Voretigene Neparvovec Gene Therapy in Clinical Practice: Treatment of the First Two Italian Pediatric Patients

Purpose: To present visual outcomes of the first two Italian patients with RPE65-related inherited retinal dystrophy (RPE65-IRD) treated with voretigene neparvovec (VN). Methods: Two pediatric patients with RPE65-IRD were treated with VN in both eyes. Patientswere evaluated by best-corrected visual acuity (BCVA), full-field stimulus threshold (FST) test, semiautomated kinetic visual field (SKVF), microperimetry, and chromatic pupillometry over 6 months. Results: No complications occurred in the first patient, whereas in the second a subretinal hemorrhage was observed in the first treated eye, and excessive resistance to drug injection occurred during treatment of the second eye. BCVA improved by at least one Early Treatment Diabetic Retinopathy Study line in all treated eyes. The FST test and SKVF showed clinically significant improvements in all eyes (i.e., change of light sensitivity > 10 decibels; area enlargement of at least 20%). Moreover, microperimetry showed better fixation stability. Finally, chromatic pupillometry showed increases in pupillary constriction that ranged from 10% to 20%. All visual changes remained stable during follow-up. Conclusions: The first VN treatments in two pediatric Italian patients in clinical practice showed significant improvements in visual outcomes, even in the case of surgical complications, which spontaneously recovered without sequelae. Translational Relevance: These findings with VN in patients with RPE65-IRD confirm the results of clinical trials.