The occurrence of Best Disease is unknown, due to its differing rates of vision loss over a lifetime. It is estimated to occur anywhere between 1 in every 10,000-20,000 children. Best Disease has been known to affect children born genetically male or female with equal likelihood, and starts to cause vision loss between the ages of 3 and 15 years old.

Best Disease is caused by a genetic mutation to the appropriately named BEST1 gene, which produces that channel protein bestrophin 1. This protein is primarily produced in the retina cells of the eye, and is responsible for the flow of chloride ions into and out of the retina. The dysfunction or lack of this protein somehow contributes to buildup of lipofuscin in the macula, responsible for childhood onset VMD, or Best Disease, and some rare cases of adult onset VMD. In fact, there are multiple mutations of the BEST1 gene known to cause varying eye conditions, known as bestrophinopathies. The bestrophin 1 channel proteins contribute to normal ocular development, and mutations cause different developmental problems to occur. It is believed that lack of transport can lead to a buildup of fluid in the macular space or leaking out below the retina. 

Children with Best Disease inherit it through autosomal dominant inheritance, meaning that one parent with the mutation in their chromosome is enough to cause this disease (see RareShare Guide on Genetic Inheritance). In most cases, the child with Best disease will be born to a parent who already has Best Disease. 

The main symptom of Best Disease is loss of central vision, with different rates of loss over differing amounts of time from person to person. This can be described as blurred vision, reduced ability to detect details such as recognizing faces, seeing things as oddly shaped such as straight lines appearing wavy (metamorphopsia), and difficulty reading and driving a car. Best disease vision loss usually occurs in both eyes, but sometimes only affects vision in one eye. While Best disease occurs in children and generally affects the middle of the eye and central vision, there is a form of adult onset vitelliform macular dystrophy (VMD). This form of VMD affects the back of the eye and causes vision loss later in life, and this disease progresses differently than Best disease.

A diagnosis for Best disease can be made by an optometrist at a regular eye exam. The doctor can detect changes in the lipofuscin buildup in the eye as a small yellow dot resembling an egg yolk. Often, these changes to the macula can be diagnosed before vision loss occurs. 

The most effective way to diagnose Best Disease is using a genetic test for mutations in the BEST1 gene. This can be performed given the medical history of the child and the child’s family whether or not vision loss has started to occur. Physical eye exams can be used to diagnose Best disease as well, and their type differs depending on the symptoms of vision loss experienced or the degree of buildup present in the macula. Some of these eye exams are listed below: 

1. Fluorescein angiography: This is an imaging test that uses dye to show blood vessels.

2. Optical coherence tomography: This type of noninvasive imaging test uses reflected light to create pictures of the back of your eye.

3. Color fundus photography: This type of imaging shows your retina, the related blood vessels and the optic nerve head.

4. Ophthalmic electrophysiology: This term describes a series of eye tests that measure electrical activity.

There is no current treatment reversing the buildup and vision loss caused by Best Disease. As vision starts to worsen, visual aids such as brightened colors and increasing lighting can help those with limited vision to see better. Some individuals with Best Disease and other forms of macular degeneration can form new blood vessels in the eye in a condition known as choroidal neovascularisation (CNV). This lack of blood flow to the macula can cause further vision loss and can be treated with a medication called anti-vascular endothelial growth factor (Anti-VEGFs). These drugs stop or reduce the growth of new blood vessels and can slow vision loss. Once Best Disease has been diagnosed, it is important to get regular eye exams to prevent development of CNV and further worsening the eyesight. 

While there is currently no cure for the vision loss of Best Disease, the progression of this disease and its effects differ from person to person. If diagnosed early in life due to vision loss and seeking an optometrist, individuals should continue to have regular eye exams to prevent against CNV from forming new blood vessels in the eye. If diagnosed during a routine eye exam but no loss of vision has yet occurred, it could be years before the disease progresses and vision loss can also be attributed to the effects of aging. While vision loss is irreparable and the fluid buildup cannot be removed, Best Disease only affects the central vision of the eye, leaving peripheral vision to allow the individual some autonomy. 

Gene therapy has been proposed as a possible treatment for Best disease. The FDA recently approved a gene therapy approach for a form of retinal blindness called Leber’s congenital amaurosis. Since Best disease is caused by mutation in one known gene, BEST1, it is considered a viable candidate for gene therapy.

1. https://www.rnib.org.uk/your-eyes/eye-conditions-az/best-disease-best-vitelliform-macular-dystrophy/#:~:text=Best%20disease%20is%20a%20type,affect%20both%20men%20and%20women.

2. https://my.clevelandclinic.org/health/diseases/24132-best-disease

3. https://eyewiki.aao.org/Best_Disease_and_Bestrophinopathies

4. https://www.fightingblindness.org/diseases/best-disease

5. https://emedicine.medscape.com/article/1227128-overview?form=fpf

6. https://medlineplus.gov/genetics/condition/vitelliform-macular-dystrophy/ 

7. https://www.macularsociety.org/

8. https://elifesciences.org/articles/67622 

9. https://www.brightfocus.org/macular/article/bests-disease#:~:text=There%20has%20been%20significant%20progress,blindness%20called%20Leber's%20congenital%20amaurosis.