What is Best Disease?
Best disease, also known as Best vitelliform macular dystrophy (BVMD), is a rare genetic eye disorder, typically passed from parent to child. It happens due to a mutation in the BEST1 gene, and its effects can vary from person to person. Although it usually starts in childhood, there are also instances where it follows a different inheritance pattern.
The disease primarily affects both eyes and is recognized by a specific change in the retina that looks like a sunny-side-up egg – this change occurs in the macula, the part of the eye responsible for high-resolution vision. Specifically, the layer under the retina known as the retinal pigment epithelium (RPE) is the main area impacted.
A common test, the electrooculogram (EOG), which measures the electrical activity of the eye, is usually affected in individuals with this disease, showing a reduced Arden ratio – a measurement used in this test to diagnose certain eye conditions. However, the overall vision outlook for individuals with Best disease tends to be positive, as most people retain reading and driving capability in at least one of their eyes throughout their lives.
The condition goes by several other names such as Best macular dystrophy, vitelliform dystrophy, early or juvenile-onset vitelliform macular dystrophy, vitelline dystrophy, and vitelliruptive degeneration. It got its name from Dr. Friedrich Best, a German eye specialist, who first wrote about a family with different stages of this eye condition in 1905.
What Causes Best Disease?
The disease is caused by changes or mutations in a gene named VMD2 or BEST1. This gene is found on a specific part of our DNA (chromosome 11q12-q13), and it creates a protein called Bestrophin 1. This protein is mainly found in the basolateral membrane of the RPE, which is part of the eye.
Bestrophin 1 has two main jobs. It helps control the signals of calcium inside the cells and it works as an anion channel, which is like a gate allowing certain particles to pass through the cell membrane.
Bestrophin 1 acts as a gate for chloride (which is activated by calcium) and it might also work as a route for other particles, including bicarbonate. Furthermore, it plays a significant role in balancing calcium in the RPE.
In short, the Bestrophin protein is key to maintaining the balance of ions (charged particles) in the RPE and/or the subretinal space (the area beneath the retina). This balance is vital because it helps the retina stick to the RPE.
The mutation of the BEST1 gene also causes a reduced Arden ratio in EOG (a test to assess eye health) in individuals suffering from Best vitelliform macular dystrophy.
Interestingly, not everyone with the BEST1 mutation shows typical signs of the disease; about 5 percent of people with the mutation will have normal-looking maculas, which is the middle part of the retina.
The BEST1 mutation can lead to multiple diseases, including:
– Vitelliform macular dystrophy 2 or BVMD (also referred to as phenotype MIM No. 153700)
– Autosomal recessive bestrophinopathy (or phenotype MIM No. 611809)
– Retinitis pigmentosa 50 (RP50)/concentric retinitis pigmentosa (or phenotype MIM No. 613194)
– Autosomal dominant microcornea, rod-cone dystrophy, cataract, and posterior staphyloma 193220 (or phenotype MIM No. 193220)
– Autosomal dominant vitreoretinochoroidopathy (or phenotype MIM No. 193220)
– Adult-onset vitelliform macular dystrophy.
Risk Factors and Frequency for Best Disease
Best vitelliform macular dystrophy affects both males and females and is a relatively rare condition, with only 1 in every 16,500 to 21,000 people having it. This was found in a study carried out in Olmsted County, Minnesota. The condition typically shows up in the first 20 years of life, and many people find out they have it by chance. But sometimes, it can take as long as 75 years to detect the first signs of this condition in the macula (the central part of the retina).
Signs and Symptoms of Best Disease
Lesions on the eyes are often discovered by chance. However, when symptoms do occur, they can consist of blurred vision, distorted vision (metamorphopsia), or blind spots (scotoma).
Testing for Best Disease
The condition we’re discussing mainly affects the eyes but does not typically show associated symptoms elsewhere in the body. It may cause a refractive error (often hypermetropia, or long-sightedness). A symptom of this disease is a distinct and symmetrical yellowish deposit in a central part of the retina known as the macula in both eyes which looks similar to an egg-yolk. Even though it can look quite alarming, the patient’s vision usually remains normal. However, some patients with a particular genetic mutation (BEST1) have reported the condition affecting only one eye.
The optic nerve and retinal vessels (parts of the eye that are essential for vision) typically look normal, and no bony spicules (speck-like spots) are observed. Over time, the yellowish macular lesion (the ‘egg-yolk’ like deposit) may either follow typical stages of progression, become less noticeable, or be accompanied by other lesions outside the macula.
Patients usually do not suffer from any peripheral visual field defect, meaning their ability to see around the edges of their field of view is unimpaired. However, central scotoma (a blind spot in the center of the visual field) might occur.
Autofluorescence, a technical procedure that generates a specific image of the eye, can highlight the vitelliform material, that ‘egg-yolk’ like substance. This substance shines brightly under autofluorescence and usually takes on a round or oval shape.
To rule out the possibility of choroidal neovascular membrane (CNVM), a condition where new blood vessels grow under the retina, a fundus fluorescein angiogram (FFA) is conducted. The vitelliform deposit often leads to lower fluorescence during this test, a phenomenon known as hypofluorescence. The late-stage disease may show a ‘window defect’. It’s important to note that contrary to Stargardt disease (an inherited form of macular degeneration), there is no ‘black choroid’ appearance on the FFA.
Optical coherence tomography (OCT), another type of eye examination, provides detailed images of the retina. OCT might reveal deposits of hyperreflective material, clear fluid, or a sharp margin of the deposited vitelliform material, depending on the disease stage.
