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Clinical and Genetic Studies of Familial Exudative Vitreoretinopathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00106756
Recruitment Status : Completed
First Posted : March 30, 2005
Last Update Posted : July 2, 2017
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

This study will examine the extent of the vision problem in familial exudative vitreoretinopathy (FEVR) and try to identify the genes responsible for this hereditary eye disorder. Patients with FEVR have incomplete formation of blood vessels in the periphery of the retina (the inner part of the eye that is responsible for vision). As a result, abnormal vessels can form and retinal detachment and vitreous bleeding can occur, causing significant vision loss. Vision loss usually begins in childhood, gradually worsening over time. Some patients eventually become blind.

Patients of all ages with FEVR and their family members may be eligible for this study. Participants undergo the following tests and procedures:

  • Family history, especially regarding eye disease. A family tree is drawn.
  • Blood draw for genetic testing related to FEVR.
  • Eye examination to assess visual acuity (eye chart test) and eye pressure, and to examine pupils, lens, retina and eye movements. The pupils are dilated with drops for this examination.
  • Fluorescein angiography to evaluate the eye's blood vessels. A yellow dye is injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina are taken using a camera that flashes a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality.
  • Patients affected with FEVR will also undergo DEXA scan to look for osteoporosis. X-rays are used to scan the hip, forearm and spine for bone density measurements.

Condition or disease
Exudatiaon Avascular Retina Retina Fold Eye Diseases Familial Exudative Vitreoretinopathy FEVR

Detailed Description:

Background: Familial exudative vitreoretinopathy (FEVR) is a rare hereditary disorder of the retinal vasculature characterized by abrupt cessation of the growth of peripheral retinal capillaries. FEVR seems to exhibit significant phenotypic and genotypic variability but since this is a rare disease the clinical and genetic characteristics of the disease have not been extensively studied so far. Correlation of phenotypes with certain genotypes have not been made yet. Clinical findings can vary from very mild disease with only subtle changes of the peripheral retinal vasculature without symptoms to severe disease with retinal neovascularization, retinal exudates, vitreoretinal adhesions, peripheral vitreous opacities, retinal folds and tractional retinal detachment. The condition remarkably resembles retinopathy of prematurity but affected patients do not have a history of prematurity or supplementary oxygen use.

The disorder is usually inherited as an autosomal dominant trait but few families show x-linked or autosomal recessive inheritance. A significant number of patients with autosomal dominant FEVR show linkage to 11q13-q23 (EVR1). Two genes in this locus have recently been shown to be associated with the disease. FZD4, the gene that encodes for Frizzled-4, the Wnt receptor, is one of them. It has been estimated by recent studies that 20-30% of patients with autosomal dominant FEVR show mutations in FZD4. LRP5 (low-density-lipoprotein receptor-related protein 5), a Wnt co-receptor, was recently shown to be mutated in approximately 15% of cases. One large autosomal dominant pedigree has shown linkage to 11p13-p12 locus (EVR3) and this gene has not yet been identified. It now becomes obvious that more genes are associated with the autosomal dominant type of the disease. Most of the patients with the x-linked type have mutations in the Norrie disease gene (EVR2). The autosomal recessive form of the disease is much rarer and linkage studies have not yet been performed.

Aims: The objectives of this protocol are to study the clinical characteristics of FEVR, and also to assist in identifying the location and sequence of corresponding genes. Since one of the genes so far identified, LRP5, is also causing the osteoporosis-pseudoglioma syndrome, an inherited disorder with severe osteoporosis, we would also like to know if FEVR patients, especially those with mutations in LRP5 also have some degree of osteoporosis. Localization and identification of the responsible gene will help us understand the pathogenesis of FEVR and possibly the mechanism of retinal angiogenesis and lead to potential treatments.

Methods: Patients as well as available family members are to be evaluated by physical examination and fluorescein angiography, in order to clinically characterize the inheritance pattern in each family. Blood will be obtained by all participating subjects for the molecular studies.

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Study Type : Observational
Enrollment : 105 participants
Official Title: Familial Exudative Vitreoretinopathy Clinical and Molecular Studies
Study Start Date : March 18, 2005
Actual Primary Completion Date : November 1, 2006
Actual Study Completion Date : November 1, 2006

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

The patients must carry the clinical diagnosis of familial exudative vitreoretinopathy. Whenever a patient fulfills the above requirement additional family members can be included in the study as participants. Subjects of any ethnic background, gender, age, sexual orientation, or health status will be included.


Prematurity and supplemental oxygen use at bith can cause a clinical picture similar to familial exudative vitreoretinopathy. The existence of either of those factors in the past medical history of a patient will necessitate exclusion from the study. Since fluorescein angiography is crucial for the correct diagnosis of the syndrome, patients with a previous allergic reaction to fluorescein dye will also be excluded. Patients inability or unwillingness to provide a blood sample is an exclusion criterion as well.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00106756

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Izaak Walton Killam Grace Health Centre
Halifax, Canada
United Kingdom
St. James University
Leeds, United Kingdom
Sponsors and Collaborators
National Eye Institute (NEI)
Layout table for additonal information Identifier: NCT00106756    
Other Study ID Numbers: 050104
First Posted: March 30, 2005    Key Record Dates
Last Update Posted: July 2, 2017
Last Verified: June 26, 2009
Keywords provided by National Institutes of Health Clinical Center (CC):
Avascular Retina
Retina Fold
Additional relevant MeSH terms:
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Eye Diseases
Retinal Diseases