Overview
Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder of retinal vascular development characterized by incomplete vascularization of the peripheral retina, leading to fibrovascular proliferation, exudation, and in severe cases retinal detachment and blindness. It closely resembles retinopathy of prematurity but occurs in full-term infants. Severity ranges from asymptomatic peripheral avascularity to total retinal detachment in early childhood.
Genetics
FEVR is caused by mutations in genes of the Norrin/Wnt signaling pathway. Multiple inheritance patterns. FZD4 and LRP5 are most common.
| Gene | Locus | Inheritance | Notes |
|---|---|---|---|
| FZD4 | 11q14.2 | AD/AR | Frizzled-4 receptor; most common AD cause |
| LRP5 | 11q13.2 | AD/AR | LDL receptor-related protein 5; also causes osteoporosis-pseudoglioma |
| NDP | Xp11.3 | X-linked | Norrin; X-linked FEVR (allelic with Norrie disease) |
| TSPAN12 | 7q31.31 | AD | Tetraspanin-12; Norrin/Wnt co-receptor |
| ZNF408 | 11p11.2 | AD | Zinc finger protein; rare cause |
Clinical Presentation
Mild (Stage 1–2)
- Asymptomatic peripheral avascularity
- Peripheral fibrovascular ridge
- Found incidentally on screening
Moderate (Stage 3)
- Exudation
- Tractional changes
- Reduced visual acuity
Severe (Stage 4–5)
- Partial or total retinal detachment
- Leukocoria
- Blindness if untreated
Diagnosis
- Fluorescein angiography (FA): Peripheral avascular retina with leakage — gold standard
- RetCam/wide-field imaging: Essential for infant screening
- Genetic testing: FEVR gene panel (FZD4, LRP5, NDP, TSPAN12)
- Family screening: All first-degree relatives should be examined
Current Research & Treatment
Treatment is primarily surgical (laser photocoagulation, cryotherapy, vitrectomy for detachment). Anti-VEGF therapy is used off-label for exudation. Gene therapy targeting the Norrin/Wnt pathway is in preclinical development.
Active Clinical Trials
The following active clinical trials are investigating treatments for Familial Exudative Vitreoretinopathy. Trial status and enrollment may change; always verify directly on ClinicalTrials.gov.