Familial Exudative Vitreoretinopathy (FEVR) is a disease affecting the retinal blood vessels, characterized by the failure of retinal capillaries to develop during the last few months of intrauterine life. In genetic terms, it is a heterogeneous disorder. Several modes of transmission have been described and several responsible genes have been identified. As far as phenotype is concerned, FEVR is also very variable and the severity of the disease can vary greatly within a single family. The prognosis is favorable for minor forms of the disease, with treatment by laser photocoagulation and appropriate monitoring. The prognosis for severe forms of the disease is more guarded, despite the frequent stabilization of lesions by surgery.
FEVR is a rare disease of unknown frequency.
Several modes of transmission have been described – autonomic dominant, X-related recessive and autonomic recessive. At present, a number of genes have been identified i.e. the Norrie disease gene (NDP) which is transmitted in an X-related recessive pattern, the FZD4 gene (Wnt receptor pair, frizzled 4) with autonomic dominant transmission and the LRP5 gene with autonomic dominant or autonomic recessive transmission. These last two genes are located on chromosome 11. They encode for proteins which, like the Norrie protein, are thought to interact with the Wnt receptors and play an important role in the development of retinal vascularisation.
Sporadic forms have also been reported.
In clinical terms, this disease closely resembles the retinopathy of premature babies but there is no notion of prematurity or low birth weight in affected patients and an examination of other members of the family confirms the familial origin of the disease. In the minor forms, there is a shutdown of retinal vascularisation in the equatorial temporal area. The retinal vessels form anastomoses and shunts at the edge of the avascular area. The superior and inferior temporal vessels (arteries and veins) follow an abnormally straight pathway between the papilla and the temporal periphery. They tend to form an acute angle at the output from the papilla and, beyond the macula, their branches stretch towards the peripheral temporal region. Moreover, there are often vitreous condensations attached to the stretched temporal vessels. These minor forms are usually asymptomatic and the peripheral vascular abnormalities remain relatively small. They are revealed by a careful examination of the fundus and more especially by fluorescein angiography.
At a more advanced stage, new vessels form between the equator and the ora serrata, a projecting fibrovascular membrane on the edge of the temporal area, covered with thick vitreous condensation. Intra- and sub-retinal exudates are sometimes observed at the posterior pole and on the periphery of the retina. These fibrovascular lesions exert tractions on the large vessels in the posterior pole and this can lead to macular ectopia and, in some cases, give to the papilla a stretched appearance. At this stage, there is some loss of visual acuity.
Among the complications is retinal detachment, which may be rhegmatogenic, linked to the traction exerted on the retina and vitreous; or exudative. At worst, there is neovascularised fibrosis of the entire vitreous cavity responsible for total retinal detachment. In the severest forms of the disease, there are abnormalities in the anterior segment e.g. cataract, posterior synechiae, band-shaped keratitis or even neovascular glaucoma. These serious forms of the disease are responsible for dense amblyopia during the second decade of life. Development is typically asymmetrical in the two eyes.
No other associated systemic disease has been described.
In minor forms, it is used to allow for a diagnosis. In all cases, it reveals the abnormal perfusion of the anterior retina. The typical appearance corresponds to a shutdown of blood circulation in the equatorial temporal area, associated with leakage of the dye on the abnormal capillary edge, marking out the perfused and non-perfused areas of the retina. There are shunt vessels here and abnormal vascular tortuosity. In some cases, there is also hyperfluorescence of the papilla and slight perimacular diffusion.
In the more advanced forms, neovessels fan out along the vascularised retina and there is a build-up of dye in the temporal fibrovascular masses.
The lesions are usually asymmetrical in the same patient. Because of this, the disease may evolve very slowly in one eye and may even appear to have stabilized before the age of 20. It may also be very severe, and develop rapidly in the other eye, sometimes leading to total retinal detachment in childhood. The severity and development of the lesions also vary greatly within a single family. The main complication of this disease is retinal detachment. The risk is higher in minor forms compared to the risk observed in the general population. It is a rhegmatogenic retinal detachment. In the absence of treatment, the severe forms of the disease may lead to tractional and exudative retinal detachment because of the intraocular changes secondary to the preretinal and intraviterous fibrovascular proliferations. The development of the disease in severe forms may also include episodes of vitreous hemorrhage.
Treatment generally consists in destroying the peripheral vascular abnormalities by laser photocoagulation to decrease exudation and limit fibrous proliferation. This, in turn, prevents progress towards complications. The treatment of complications (retinal detachment) is surgical.
Monitoring of the fundus in high-risk patients is essential.