Introduction
Background
Best disease, also termed vitelliform macular dystrophy, is an autosomal dominant disorder, which classically presents in childhood with the striking appearance of a yellow or orange yolklike lesion in the macula. Dr Franz Best, a German ophthalmologist, described the first pedigree in 1905.1
The lesion evolves through several stages over many years, with increasing potential for adverse visual outcome. A hallmark of the disease is a markedly abnormal electro-oculogram (EOG) in all stages of progression and in phenotypically normal carriers.
Pathophysiology
Lesions in this disease are restricted to the eye. No systemic associations exist. Abnormalities in the eye result from a disorder in the retinal pigment epithelium (RPE). Lipofuscin (periodic acid-Schiff [PAS] positive) accumulates within the RPE cells and in the sub-RPE space, particularly in the foveal area. The RPE appears to have degenerative changes in some cases, and secondary loss of photoreceptor cells has been noted.
Frequency
United States
Rare
International
Rare
Mortality/Morbidity
Visual acuity is good in the previtelliform stage. Even with the egg-yolk appearance, visual acuity is maintained in the range of 20/20 to 20/50 (6/6 to 6/15) for many years. The breakup of the vitelliform stage, leading to the scrambled egg stage, may be accompanied by visual acuity deterioration. It is the final stages of geographic RPE atrophy with possible development of choroidal neovascular membrane that is associated with further deterioration in acuity.
These changes usually occur in individuals older than 40 years. Various studies have shown that most individuals retain reading and driving vision in at least 1 eye into adulthood (88% have 20/40 or better vision). Only 4% of these individuals develop vision less than 20/200 in the better eye.
Race
Best disease is found in individuals of European, African, and Hispanic ancestry.
Sex
No known gender predilection exists.
Age
Usual onset is from 3-15 years, with an average age of 6 years. The condition often is not detected until much later in the disease because visual acuity may remain good for many years. The atrophic stage usually occurs after age 40 years.
Clinical
History
Many individuals initially are asymptomatic, with fundus lesions noted on examination. Visual symptoms can include decreased acuity (blurring) and metamorphopsia. These symptoms may worsen if the disease progresses to the atrophic stage.
Physical
This disorder has variable clinical expression. Some carriers have a normal examination and remain asymptomatic. Findings are usually bilateral and can be asymmetric.
- Visual acuity
- Previtelliform stage - 20/20
- Vitelliform stage - 20/20 to 20/50
- Pseudohypopyon stage - 20/20 to 20/50
- Vitelliruptive stage - 20/20 to 20/100
- Atrophic stage - Acuity may reduce to less than 20/200
- Several stages of fundus appearance are described. Not all individuals progress beyond the early stages. Other individuals can skip from the earliest stages to an atrophic-appearing macula. Unilateral findings and multifocal lesions have been described.
- Stage 1 (previtelliform) - Normal macula or subtle RPE pigment changes, EOG abnormal
- Stage 2 (vitelliform) - Well-circumscribed, 0.5-5 mm round, elevated, yellow or orange lesion; described as an egg-yolk appearance; usually centered on the fovea; can be multifocal; the rest of the fundus has a normal appearance.
- Stage 3 (pseudohypopyon) - Yellow material can break through the RPE and accumulate in the subretinal space in a cyst with a fluid level formed. The yellow material will shift with extended changes in position (60-90 min). This stage most often is found in the teenage years, but it has been described in individuals aged 8-38 years.
- Stage 4 (vitelliruptive) - Scrambled egg appearance is due to the breakup of the uniform vitelliform lesion. Pigment clumping and early atrophic changes may be noted. Visual acuity may deteriorate moderately.
- Stage 5 (atrophic) - As the yellow material disappears over time, an area of RPE atrophy remains. This appearance is difficult to distinguish from other causes of macular degeneration. Visual acuity can deteriorate more markedly at this stage.
- Stage 6 (choroidal neovascular/cicatricial) - Following the atrophic stage, choroidal neovascularization can develop, leading to a whitish subretinal fibrous scar.
- Hyperopia is common.
Causes
Best disease is autosomal dominant with variable penetrance. Genetic linkage has mapped the disease to the long arm of chromosome 11 (11q12-q13). The abnormality is in the RPE, as noted on histopathology and electrophysiology testing.
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References
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Stöhr H, Marquardt A, Rivera A, Cooper PR, Nowak NJ, Shows TB, et al. A gene map of the Best's vitelliform macular dystrophy region in chromosome 11q12-q13.1. Genome Res. Jan 1998;8(1):48-56. [Medline].
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Further Reading
Keywords
Best’s disease, vitelliform macular dystrophy, vitelline dystrophy, vitelliruptive degeneration
