Best vitelliform macular dystrophy (ORPHA:1243)
Best vitelliform macular dystrophy (BVMD) is a genetic macular dystrophy characterized by loss of central visual acuity, metamorphopsia and a decrease in the Arden ratio secondary to an egg yolk-like lesion located in the foveal or parafoveal region.
Epidemiology
The prevalence is estimated to be between 1/5,000 and 1/67,000 in northern Sweden and Denmark respectively. Males are more affected than females (3:1).
Clinical description
Onset of BVMD is in childhood and sometimes in later teenage years (5-13 years). Affected individuals have normal vision at birth. BVMD then progresses through distinct stages that include an asymptomatic previtelliform phase (stage 1) followed by the formation of a yellow, egg yolk-like (vitelliform) lesion in the macula (stage 2). The contents become less homogenous and develop a "scrambled-egg" appearance (stage 2a). The lesion eventually develops a fluid, yellow-colored vitelline substance (pseudohypopyon or stage 3) and finally breaks down, leaving a scar that causes central visual acuity deterioration (20/200). This may be complicated by a subfoveal choroidal neovascular (CNV) membrane (rare in children). Anomalous color discrimination (mainly the protan axis) and metamorphopsia may be observed but patients retain normal peripheral vision and dark adaptation. Some affected individuals remain asymptomatic.
Etiology
BVMD is characterized by atrophy of the retinal pigment epithelium (RPE) affecting photoreceptors with impaired central visual function. In most cases, BVMD is caused by mutations in BEST1 (11q12), encoding for bestrophin-1, a chloride channel expressed in RPE. A defect in this protein leads to accumulation of lipofuscin secondary to abnormal ion exchange.
Diagnostic methods
The clinical diagnosis is based on family history, visual-acuity testing and funduscopy (showing yellow, round deposits of lipofuscin at the center of the macula). Full-field electroretinogram (ERG) is normal. Electro-oculography (EOG) measures standing potential of the eye by recording the Arden ratio (AR; ratio of light peak/dark trough; normal value ≥1.8). AR is usually decreased in BVMD (1.0-1.3). High-resolution optical coherence tomography may identify abnormal accumulation of lipofuscin between photoreceptors and RPE. Diagnosis is confirmed by genetic screening of BEST1.
Differential diagnosis
Differential diagnosis of BVMD includes adult-onset foveomacular vitelliform dystrophy, age-related macular degeneration, autosomal recessive bestrophinopathy, autosomal dominant vitreoretinochoroidopathy, retinitis pigmentosa (see these terms) and Bull's-eye maculopathy.
Antenatal diagnosis
Prenatal diagnosis and preimplantation genetic diagnosis is possible for families in which the disease-causing mutation is known.
Genetic counseling
BVMD is inherited in an autosomal dominant manner with complete penetrance. Age of onset and severity of vision loss show inter- and intrafamilial variability.
Management and treatment
Management is symptomatic and includes use of low vision aids for individuals with significant deterioration in visual acuity. Annual ophthalmologic examination for persons of all ages is recommended. Smoking should be avoided as it increases the risk of neovascular macular degeneration. Photodynamic therapy using verteporfin, direct laser photocoagulation or anti-VEGF agents (bevacizumab) may be options for treating CNV. Transcorneal electrical retinal stimulation may be used to treat BVMD.
Prognosis
BVMD may progress to geographic atrophy and in some cases is complicated by development of CNV. 7-9% of patients never experience vision loss, but have an aberrant EOG with normal ERG.

                            Last update: 
                            December 2013


                            - Expert reviewer(s): 
                            Pr Ian MACDONALD