Familial Exudative Vitreoretinopathy (FEVR)

Introduction and History

Familial Exudative Vitreoretinopathy, or FEVR, is a rare genetic eye condition that affects the development of blood vessels in the retina, whereby the blood vessels at the edges of the retina don’t form properly. This can lead to a lack of blood supply and oxygen, causing the growth of new, abnormal blood vessels. These weak vessels can leak fluid (exudate) or bleed, sometimes leading to the formation of scar tissue, retinal detachment (where the retina pulls away from the back of the eye), and vision loss.

FEVR is “familial,” meaning it can be passed down through families. However, the severity of FEVR can vary significantly, even among family members. Some people may exhibit no symptoms, while others may experience severe vision problems.

FEVR was first identified and described as a distinct eye disease in 1969 by doctors Criswick and Schepens. They observed a pattern of abnormal retinal blood vessel development in several families, distinct from other known eye conditions.

Who Is Affected?

FEVR is a rare condition, and its exact frequency isn’t precisely known, partly because mild cases may go undiagnosed. It affects both males and females, though the pattern of inheritance can differ depending on the specific gene involved. FEVR can occur in people of all racial and ethnic backgrounds. Because it’s a genetic condition, individuals with a family history of FEVR are at a higher risk. The age at which FEVR is discovered can vary from early infancy to adulthood, though symptoms often begin in childhood.

Diagnosis

Diagnosing FEVR involves a careful eye examination by an ophthalmologist (eye doctor), often a specialist in retinal diseases. The doctor will look for characteristic signs in the retina, such as:

• Avascular periphery: Areas at the edge of the retina where blood vessels haven’t developed.
• Dragged vessels: Retinal blood vessels that appear stretched or pulled out of place.
• Exudates: Leaky fluid from abnormal blood vessels.
• Neovascularization: Growth of new, abnormal blood vessels.
• Retinal folds (Figure) or detachments.

A key diagnostic test is wide-field fluorescein angiography, which highlights any abnormalities, such as missing vessels or leakage. Genetic testing can also help confirm the diagnosis by identifying mutations in genes known to cause FEVR, such as FZD4, LRP5, TSPAN12, and NDP. Examining family members can also be important.

Treatment

Treatment for FEVR aims to prevent the disease from worsening and to preserve vision. The specific treatment depends on how severe the condition is:

• Observation: Mild cases with no vision problems may only need regular monitoring.
• Laser Photocoagulation: This is a standard treatment that uses a laser to treat avascular (lacking blood vessels) areas of the retina. This can help prevent abnormal blood vessels from growing and leaking.
• Anti-VEGF Injections: Medications called anti-vascular endothelial growth factor (anti-VEGF) drugs can be injected into the eye.^1. These drugs help to reduce the growth of abnormal blood vessels and decrease leakage.
• Surgery (Vitrectomy and/or Scleral Buckle): If FEVR leads to significant bleeding in the vitreous (the gel-like substance filling the eye) or causes a retinal detachment, surgery may be needed. A vitrectomy removes the vitreous gel and any blood or scar tissue. Sometimes a scleral buckle, a tiny silicone band, is placed around the eye to support the retina.

Prognosis

The outlook for individuals with FEVR varies greatly. With early diagnosis and timely treatment, vision can often be stabilized, and severe vision loss can be prevented in many cases. However, FEVR is a lifelong condition and can sometimes progress despite treatment, especially in more severe forms. Some individuals may experience significant vision impairment. Regular follow-up appointments with an eye doctor are crucial for monitoring the condition.

Current Research

Researchers are working diligently to gain a deeper understanding of FEVR and develop new treatments. Current research focuses on:

• Genetics: Identifying more genes that cause FEVR and understanding how these genes affect retinal development. This could lead to better genetic counseling and potentially gene-based therapies in the future.
• Improved Imaging and Diagnosis: Developing more advanced ways to see and assess the retinal changes in FEVR.
• New Medications: Investigating new drugs that could more effectively stop abnormal blood vessel growth or promote normal vessel development. One such area involves drugs that mimic a naturally occurring protein called norrin, which is crucial for the formation of healthy retinal blood vessels.
• Surgical Techniques: Refining surgical methods to improve outcomes for retinal detachments and other complications.

Continued research holds promise for even more effective ways to manage FEVR and preserve the vision of those affected.

References

1. Criswick, V. G., & Schepens, C. L. (1969). Familial exudative vitreoretinopathy. American Journal of Ophthalmology, 68(4), 578–594.
2. Orphanet: Familial exudative vitreoretinopathy. (Consult an up-to-date version on www.orpha.net)
3. MedlinePlus Genetics: Familial exudative vitreoretinopathy. (Consult an up-to-date version on medlineplus.gov/genetics)
4. Drenser Ranchod TM, Ho LY, Drenser KA, Capone A Jr, Trese MT. Clinical presentation of familial exudative vitreoretinopathy. Ophthalmology. 2011 Oct;118(10):2070-5.
5. Cicerone AP, Dailey W, Sun M, Santos A, Jeong D, Jones L, Koustas K, Drekh M, Schmitz K, Haque N, Felisky JA, Guzman AE, Mellert K, Trese MT, Capone A, Drenser KA, Mitton KP. A Survey of Multigenic Protein-Altering Variant Frequency in Familial Exudative Vitreo-Retinopathy (FEVR) Patients by Targeted Sequencing of Seven FEVR-Linked Genes. Genes (Basel). 2022 Mar 11;13(3):495.