Bilateral, Solitary, Extramacular Vitelliform Retinal Lesions in a Patient With Best Disease

Abstract

Purpose:

This work describes the first published case of Best vitelliform macular dystrophy (BVMD) with bilateral, solitary, extramacular retinal lesions.

Methods:

A case report is presented.

Results:

An 8-year-old girl with a family history of BVMD was referred for suspicious peripheral retinal lesions. Multimodal imaging disclosed bilateral, solitary, extramacular lesions consistent with the vitelliform lesions found in BVMD. There were no abnormalities in the macula.

Conclusions:

This is the first documented case of solitary, bilateral, extramacular vitelliform lesions in BVMD.

Introduction

Best vitelliform macular dystrophy (BVMD), also called Best disease, is an uncommon inherited retinal disorder with incomplete penetrance and variability in expression. ¹ It is characterized by the accumulation of lipofuscin within the retinal pigment epithelium (RPE) in the central macula of both eyes. The disorder is related to mutations in the BEST1 gene. ² This gene encodes the protein bestrophin-1, which operates as a calcium ion–sensitive chloride channel on the basolateral plasma membrane of the RPE. Diagnosis is based on family history, fundus appearance, reduced Arden ratio on electrooculography (EOG), and genetic testing. ³ Optical coherence tomography (OCT), fundus autofluorescence (FAF), and fluorescein angiography (FA) can be used to evaluate and monitor disease progression.

In this report, we describe the first presentation to our knowledge of BVMD with exclusively extramacular vitelliform lesions with multimodal imaging.

Case Report

An 8-year-old girl was referred to the retina clinic for evaluation of peripheral lesions. Her ocular history included hyperopia with astigmatism in both eyes. Her family history was notable for a mother, brother, maternal uncle, and maternal grandfather with Best disease with positive genetic testing.

Vision was 20/25 in both eyes with mild hyperopic correction. Spherical equivalent of the refraction was +1.00 diopters in both eyes. Intraocular pressure was 13 and 12 in the right eye and left eye, respectively. There was no afferent pupillary defect noted. Confrontational visual fields were full in both eyes.

Anterior slit-lamp examination was normal. Fundus examination revealed a single, 1–disc diameter, yellow, vitelliform lesion superior to the optic nerve in each eye (Figure 1). The locations of the lesions were symmetrical between the eyes. The optic nerve, vessels, macula, and periphery were otherwise healthy.

Figure 1.

Color fundus photograph and macular spectral-domain optical coherence tomography of an 8-year-old girl with peripheral vitelliform lesions. Ultra-widefield color fundus photographs of the right and left eyes disclose symmetrical yellow lesions superior to the optic nerve. Spectral-domain optical coherence tomography of the right and left eyes through the macula was unremarkable.

Spectral-domain OCT in both eyes was unremarkable. Spectral-domain OCT through the lesion in the left eye showed a hyperreflectivity and thickening between the RPE and neurosensory retina with disruption of the ellipsoid zone (Figure 2). There was no subretinal fluid. FAF revealed marked hyperfluorescence in the area of the lesion in both eyes. Optos FA showed hypofluorescence due to blocking in the area of the vitelliform-like lesion superior to the optic nerve in both eyes. There was no leakage or evidence of choroidal neovascular membrane. At the time of this writing, the patient has been observed without treatment.

Figure 2.

Multimodal imaging of vitelliform lesions in an 8-year-old girl with presumed Best disease. Extramacular spectral-domain optical coherence tomography through the vitelliform lesion showed hyperreflectivity and thickening between the retinal pigment epithelium and neurosensory retina with disruption of the ellipsoid zone. Fluorescein angiogram showed hypofluorescence due to blocking in the area of the vitelliform-like lesion. Fundus autofluorescence with marked hyperfluorescence appears in the area of the lesion.

The patient’s mother, who was previously diagnosed with BVMD by an outside provider, underwent a dilated examination and fundus photographs (Figure 3) were taken. However, a complete ocular examination was not performed at the time of the proband’s visit. On examination, there were bilateral, single, central macular vitelliform lesions about 1 disc diameter in size with pigment changes throughout the macula. In the superior and temporal macula, there was an arcuate ring of discrete yellow lesions that appeared symmetric in both eyes. There were no lesions in the periphery and the optic nerve and vessels were otherwise healthy.

Figure 3.

Fundus photographs of both eyes of the proband’s mother. In both eyes, there is a single, central macular vitelliform lesion about 1 disc diameter in size with pigment changes throughout the macula. In the superior and temporal macula, there is an arcuate ring of discrete yellow lesions. There are no lesions in the periphery.

Results

The atypical nature of this case is the presentation of extramacular vitelliform lesions without central involvement in a patient with a positive family history of BVMD.

BVMD has previously been well described. Retinal findings typically manifest at ages 5 to 10 years. ^4,5 A staging system was developed by Gass to characterize the progression in the appearance of the macula findings in BVMD. ³ As imaging technology has advanced, this disease has been further categorized with OCT, FAF, FA, and EOG. ^{6 -10}

The lesions discovered in this case were characterized by multimodal imaging and were consistent with prior descriptions of BVMD. The egg yolk–like yellow appearance and 1 to 2 disc diameters in size represent stage 2 disease according to the Gass classification. ³ OCT demonstrating subretinal hyperreflectivity, FAF showing marked hyperfluorescence in the area of the vitelliform lesion, and FA with hypofluorescence due to blockage are all consistent with previously published descriptions of stage 2 disease. ^{5 -7}

This case is unusual, however, because of the solitary, extramacular location of the vitelliform lesions. Lesions eccentric to the fovea have been reported but they are typically found with a classic central lesion. ^11,12 Multifocal Best disease is considered an atypical variant of BVMD. ^13,14 It is characterized by multiple sharply demarcated yellow lesions in the posterior pole beyond the major vascular arcades. Atypical presentations in individuals with biallelic pathogenic variants in BEST1 have been described. These individuals may have multiple vitelliform lesions, lesions with fibrosis, or variable presentations within families. A case report of a 52-year-old man with BVMD with bilateral vitelliform lesions in the peripheral macula is the only documented case of single vitelliform lesions not involving the central macula. ¹⁵ No prior reports of solitary extramacular lesions exist.

The cause of the solitary extramacular lesions in this patient is unknown. In classic Best disease, vitelliform material is thought to accumulate in the macula because of topographic differences in levels of bestrophin expression in the macula. Using immunohistochemical labeling, Western blot, and quantitative polymerase chain reaction of bestrophin in healthy human eyes, Mullins et al in 2007 found that levels of bestrophin expression in the retina were generally higher in the peripheral RPE compared with macular RPE. ¹⁶ The authors theorize that there is a macular predilection in Best disease because the macula cannot compensate with only 1 wild-type copy of the bestrophin gene, whereas the periphery is able to maintain the ionic environment with only 1 functional copy of the gene.

A limitation of this report includes length of follow-up. It could be possible that this patient may develop central macular lesions in the future, and further, long-term monitoring for disease progression is needed. Additionally, EOG testing was not possible because of the patient’s young age and cooperation required. Genetic testing has not been performed in this case, but inferences can be made because of the positive genetic testing results in relatives, strong family history supporting dominant inheritance, and the fundus examination of the proband’s mother. Genetic testing for this patient may be considered in the future.

Conclusions

This report is the first documented case of solitary, bilateral, extramacular vitelliform lesions in BVMD. The case adds to the literature an atypical presentation of a well-described disease.