Abstract
Purpose :
Voretigene neparvovec (VN) is the first approved ocular gene therapy for patients with RPE65-mediated inherited retinal dystrophy. While improvement in visual function after treatment with VN have been described, limited quantitative objective evaluations test are available. Here, long-term safety and effectiveness of VN in a real-world setting evaluated are reported.
Methods :
This study includes a comprehensive review of all consecutive patients treated, at a single site, with VN with at least one year follow-up after treatment. The treatment effects were assessed using best-corrected visual acuity (BCVA), full-field stimulus threshold test (FST), semi-automated kinetic visual field (SKVF), chromatic pupillometry and color fundus imaging.
Results :
Twelve patients were treated bilaterally with VN at a mean age of 13.5 ± 7.9 years. The 12-month follow-up, compared to baseline, showed a significant improvement in BCVA (-0.21 ± 0.14; p-value <0.001) and white light sensitivity thresholds evaluated with FST (-26.3 ± 10.7, p-value<0.001). Moreover, we observed a significant enlargement of SKVF area using I4e (1921.7 ± 3247.3°2; p-value=0.011) and III4e (2478 ± 3659.7°2; <0.001). Chromatic pupillometry showed statistically significant improvements (p-value<0.05) of maximum pupillary constriction in response to blue and white stimulus at 10 lux level. We observed a significant (p-value<0.01) relationship between improvements of sensitivity threshold and maximum pupillary constriction at 10 Lux both with white and blue light. Retinal atrophy after treatment with VN was observed bilaterally in four (25.0%) patients at the 6-month timepoint. Retinal atrophy was not associated with worst treatment effects, except for SKVF with I4e stimulus size that showed a significantly lower improvement in eyes developing retinal atrophy compared to those without retinal atrophy (159.9 ± 1309.9°2 vs. 2802.6 ± 3589.6°2; p-value=0.033).
Conclusions :
Our findings showed significant improvements in visual outcomes, even in the case of retinal atrophy, after VN treatment. Moreover, our results show, for the first time, the usefulness of chromatic pupillometry as an objective outcome measurement to evaluate treatment effects in patients with inherited retinal dystrophies.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.