Abstract
PurposeTo present visual outcomes of the first two Italian patients with RPE65-related inherited retinal dystrophy (RPE65-IRD) treated with voretigene neparvovec (VN).MethodsTwo pediatric patients with RPE65-IRD were treated with VN in both eyes. Patients were 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.ResultsNo 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.ConclusionsThe 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 RelevanceThese findings with VN in patients with RPE65-IRD confirm the results of clinical trials.
Highlights
Biallelic mutations in RPE65 are associated with severe, rod-mediated inherited retinal dystrophy, which presents as night blindness in early childhood that eventually progresses to complete blindness.[1,2,3] In 2008, gene therapy with unilateral injection of the recombinant adenoviral vector voretigene neparvovec (VN) in three patients with RPE65-related inherited retinal dystrophy (RPE65-IRD) was performed, and improvements in visual function were noted.[4]
Patients were 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
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
Summary
Biallelic mutations in RPE65 are associated with severe, rod-mediated inherited retinal dystrophy, which presents as night blindness in early childhood that eventually progresses to complete blindness.[1,2,3] In 2008, gene therapy with unilateral injection of the recombinant adenoviral vector voretigene neparvovec (VN) in three patients with RPE65-related inherited retinal dystrophy (RPE65-IRD) was performed, and improvements in visual function were noted.[4] Following phase 1 and 2 trials, an open-label, randomized, controlled phase 3 trial was carried out in 31 patients with RPE65IRD.[5] After 1 year, improvements were seen in light sensitivity and visual fields, as well as navigational ability under dim lighting conditions Based on these results, in 2017 VN was approved by the US Food and Drug Administration for treatment of patients with RPE65-IRD and in 2018 by the European Medicines Agency for the same indication. There is little experience in clinical practice with VN in treatment of RPE65-IRD, and outcomes and surgical techniques in only small numbers of patients have been reported.[6,7,8] we present visual outcomes of the first two Italian patients with RPE65-IRD treated with VN
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