Best Vitelliform Macular Dystrophy

What is the best disease? 

A dystrophinopathy, known as Best Disease or Best Vitelliform macular dystrophy, affects the retinal pigment epithelium (RPE) cells in the back of the eye.¹ Dr. Friedrich Best, an ophthalmologist at Moorfields Eye Hospital, was the first to diagnose Best disease, and this condition was named after him following the examination a large family with the condition in the early 1900's.¹

What are the symptoms of the best disease? 

Symptoms of Best disease include vision loss, which can be slow and gradual or can occur rapidly.² Progression through the stages of the disease can vary between individuals and families. Many patients report problems reading small print (hyperopia) and may have astigmatism (eyes having a “rugby ball” shape).³ One in four patients may also have multiple retinal lesions, some of which may be distant from the macula.³ 

Another commonly observed symptom is the formation of a yellow or orange-coloured vitelliform lesion (Latin for 'egg-yolk') on the macula, and the yellow or orange color appears in both eyes.³ There can be differences amongst those affected with Best's, even within the same family, despite being a disease inherited by dominant means and exhibiting incomplete penetrance and variable expressivity.³ 

The prevalence of Best disease has been studied extensively, and it is estimated that between 1 and 9 people out of 100,000 have it.³ Adult vitelliform macular degeneration is a version of Best disease affecting adults.³ An 'egg yolk' lesion is most commonly seen between the ages of 3 to 15 years old in children with Best Disease.^3,4 

How does Best disease impact the eye? 

Best disease is thought to progress through a number of distinct stages:^2,3

Stage I - In this early stage of Best, vision can be as good as 6/6 on a Snellen chart. RPE may be normal or there may be very minor changes such as the presence of small honeycomb-like structures. They can appear on the retina as yellowish pigment changes in the center.

Stage II & III  – There may be mild vision loss at this stage of the disease, or vision may be normal. The vitelliform stage is the classic stage in which Bests are most easily identified by the presence of a yellow “egg yolk”-like lesion on the macula that is typically 2 to 3 mm in diameter. 

A buildup of fat, called lipofuscin, can lead to pseudohypopyon formation, where cells related to inflammation accumulate in the anterior chamber of the eye.

Stage IV – “egg yolk” lesions fragment into “scrambled egg” lesions. Abnormal yellow deposits may also be seen behind the eyes. Visibility will be similar to previous stages or even slightly reduced compared to previous stages. 

Stage V – Vision will decrease significantly at this stage, typically vision can range from 6/12 on the Snellen chart to 6/60 or less. RPE death in the macular region can lead to loss of retinal cells, including photoreceptors necessary for normal vision. Scar tissue forms behind the eye.

Stage VI – at this stage, vision is usually 6/60 or worse. This stage of Choroid neovascularisation (CNV)  occurs in about 1 in 5 patients with Best disease. CNV is the growth of new blood vessels originating from the choroidal blood supply at the back of the eye. The RPE forms a barrier between the retina and the blood supply. As RPE cells disappear from the macula, new blood vessels can grow from the choroid to the retina. Normally, these new blood vessels are very weak and may even rupture and leak, causing fluid to accumulate in the retina. A sudden change in vision may indicate CNV, which can be treated with photodynamic therapy, laser treatment, or VEGF therapy injections.

Vision loss in Best disease can be slow and gradual or can occur rapidly, and progression through the stages of the disease can vary between individuals and families. Many patients report problems reading small print (hyperopia) and may have astigmatism (eyes having a “rugby ball” shape). One in four patients may also have multiple retinal lesions, some of which may be distant from the macula. 

What causes best disease?

The best disease is an autosomal recessive disease.⁵ This means that only one parent must have the altered gene to pass it on and that half of the children of parents with an autosomal trait will have that trait. In this case, the trait is the best disease.⁵ The gene affected in Best's disease is the same gene that can be affected in certain types of retinitis pigmentosa, a group of inherited eye diseases.⁵ 

How is best disease diagnosed? 

The disease can be best diagnosed by looking for the characteristic egg yolk-like lesions at the back of the eye seen in stages II, III, and IV.^3,6 Other tests are available to confirm the diagnosis.

Optical Coherence Tomography (OCT) can be used to localize the lesion and examine its thickness, which may show elevated RPE with lipofuscin and fluid accumulation.⁷

Autofluorescence imaging can be used to detect fat accumulation in the back of the eye. Autofluorescence may be increased in the early stages of the disease.⁸

Ophthalmic Electrophysiological testing is used to evaluate the activity and health of the RPE cells in the back of the eye. The test is used to calculate the Arden ratio. Typically, patients with Best disease have a ratio of 1.5 or less, but recordings in some patients may be normal.⁹ 

The disease can best be confirmed by genetic testing.⁵ 

What are the complications of the best disease? 

Complications of Best disease often occur in the late stages of the disease, leading to rapid vision loss.^2,3

Geographic atrophy -The progressive disease is associated with the formation of scar tissue as RPE cells in the back of the eye degenerate.^2,3 RPE death leads to more widespread death of photoreceptors in the retina, known as geographic atrophy, leading to progressive and irreversible vision loss.^2,3

Choroidal neovascularization (CNV) -Loss of RPE cells as the disease progresses can lead to the formation of new blood vessels from the choroid to the retina.^2,3 These new blood vessels may be weak and fragile, causing leaks and fluid to accumulate under the retina, significantly reducing vision.^2,3 This bleeding can occur with minor trauma.^2,3

Macular hole -A macular hole is a tear in the macular area that can cause sudden vision loss in one eye.³ Macular hole formation is a rare complication of Best disease.³  

What are the treatment options for the best disease?  

There are currently no medical or surgical treatment options available for Best disease.^2,3 However, treatments are available for the complications of Best disease.^2,3 

Long-sightedness (hyperopia) -Hyperopia and astigmatism can be corrected using prescription glasses and contact lenses.³  

Choroid neovascularisation (CNV) -CNV can be treated by injecting anti-VEGF drugs (e.g. Avastin, Bevacizumab) into the back of the eye in an eye clinic.³ These injections can stop the growth of newer vessels, with the aim of preserving vision.³ CNV can also be treated using photodynamic therapy or laser therapy to shrink or seal the leaky blood vessels.³ 

Macular holes -Macular holes can be treated in a surgical procedure.³ 

Summary

Best disease is a progressive condition that is the result of one parent carrying an autosomal recessive gene. Half of the children of that one parent will have the condition. The symptoms include severe deterioration of vision due to damage of the retinal pigment epithelium (RPE), which eventually leads to the formation of an “egg-yolk” lesion. There is currently no cure for Best disease, but there are some treatment options available to deal with the complications resulting from the damage to the eyes.