Marc Spirn
BASICS
DESCRIPTION
• Best’s disease (vitelliform macular dystrophy) is a rare, autosomal dominant, bilateral, central retinal dystrophy.
• It is caused by mutations in the BEST1 (formerly VMD2) gene on chromosome 11q13 that encodes the bestrophin-1 protein.
• Age of onset is variable, although most commonly presents in early teenage years.
• It is clinically characterized by a classic yellow, “egg-yolk” (i.e., vitelliform), appearance in the central macula between the neurosensory retina and the retinal pigment epithelium (RPE).
• Visual function tests demonstrate a normal full-field electroretinogram (ERG) coupled with an abnormal electrooculogram (EOG).
EPIDEMIOLOGY
Due to the rarity and variable expressivity of the disease, the true incidence or prevalence is unknown.
RISK FACTORS
Family history of Best’s disease
Genetics
• Autosomal dominant
• BEST1 gene on chromosome 11q13 encodes the bestrophin-1 protein
• Multiple different mutations (>100) responsible for variable expressivity and genotype–phenotype correlations (1)[A]
PATHOPHYSIOLOGY
• Bestrophin-1 is a transmembrane protein located on the basolateral membrane of the RPE cell that functions as a Ca2+-activated Cl– channel.
• The abnormal bestrophin-1 protein causes impaired ion transport across the RPE leading to accumulation of lipofuscin between the neurosensory retina and the RPE (1)[C].
ETIOLOGY
Mutations in BEST1 gene
COMMONLY ASSOCIATED CONDITIONS
Best’s disease is not associated with any systemic conditions.
DIAGNOSIS
HISTORY
• Family history of retinal dystrophy
• Blurry vision
• Metamorphopsia
PHYSICAL EXAM
• Normal ocular anterior segment
• Classic fundus findings include bilateral “egg-yolk” (i.e., vitelliform) lesions in central macula.
• Previously characterized by the following stages (2)[C]:
– Stage 0: Normal fundus or subtle RPE changes
– Stage 1: Definite RPE changes
– Stage 2 (vitelliform stage): Classic yellow “egg-yolk” lesion
– Stage 2a (scrambled-egg or vitelliruptive stage): Multiple irregular yellow subretinal deposits
– Stage 3 (pseudohypopyon stage): Layering of yellowish material in vitelliform cyst
– Stage 4a (atrophic stage): Absence of yellow deposits leaving atrophic RPE
– Stage 4b (Cicatricial stage): White fibrous subretinal scar
– Stage 4c (Choroidal neovascularization stage): Subretinal hemorrhage, serous retinal detachment
• NOTE: There may be great variation in lesion appearance between patients, between the two eyes of the same patient, and even within the same eye of a patient over time.
• Patients may not progress through all stages of disease.
DIAGNOSTIC TESTS & INTERPRETATION
Lab
Genetic testing for BEST1 gene mutations
Imaging
• Fundus photography to document progression of vitelliform lesions
• Fundus fluorescein angiography (FFA):
– Hypofluorescence due to blockage from vitelliform lesions
– Hyperfluorescence due to either window defects from RPE atrophy or leakage from choroidal neovascularization (if present)
• Fourier-domain optical coherence tomography (FD-OCT):
– Thickened hyper-reflective band between photoreceptor outer segments and RPE/Bruch’s complex (3)[C]
• Fundus autofluorescence (FAF):
– Hyper-autofluorescence of vitelliform lesions (3)[C]
Diagnostic Procedures/Other
• Full-field electroretinogram (ERG): Measures total photoreceptor (rod and cone) function:
– Characteristically normal in Best’s disease
• Electrooculogram (EOG): Measures standing potential of RPE:
– Characteristically abnormal in Best’s disease even in the absence of fundus findings
• Arden ratio (light peak/dark trough ratio):
– Normal = 1.8; Best’s disease <1.5
Pathological Findings
Accumulation of lipofuscin in RPE cells
DIFFERENTIAL DIAGNOSIS
• Adult-onset vitelliform dystrophy
• Pattern dystrophy
• Age-related macular degeneration
• Choroidal neovascularization
TREATMENT
MEDICATION
No medical treatment is indicated for patients with Best’s disease.
SURGERY/OTHER PROCEDURES
• For cases complicated by choroidal neovascularization, consider:
– Photodynamic therapy (4)[C]
– Intravitreal anti-VEGF agents (i.e., bevacizumab) (5)[C]
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
• Serial fundus ophthalmoscopy with retina specialist
• Low vision aids for decreased vision
PATIENT EDUCATION
Genetic counseling for family members of affected patients
PROGNOSIS
Most patients retain 20/40 or better vision (2)[C].
COMPLICATIONS
Choroidal neovascularization
REFERENCES
1. Boon C, Klevering BJ, Leroy BP, et al. The spectrum of ocular phenotypes caused by mutations in the BEST1 gene. Prog Retin Eye Res 2009;28:187–205.
2. Mohler CV, Fine SL. Long-term evaluation of patients with Best’s vitelliform dystrophy. Ophthalmol 1981;88:688–692.
3. Ferrara DC, Costa RA, Tsang S, et al. Multimodal fundus imaging in Best vitelliform macular dystrophy. Graefes Arch Clin Exp Ophthal 2010
4. Andrade RE, Farah ME, Costa RA. Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in Best’s disease. Am J Ophthalmol 2003;136:1179–1181.
5. Rishi E, Rishi P, Mahajan S. Intravitreal bevacizumab for choroidal neovascular membrane associated with Best’s vitelliform dystrophy. Indian J Ophthalmol 2010;58:160–162.
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