Full-field Scotopic Threshold Improvement after Voretigene Neparvovec-rzyl Treatment Correlates with Chorioretinal Atrophy

Abstract

To analyze demographic and ophthalmologic data in patients with and without chorioretinal atrophy after voretigene neparvovec-rzyl (VN) in order to identify possible causes for this phenomenon. Retrospective cohort study with longitudinal follow-up. 71 eyes of 38 patients aged 2 to 44 years with RPE65-mediated retinal dystrophy treated with VN across two large gene therapy centers in the USA and Germany. VN-treated patients who developed atrophy were compared to those who did not. Gender, age, surgical center, spherical equivalent refraction, BCVA, baseline FST, and post-treatment change in full-field scotopic threshold testing (FST). 20 eyes of 12 patients developed atrophy following 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 than 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 following 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 as it may not be limited to VN.