Best Disease: An Overview

Orkun Kaymaz

Introduction

Best disease or Best vitelliform macular dystrophy (BVMD) is a rare autosomal dominant condition due to a BEST1 gene mutation with highly variable expression. It typically presents in childhood; however, most patients retain reading vision beyond the fifth decade. It is characterised by egg-yolk-like vitelliform lesions in the macula. The condition is named after Dr Friedrich Best who described the detailed pedigree of the disease in 1905. This overview will summarise the aetiology, pathophysiology, diagnosis and management of Best disease.

Aetiology

BVMD is primarily attributed to mutations in the BEST1 gene located on chromosome 11q13. The BEST1 gene encodes the bestrophin-1 protein, which is predominantly expressed in the retinal pigment epithelial (RPE) (1). The protein plays a crucial role in maintaining RPE cell function. Mutations in the BEST1 gene lead to dysfunctional RPE cells and the accumulation of lipofuscin-like material between the RPE and the Bruch’s membrane. The genetic inheritance pattern of BVMD is typically autosomal dominant, indicating that individuals with one affected parent have a 50% chance of inheriting the mutation.

Pathophysiology

The pathophysiological mechanisms underlying BVMD are closely tied to the dysfunction of RPE cells and the accumulation of lipofuscin within the macula. Lipofuscin, a waste product generated during the visual cycle, accumulates abnormally in BVMD patients due to bestrophin-1 dysfunction. This accumulation disrupts the normal metabolic exchange between RPE cells and photoreceptor cells, leading to the formation of a characteristic yellowish lesion known as the vitelliform deposit. It is believed that BVMD has 6 clinical stages (2, 3):

  • Stage I (pre-vitelliform): showing EOG findings only, vision is normal.
  • Stage II (vitelliform): showing yolk-like macular lesion. Vision is usually normal, mild loss may be present.
  • Stage III (pseudohypopyon): lipofuscin layering, vision normal or mildly affected.
  • Stage IV (Vitelliruptive): ‘scrambled’ appearance, vision usually preserved.
  • Stage V (end-stage): scarring or atrophy in the RPE.
  • Stage VI (choroidal neovascularisation): results in significant loss of vision (6/60 or worse). This complication can occur in up to 20% of patients (1, 2).

Clinical presentation

Initially, BVMD impairs central vision, making tasks like reading and recognizing faces challenging. The hallmark of the disease is the presence of distinct yellow, egg-yolk-like vitelliform lesions within the macula, which can evolve through various stages, including pseudohypopyon and vitelliruptive stages (3). Some patients experience distorted or wavy vision, a phenomenon known as metamorphopsia, while others note changes in colour perception, often describing a perceived yellowish tint. As BVMD advances, a central scotoma, or blind spot, may develop within an individual’s visual field. In rare instances, spontaneous subretinal haemorrhages can occur overlying the vitelliform deposit (2, 3).

Diagnosis

The diagnosis of Best Vitelliform Macular Degeneration (BVMD) relies on specific criteria that collectively confirm the presence of this hereditary retinal disorder. These criteria include the identification of one of the characteristic lesions associated with BVMD, the presence of an abnormal electrooculogram (EOG) that indicates functional changes in the retinal pigment epithelial (RPE) cells, the observation of a dominant mode of inheritance within affected families, and the alignment of the natural course and onset of the disease with typical BVMD characteristics. The following investigations aid the diagnosis:

  • Clinical Examination: including visual acuity testing, fundoscopy, and macular assessment.
  • Imaging: Optical coherence tomography (OCT) is invaluable for visualizing macular structure and vitelliform lesions. Fundus autofluorescence reveals lipofuscin accumulation (1).
  • Genetic Testing: Confirmation of BEST1 gene mutations aids in diagnosis and genetic counselling (1).
  • Electrooculogram (EOG): EOG testing assesses RPE cell function and can be abnormal in BVMD. The Arden ratio is usually reduced on EOG (1, 2).

Management

Patients with Best Vitelliform Macular Degeneration (BVMD) benefit from a multifaceted approach to care. This encompasses regular ophthalmologic assessments to track disease progression. Early detection of complications especially choroidal neovascular membrane (CNVM). CNVM may require anti-VEGF agents such as bevacizumab (1,3). Providing access to a variety of low vision aids and rehabilitation services such as magnifiers, specialized glasses, and adaptive technologies to optimize remaining vision, and offering essential genetic counselling (2).

Conclusion

BVMD is a hereditary retinal disorder characterized by lipofuscin accumulation in the macula. While there’s no evidence-based treatment, early diagnosis, regular monitoring, low vision aids, and ongoing research provide hope for improved management and potential treatments in the future.

References:

  1. Tripathy K, Salini B. Best Disease. [Updated 2023 Feb 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537290/
  2. Best disease and Bestrophinopathies (no date) EyeWiki. Available at: https://eyewiki.aao.org/Best_Disease_and_Bestrophinopathies (Accessed: 01 September 2023).
  3. Boon CJ, Klevering BJ, Leroy BP, et al. The spectrum of ocular phenotypes caused by mutations in the BEST1 gene. Progress in Retinal and Eye Research. 2009;28(3):187-205

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