Familial Exudative Vitreoretinopathy, or FEVR, is a genetic disorder affecting the eye’s retina. It is characterized by the incomplete development of blood vessels at the edges of the retina, the light-sensitive tissue lining the back of the eye. This condition disrupts normal blood flow, which can lead to leakage from abnormal vessels or the growth of new, fragile ones. The severity of FEVR varies significantly among individuals, even within the same family. Some people may have no symptoms and are only diagnosed during a routine eye exam, while others can experience substantial vision loss.
The Genetic Basis of the Condition
As a “familial” condition, FEVR is caused by mutations in genes responsible for the proper development of the eye’s retinal blood vessels. These genetic alterations disrupt a signaling pathway, known as the Wnt signaling pathway, which orchestrates the formation of these vessels. The inheritance pattern of FEVR can differ, but it most commonly follows an autosomal dominant pattern, where a mutation from just one parent is enough to cause the condition.
FEVR can also be inherited in an autosomal recessive manner, which requires inheriting a mutated gene from both parents. A rarer form is X-linked, associated with a gene on the X chromosome, which typically affects males more severely. Genes implicated in FEVR include LRP5, FZD4, TSPAN12, and NDP. It is also possible for the condition to arise from a spontaneous, new mutation in an individual without any known family history of the disorder.
Clinical Manifestations and Staging
Many individuals with the mildest forms of Familial Exudative Vitreoretinopathy are asymptomatic and may only be identified during a family screening after a relative is diagnosed. When symptoms do occur, they can include diminished vision, misaligned eyes (strabismus), or a whitish reflection in the pupil known as leukocoria. These signs often appear in childhood and prompt an initial visit to an eye specialist. The condition’s progression is categorized into five clinical stages.
Stage 1 is the mildest form, characterized by an incomplete formation of blood vessels in the peripheral retina. In Stage 2, the lack of blood supply can trigger the growth of new, abnormal blood vessels, a process called neovascularization. These new vessels are weak and may leak fluid or bleed.
As the condition advances, Stage 3 involves a partial detachment of the retina, caused by the contraction of scar tissue. Stage 4 is defined by a more extensive retinal detachment that includes the macula, the central part of the retina responsible for sharp, detailed vision. Stage 5 represents a total, funnel-shaped retinal detachment, which can lead to severe vision loss.
The Diagnostic Process
Diagnosing FEVR begins with a comprehensive dilated fundus examination, which allows an ophthalmologist to view the back of the eye, including the retina and its blood vessels. The specialist looks for characteristic signs, such as an avascular periphery, where blood vessels at the retina’s edge have failed to develop.
A more detailed view is achieved through wide-field fluorescein angiography. During this procedure, a dye is injected into a vein in the arm, and a specialized camera takes a series of photographs that highlight the structure of the eye’s vessels. This reveals any areas of leakage, abnormal growth, or regions lacking blood supply. This test is particularly useful for identifying the disease in its early stages and in asymptomatic family members.
Additional imaging techniques like optical coherence tomography (OCT) can provide cross-sectional images of the retina to assess for fluid or structural changes. Ultrasound may be used if the view of the retina is obscured. To confirm the diagnosis and assist with family counseling, genetic testing can identify the specific mutation in genes known to cause FEVR.
Management and Treatment Strategies
The management of FEVR is tailored to the specific stage of the disease and its activity. For individuals with mild, asymptomatic cases, the primary strategy is careful observation. Regular, lifelong monitoring by a retinal specialist is necessary because the condition can progress or become active later in life, even after long periods of stability.
For patients showing active disease, such as the growth of new, leaky blood vessels, laser photocoagulation is a common procedure. A laser is used to treat the avascular portions of the retina, which helps reduce the signals that stimulate abnormal vessel growth and can halt leakage. Cryotherapy, which uses a freezing probe to achieve a similar outcome, may be used as an alternative.
In the more advanced stages of FEVR where retinal detachment has occurred, surgical interventions are required. A scleral buckle procedure involves placing a flexible band around the eye to gently push the eye wall against the detached retina, helping it to reattach. Another surgical technique is a vitrectomy, where the vitreous gel that fills the eye is removed to allow the surgeon to repair the retinal detachment and remove any scar tissue.
Long-Term Outlook and Associated Complications
The long-term prognosis for individuals with FEVR is highly variable and linked to the condition’s severity at diagnosis and the success of treatments. With early detection and timely intervention, vision can often be stabilized, and in many cases, severe vision loss can be prevented. However, FEVR is a lifelong disease that requires ongoing management.
Several complications can arise from FEVR over a person’s lifetime. These include retinal tears and detachments, which can be sudden and require urgent surgical repair. Other potential issues include the development of cataracts, where the lens of the eye becomes cloudy, and glaucoma, a condition characterized by increased pressure inside the eye that can damage the optic nerve. In the most severe cases, these complications can lead to partial or complete vision loss.