的基线BCVA优于未发生萎缩的患者(P=0.006)。术后1个月FST改善明显高于无萎缩组(P=0.0005),而这一差异在1年时仍有统计学意义(P=0.0001).与基线FST无相关性,炎症,或者先治疗哪只眼睛。
结论:VN后FST改善的程度似乎与VN相关脉络膜视网膜萎缩的发展密切相关。这一发现增加了萎缩可能发展为载体介导的RPE65表达的毒性或代谢后遗症的可能性。鉴于视网膜基因治疗临床试验的数量不断扩大,这种并发症值得进一步研究,因为它可能不限于VN.
OBJECTIVE: 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.
METHODS: Retrospective cohort study with longitudinal follow-up.
METHODS: 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.
METHODS: Patients treated with VN who developed atrophy were compared with those who did not.
METHODS: Gender, age, surgical center, spherical equivalent refraction, best-corrected visual acuity (BCVA), baseline full-field scotopic threshold testing (FST), and posttreatment change in FST.
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: Proprietary or commercial disclosure may be found after the references.