Chorioretinal atrophy after gene therapy with Voretigene Neparvovec-Rzyl (Luxturna) for RPE65-Mediated Retinal Degeneration: a Review

The primary objective of this review is to evaluate the occurrence of chorioretinal atrophy (CRA) following treatment with Voretigene Neparvovec-Rzyl (VN), commercially available as "Luxturna," in patients with RPE65-related retinal dystrophies. It emphasizes the prevalence and impact of CRA and offers new guidelines regarding predisposing factors for candidates undergoing VN treatment, as well as suggesting modifications in patient selection and drug administration to prevent its development. The evaluation was carried out by searching relevant articles concerning Luxturna in PubMed and the Cochrane Database. All studies reporting CRA as an adverse effect of therapy in both adult and pediatric patients were included. Quantitative data were analyzed using the Excel Data Analysis ToolPak. The data indicate that, following VN treatment, 26.3% of eyes developed atrophy at some stage, with atrophy typically first observed three months post-treatment. The most common type of atrophy observed is touchdown atrophy at the injection site, while the second most common involves the development of more than one type of atrophy within the same eye. Perifoveal and nummular atrophy are also common types of atrophy. Touchdown atrophy exhibits the lowest growth rate, whereas mixed atrophy shows the highest expansion rate. Factors related to the surgeon, properties of the vector used for injection, and ocular conditions such as inflammation induction and immune activation have been identified as potential mechanisms contributing to CRA. The impact of CRA on functional vision remains inadequately documented in the literature. Nonetheless, certain factors can be avoided or corrected during the surgical procedure or prior to it. It remains essential to conduct further research on predisposing factors and post-treatment visual outcomes to establish comprehensive guidelines and enhance the safety of the procedure.