Optical Coherence Tomography Angiography in Familial Exudative Vitreoretinopathy: Clinical Features and Phenotype-Genotype Correlation

Invest Ophthalmol Vis Sci. 2018 Dec 3;59(15):5726-5734. doi: 10.1167/iovs.18-25377.


Purpose: To evaluate the microstructure of the fovea in patients with familial exudative vitreoretinopathy (FEVR) compared to healthy controls using optical coherence tomography angiography (OCTA).

Methods: In this consecutive, cross-sectional, observational case series, 41 eyes of 41 patients diagnosed as FEVR and 37 eyes in 37 control subjects were studied. OCTA was utilized to automatically measure the foveal avascular zone (FAZ) and the vessel density (VD). Inner retinal thicknesses (IRT) and central retinal thickness (CRT) were measured with the instrument caliper. Targeted next-generation sequencing was performed, and phenotype-genotype association was analyzed.

Results: Small FAZ was found in 31.70% (13/41) FEVR eyes but not in controls. Greater CRT and lower superficial foveal VD were noted in FEVR patients. FAZ is negatively correlated with IRT. Persistence of the inner retinal layer (IRL) in fovea was present in 48.78% (20/41) FEVR eyes but not found in controls. Zero percent (0/10) of patients with the low-density lipoprotein receptor-related protein 5 (LRP5) mutation, 50% (1/2) with the frizzled-4 (FZD4) mutation, and 66.67% (3/4) with the tetraspanin-12 (TSPAN12) mutation had preserved foveal IRL and small FAZ.

Conclusions: Our data indicate FEVR status is associated with a significantly smaller FAZ, decreased vascular density in both the superficial and deep layers of parafoveal area, a thicker fovea, and an abnormally preserved IRL in fovea. In addition, patients with the LRP5 mutation had a milder phenotype than those with the FDZ4 or TSPAN12 mutations. These novel findings could provide insight into the understanding of the pathogenesis of FEVR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Cross-Sectional Studies
  • Eye Diseases, Hereditary / diagnosis*
  • Eye Diseases, Hereditary / genetics*
  • Eye Diseases, Hereditary / physiopathology
  • Familial Exudative Vitreoretinopathies
  • Female
  • Fluorescein Angiography / methods*
  • Fovea Centralis / blood supply
  • Fovea Centralis / pathology
  • Frizzled Receptors / genetics*
  • Genetic Association Studies*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-5 / genetics*
  • Male
  • Retinal Diseases / diagnosis*
  • Retinal Diseases / genetics*
  • Retinal Diseases / physiopathology
  • Retinal Vessels / pathology
  • Tetraspanins / genetics*
  • Tomography, Optical Coherence / methods*
  • Visual Acuity / physiology
  • Young Adult


  • FZD4 protein, human
  • Frizzled Receptors
  • LRP5 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-5
  • TSPAN12 protein, human
  • Tetraspanins