Familial Exudative Vitreoretinopathy (FEVR) is a complex inherited retinal disorder requiring specialized knowledge for effective management. Find a top optometrist or ophthalmologist near you with expertise in genetic retinal conditions.
This page provides detailed information about Familial Exudative Vitreoretinopathy (FEVR), covering its background, clinical features, diagnostic approaches, management strategies, and guidance for patients and families.
Familial Exudative Vitreoretinopathy (FEVR) is a group of inherited retinal disorders marked by abnormal retinal blood vessel development. This condition leads to incomplete vascularization, especially in the peripheral retina, which may cause retinal ischemia and subsequent complications. Early identification is essential for proper management and to preserve vision over a lifetime.
FEVR is an inherited retinal disease characterized by abnormal vessel growth in the peripheral retina. These blood vessels are responsible for supplying oxygen to retinal tissue; when their development is incomplete, the resulting hypoxia can trigger abnormal neovascularization. Over time, this abnormal growth may lead to vitreoretinal traction, subretinal exudation, retinal folds, and even tractional retinal detachments that jeopardize vision.
First described by Criswick and Schepens in 1969, FEVR was noted in families without histories of prematurity or oxygen therapy—a key feature that distinguishes it from retinopathy of prematurity (ROP). Researchers observed organized vitreous membranes and traction on the retina that continued to progress after birth. Over the years, studies by Gow and Oliver and later reports using imaging techniques established a clinical staging system and expanded our understanding of the disease’s progression and genetic implications.
Familial Exudative Vitreoretinopathy is recognized as a genetically heterogeneous disorder, meaning several genes can be involved in its development. Mutations in roughly 11 genes have been associated with FEVR, with known pathogenic variants accounting for about half of all cases worldwide. The genetic inheritance can be autosomal dominant, autosomal recessive, or even X-linked recessive, which explains why affected members in a family might display different levels of severity, from asymptomatic findings to profound vision loss.
Researchers have identified a number of genes associated with FEVR, including:
It is important to note that mutations in these genes account for less than 50% of FEVR cases, suggesting that additional genetic factors remain to be discovered.
The hallmark of FEVR is an incomplete development of the retinal vasculature, particularly affecting the periphery. Insufficient blood supply leads to retinal hypoxia, which in turn stimulates abnormal blood vessel growth in an attempt to provide the needed oxygen. However, these newly formed vessels are fragile, often leaking fluid or blood into the surrounding tissues, and can result in traction and distortion of the retina.
Here’s the thing: the development of the retinal vasculature is a complex process, and when it goes awry, it can mimic patterns seen in other retinal diseases such as ROP. In FEVR, the peripheral retina remains avascular due to incomplete vascularization—a process that is compounded by genetic influences. The subsequent retinal ischemia induces an abnormal neovascular response, often leading to vitreoretinal traction and even the formation of epiretinal membranes. These membranes can distort the retinal layers, as confirmed by optical coherence tomography (OCT) studies that reveal structural abnormalities in the posterior segment.
FEVR can present in many ways, largely due to its variable penetrance. Some individuals may never notice symptoms, while others experience severe visual disturbances at an early age. The clinical signs are often key to distinguishing FEVR from other vitreoretinal diseases.
During a comprehensive retinal examination performed by our retina specialists, several signs may point to FEVR:
Seen as an absence of blood vessels, primarily in the temporal quadrant though it can extend fully around the retina. This area sometimes appears as a “brush-border” demarcation where vascularization stops abruptly.
The retinal arteries and veins may appear displaced, often pulling towards the temporal aspect of the eye, with the macula sometimes following suit.
These are radial, often seen in the periphery and can be a sign of underlying tractional forces on the retina.
The hypoxic areas of the retina stimulate the growth of new, abnormal vessels. These vessels are fragile and can cause complications such as leakage or even hemorrhage.
Fluid leakage from permeable vessels may deposit beneath the retina. In severe cases, massive exudation can mimic other conditions like Coats’ disease.
Both tractional and rhegmatogenous detachments have been observed, particularly in advanced disease.
Some cases exhibit remnants of fetal vasculature, which further complicate the retinal landscape.
Pigment changes may occur in regions associated with chronic avascularity.
Accurate diagnosis of FEVR hinges on thorough clinical evaluation combined with a variety of imaging techniques. With advanced imaging, the subtle findings of FEVR become far more apparent, assisting our retina specialists in determining the stage and severity of the disease.
