Best vitelliform macular dystrophy (BVMD) is a slowly progressive form of macular degeneration. It usually begins in childhood or adolescence, but age of onset and severity of vision loss can vary. Affected people first have normal vision, followed by decreased central visual acuity and distorted vision (metamorphopsia). Peripheral vision is not affected. BVMD is characterized by atrophy of the retinal pigment epithelium (The retina is the back part of the eye that contains the specialized cells that respond to light, known as photoreceptors) and impaired central visual function. BVMD is usually inherited in an autosomal dominant manner, but autosomal recessive inheritance has been reported. The condition is typically caused by mutations in the BEST1 gene; in a few cases the cause is unknown. Treatment is symptomatic and involves the use of low vision aids, and direct laser treatment or photodynamic therapy. Newer treatment includes anti-VEGF agents (bevacizumab) and transcorneal electrical retinal stimulation.

BEST1 gene. This gene gives the body instructions for making a protein called bestrophin. Bestrophin acts as a channel that controls the movement of chloride ions within the retina. It is thought that mutations in the BEST1 gene affect the shape of the channel and its ability to properly regulate the flow of chloride. However, it is unclear how exactly this relates to the specific features of BVMD.

In autosomal dominant inheritance, having one changed (mutated) copy of the responsible gene in each cell is enough to cause symptoms of the condition. When a person with an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit the mutated gene. Most people with BVMD have an affected parent, but some people have the condition as the result of a new mutation that occurred for the first time.

Autosomal recessive inheritance means that a person must have a mutation in both copies of the responsible gene in each cell to be affected. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

Best vitelliform macular dystrophy causes a fatty yellow pigment (lipofuscin) to build up in cells underlying the macula. Over time, the abnormal accumulation of this substance can damage cells that are critical for clear central vision. As a result, people with this disorder often lose their central vision, and their eyesight may become blurry or distorted. Best vitelliform macular dystrophy typically does not affect side (peripheral) vision or the ability to see at night.

Studies have shown that most people with Best vitelliform macular dystrophy retain enough vision for reading and driving in at least one eye into adulthood (88% have 20/40 or better vision). Vision usually deteriorates slowly and does not become significant until after age 40.

The EOG, which reflects the retinal pigmentary epithelium function, is the most diagnostic test for evaluating vitelliform macular dystrophy. In the majority of the cases, a severe decrease occurs in light response, reflected by an Arden (light-peak/dark-trough) ratio of 1.1-1.5. (The normal Arden ratio is 1.8.) Carriers will also have an abnormal EOG result.No correlation exists between EOG result and disease stage, visual acuity, or patient age. EOG results are usually symmetric for both eyes.

The family history in affected people is often consistent with either autosomal dominant or autosomal recessive inheritance.

Genetic testing may also be used to make a diagnosis of BVMD. A BEST1 mutation is detected in about 96% of affected people who have an affected family member. In people with no family history of BVMD, the mutation detection rate ranges between 50-70%. A mutation in BEST1 gene is more probable when a vitelliform lesion is accompanied by a reduced Arden ratio on EOG testing. The exact type of genetic test ordered to confirm a diagnosis may depend on a person's ancestry, family history, and/or whether other eye disorders are also being considered.

There is no specific treatment for Best vitelliform macular dystrophy (BVMD) at this time. Low vision aids help affected people with significant loss of visual acuity. Laser photocoagulation, photodynamic therapy, and anti-VEGF (vascular endothelial growth factor) agents such as bevacizumab have shown limited success in treating some of the secondary features of BVMD such as choroidal neovascularization (when abnormal blood vessels grow under the macula and retina).

• Adult-onset vitelliform macular dystrophy (AVMD). This form of vitelliform macular dystrophy affects mainly middle-aged people and is inherited in an autosomal dominant manner. The findings on a fundus exam can easily be mistaken for BVMD, but the electrooculogram (EOG) is normal or only slightly reduced in affected people. There is significant overlap of signs and symptoms between BVMD and AVMD.

• Age-related macular degeneration (AMD). This common disorder is characterized by drusen (yellow deposits under the retina); disruption of the pigmented layer of the retina (retinal pigment epithelium); and choroidal neovascularization (growth of new blood vessels in the choroid).

• Bull's eye maculopathy. This descriptive clinical diagnosis can be seen in people with cone dystrophy, cone-rod dystrophy, Stargardt disease, and other conditions of the macula.

Other conditions that may be part of the differential diagnosis of BVMD include autosomal dominant vitreoretinochoroidopathy and retinitis pigmentosa.