Exudative Vitreoretinopathy 3

Description

Familial exudative vitreoretinopathy (FEVR) is an inherited disorder characterized by the incomplete development of the retinal vasculature. Its clinical appearance varies considerably, even within families, with severely affected patients often registered as blind during infancy, whereas mildly affected patients with few or no visual problems may have such a small area of avascularity in their peripheral retina that it is visible only by fluorescein angiography. It is believed that this peripheral avascularity is the primary anomaly in FEVR and results from defective retinal angiogenesis. The sight-threatening features of the FEVR phenotype are considered secondary to retinal avascularity and develop because of the resulting retinal ischemia; they include the development of hyperpermeable blood vessels, neovascularization, vitreoretinal traction, retinal folds, and retinal detachments (summary by Poulter et al., 2010).

For a discussion of genetic heterogeneity of familial exudative vitreoretinopathy, see EVR1 (133780).

Clinical Features

Bamashmus et al. (2000) reported a large 6-generation family segregating autosomal dominant exudative vitreoretinopathy, in which there were 6 affected males and 12 affected females, as well as 2 asymptomatic female obligate carriers. Both males and females exhibited a spectrum of abnormalities ranging from mild to severe, and there were 4 instances of male-to-male transmission. The female proband was first examined for small right convergent squint and mild hypermetropia at 3.5 years of age. At age 7, she had visual acuity of 20/20 in the left eye and 20/40 in the right. However, retinal traction developed by age 7.5 years, with inferior displacement of the right macula and a peripheral retinal mass inferotemporally in the same eye. Bilateral pseudoptosis at age 8 years was suggestive of inferior traction at both maculae, and bilateral retinal folds were present by 9 years of age, with deterioration of visual acuity to approximately 20/100 over the next 2 years. At 15 years of age, she had visual acuity of 20/60 in the right eye but could only count fingers with the left eye. At age 19 years, she was diagnosed as having FEVR without exudation, at which time she exhibited bilateral tractional retinal detachment, which was progressive in the right eye. Following treatment, visual acuity remained stable at 20/30 in that eye over 10 years of follow-up. The proband's older brother had similar retinal traction and recurrent vitreous hemorrhage. Bamashmus et al. (2000) noted great variability in the clinical appearance of FEVR in the patients examined, varying from mild abnormalities of the peripheral retinal vasculature to rapid progression to rhegmatogenous and/or tractional retinal detachment. Overall, the phenotype differed from classic FEVR by the relatively infrequent occurrence of retinal exudation, which was observed in only 4 affected individuals, and the frequent occurrence of holes in the peripheral retina, which was the only finding in 1 obligate carrier.

Downey et al. (2001) restudied the family reported by Bamashmus et al. (2000) and noted that although the affected individuals exhibited the usual variations in expression of disease, defective peripheral vascularization was present in all. Retinal detachment was a frequent finding, as was macular ectopia, with more than half of patients having Snellen acuity of 20/200 or worse in at least 1 eye. The most severely affected family members presented in childhood with poor vision due to macular traction. In addition, Downey et al. (2001) noted that small atrophic peripheral retinal holes were an unusually prevalent feature of the phenotype in this pedigree.

Mapping

Bamashmus et al. (2000) reported a large pedigree with autosomal dominant FEVR in which the EVR1 locus on 11q13-q23 could be excluded. By linkage studies in this family, Downey et al. (2001) mapped the disease locus, which they designated EVR3, to 11p13-p12, approximately 30 cM from the EVR1 locus.