Chorioretinal Atrophy after Voretigene Neparvovec Therapy in RPE65 Mutation-Associated Inherited Retinal Disease:...

Introduction: The detection of chorioretinal atrophy (CRA) following voretigene neparvovec (VN) therapy for RPE65-IRD highlights the need for long-term monitoring to better understand the safety and efficacy of this gene augmentation treatment. This study aimed to longitudinally assess the development of VN-associated CRA, its presentation in multimodal retinal imaging, and potential implications on visual function in patients with RPE65-IRD.

This single-center, prospective cohort study was conducted at the University of Bonn. A total of 21 patients with confirmed RPE65-IRD underwent subretinal VN therapy. Multimodal imaging, including blue-light fundus autofluorescence (BAF), near-infrared imaging (IR), near-infrared fundus autofluorescence (IRAF), and color fundus photography (CFP), assessed atrophy development. The primary outcome measure was the incidence and size of CRA, while secondary outcomes included the relationship between CRA and changes in visual function.

The study reported a 50% (16/32 eyes) incidence of CRA, with lesions primarily located in the macula (86.7%), bleb area (86.67%), injection site (80%), and periphery (80%). Lesion detection and size varied between BAF, IR, IRAF, and CFP, with the largest CRA detected in BAF imaging. Initially, the median enlargement rate of CRA was 60.50 mm2/year (131.20). Notably, eyes with CRA development had significantly better baseline low luminance visual acuity.

This study highlights the crucial role of multimodal imaging in monitoring VN-associated CRA. Differences in lesion detection and size assessment across imaging modalities were observed, with the largest CRA extent detected in BAF imaging. Median visual function remained stable. These findings emphasize the complexity of VN therapy outcomes and the need for close surveillance using combined multimodal imaging to better understand the long-term clinical implications.