Best Disease – An Overview

Aarij Elahi

Introduction

Best vitelliform macular dystrophy, also known as Best disease, was initially described by Adams in 1883 but was named after Dr. Friedrich Best, who provided a detailed account of the condition in 1905. It is the second most common macular dystrophy after Stargardt disease and the most prevalent autosomal dominant macular dystrophy. The disease arises from mutations in the BEST1 gene located on chromosome 11q13, which encodes bestrophin, a transmembrane ion channel found on the plasma membrane of the retinal pigment epithelium (RPE) (1).

Best disease is characterized by a distinctive bilateral yellow “egg-yolk” lesion in the macula due to the accumulation of lipofuscin. The condition typically presents in childhood or early adulthood and is often associated with a favourable prognosis (2).

Clinical Stages

Best disease progresses through five distinct stages:

  1. Stage I (Previtelliform):
    • Normal vision with minimal or no RPE changes.
    • Electro-oculogram (EOG) is abnormal.
  2. Stage II (Vitelliform):
    • Classic “egg-yolk” lesion develops.
    • Most patients maintain normal vision, though mild vision loss may occur.
  3. Stage III (Pseudohypopyon):
    • Lesion begins to regress, often during puberty.
    • Vision remains comparable to Stage II.
  4. Stage IV (Vitelliruptive):
    • Material fragmentation creates a “scrambled egg” appearance.
    • Visual acuity declines during this stage.
  5. Stage V (Atrophic):
    • Pigment is completely resorbed, leaving an atrophic RPE area.
    • Vision ranges from 6/9 to 6/60.

While lesions are typically bilateral and symmetrical, rare cases of unilateral involvement can occur. About 30% of patients present with multiple lesions, known as multifocal Best disease. These lesions vary in size, with smaller, extrafoveal lesions often located superiorly (3).

Investigations

Although Best disease is primarily a clinical diagnosis, various imaging modalities can confirm and assess its progression:

  • Electro-oculogram (EOG): Universally abnormal across all stages, with an Arden ratio (light: dark) below 1.5.
  • Electroretinogram (ERG): Typically, normal.
  • Optical Coherence Tomography (OCT): Visualizes subretinal vitelliform material and fluid associated with choroidal neovascularization (CNV).
  • Fundus Autofluorescence (FAF): Shows hyperautofluorescent yellowish material. Hypoautofluorescent areas emerge in later stages.
  • Fluorescein Angiography (FA): Highlights hypofluorescence corresponding to vitelliform lesions, with mixed patterns appearing as the disease advances (4).

Differential Diagnosis

Conditions to differentiate from Best disease include:

  • Adult Foveomacular Vitelliform Dystrophy: Similar yellowish macular lesions in older patients (5).
  • Age-Related Macular Degeneration (AMD): Accumulation of drusen in Bruch’s membrane, causing decreased visual acuity.
  • Other considerations: Central Serous Retinopathy, Macular Hole, and Solar Retinopathy (6).

Management

There is currently no definitive medical or surgical treatment for Best disease. However, complications like choroidal neovascularization (CNV) can be managed effectively with anti-VEGF therapy, which improves outcomes. Photodynamic therapy has also been attempted in some cases (2).

Prognosis

The visual prognosis for Best disease is generally favourable, especially in early stages. Vision loss is often asymmetrical and may not correlate with fundus findings. In a large study, 77% of patients retained at least 6/12 vision, although 19% lost two or more lines over 8–10 years.

Complications that worsen prognosis include:

  • Sub-RPE fibrosis
  • Geographic atrophy
  • Choroidal neovascularization
  • Rarely, subretinal haemorrhage or macular hole

Patients in advanced stages may report decreased visual acuity, central scotoma, or metamorphopsia (7).

Conclusion

Best vitelliform macular dystrophy is a progressive autosomal dominant condition with a generally favourable prognosis, particularly in the early stages. Diagnosis is based on characteristic clinical features supported by imaging, while management focuses on addressing complications like choroidal neovascularization. Early recognition and monitoring are crucial for optimizing patient outcomes and maintaining visual function.

References

  1. Budiene B, Liutkeviciene R, Zaliuniene D. Best vitelliform macular dystrophy: literature review. Central European Journal of Medicine. 2014 Dec;9:784-95.
  2. Boon CJ, Theelen T, Hoefsloot EH, Van Schooneveld MJ, Keunen JE, Cremers FP, Klevering BJ, Hoyng CB. Clinical and molecular genetic analysis of best vitelliform macular dystrophy. Retina. 2009 Jun 1;29(6):835-47.
  3. Spaide RF, Noble K, Morgan A, Freund KB. Vitelliform macular dystrophy. Ophthalmology. 2006 Aug 1;113(8):1392-400.
  4. Bianco L, Arrigo A, Antropoli A, Berni A, Saladino A, Vilela MA, Mansour AM, Bandello F, Battaglia Parodi M. Multimodal imaging in Best Vitelliform Macular Dystrophy: Literature review and novel insights. European journal of ophthalmology. 2024 Jan;34(1):39-51.
  5. Spaide RF, Noble K, Morgan A, Freund KB. Vitelliform macular dystrophy. Ophthalmology. 2006 Aug 1;113(8):1392-400.
  6. Gupta A, Bansal R, Sharma A, Kapil A. Macular Degeneration, Geographic Atrophy, and Inherited Retinal Disorders. InOphthalmic Signs in Practice of Medicine 2024 Feb 14 (pp. 351-396). Singapore: Springer Nature Singapore.
  7. Tripathy K, Salini B. Best disease.

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