Best Disease

Best Disease
SYMPTOMS Progressive vision loss, Metamorphopsia, Central scotomas, Color vision deficiencies
SIGNS Bilateral
Egg-yolk lesion (composed of lipofuscin) at the macula (involving the RPE, subretinal space, and photoreceptors), Photoreceptor disruption (especially in the location of lipofuscin), RPE proliferation, Chorioretinal atrophy, Possible choroidal neovascular membrane
There are 6 stages of Best disease
Stage I (Previtelliform stage): Fundus typically looks normal (VA is 20/20)
Stage II (Vitelliform stage): Involves an elevated round yellow to light red egg yolk typically in the foveal region at the level of the RPE (VA is anywhere from 20/20 to 20/60)
Stage III (Pseudohypopyon stage): Egg yolk material sinks down into the subretinal space and is associated with fluid (VA is anywhere from 20/20 to 20/60)
Stage IV (Vitelliruptive stage): Egg yolk becomes scrambled due to disruption and breakup of lipofuscin (VA is anywhere from 20/20 to 20/100)
Stage V (Atrophic stage): Includes RPE proliferation and chorioretinal atrophy (VA is typically 20/200 to 20/400 )
Stage VI (CNVM stage): Development of a choroidal neovascular membrane which may include fibrous scarring (VA is typically 20/200 to 20/400)
WORK-UP Color vision (mild dyschromatopsia), Full eye exam with dilated retinal exam, Visual field (central scotoma may be present especially in the later stages), OCT analysis of the macula (Stage I: Interdigitation zone is thicker especially at the fovea / Stage II: Presence of hyper-reflective lipofuscin at the level of the RPE / Stage III: Presence of hyper-reflective lipofuscin within the subretinal space with associated fluid / Stage IV: Presence of hyper-reflective lipofuscin within the subretinal space with associated fluid and thinning of the outer segments of the photoreceptors and outer nuclear layer / Stage V: RPE disruption, Ellipsoid zone disruption with loss, and almost no foveolar outer nuclear layer. Subretinal fluid is typically resolved / Stage VI: Presence of a choroidal neovascular membrane), OCT-Angiography, Fundus Autofluorescence (Stage I: Typically normal / Stage II: Increase in AF in area of central egg yolk / Stage III: Increase in AF in area of inferiorly deposited lipofuscin / Stage IV: Increase in AF in area of lipofuscin and decrease in AF in area of retinal thinning / Stage V: Decrease in AF in area of retinal atrophy / Stage VI: Combination of a decrease and increase in AF in area of CNVM and fibrovascular scarring), Fluorescein Angiography, Indocyanine Green Angiography, Fundus photos, Infrared photos, Electrodiagnostic testing (Multifocal ERG: Typically normal / EOG: Reduced Arden ratio in patients and carriers), Dark adaptation (typically normal), Watzke-Allen test, Macular photostress test, Amsler grid
TREATMENT Give take home Amsler grid in order to monitor for change
Recommend AREDS II vitamins
Recommend genetic counseling for other family members
Stage I - V: Monitor. No treatment is effective
Stage VI (CNVM stage): Refer to a retinal specialist ASAP for anti-VEGF treatment
If patient presents with reduced vision (typically found in stage IV - VI): Refer to low vision
FOLLOW-UP Stage I - V: Should see patient back in 4-6 months
Once a patient with Stage VI is treated by a retinal specialist and the retina is stable. the patient should be seen back every 4-6 months
ETIOLOGY Autosomal dominant progressive macular dystrophy (mutation in the VMD2 or BEST1 gene)
Dysfunction of the protein bestrophin affects the RPE’s ability to transport fluid and ions
DIFFERENTIAL DX Age-related macular degeneration, Pattern dystrophy, Stargardt disease, Cone dystrophy, Central serous chorioretinopathy
NOTES Best disease is also called Best vitelliform macular dystrophy (BVMD) and is part of a spectrum of diseases that involve a mutation in the BEST1 gene called bestrophinopathies
Stage I and II of Best disease typically is seen within the first two decades of life (average age of onset is 6 years old)
Stage V of Best disease typically occurs after a patient reaches 40 years of age
An abnormal EOG is seen even in Best disease Stage I