Novel objective outcomes to evaluate Voretigene Neparvovec treatment effects in clinical practice

Aim: To assess the efficacy of Voretigene Neparvovec (VN) treatment by objective fixation stability and chromatic pupillometry testing in clinical practice. Design: Retrospective cohort study with longitudinal follow-up. Subjects: Twelve patients (aged 7 to 34 years) with RPE65-related inherited retinal dystrophies were treated at the same center with VN in both eyes. Methods: Patients treated at the same center with VN were evaluated over a 12-month post-treatment follow-up by subjective and objective tests. Furthermore, patients treated with VN who developed atrophy were compared to those who did not. Main outcome measures: Best corrected visual acuity (BCVA), full field stimulus threshold test (FST), semi-automated kinetic visual field (SKVF), microperimetry, and chromatic pupillometry over a 12-month follow-up RESULTS: Significant improvements of BCVA (p<0.001), SKVF (p<0.05) and FST (p<0.001) were already observed 45 days after treatment and were maintained at the 12-month timepoint. Fixation stability, assessed by microperimetry, improved significantly (p<0.05) after treatment. Chromatic pupillometry showed significant improvements (p<0.05) at the 6- and 12-month timepoints. The increase in maximum pupillary constriction significantly (p<0.001) correlated with higher retinal sensitivity in FST. Four patients developed multifocal retinal atrophy in both eyes, detected at the 6-month timepoint, but this atrophy was not generally associated with worse visual function outcomes. Conclusions: This study is the first attempt to demonstrate the efficacy of VN treatment in real life using objective tests in addition to those normally performed in clinical practice. Our findings show a significant improvement of retinal function both in subjective assessments, such as BCVA, SKVF and FST, and in objective measurements of fixation stability and maximum pupillary constriction. Moreover, the significant correlation between maximum pupillary constriction and light sensitivity thresholds corroborates the introduction of chromatic pupillometry as an objective test to better assess treatment outcomes in patients with inherited retinal dystrophies.