Patient Reports Support Retinal Disease Gene Therapy

A doctor in medical protective gloves takes a medicine or vaccine from a glass ampoule into a syringe. concept of treatment and prevention of spread of covid-19 infection, virus and pneumonia.
A doctor in medical protective gloves takes a medicine or vaccine from a glass ampoule into a syringe. concept of treatment and prevention of spread of covid-19 infection, virus and pneumonia.
The study also shows decreases in foveal thickness and no persistent statistically significant vision changes.

A gene therapy improved self-reported vision among patients with retinal pigment epithelium-specific 65 kDa protein (RPE65)-associated retinal disease, according to findings from a multicenter, retrospective, consecutive case series and cross-sectional prospective survey published in Ophthalmology Retina. However, investigators reported no persistent statistically significant changes in vision.

Patients (N=41) who received the therapy voretigene neparvovec-rzyl at 3 tertiary referral centers in the US since the drug’s approval in 2018 were retrospectively reviewed for visual outcomes. In the summer of 2020, these patients were prospectively contacted by telephone and were surveyed about their perception of their visual outcomes.

Patients were mostly children when they received treatment (61%). The patient population had a mean age of 17 (range, 2-44) years at the time of first surgery and 51% were girls or women.

A total of 77 eyes were treated. No cases of intraoperative foveal dehiscence were observed. Postoperative choroidal effusion, endophthalmitis, full-thickness macular hole, and retinal inflammation or detachment did not occur. Complications included postoperative intraocular pressure elevation (n=7), prolonged anterior chamber cells (n=4), sclerotomy leak (n=1), and iatrogenic visually significant cataract (n=1).

The mean follow-up time was 10 months (range, 1 week to 18.5 months).

Mean best corrected visual acuity (BCVA) at baseline was 41.70±18.9 approximate ETDRS letters among the pediatric cohort and 27.4±22.6 approximate ETDRS letters for the adults. At last follow-up, 29% of pediatric and 12% of adult eyes improved by ≥2 lines (P =.15).

Compared with baseline, change in letter score was significantly improved among the pediatric cohort at 2 to 3 (P <.001) and 10 to 15 (P =.004) months. At 1 month, there was a significant age effect for change in letter score (P =.03). Signiant changes to mean visual acuity were not observed.

Mean central foveal thickness (CFT) change decreased significantly at months 1 (P <.001) and 2 to 3 (P =.004) among the pediatric cohort and at months 2 to 3 among adults (P =.04). There was a significant age effect at month 1 (P =.01).

Most patients (78%) were successfully reached by telephone for the survey. The average time since surgery was 1.15±0.50 years for the first eye. Most reported improvement to their night vision (72%), day vision (69%), and color vision (56%). A single individual reported worsening vision in each category. The patients noted that the visual changes occurred during the first 1 to 2 months after therapy with themes of increased brightness, ability to see in dim light, more light sensitivity, and rapid adaptation from light to dark.

This study was limited by its wide range in follow-up time, lack of uniform ancillary testing, the heterogeneous population, and disruption of clinical care due to the COVID-19 pandemic.

These data indicated that after receiving the gene therapy VN for RPE65-associated retinal disease, the most changes to vision occurred soon after therapy and have remained stable in the short term. Pediatric patients tended to have more improvement to vision than adults and most self-reported improved vision.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Sengillo JD, Gregori NZ, Sisk RA, et al. Visual acuity, retinal morphology, and patients’ perceptions after voretigene neparvovec-rzyl for RPE65-associated retinal disease. Ophthalmol Retina. 2021;S2468-6530(21)00378-X. doi:10.1016/j.oret.2021.11.005