Clinical and Multimodal Imaging Features of Familial Exudative Vitreoretinopathy: The Genetic and Phenotypic Spectrum.

Abstract

Objective: This study aimed to characterize the genetic, clinical, and multimodal imaging findings in a cohort of patients with familial exudative vitreoretinopathy (FEVR).

Methods: This retrospective cross-sectional study included patients diagnosed with FEVR at a tertiary referral center. Clinical findings, fluorescein angiography, optical coherence tomography (OCT), OCT angiography (OCTA), treatment records, and whole-exome sequencing results were reviewed.

Results: A total of 28 patients were included in the analysis, of whom 22 (78.6%) were probands and 6 (21.4%) were family members.Fifteen patients (53.6%) were male and 13 (46.4%) female. Mean age was 11.75±9.63 (2-47) years, with a mean follow-up of 21.57±14.24 (2-50) months. Visual acuity ranged from light perception to 20/20, with a median BCVA of 20/32. Among 56 eyes, mild disease (stage 1-2) was observed in 67.9%, compared with 32.1% for advanced disease (stage 3-5). Genetic variants were identified in 17 patients (60.7%), whereas no disease-associated variant was detected in 11 (39.3%). The most commonly affected genes were FZD4 (21.4%), LRP5 (17.9%), KIF11 (14.3%), TSPAN12 (3.6%), and NDP (3.6%). Clinical manifestations ranged from asymptomatic peripheral vascular anomalies to advanced retinal detachment and severe vision loss. One LRP5-mutant patient exhibited PFV, stage 5 disease, and glaucoma. The four KIF11-mutant cases demonstrated marked phenotypic variability. A FEVR phenotype was also identified in a case with an EPHA2 mutation. OCT, OCT-A, and fluorescein angiography were available in 29 (51.8%), 10 (17.9%), and 27 eyes (48.2%), respectively. Combined imaging revealed posterior pole, vitreoretinal interface, and retinal microvascular abnormalities, including foveal and vitreomacular alterations, that were not fully reflected by stage classification alone. Laser photocoagulation was performed in 26.8% of eyes, combination therapy in 14.2%, and anti-VEGF monotherapy in 1.8%.

Conclusion: FEVR demonstrated marked genetic and phenotypic heterogeneity, while multimodal imaging provided complementary information beyond conventional stage classification.