Work

Risk Analysis of Retinal Hemangioblastomas in Nonadvanced Stages of von Hippel–Lindau Syndrome Using Ultra-widefield Imaging: The ULTRA von Hippel–Lindau Study

Year: 2025

Type: article

Abstract: Purpose To investigate the longitudinal progression, risk factors, and complications associated with retinal hemangioblastomas (RHs) in non-advanced stages of von Hippel-Lindau (VHL) syndrome using ultra-widefield (UWF) imaging. Design Single-center, longitudinal cohort study. Subjects Caucasian patients with genetically confirmed VHL syndrome. Methods Annual evaluations included dilated fundus examinations, UWF pseudocolor fundus retinal images, UWF fluorescein angiography, and optical coherence tomography. Genetic analysis classified VHL mutations. Baseline RH counts and anatomical distributions were recorded as central (juxtapapillary, macular), peripheral, or both. Longitudinal follow-up tracked new RH formation and visual acuity values. Main Outcome Measures Cumulative incidence, incidence rate ratios (IRRs), and risk factors of new RHs assessed using mixed-effects negative binomial regression models. Hazard of recurrent RHs evaluated through Cox frailty models, and longitudinal changes in visual acuity. Results Among 78 eyes of 43 patients (mean age: 47.8±13.6 years), 110 RHs were documented at baseline, with 3 (3%) centrally located, 35 (32%) peripherally, and 72 (65%) spanning both zones. VHL variants were investigated in 37 patients: 19 had missense variants (51%) and 18 had presumed null alleles (49%), including nonsense (10/37, 27%), frameshift (1/37, 3%), splice-site (1/37, 3%), and exon deletion mutations (6/37, 16%). Over a median follow-up of 31 months (IQR: 27–109), 35 (43%) eyes developed new RHs, with an incidence rate of 0.22 RHs per eye-year (95% CI: 0.17–0.27). By the last available examination, 26 eyes (34%) remained disease-free, while 17 (23%) showed no progression of existing RHs. Age reduced the IRR of new RHs by 4.2% annually (p=0.003), while higher baseline tumor burden and vascular leakage increased the IRR significantly (p<0.001 and p=0.03, respectively). Peripheral RHs were the strongest predictor of recurrence (HR=16.4, p<0.001), while older age remained protective (HR=0.96, p=0.04). Visual acuity (logMAR) worsened from 0.05±0.2 (Snellen equivalent: 20/22) at baseline to 0.11±0.3 (Snellen equivalent: 20/25) at the final visit. Conclusion Peripheral RHs and vascular leakage are significant risk factors for RH progression and recurrence in VHL syndrome. While older age provides a protective effect, close monitoring of high-risk eyes is essential to enable timely intervention and preserve vision.

Source: Ophthalmology Science

DOI: 10.1016/j.xops.2025.100846