Laboratory Studies
Genetic testing: This disorder has been mapped to a genetic defect in chromosome 11 (region q12-q13.1). [10, 20, 21, 22] A mutation in BEST1 is more probable when a vitelliform lesion is accompanied by a reduced Arden ratio on EOG testing. [23] Although most individuals with Best disease have an autosomal dominant defect, there are individuals with autosomal recessive inheritance. [14]
Imaging Studies
Fluorescein angiogram reveals blockage of choroidal fluorescence by the vitelliform lesion. The angiogram is otherwise normal at this stage. In the atrophic stage, a transmission defect is noted; this is shown in the image below. If a choroidal neovascular membrane develops, then a corresponding area of hyperfluorescence with leakage will be found in fluorescein or indocyanine green angiography. [7, 24]
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.
Fundus photography is useful for documentation and follow-up of fundus lesions.
Spectral-domain optical coherence tomography (SD-OCT) demonstrates abnormality in the region between the RPE and the inner segment/outer segment line visualized on high resolution studies. Disruption of the outer retina is noted in stages 2-4, while absence is seen in stage 5 (atrophic). [25] Enhanced depth imaging reveals choroidal thinning in advanced disease, correlating to a decline in visual acuity. [26] Cystoid macular edema and choroidal neovascularization can be identified on OCT (see image below). [27] Subretinal fluid is associated with worse visual acuity. [25]
Spectral domain optical coherence tomography demonstrates subretinal lesion with adjacent cystoid macular edema.
Adaptive optics demonstrates disruption of photoreceptor integrity with some retention of function, [28] consistent with the retention of visual function found through the earlier stages of Best disease.
Other Tests
Electro-oculogram
The EOG, which reflects RPE function, is the most diagnostic test for evaluating vitelliform macular dystrophy. In the majority of such individuals, a severe decrease occurs in light response, reflected by an Arden (light-peak/dark-trough) ratio of 1.1-1.5. (The normal Arden ratio is 1.8.) Carriers will also have an abnormal EOG result. [29] No correlation exists between EOG result and disease stage, visual acuity, or patient age. EOG results usually are symmetric for both eyes. [30]
The EOG is very useful for distinguishing this diagnosis from its differential. The EOG result is usually normal in adult foveomacular dystrophy.
Electroretinogram
The full-field electroretinogram (ERG) result is normal in this condition. A focal ERG or multifocal ERG, concentrating on macular function, reveals abnormal function corresponding to the area of anatomical disruption. [31]
Histologic Findings
This disease primarily affects the RPE. Lipofuscin accumulates within RPE cells and in the sub-RPE space. This material stains PAS-positive. The RPE can degenerate, and macrophages containing PAS-positive material have been found to migrate into the outer retina. The choriocapillaris is normal. Choroidal neovascularization has been demonstrated. [5, 32]
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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.
