Best Vitelliform Macular Dystrophy

Disease Overview

Best vitelliform macular dystrophy (BVMD) is a genetic form of macular degeneration (damage to a part of the eye called the macula) that occurs in about 1 in 10,000 individuals. The physical cause of BVMD is breakdown of the tissue in the retina called retinal pigment epithelium (RPE). The condition gets worse over time, starting with blurred central vision, and possibly leading to complete loss of central vision. Peripheral vision (vision from the sides of the eye) and the ability of the eye to adjust to dark are unaffected. The age of onset of BVMD can vary. Many individuals with BVMD have symptoms in childhood or early adulthood. BVMD is associated with a harmful genetic change (mutation) in the BEST1 gene. There is no cure for BVMD, although some treatments and medications exist that can minimize the damage caused by breakdown of the RPE including anti-VEGF therapy (medicine used to prevent growth of new blood vessels in the eye), laser photocoagulation (laser treatment used to destroy leaky blood vessels), and photodynamic therapy (a combination of medicine and laser treatment used to get rid of bad eye cells).

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Synonyms

• Best macular dystrophy
• Best disease
• vitelline dystrophy
• vitelliruptive degeneration
• macular degeneration, polymorphic vitelline
• vitelliform macular dystrophy, early-onset
• vitelliform macular dystrophy, juvenile-onset
• vitelliform macular dystrophy, type 2

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Signs & Symptoms

BVMD has an average age of onset between age 5 and 10 but can vary from person to person. Affected individuals initially have normal vision and then experience blurred vision, reduced sharpness or clarity of vision or the appearance of objects that have a distorted shape (metamorphosia). BVMD affects central vision but usually not peripheral vision and varies in severity.

Some people with the disorder do not notice a decline in vision and may be diagnosed in passing from a routine eye exam. Others experience significant loss of vision, which can occur because of the formation of blood vessels under the macula and retina (choroidal neovascularization). The degree of visual loss can be different in each eye. Most individuals with BVMD have one eye more severely affected than the other and can continue to perform daily tasks such as driving well into the later decades of life.

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Causes

The macula is the region of the retina that contains the light-sensing cells necessary for central vision. Individuals with BVMD develop a yellowish material under the macula that resembles an egg yolk (vitelliform means yolk-like). This material eventually breaks up and spreads throughout the macula, leading to a reduction in central vision. Lipofuscin, a chemical made by the body, makes up this yolk-like material.

BVMD is inherited as an autosomal dominant genetic condition and is usually associated with the mutations in the BEST1 gene. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent. It can also occur as a new gene change in the affected individual. Most individuals affected with BVMD have an affected parent. The chance of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.

When working normally, the BEST1 gene acts as a gate to help move chemicals between cells in the retina. When this “gate” isn’t working properly, this can cause the build up of fluid and lipofuscin in the retinal tissue. Because BVMD is a progressive condition, there are different stages that are recognized.

• vitelliform stage (stage 1): The stage most commonly seen in new diagnoses of BVMD. In this stage, the macula has the characteristic pocket of yellow-material that can be seen upon examination.
• pseudohypopyon stage (stage 2): The pocket of yellow material moves towards the bottom of the eye. This creates fluid layers where the bottom is the yellow yolk-like fluid and the top is a clear fluid.
• vitelliruptive stage (last stage): The common fluid layers become more spread out in the retina tissue. This spreading can lead to the formation of blood vessels under the macula (choroidal neovascularization) and can significantly impair central vision.

The BEST1 gene is one of two genes associated with this condition. This gene is linked to the early onset form of this condition typically presenting in late childhood or early adolescence. BVMD-like symptoms diagnosed after age 20 with no gene abnormality in the BEST1 gene may be associated with mutations in the PRPH2 gene which is linked to adult-onset BVMD.

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Affected populations

BVMD is fairly common form of macular degeneration affecting about 1 in 10,000 individuals. Typical age of onset is between the ages of 5 and 10 but can occur earlier or later. BVMD occurs equally often in men and women. This condition has been diagnosed in individuals of European, African and Hispanic ancestry.

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Disorders with Similar Symptoms

Symptoms of the following disorders can be similar to those of BVMD. Comparisons may be useful for a differential diagnosis:

Adult vitelliform macular dystrophy is an autosomal dominant form of macular dystrophy that usually begins in middle age. A yolk-like mass is often present on the macula, but a special light test used to evaluate the function of the layer of cells between the retina and eye wall (retinal pigment epithelium) is usually normal. Some affected individuals have an abnormality in either the BEST1 or PRPH2 gene.

