Gene therapy outcomes in young patients with RPE65-retinal degeneration

RPE65-associated Leber's congenital amaurosis (RPE65-LCA) is now treatable with a subretinal injection of voretigene neparvovec-rzyl (VN). Outcomes specific to young patients are not often reported. We present outcomes of young patients ≤21 years old with RPE65-LCA who have received VN.

A single-centre, retrospective review of 18 patients ≤21 years old (mean age: 14.6 ± 3.4 years, 10 females) with biallelic RPE65-LCA treated with VN (mean follow-up: 14.8 ± 7.6 months).

Outcomes studied include best-corrected visual acuity (BCVA), Goldmann visual field (GVF), white full-field stimulus test (FST_w), and central retinal thickness (CRT) and ellipsoid zone width from optical coherence tomography (OCT). Thresholds for significant change were BCVA ≥0.3 logMAR, GVF ≥30%, FST ≥5 dB, and CRT ≥10%.

While significant improvement in BCVA, GVF V4e, and III4e isopters were noted in 11%, 11%, and 39%, respectively, FSTw values improved significantly in 100%. (mean -2.8 ± 1 log, i.e., 256X). Chorioretinal atrophy (CRA) at baseline was observed in 38%, while at the last visit, some CRA was observed in all patients. The presence of nummular and/or perifoveal atrophy at baseline correlated with poorer functional outcomes. Neither postoperative elevated intraocular pressure nor return of inflammation after cessation of steroids affected functional outcomes; however, inflammation was associated with the development of nummular atrophy.

VN treatment is safe and effective in improving retinal sensitivity in patients 21 years old or less with RPE65-LCA despite the occurrence of CRA post-treatment.