ExudatiaonNCT00106756
Clinical and Genetic Studies of Familial Exudative Vitreoretinopathy
An observational study of Exudatiaon and Avascular Retina, run by National Eye Institute (NEI) at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Exudatiaon, Avascular Retina, Retina Fold
- How many people
- 105 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 18 Mar 2005to 1 Nov 2006
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Familial Exudative Vitreoretinopathy Clinical and Molecular Studies
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.
Read the 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.
- Conditions
- Exudatiaon, Avascular Retina, Retina Fold, Eye Diseases, Familial Exudative Vitreoretinopathy, FEVR
- Keywords
- Exudation, Avascular Retina, Retina Fold
- Medical subject headings
- Eye Diseases, Familial Exudative Vitreoretinopathies
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2005 (estimated)
- Study start18 Mar 2005
- Primary completion1 Nov 2006
- Study completion1 Nov 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ExudatiaonStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 105 participants
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00106756
- Sponsor's protocol ID
- 050104
- Other IDs
- 05-EI-0104
- Status last verified
- 26 Jun 2009
- First submitted
- 29 Mar 2005
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Criswick VG, Schepens CL. Familial exudative vitreoretinopathy. Am J Ophthalmol. 1969 Oct;68(4):578-94. doi: 10.1016/0002-9394(69)91237-9. No abstract available.
PubMed 5394449Gow J, Oliver GL. Familial exudative vitreoretinopathy. An expanded view. Arch Ophthalmol. 1971 Aug;86(2):150-5. doi: 10.1001/archopht.1971.01000010152007. No abstract available.
PubMed 5571414Laqua H. Familial exudative vitreoretinopathy. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1980;213(2):121-33. doi: 10.1007/BF00413539.
PubMed 6906151
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Familial Exudative Vitreoretinopathy Clinical and Molecular Studies
- ClinicalTrials.gov ID
- NCT00106756
- Acronym / sponsor ID
- 050104
- Conditions
- Exudatiaon, Avascular Retina, Retina Fold, Eye Diseases, Familial Exudative Vitreoretinopathy, FEVR
- Keywords
- Exudation, Avascular Retina, Retina Fold
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 105 participants
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- 18 Mar 2005
- Primary completion
- 1 Nov 2006 (actual)
- Study completion
- 1 Nov 2006 (actual)
- First posted
- 30 Mar 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 5394449Criswick VG, Schepens CL. Familial exudative vitreoretinopathy. Am J Ophthalmol. 1969 Oct;68(4):578-94. doi: 10.1016/0002-9394(69)91237-9. No abstract available.
- Background: PubMed 5571414Gow J, Oliver GL. Familial exudative vitreoretinopathy. An expanded view. Arch Ophthalmol. 1971 Aug;86(2):150-5. doi: 10.1001/archopht.1971.01000010152007. No abstract available.
- Background: PubMed 6906151Laqua H. Familial exudative vitreoretinopathy. Albrecht Von Graefes Arch Klin Exp Ophthalmol. 1980;213(2):121-33. doi: 10.1007/BF00413539.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Exudatiaon and Avascular Retina, run by National Eye Institute (NEI) at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00106756, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.