Familial exudative vitreoretinopathy (FEVR, pronounced as fever) is a

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders ...

affecting the growth and development of

blood vessels Blood vessels are the tubular structures of a circulatory system that transport blood throughout many animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the tissues of a body. They also take waste an ...

in the

retina The retina (; or retinas) is the innermost, photosensitivity, light-sensitive layer of tissue (biology), tissue of the eye of most vertebrates and some Mollusca, molluscs. The optics of the eye create a focus (optics), focused two-dimensional ...

of the eye. This disease can lead to visual impairment and sometimes complete blindness in one or both eyes. FEVR is characterized by incomplete vascularization of the peripheral retina. This can lead to the growth of new blood vessels which are prone to leakage and

hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, ...

and can cause retinal folds, tears, and detachments. Treatment involves laser photocoagulation of the avascular portions of the retina to reduce new blood vessel growth and risk of complications including leakage of retinal blood vessels and

retinal detachment Retinal detachment is a condition where the retina pulls away from the tissue underneath it. It may start in a small area, but without quick treatment, it can spread across the entire retina, leading to serious vision loss and possibly blindness. ...

Pathophysiology

FEVR is caused by genetic defects involving the regulation of blood vessel growth in developing eyes. As a result, there is poor blood vessel growth to the periphery of the retina. The lack of blood supply to the peripheral retina triggers the release of molecules that stimulate blood vessel growth, such as

vascular endothelial growth factor Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors ...

(VEGF). However, this new blood vessel growth, also known as

neovascularization Neovascularization is the natural formation of new blood vessels ('' neo-'' + ''vascular'' + '' -ization''), usually in the form of functional microvascular networks, capable of perfusion by red blood cells, that form to serve as collateral circu ...

, can lead to further complications such as the leakage and hemorrhage of retinal blood vessels, retinal tears, and detachments.

Genetics

There have been several gene mutations associated with FEVR. These genes code for proteins involved in the

WNT signaling pathway In cellular biology, the Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt, pronounced "wint", is a portmanteau created from the ...

, which is involved in the development of the human eye and regulation of blood vessel growth. Depending on the genes involved, FEVR can follow an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

, or

X-linked Sex linkage describes the sex-specific patterns of inheritance and expression when a gene is present on a sex chromosome (allosome) rather than a non-sex chromosome ( autosome). Genes situated on the X-chromosome are thus termed X-linked, and ...

inheritance pattern. There is varying

penetrance Penetrance in genetics is the proportion of individuals carrying a particular variant (or allele) of a gene (genotype) that also expresses an associated trait (phenotype). In medical genetics, the penetrance of a disease-causing mutation is the pr ...

and expressivity depending on the genes involved. While

genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

may be useful in the diagnosis of FEVR, a negative genetic test does not rule out the disease.

Diagnosis

Human_eye_cross-sectional_view_grayscale

Diagnosis of FEVR is often made through direct visualization of the retina and

fluorescein angiography Fluorescein angiography (FA), fluorescent angiography (FAG), or fundus fluorescein angiography (FFA) is a technique for examining the circulation of the retina and choroid (parts of the fundus) using a fluorescent dye and a specialized camera. ...

, along with personal and family medical history. Hallmark characteristics of FEVR include lack of blood vessels in the peripheral retina. Other findings may include vessel and macular dragging, sub-retinal exudates, neovascularization, retinal folds, and retinal detachments. FEVR must be differentiated from other diseases involving incomplete vascularization of the retina including

retinopathy of prematurity Retinopathy of prematurity (ROP), also called retrolental fibroplasia (RLF) and Terry syndrome, is a disease of the eye affecting prematurely born babies generally having received neonatal intensive care, in which oxygen therapy is used beca ...

(ROP),

Norrie disease Norrie disease is a rare X-linked recessive genetic disorder that primarily affects the eyes and almost always leads to blindness. It is caused by mutations in the Norrin cystine knot growth factor gene, also referred to as Norrie Disease Pseudog ...

, Coat's disease, and others. Severity of disease is highly variable and can range from mild visual impairment to complete vision loss. Based on the severity of the disease, FEVR is diagnosed based on a clinical staging scale from 1 to 5. Since FEVR often runs in families, immediate relatives of someone diagnosed with FEVR should be examined by an ophthalmologist because the disease can have no symptoms before complications arise including retinal detachments.

Treatment

Treatment is largely aimed at reducing the amount of new blood vessel growth and preventing complications that may arise as a result, including retinal tears and detachments. Using a laser, an ophthalmologist burns the portions of the retina that are not supported by blood vessels, a technique known as laser photocoagulation. By doing so, this tissue will no longer release molecules that stimulate blood vessel growth. If a retinal detachment occurs, laser therapy or

surgery Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...

may be required to repair the retina. Photocoagulation

References

External links

GeneReviews/NCBI/NIH/UW entry on Familial Exudative Vitreoretinopathy, Autosomal Dominant

NCBI Genetic Testing Registry
{{Other cell membrane protein disorders Blindness Disorders of choroid and retina