History
Many individuals with Best disease 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
Best disease has variable clinical expression. Some carriers have a normal examination and remain asymptomatic. Findings usually are bilateral and can be asymmetric, but unilateral presentations have been reported. [11] Hyperopia is common. [8, 12, 13, 14]
Visual acuity
Visual acuity varies by stage, as follows:
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Previtelliform stage - 20/20
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Vitelliform stage - 20/20 to 20/50
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Pseudohypopyon stage - 20/20 to 20/50
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Vitelliruptive stage - 20/20 to 20/100
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Atrophic stage - Acuity may reduce to less than 20/200
Fundus appearance
Several stages of fundus appearance are described. [15, 16] Not all individuals progress beyond the early stages. [17] Other individuals can skip from the earliest stages to an atrophic-appearing macula. Unilateral findings and multifocal lesions have been described. [14, 18]
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Stage 1 (previtelliform) - Normal macula or subtle RPE pigment changes, EOG abnormal
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Stage 2 (vitelliform), shown below - 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.
Classic egg-yolk appearance in the second (vitelliform) stage of vitelliform macular dystrophy. The 0.5-6 mm diameter yellow or orange lesion results from an accumulation of lipofuscin beneath and within the retinal pigment epithelium. This lesion is usually noted in individuals aged 3-15 years. Visual acuity is most often preserved in the 20/20 to 20/40 range.
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Stage 3 (pseudohypopyon), shown below - 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.
The pseudohypopyon (stage 3) lesion is found in the teenage or later years. It results from a break in the retinal pigment epithelium, allowing accumulation of the yellow substance in the subretinal space with the formation of a fluid level. This fluid can shift over 60-90 minutes with positioning.
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Stage 4 (vitelliruptive), shown below - 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.
The scrambled egg appearance of stage 4 results from a deterioration of the uniform cystic lesion noted in stage 2 (egg-yolk appearance). At this point, the visual acuity can begin to worsen.
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Stage 5 (atrophic), shown below - 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.
The atrophic stage (stage 5) may be accompanied by the deposition of pigment or choroidal neovascularization, both of which can lead to visual deterioration.
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Stage 6 (choroidal neovascular/cicatricial) - Following the atrophic stage, choroidal neovascularization can develop, [7] leading to a whitish subretinal fibrous scar.
Causes
Best disease is generally autosomal dominant with variable penetrance. Genetic linkage has mapped the disease to the long arm of chromosome 11 (11q12-q13). The gene responsible has been named bestrophin1 (BEST1). The abnormality is in the RPE, as noted on histopathology and electrophysiology testing. An autosomal recessive form of Best disease has been described. [19]
Complications
Although uncommon, choroidal neovascularization can occur following the atrophic stage, and it can be responsible for further deterioration in visual acuity. A disciform scar may result.
Plaques of white subretinal fibrous tissue can develop in conjunction with the atrophic stage. Visual acuity is often reduced to 20/100 or worse with this appearance.
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Classic egg-yolk appearance in the second (vitelliform) stage of vitelliform macular dystrophy. The 0.5-6 mm diameter yellow or orange lesion results from an accumulation of lipofuscin beneath and within the retinal pigment epithelium. This lesion is usually noted in individuals aged 3-15 years. Visual acuity is most often preserved in the 20/20 to 20/40 range.
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The pseudohypopyon (stage 3) lesion is found in the teenage or later years. It results from a break in the retinal pigment epithelium, allowing accumulation of the yellow substance in the subretinal space with the formation of a fluid level. This fluid can shift over 60-90 minutes with positioning.
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The atrophic stage (stage 5) may be accompanied by the deposition of pigment or choroidal neovascularization, both of which can lead to visual deterioration.
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The scrambled egg appearance of stage 4 results from a deterioration of the uniform cystic lesion noted in stage 2 (egg-yolk appearance). At this point, the visual acuity can begin to worsen.
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Adult vitelliform macular dystrophy resembles Best disease, but it can be differentiated by its later age of onset, smaller lesion, and normal electro-oculogram testing.
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The fluorescein angiogram of the latter lesion reveals a transmission defect consistent with atrophic changes in the retinal pigment epithelium. This appearance also can be found in the later stages of Best disease.
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Spectral domain optical coherence tomography demonstrates subretinal lesion with adjacent cystoid macular edema.
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Autosomal-recessive bestrophinopathy: Atrophic central lesion and white subretinal deposits along the vascular arcades in a 14-year-old female with 20/70 vision and no family history of Best macular dystrophy.