Age-related macular degeneration is a common type of macular degeneration that usually occurs in people over 60 years of age.

Autosomal recessive bestrophinopathy (ARB) is a form of macular degeneration inherited in an autosomal recessive fashion (both copies of the gene must be non-working in order to have the disease). The disease is caused by two non-working copies of the BEST1 gene. In this condition, the same yellowish material and fluid pocket in the retinal tissue can be found. Farsightedness and an abnormal EOG are common. In some people, multiple pockets of fluid can be seen in the retina, many of which are smaller than those seen in BVMD.

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Diagnosis

Best vitelliform macular dystrophy is diagnosed by the appearance of a yellow mass on the macula during an eye exam. There are different eye tests that can detect or lead to a suspicion of BVMD including a test called an electrooculogram (EOG) which can measure how well the eye responds to light. The test measures how well the eye responds to light by looking at how retina reacts to different amounts of light. A very low score on this test, indicated as a number called an Arden ratio, is a strong indicator for BVMD. Another test called a fundus exam can identify the yolk-like mass on the macula that is characteristic of BVMD.

Other family members like siblings or parents with similar symptoms may help in diagnosing BVMD in an individual. Molecular genetic testing for the BEST1 gene is available to confirm the diagnosis. Sequencing of BEST1 (reading every letter of the gene from start to finish) can detect more than 96% of harmful genetic changes if there is a family history of BVMD. This means that only 4% of harmful changes in the BEST1 gene are not detected in an individual with BVMD. If there is no family history, sequencing can detect 50 – 70% of harmful genetic changes known to cause BVMD.

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Standard Therapies

Treatment
There is no cure for BVMD but there are treatment options available that can help reduce the effects of vision loss. For individuals with BVMD who have choroidal neovascularization, anti-VEGF therapy is available to help limit the formation of blood vessels in the macula.

Affected individuals should have regular eye examinations to monitor the progression of the disease. Devices or aids to help with poor vision are beneficial for those who experience significant vision loss.

If the eye lesions are large enough, sudden injury to the eye or head may lead to bursting of the lesions. People with BVMD should avoid strenuous exercise or high contact activity that may lead to head trauma.

Genetic counseling is beneficial for affected individuals and their families. These specialists can provide information on the genetic causes of certain inherited conditions, counsel on the chance of genetic disease reoccurring in the family, discuss the availability of different genetic testing options, and provide resources related to genetic disease.

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Clinical Trials and Studies

Direct laser photocoagulation may be useful in the treatment of Best vitelliform macular dystrophy, but clinical trials have not been conducted to evaluate this approach.
Stem cell therapies to create retinal tissue is in the beginning stages of investigation.

Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/ All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]

Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/

For information about clinical trials sponsored by private sources, contact: https://www.centerwatch.com/

For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/

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References

TEXTBOOKS
Wilkinson, C.P., MD; Hinton, David R., MD; Sadda SriniVas R., MD;Wiedemann, Peter, MD. (2018). Macular Dystrophies. In Sohn E, Mullins R, Stone E (6th edition), Ryan’s Retina (pp. 953-996).

JOURNAL ARTICLES

Tewari R, Kumar V, Ravani R, Dubey D, Chandra P, Kumar A. Macular hole-associated retinal detachment in Best vitelliform dystrophy: Series of two cases and literature review. Indian J Ophthalmol. 2018;66(5):708-711.

Altschwager P, Ambrosio L, Swanson EA, Moskowitz A, Fulton AB. Juvenile macular degenerations. Semin Pediatr Neurol. 2017;24(2):104-109.
Song Min J, Bharti K. Looking into the future: Using induced pluripotent stem cells to build two and three dimensional ocular tissue for cell therapy and disease modeling. Brain Res. 2016;1638:2-14.

INTERNET

Best vitelliform macular dystrophy. Genetic and Rare Diseases Information Center (GARD). Last updated: 10/13/2016. https://rarediseases.info.nih.gov/diseases/182/best-vitelliform-macular-dystrophy. https://www.ncbi.nlm.nih.gov/pubmed/. Accessed May 15, 2019.

MacDonald IM, Lee T. Best Vitelliform Macular Dystrophy. 2003 Sep 30 [Updated 2013 Dec 12]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1167/ Accessed May 15, 2019.

Online Mendelian Inheritance in Man (OMIM). Johns Hopkins University, Baltimore, MD. MIM Number 153700. Last update 08/18/2016. https://www.omim.org/entry/153700 Accessed May 15, 2019.

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