Phenotyping and genotyping FEVR: Molecular genetics, clinical and imaging features, and therapeutics

Familial exudative vitreoretinopathy (FEVR) is a genetically complex retinal vascular disorder, often manifesting in infancy or early childhood, and characterized by peripheral retinal avascularity, neovascularization, and retinal detachment. The disease, predominantly inherited in an autosomal dominant manner, is associated with mutations in genes such as LRP5, FZD4, and TSPAN12, which disrupt the Wnt/β-catenin and Norrin signaling pathways, critical for retinal vascular development. FEVR's clinical spectrum ranges from asymptomatic cases to severe vision loss, making early diagnosis and intervention essential for preserving sight. Management strategies include laser photocoagulation, anti-VEGF therapy, and surgery, tailored to disease stage and patient age. The future of FEVR treatment lies in predictive genetics, early screening, and proactive therapy. Ongoing research into the molecular mechanisms of FEVR offers the potential for transforming this progressive disease into a preventable one, improving outcomes for affected individuals.