Take the Retina Quiz

1. What additional test would help confirm any tentative diagnosis you might have?
a. Electroretinogram.
b. Electro-oculogram.
c. B-scan ultrasonography.
d. Optical coherence tomography.

2. How would you characterize the lesion in the left fundus?
a. Silent choroid.
b. Occult choroidal neovascularization.
c. Vitelliform.
d. Vitelliruptive.

3. What is the correct diagnosis for this patient?
a. Stargardts macular dystrophy.
b. Bests vitelliform macular dystrophy.
c. Idiopathic central serous chorioretinopathy.
d. Toxocara canis.

4. What is the typical inheritance pattern of this condition?
a. Autosomal dominant.
b. X-linked.
c. Autosomal recessive.
d. No inheritance pattern.

5. Which of these is a complication of this condition?
a. Deafness.
b. Formation of choroidal neovascular membrane.
c. Exudative retinal detachment.
d. Cystoid macular edema.

Discussion
Based on the fundus appearance, we diagnosed our patient with Bests disease, also referred to as vitelliform macular dystrophy. The esotropia is probably a result of sensory distance esotropia due to the 20/200 acuity in the left eye. So, it is probably indirectly related to her condition, although we have no way to really know for sure.

Bests disease is a hereditary macular dystrophy that affects the retinal pigment epithelium and retina. It is autosomal dominant with varied penetrance and expression. While the condition is present at birth, it may not be detected clinically until years afterward. Bests has been linked to chromosome 11q, and the gene responsible has been named VMD2. It encodes a protein referred to as bestrophin.¹

A yellow, round subretinal lesion in the macula is the classic finding associated with Bests disease. This lesion has been described as having a sunny-side up, egg yolk appearance. Histopathologically, the material within the lesion represents an abnormally high amount of lipofuscin.

Traditionally, we have viewed Bests disease as progressive and used a staging system to characterize the disease as it passes through these various stages:

• Previtelliform stage. In this earliest stage, the patient has an essentially normal fundus appearance.
• Vitelliform stage. The fundus now exhibits the classic round lesion similar to an egg yolk. We observed this in our patients right eye.
• Pseudohypopyon stage. There is layering of the material as it is being cast out of the RPE.
• Extensive disruption of the RPE. The lesion now has a scrambled egg appearance. Our patients left eye shows this type of vitelliruptive appearance.
• Atrophic stage. In this final stage, the patient has a disciform scar in the macula.

More recently, we have been moving away from this staging system, because staging implies a sequential evolution from one stage to the next. This does not necessarily occur in all patients.² While Bests disease is bilateral, patients may have varied stages in one eye vs. the fellow eye. Also, 10% of patients can have multiple lesions in one eye.³

The visual prognosis for this condition is quite good. In most instances, the visual acuity remains normal throughout childhood and even into adulthood despite the macular appearance. The progression of vision loss is slow and most often occurs after age 40. Most patients will retain reading vision in at least one eye throughout life. However, the disease can be complicated by the development of choroidal neovascularization.

Differential diagnosis of Bests disease includes Stargardts disease, any of the pattern dystrophies and age-related macular degeneration. An electro-oculogram (EOG) is useful for differentiating Bests from these other conditions and is a cost-effective method for screening family members. The EOG measures the Arden ratio, the highest potential when the subject is in the light divided by the lowest potential achieved in the dark. In normal patients, this ratio is 1.7 or higher. Bests disease is characterized by an Arden ratio below 1.5 with a normal electroretinogram (ERG).

Fluorescein angiography and optical coherence tomography (OCT) are of little diagnostic significance, although fluorescein can help determine if a patient has choroidal neovascularization. CNV associated with Bests disease is often masked by the lipofuscin and tends to be occult in nature.

Presently, there is no treatment for Bests disease. Photocoagulation or photodynamic therapy can be used to treat choroidal neovascularization. Otherwise, management includes screening of family members and genetic counseling. Patients should understand there are a variety of visual outcomes associated with the disease but most patients can maintain good enough vision to drive (20/40 or better).

Remember that the vitelliform lesion can be resorbed, and patients often have a good visual prognosis. Right now, we are watching the patient and are more concerned with development of a CNVM, a more vision-threatening complication.

If her vision stabilizes at 20/200, then low vision aids would be an option. Meanwhile, because she has 20/20 acuity in her good eye, she has good visual function with both eyes together.

(RETINA QUIZ ANSWERS: 1) b; 2)d; 3)b; 4)a; 5)b. )

George W. Meers, staff O.D. at Bascom Palmer Eye Institute in Miami, co-authored this column.

1. Seddon JM, Afshari MA, Sharma S, et al. Assessment of mutations in the Best macular dystrophy (VMD2) gene in patients with adult-onset foveomacular vitelliform dystrophy, age-related maculopathy, and bulls-eye maculopathy. Ophthalmology 2001 Nov;108(11):2060-7.
2. Park D, Arbour N, Brown D, et.al. Bests Disease. In: Guyer DR, Yanuzzi LA, Chang S, et al., editors. Retina, Vitreous, Macula. Philadelphia: W.B. Saunders, 1998:989-1004.
3. Laloum JE, Deutman AF. Peripheral vitelliform lesions in vitelliform macular dystrophy. J Fr Ophtalmol 1991;14(2):74-8.