A careful dilated fundus examination is essential for spotting the typical signs of FEVR. Fluorescein angiography plays a vital role by revealing the extent of capillary nonperfusion and neovascularization, particularly valuable in detecting small vascular anomalies that can be easily missed during a routine exam. This imaging typically shows a characteristic v-shaped avascular zone in the temporal periphery—though in some patients, this may extend around the full circumference of the retina.
Optical coherence tomography helps visualize the microstructures of the retina, providing detailed cross-sectional images of the retinal layers. In cases of FEVR, OCT can reveal:
Showing how the vitreous and retinal interface might be altered.
Evidence of pulling forces on the retina that can lead to detachment.
Indicating disruption in the normal foveal structure.
Which explain some of the visual disturbances experienced by patients.
Recent advances in OCT angiography (OCTA) provide noninvasive imaging of the retinal vasculature. Studies have shown that OCTA can detect smaller changes such as reduced vascular density and subtle tractional forces in the central retina. This noninvasive method is promising in identifying both early and progressive changes in FEVR.
Because FEVR is a genetically complex disorder, genetic testing is often recommended for a firm diagnosis and for screening family members of an affected patient. The identification of specific gene mutations not only confirms the diagnosis but also may alert healthcare providers to other systemic concerns, such as the potential for osteoporosis when mutations involving the LRP5 gene are present. It is worth mentioning that current known mutations account for less than 50% of FEVR cases, meaning a negative test does not rule out the diagnosis.
When evaluating a patient, it is essential to distinguish FEVR from other retinal conditions that may present with similar features. Accurate diagnosis relies heavily on both the clinical history and detailed imaging results.
Our retina specialists compare clinical and imaging findings to differentiate FEVR from conditions such as:
Retinopathy of Prematurity (ROP)
Although both conditions share features like peripheral avascular retina and neovascularization, ROP is typically noted in premature infants with a history of oxygen supplementation. In contrast, FEVR occurs in full-term patients.
This condition is characterized by retinal abnormalities along with systemic findings such as microphthalmia, developmental delays, and even hearing impairments.
Usually affecting one eye in young males, Coats’ disease features retinal exudation but lacks the retinal traction and neovascularization common in FEVR.
Distinguished by significant dermatologic and neurological findings present at birth, making it easier to differentiate from FEVR.
While FEVR can sometimes mimic this sporadic, unilateral condition, genetic testing and bilateral findings help in making the proper diagnosis.
This parasitic infection usually presents with uveitis and is unilateral, which contrasts starkly with the familial and bilateral tendencies seen in FEVR.
Both historical and more recent classification systems have been proposed to understand FEVR’s progression over time. Early systems described three to five stages based on clinical and angiographic findings, while later revisions have incorporated more advanced imaging techniques.
A classic staging system divided the disease progression into several stages:
For personalized guidance and management options for Familial Exudative Vitreoretinopathy, reach out to our experienced retina specialists. Schedule your consultation today to discuss your concerns before significant vision loss occurs!
Avascular peripheral retina with no signs of exudation or abnormal vessel proliferation.
Involves extraretinal vascularization, which can appear with or without exudation.
Characterized by partial retinal detachments with exudative or tractional features.
Represent increasingly severe involvement, including macular displacement and total retinal detachments.
With the advent of wide-field angiography, a revised staging system helps clinicians better characterize the retinal changes observed in FEVR. In this newer framework, the presence of leakage or exudate is carefully documented, and both the extent of avascular zones and neovascularization are used to grade the disease. This system provides a clearer view of the disease status, assisting with the decision-making process for treatment plans.
In many patients, symptoms may not appear during early childhood even though retinal abnormalities are present. The following points outline common progression patterns:
The most active period of progression. In this phase, the avascular areas of the retina can provoke neovascularization and subsequent complications such as tractional retinal detachments or vitreous hemorrhage. Studies have shown that patients diagnosed before age 3 often follow a more severe course.
If FEVR does not progress significantly by early adulthood, the disease can remain relatively stable. However, late-onset complications, including retinal detachments, can occur even after long periods of quiescence.
It is not uncommon for the two eyes to be affected in different ways, which can complicate the clinical picture. In some patients, one eye may present with only subtle findings while the other shows advanced changes.
Given the unpredictable nature of FEVR, regular long-term follow-up is essential. Routine examinations using comprehensive imaging techniques allow our retina specialists to monitor disease stability and intervene at the earliest signs of progression. This careful surveillance is vital, particularly because the range of presentation can be so broad—from subtle, asymptomatic changes in family members to severe, vision-threatening complications in others.
