Supplementary Material for: Chorioretinal atrophy after Voretigene Neparvovec-therapy in RPE65-mutation-associated IRD: Longitudinal characterization in multimodal imaging.

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 aims 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.
Methods: This single-center, prospective cohort study was conducted at the University of Bonn. A total of 21patients 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.
Results: 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 60.50mm²/year[131.20]. Notably, eyes with CRA development had significantly better baseline low luminance visual acuity.
Discussion: 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.

引言：针对RPE65相关遗传性视网膜变性（RPE65-IRD）患者接受维替吉内·内帕韦克（Voretigene Neparvovec，VN）治疗后出现脉络膜视网膜萎缩（CRA）的现象，提示需开展长期监测以深入阐明该基因增补治疗的安全性与有效性。本研究旨在纵向评估VN相关CRA的发生发展、其在多模态视网膜成像中的影像学特征，以及对RPE65-IRD患者视觉功能的潜在影响。
方法：本研究为单中心前瞻性队列研究，于波恩大学开展。共纳入21例经确诊的RPE65-IRD患者，接受视网膜下VN治疗。采用多模态成像技术评估萎缩进展，包括蓝光眼底自发荧光（BAF）、近红外成像（IR）、近红外眼底自发荧光（IRAF）及彩色眼底照相（CFP）。本研究的主要结局指标为CRA的发生率与病灶大小，次要结局指标则包括CRA与视觉功能变化之间的关联。
结果：本研究中CRA的发生率为50%（16/32眼），病灶主要位于黄斑区（86.7%）、注射后隆起区（86.67%）、注射部位（80%）及周边视网膜（80%）。不同成像模态（BAF、IR、IRAF及CFP）对病灶的检出效果及病灶大小评估存在差异，其中BAF成像可检出最大范围的CRA。随访初期，CRA的中位年扩大速率为60.50mm²/年[131.20]。值得注意的是，出现CRA的患眼基线低亮度视力显著更优。
讨论：本研究阐明了多模态成像在监测VN相关CRA中的关键作用。不同成像模态在病灶检出及大小评估方面存在差异，其中BAF成像可显示最大范围的CRA。患者的中位视觉功能保持稳定。上述结果凸显了VN治疗结局的复杂性，提示需采用联合多模态成像技术开展密切监测，以深入阐明该治疗的长期临床意义。