Electrooculography (EOG), a technique which measures the electrical activity of the eye, has observed decreased light peak response, resulting in an altered Arden ratio in all disease stages.
The criteria required to confirm a diagnosis of BVMD include presence of atypical lesion of BVMD, abnormal EOG, a dominant inheritance pattern in families, and typical disease course and onset of the disease.
Usually, electroretinogram (ERG), a test to measure the electrical response of various cells in the eye, is normal in this condition. Dark adaptation test, which measures how well the eyes adjust to darkness after exposure to bright light, is generally normal as well. However, color vision and object contrast sensitivity may be affected.
Treatment Options for Best Disease
If someone has Best vitelliform macular dystrophy, but doesn’t have a choroidal neovascular membrane (CNVM), they usually don’t need treatment. To clarify, Best vitelliform macular dystrophy is a condition which can affect the eye’s central vision. A choroidal neovascular membrane refers to new, unwelcome blood vessels that grow beneath the retina.
Despite there being no need for treatment, regular check-ups are crucial. These check-ups are not only for the affected individual, but also for the family, as this is a genetic condition. Tests that may be carried out include dilated eye examinations and electrophysiological testing, which measures the electrical activity in the eye. Genetic analysis can confirm the diagnosis. These regular checks help in the early detection of any complications.
However, if a choroidal neovascular membrane does occur in someone with Best vitelliform macular dystrophy, certain treatments can be effective. For instance, anti-vascular endothelial growth factor treatments, which are drugs (such as bevacizumab, ranibizumab, or aflibercept) that help limit the growth of new blood vessels, can be effective. Other treatment options include laser therapy and photodynamic therapy which uses light to damage unwanted blood vessels. Sometimes the membrane shrinks on its own, but typically the anti-vascular endothelial growth factor treatments provide the best result.
All patients should have regular eye tests, to ensure they have the right glasses or contact lenses if required. If the patient develops significant cataracts, they may potentially see some improvements in their vision after cataract surgery.
Something known as an Amsler grid, a tool used at home, can be used by the patient to detect any changes in their vision. This can be especially useful in spotting a condition known as metamorphopsia, which causes straight lines to appear wavy. Apart from this, patients with poor vision due to this condition can benefit from low vision aids like magnifiers and telescopes.
What else can Best Disease be?
When it comes to diagnosing certain eye conditions, doctors might consider a variety of different diseases as they try to arrive at the correct diagnosis:
- Central serous chorioretinopathy with fibrin: This condition features a specific type of detachment in the eye’s pigment and a location of subretinal transparency. A test called Fluorescein Angiography (FFA) shows typical signs and leaks.
- Adult-onset vitelliform macular dystrophy: This is a type of pattern dystrophy, where patients present at late-middle or old age with visual decline. The affected area is usually smaller and does not necessarily go through the typical progressions of a related condition, Best vitelliform macular dystrophy (BVMD). There may also be a mutation in the BEST1 or PRPH2 (RDS) gene, causing abnormal EOG results and resulting in a disease that is passed down through generations.
- Subretinal granuloma due to choroidal tuberculosis/sarcoidosis: This refers to granulomas, or inflammation, underneath the retina due to diseases such as tuberculosis or sarcoidosis.
- Wet age-related macular degeneration: Key signs of this condition include advanced age and an irregular lesion. Older scars in the disciform stage of this disease tend to have a white appearance as opposed to the typical yellow, smooth appearance of BVMD.
- Acute exudative vitelliform maculopathy: This is another condition that doctors might consider.
- Fundus flavimaculatus with large flecks: This involves distinctive flecks or spots in the retina.
- Large dehemoglobinized subretinal hemorrhage: Refers to a large hemorrhage, or bleed, underneath the retina that has lost some of its hemoglobin.
- Basal laminar drusen: This is a condition characterized by small yellow deposits, known as drusen, forming in a layer of the retina.
Each condition has distinguishing symptoms and signs, so the doctor will need to take a careful approach to make the correct diagnosis.
What to expect with Best Disease
The outlook for your vision is typically very positive. The term ‘best-corrected visual acuity’ refers to the sharpest vision possible with glasses or contact lenses. Here’s what it looks like for different stages of the disease:
* Before any signs of the disease (the pre-vitelliform stage), vision is usually 20/20, which is considered normal.
* In the vitelliform or pseudohypopyon stage, your vision will be between 20/20 to 20/60. This range from normal vision to potentially a bit blurry, but you should generally still be able to carry out most activities.
* In the vitelliruptive stage, vision may go down to 20/120, which is quite blurry and may affect your daily activities.
* In the later stages of the disease (the atrophic or cicatricial/CNVM stage), your vision may worsen and could possibly be worse than 20/200 which is considered legally blind.
In a large study, 77% of the patients with Best vitelliform macular dystrophy, a concerning eye condition, retained quite good sight – at least 20/40. However, over a period of 8-10 years, 19% of patients, who reached a stage involving scarring or tissue death, saw their vision decrease significantly.
Possible Complications When Diagnosed with Best Disease
The disease could lead to a number of complications, including:
- A choroidal neovascular membrane which can result in a disciform scar
- Subretinal fibrosis
- Macular hole, though this is rare
Preventing Best Disease
Patients need to be informed about the possibility of complications that may occur later on and the importance of regular check-ups. The use of an Amsler chart, a tool used to detect eye problems, should be part of their routine. This is because it can help identify changes in vision, known as metamorphopsia, early on. Metamorphopsia could be a sign of a new growth in the layer of blood vessels in the back of the eye, called a choroidal neovascular membrane.
