Best Disease or Best Vitelliform Dystrophy
Individuals affected by Best disease frequently develop a yellow, egg yolk–like (vitelliform) macular lesion in childhood, which eventually breaks down, leaving a mottled geographic atrophic appearance (Fig 13-13). Late in the course of the disease, the geographic atrophy may be difficult to distinguish from other types of macular degeneration or dystrophy. Some patients (up to 30% in some series) have extrafoveal vitelliform lesions in the fundus. The macular appearance in all stages is deceptive, as most patients maintain relatively good visual acuity throughout the course of the disease. Even patients with “scrambled-egg” macular lesions typically have visual acuities from 20/30 to 20/60. In approximately 20% of patients, a choroidal neovascular membrane develops in at least 1 eye during the course of the disease and, if untreated, may result in poor vision.
The ERG response is characteristically normal, but the electro-oculogram (EOG) result is almost always abnormal, even in “unaffected,” asymptomatic individuals who have the causative genetic variant but have normal-appearing fundi. The light rise of the EOG (see Chapter 3) is typically severely reduced or absent. Before ordering an EOG to rule out Best disease, clinicians should ensure that the full-field ERG is normal. Molecular genetic studies are more sensitive in detecting carriers than electrophysiologic testing is. In addition to incomplete penetrance, there is also variable expressivity, and some cases may show multifocal vitelliform lesions rather than a single subfoveal lesion.
Best disease is an autosomal dominant maculopathy caused by mutations in the BEST1 gene (VMD2). The encoded protein bestrophin localizes to the basolateral plasma membrane of the RPE and functions as a transmembrane ion channel. Although some BEST1 variants will cause autosomal dominant disease, other mutations, when present as homozygous or compound heterozygous variants, can give rise to autosomal recessive bestrophinopathy (ARB). Unlike Best disease, ARB is associated with progressive retinal dysfunction on the full-field ERG, loss of visual acuity, diffuse irregularity of the RPE, and dispersed punctate flecks, which are distinct from extramacular vitelliform lesions.
Agarwal A. Gass’ Atlas of Macular Diseases. 5th ed. Philadelphia: Saunders; 2012:278–280.
Boon CJ, Klevering BJ, Leroy BP, Hoyng CB, Keunen JE, den Hollander AI. The spectrum of ocular phenotypes caused by mutations in the BEST1 gene. Prog Retin Eye Res. 2009;28(3): 187–205.
Figure 13-13 Color fundus photographs of Best vitelliform dystrophy. A, Characteristic “yolk” stage, during which visual acuity is typically good. B, Atrophy and scarring after the yolk breaks down.
(Courtesy of Mark W. Johnson, MD.)
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.