Best’s disease is an autosomal dominant disorder characterized by bilateral vitelliform macular lesions that progress through several stages throughout life. The authors describe a 20-month-old child with hereditary Best’s disease inherited from his father. To their knowledge, this is the youngest child to be diagnosed as having Best’s disease using photographic documentation.
From Bascom Palmer Eye Institute, Miami, Florida.
The authors have no financial or proprietary interest in the materials presented herein.
Partially supported by NIH center grant P30-EY014801 and by an unrestricted grant to the University of Miami from Research to Prevent Blindness, Inc., New York, New York.
Address correspondence to Jaclyn L. Kovach, MD, Bascom Palmer Eye Institute, Retina Center at Naples, 311 9th Street North, Suite 100, Naples, FL 34102.
Received: October 06, 2008
Accepted: February 03, 2009
Posted Online: May 21, 2010
Best’s disease (vitelliform macular dystrophy type 2) is a progressive autosomal dominant disease of the macula caused by a mutation in the bestrophin-1 gene (Best1), which codes for a calcium-sensitive chloride channel present on the basolateral membrane of the retinal pigment epithelial cell.1 The clinical manifestation of this genetic defect is the deposition of lipofuscin in the retinal pigment epithelium.
The macular lesion, first described by Best in 1905,2 evolves through six stages. The previtelliform stage is defined by subtle retinal pigment epithelial mottling. The vitelliform stage is usually seen in children ages 5 to 15 years and is defined by a yellow, round subretinal lesion between 0.5 and 2 disc diameters in size. Patients will generally maintain normal visual acuity throughout this stage because of the absence of photoreceptor disruption. In the pseudohypopyon stage, often seen in the teenage years, the yellowish material precipitates inferiorly. In the vitelliruptive or scrambled-egg stage, there is further disruption of the lipofuscin material to the perimeter of the original vitelliform lesion. The atrophic stage can cause visual acuity to decrease to legal blindness and subretinal neovascular membrane formation can occur, likely as a consequence of retinal pigment epithelial damage.3
There are two cases in the literature with photographic documentation of Best’s disease at age 5 years.4,5 We describe what appears to be the youngest child with photographic documentation of Best’s disease.
The patient was observed closely beginning at 6 months of age because of a positive family history for Best’s disease. Results of dilated fundus examinations performed with non-sedated indirect ophthalmoscopy at 6 months and 1 year of age were normal. The child’s parents reported that he appeared to see normally. There was no significant medical history. Ophthalmic evaluation at age 20 months was completely normal except for small vitelliform macular lesions in both eyes (Fig. 1). On visual acuity examination, the patient alternated by induced tropia test at near. The diagnosis of Best’s disease was made clinically and was confirmed by a positive Best1 gene mutation. The child was observed. At his most recent examination, at age 3.5 years, uncorrected visual acuity with Allen pictures was 20/20 in each eye. The ophthalmologic examination showed stable bilateral macular vitelliform lesions.
Figure 1. Right (A) and Left (B) Fundus Photographs of the Bilateral Vitelliform Lesions in the Patient at Age 20 Months.
The patient inherited Best’s disease from his father who, at age 40 years, maintains visual acuity of 20/20 in the right eye and 20/15 in the left eye in the vitelliruptive stage (Fig. 2). The patient’s sister is currently 6 years old and has a normal retinal examination and visual acuity of 20/20 in both eyes.
Figure 2. Right (A) and Left (B) Fundus Photographs of the Bilateral Vitelliruptive Lesions in the Patient’s Father.
Best’s disease (vitelliform macular dystrophy type 2) is commonly diagnosed by a bullous, yellow subretinal lesion in the central macula, which is formed by the accumulation of lipofuscin and other autofluorescent byproducts of photoreceptor degeneration. As the disease progresses, subretinal fluid is also thought to accumulate, likely due to the mutation that compromises the natural pump function of the retinal pigment epithelial cells. The yellow material gradually moves inferiorly, breaks apart, and is partially reabsorbed in the vitelliruptive stage. The presence of this material could have a toxic effect on the retinal pigment epithelial cells, which would contribute to the atrophy of the retinal pigment epithelial and photoreceptor cells. Optical coherence tomography6 and autofluorescence7 analysis have been useful in confirming the location of the material and the degree of retinal pigment epithelial damage.
Patients usually maintain visual acuity better than 20/40 through the vitelliruptive stage,8 as is the case with this patient’s father. It is in the atrophic stage that visual acuity can deteriorate to the level of legal blindness because of retinal pigment epithelial cell and photoreceptor disruption and death. However, 50% of older patients (aged 60 to 84 years) can maintain a visual acuity of at least 20/40.8
There is no effective treatment available to slow the progression of Best’s disease. Antioxidant supplementation might have a theoretical benefit, given the role of free radicals in the formation of lipofuscin.9 Progressive vision loss in patients with subretinal neovascularization may be prevented by the use of an anti-vascular endothelial growth agent. This treatment was tried by Leu et al. for a 13-year-old child with choroidal neovascularization with resultant improvement in vision and OCT appearance.10
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- Best F. Ueber eine hereditaere Makulaaffection. Beitraege zur Vererbungslehre. Zschr Augenheilk. 1905;13:199–212.
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- Schmitz-Valckenberg S, Holz FG, Bird AC, Spaide RF. Fundus autofluorescence imaging: review and perspectives. Retina. 2008;28:385–409. doi:10.1097/IAE.0b013e318164a907 [CrossRef]
- Leu J, Schrage NF, Degenring RF. Choroidal neovascularization secondary to Best’s disease in a 13-year-old boy treated by intravitreal bevacizumab. Graefes Arch Clin Exp Ophthalmol. 2007;245:1723–1725. doi:10.1007/s00417-007-0604-7 [CrossRef]