Best Disease (Vitelliform Macular Dystrophy)

Overview

Best disease, also known as vitelliform macular dystrophy type 2 (VMD2), is an autosomal dominant macular dystrophy caused by mutations in the BEST1 gene. It is characterized by a distinctive egg-yolk (vitelliform) lesion in the macula, which typically develops in childhood and progresses through several stages. Visual acuity is often preserved until later stages when the lesion atrophies or is complicated by choroidal neovascularization.

Genetics

Best disease is caused by heterozygous mutations in BEST1 (VMD2), encoding bestrophin-1, a calcium-activated chloride channel expressed in the RPE. Over 250 pathogenic variants have been identified.

Clinical Presentation

Diagnosis

• Electro-oculogram (EOG): Reduced Arden ratio (<1.5) — pathognomonic for Best disease
• Fundus examination: Characteristic vitelliform lesion in fovea
• OCT: Subretinal material accumulation; photoreceptor changes
• Fundus autofluorescence: Hyperautofluorescent lesion
• ERG: Normal (distinguishes from other macular dystrophies)
• Genetic testing: BEST1 sequencing

Current Research & Treatment

Gene therapy for Best disease faces challenges due to its dominant-negative mechanism. Antisense oligonucleotide and RNA interference approaches to suppress the mutant allele are in preclinical development. Stem cell-derived RPE transplantation is also being explored. Anti-VEGF therapy is used for choroidal neovascularization complications.

Active Clinical Trials

The following active clinical trials are investigating treatments for Best Disease (Vitelliform Macular Dystrophy). Trial status and enrollment may change; always verify directly on ClinicalTrials.gov.

Supporting Organizations

The following nonprofit organizations fund research, support patients, and advocate for advances in the treatment and cure of Best Disease (Vitelliform Macular Dystrophy).