Introduction

Presentation of the results of gene therapy with voretigene neparvovec (Luxturna) in the first four Polish patients with biallelic RPE65 gene mutations causing inherited retinal dystrophies (IRDs).

Material and methods

Four patients (n = 4 eyes) with genetically confirmed biallelic mutations in the RPE65 gene underwent treatment with a single subretinal injection of voretigene neparvovec. The analysis included patients diagnosed with Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) who additionally met the eligibility criteria based on imaging (OCT) results and perimetry tests. Assessments before and after treatment included best-corrected visual acuity (BCVA, logMAR), visual field testing using Goldmann perimetry (VF), and a mobility test conducted at various luminance levels (Multi-Luminance Mobility Test, MLMT). Follow-up visits were conducted at 1 and 7 days, 1 and 3 months (n = 4 eyes), 6 months (n = 3 eyes), 12 months (n = 2 eyes), 18 months (n = 2 eyes), and 42 months (n = 1 eye) after the injection.

Results

The subretinal injections proceeded without intraoperative complications in all cases. A varied response in BCVA was observed, ranging from improvement to stabilization or slight deterioration. In patient P3 (RP), the greatest improvement was observed, with BCVA increasing from 0.3 to 0.12 logMAR after 6 months. Additionally, all patients showed improvement in visual field parameters and enhanced navigational abilities as assessed by the MLMT.

Conclusions

Early experiences with voretigene neparvovec gene therapy in Polish patients with RPE65 gene mutations align with previous clinical studies, demonstrating the therapy’s potential to improve visual function and quality of life, while also revealing variability in treatment response. Gene therapy represents a significant advancement in the treatment of these rare, genetic retinal diseases.