Detection of far peripheral retinal vascular changes in von Hippel-Lindau syndrome using widefield fluorescein angiography: The Beijing Rare Eye Disease Study (BREDS)

Abstract Background Von Hippel-Lindau (VHL) syndrome is an autosomal dominant disorder in which retinal hemangioblastomas (RHs) occur in up to 60% of patients and can lead to severe vision loss. While widefield imaging detects more peripheral RHs than conventional methods, the quantitative relationships between peripheral retinal vascular changes and RH characteristics remain unexplored. This study aimed to characterize far peripheral retinal vascular changes in VHL patients using widefield fluorescein angiography (FFA) and evaluate their associations with RH characteristics. Methods In this retrospective study, 63 eyes from 33 genetically confirmed VHL patients who underwent widefield FFA between January 2015 and September 2021 were reviewed. Eyes with prior RH treatment or other chorioretinal diseases were excluded. All patients also underwent conventional seven-field (7SF) color fundus photography. Two masked graders evaluated peripheral capillary leakage, abnormal capillary network (ACN), and nonperfusion. RH number, size, and location were recorded, and detection rates were compared between imaging modalities. Descriptive statistics are presented for all 63 eyes; inferential analyses were restricted to the right eye of each patient ( n = 33) to avoid inter-eye correlation. Results RHs were detected in 68.25% of eyes (43/63), with a total of 109 RHs identified. Only 25 lesions (22.94%) were located within regions covered by conventional 7SF photography, while 84 lesions (77.06%) were situated in the midperipheral to far peripheral retina beyond its reach. Peripheral capillary leakage was present in 22.22% of eyes and was significantly associated with RHs located between the equator and ora serrata ( p = 0.0005). ACN was observed in 4.76% of eyes and nonperfusion in 3.17%, and because of the small number of affected right eyes, these findings are reported descriptively only. Conclusions Widefield FFA reveals peripheral retinal vascular abnormalities associated with RH characteristics. Peripheral capillary leakage correlates selectively with far-peripheral RH location, while ACN and nonperfusion were too rare for statistical analysis. The 77.06% of RHs undetectable by conventional photography underscores widefield FFA’s critical role in comprehensive VHL surveillance, enabling earlier detection of vision-threatening lesions.