Researchers led by Dorothy A. Thompson, PhD, at the Great Ormond Street Hospital for Children at NHS Foundation Trust in London recently studied visual outcomes and complications in children after treatment with the gene therapy voretigene neparvovec (VN, Luxturna; Spark Therapeutics). VN is the first approved gene therapy for severe RPE65-related retinal dystrophy, and in adult trials, improvement in vision was demonstrated using low-luminance visual acuity testing. Because low-luminance tests can pose challenges for pediatric patients, the researchers measured visual outcomes of pattern visual evoked potentials (VEPs), which are objective and require minimal cooperation, in addition to standard measures. The results were published in JAMA Ophthalmology.

The retrospective case series studied 14 pediatric patients with biallelic pathogenic variants in RPE65 who received VN from February 2020 to December 2023 at a single-center, specialist pediatric hospital in the United Kingdom. Ten of those patients were evaluated with posttreatment testing. The study found 7 of 10 patients showed clinically meaningful improvement in pattern VEPs. Patients and their parents also reported subjective measures of visual improvement. Complications included intraoperative retinal schisis in 2 patients, transient intraocular inflammation or localized chorioretinal atrophy or both in nearly half of patients, temporary subretinal inflammatory deposits in 5 patients, injection-site retinal pigment epithelium atrophy in 6 patients, chorioretinal atrophy in 1 patient, and elevated intraocular pressure in 3 patients.

The researchers concluded that the clinically meaningful enhancements in pattern VEPs support the potential of early intervention for development and preservation of visual function in these patients. “We illustrated the difficulties of using existing mixed-acuity testing methodologies in pediatric populations and variable complications such as atrophy and inflammation,” the authors wrote. “The introduction of pattern VEPs as a potentially reliable, reproducible outcome measure addresses a critical gap in assessing pediatric retinal gene therapy, offering a potentially standardized tool for future trials and should be considered for pediatric core outcome sets for gene therapy in [early-onset inherited retinal dystrophies].” RP