Gene therapy outcomes in young patients with RPE65-retinal degeneration

Area of Science:

• Ophthalmology
• Genetics
• Retinal Diseases

Background:

• Leber's congenital amaurosis (LCA) is a severe inherited retinal dystrophy.
• RPE65 gene mutations cause a significant subset of LCA cases.
• Voretigene neparvovec-rzyl (VN) is an approved gene therapy for RPE65-LCA.

Purpose of the Study:

• To evaluate the safety and efficacy of VN gene therapy in young patients (≤21 years) with RPE65-LCA.
• To report visual acuity, visual field, and retinal sensitivity outcomes in this specific demographic.
• To assess the impact of chorioretinal atrophy on functional outcomes post-treatment.

Main Methods:

• Retrospective review of 18 patients (≤21 years) with biallelic RPE65-LCA treated with VN.
• Mean follow-up duration of 14.8 months.
• Outcomes measured included best-corrected visual acuity (BCVA), Goldmann visual field (GVF), white full-field stimulus test (FSTw), central retinal thickness (CRT), and ellipsoid zone width.

Main Results:

• 100% of patients showed significant improvement in FSTw (retinal sensitivity).
• Improvements in BCVA and GVF were observed in 11% and 39% of patients, respectively.
• Chorioretinal atrophy (CRA) was present in all patients by the last visit; baseline atrophy correlated with poorer outcomes, but inflammation did not affect functional results.

Conclusions:

• VN gene therapy is safe and effective for improving retinal sensitivity in young RPE65-LCA patients.
• The treatment demonstrates positive functional outcomes despite the development of post-treatment CRA.
• VN offers a viable therapeutic option for pediatric and young adult populations with RPE65-LCA.