While FEVR is a complex retinal disorder, early and appropriate management can preserve vision and prevent further complications. Treatment strategies are tailored to the stage of the disease and the individual patient’s presentation. Our retina specialists focus on a personalized approach that considers both the retinal findings and the genetic background of the patient.
For patients diagnosed in the early stages of FEVR—especially those with minimal signs or no symptoms—watchful waiting with regular retinal examinations is often the initial course of action. In many cases, early FEVR may not necessitate immediate intervention, although periodic imaging such as fluorescein angiography helps document any evolving changes.
In cases where there is significant peripheral avascular retina with extraretinal neovascularization, laser photocoagulation is a valuable treatment option. By targeting the avascular zones, our retina specialists can help induce regression of abnormal vessels and reduce the leakage that leads to subretinal exudation. This treatment aims to stabilize the retinal environment and prevent the progression to more severe stages.
As FEVR progresses, the risk of tractional and rhegmatogenous retinal detachments increases. For patients with advanced retinal detachment or significant vitreoretinal traction, surgical options such as scleral buckling or pars plana vitrectomy become necessary. These procedures help reattach the retina and relieve the mechanical forces contributing to its distortion. In selected cases, combining surgery with adjunct laser treatment has shown favorable outcomes in achieving retinal stability.
Targeting the abnormal neovascularization pathway, anti-vascular endothelial growth factor (anti-VEGF) injections have been explored as an adjunct in the treatment protocol for FEVR. Although preliminary reports suggest that some patients show regression of neovascularization after a course of anti-VEGF therapy, the response can be variable. In fact, caution is advised since rapid progression of tractional detachment has been observed in certain advanced cases. These findings underscore the need for individualized treatment planning based on precise diagnostic imaging and careful clinical judgment.
Given the genetic heterogeneity of FEVR, genetic testing plays an essential role in confirming diagnoses and guiding treatment decisions. For instance, patients with mutations in the LRP5 gene may require additional evaluations to assess for associated osteoporosis. In such cases, a DEXA scan is recommended, and if necessary, referral to specialists for potential bisphosphonate therapy is made. This holistic approach ensures that all aspects of the patient’s health are addressed in the management plan.
Due to the inherited nature of FEVR, screening family members is an important aspect of overall disease management. Many relatives who may appear asymptomatic can exhibit subtle retinal findings that are only identifiable through detailed examination and advanced imaging such as wide-field fluorescein angiography. Detecting these early changes allows for timely intervention before significant vision loss occurs.
Screening can help identify other family members at risk even if they do not report visual complaints. Since the severity of FEVR can vary significantly within the same family, it is critical to provide guidance and counseling based on individual findings. Genetic counseling is an invaluable resource, offering insights on inheritance patterns and helping families understand the implications of the genetic test results.
Ongoing research continues to uncover new genetic factors and better imaging methods to improve the diagnosis and management of FEVR. As our understanding deepens, several areas of focus include refining staging systems, optimizing laser and surgical techniques, and exploring novel treatment protocols that target the molecular pathways involved in abnormal retinal angiogenesis.
Advances in imaging technologies such as OCT angiography are making it possible to detect and monitor subtle changes earlier than ever before. These tools provide a more complete picture of the retinal vasculature and help our retina specialists devise targeted treatment strategies. Moreover, as genetic research identifies additional mutations associated with FEVR, personalized medicine approaches may become more widely available, offering hope for more effective interventions in the future.
Living with an inherited retinal condition like FEVR can be daunting, and understanding the nuances of the disease is key to managing it effectively. We encourage families with a history of FEVR to seek regular examinations even if visual symptoms are minimal. Early detection and intervention can significantly alter the course of the disease, preserving vision and quality of life.
FEVR is a complex, genetically variable disorder that demands timely intervention and ongoing monitoring by our retina specialists. Regular follow-up, family screening, and individualized management are essential to preserve vision. If you have concerns or a family history of retinal diseases, please contact our office for personalized guidance.
For personalized guidance and management options for Familial Exudative Vitreoretinopathy, reach out to our experienced retina specialists. Schedule your consultation today to discuss your concerns before significant vision loss occurs!
Learn about Familial Exudative Vitreoretinopathy (FEVR), its symptoms, diagnosis, and management options. Find expert care near you.
