A child or young adult has a round, yellow lesion at the macula that looks like an egg yolk. Vision is often better than the fundus suggests. That is the typical picture of Best disease. This article shows how the lesion changes through its five stages, how it looks on fundus autofluorescence (FAF) and optical coherence tomography (OCT), and why the electro-oculogram (EOG) is the key test.

Think of Best disease when
  1. A young patient has a round yellow lesion at the macula, often in both eyes.
  2. The lesion is intensely bright on FAF.
  3. OCT shows material under the retina.
  4. The EOG is abnormal, but the electroretinogram (ERG) is normal.

What is Best disease?

Best disease is an inherited macular dystrophy. Its full name is Best vitelliform macular dystrophy. It is the second most common macular dystrophy after Stargardt disease.

Inheritance is autosomal dominant. The gene is BEST1. It makes bestrophin, an ion channel in the retinal pigment epithelium (RPE) that is involved in chloride transport. When bestrophin does not work, RPE function fails, and yellow material builds up under the macula.

Severity varies widely, even within the same family[1].

Symptoms

Typical cases present before about age 20 with reduced vision or a central scotoma.

While the yellow "yolk" is intact, vision is often still good. Vision drops later, when the lesion breaks up and the macula becomes atrophic or scarred[1].

The five stages

Best disease is staged by its fundus appearance. The classic system has five stages[2].

Stage 1: Previtelliform

The fundus is normal, but the EOG is already abnormal. People with a BEST1 variant and a normal fundus also have an abnormal EOG.

Stage 2: Vitelliform

A round, sharply outlined yellow lesion appears at the macula, like the yolk of a sunny-side-up egg. It is 0.5 to 2 disc diameters across. The two eyes can be at different stages, and sometimes only one eye is affected at first. Vision is usually not affected yet[1].

The yellow material is thought to be lipofuscin. On OCT, it sits between the retina and the RPE as a dome. Lipofuscin is autofluorescent, so on FAF the lesion is intensely bright.

Best disease: color fundus photograph with a round yellow-orange lesion at the macula, autofluorescence image in which the lesion is intensely bright, and OCT showing a dome of material beneath the fovea
Vitelliform stage in a 32-year-old woman. Top left, color fundus photograph: a round yellow-orange egg-yolk lesion at the macula. Top right, autofluorescence: the lesion is intensely bright. Bottom, OCT: a dome of material under the fovea. Labels are in Japanese, as in the original.

Stage 3: Pseudohypopyon

Part of the material breaks down, often around puberty[1]. The remaining yellow material settles to the bottom of the lesion, with a flat upper edge, like a hypopyon in the anterior chamber. OCT shows subretinal fluid above the settled material[3].

Two color fundus photographs, two autofluorescence images and two OCT scans of both eyes of one patient
Pseudohypopyon stage in both eyes. a, b: yellow material settled in the lower part of the lesion. c, d: autofluorescence is bright along the edge and at the bottom of the lesion. e, f: OCT shows subretinal fluid. From de Souza et al. 2019, CC BY 4.0.

Stage 4: Vitelliruptive

The material breaks up into patches, like scrambled eggs, and vision drops[1]. As the deposit disappears, OCT shows the subretinal fluid more clearly.

Four rows of OCT scans and autofluorescence images, one row for each of stages 1 to 4
Stages 1 to 4 on OCT (left) and short-wavelength autofluorescence (right). A, B: previtelliform, with normal retinal layers. D, E: vitelliform, with a dome of bright material under the fovea (asterisk) that is bright on autofluorescence. G, H: pseudohypopyon, with subretinal fluid, a thickened band at the outer segment tips (arrow) and the bright material displaced downward. J, K: vitelliruptive, with subretinal fluid and clumps of outer segments (arrow). The dotted lines come from the original study and can be ignored. From Jauregui et al. 2021, CC BY 4.0, cropped.

Stage 5: Atrophic

The yellow material is gone, leaving an atrophic area of RPE. FAF is now dark (hypoautofluorescent) in this area, and vision is clearly reduced. Some eyes end with a fibrotic scar instead[2].

EOG findings

The EOG is the key test for Best disease. It mainly reflects RPE function. It is usually abnormal at every stage, even before the fundus changes. The Arden ratio (the light peak divided by the dark trough, now called the LP:DT ratio) is typically below 1.5[1].

Hand-drawn EOG curves over 45 minutes: the normal curve dips in the dark and rises to a high peak in the light, while the Best disease curve stays low and flat
EOG in a normal eye (black) and in Best disease (blue). The normal potential falls to a dark trough (DT) in the dark and rises to a light peak (LP) in the light. In Best disease, the light rise is almost absent. FO and SO mark the fast and slow oscillations.

The full-field ERG is usually normal. An abnormal EOG with a normal ERG points to a problem in the RPE. The EOG article explains how the ratio is measured.

A few genetically confirmed eyes have a ratio above 1.5, so a normal EOG does not completely rule out Best disease. Genetic testing for BEST1 confirms the diagnosis[2].

A vitelliform lesion in someone over 40 is not always Best disease. Adult-onset vitelliform macular dystrophy gives a smaller lesion, and its ERG and EOG are usually normal[1].

Treatment

As with other macular dystrophies, there is no treatment for the disease itself.

Choroidal neovascularization (CNV) can develop and cause bleeding under the macula. It is treated with anti-VEGF injections. In a large UK series, about 1 in 6 patients had CNV during a mean follow-up of 8 years, and treated eyes kept better vision than untreated eyes[2].

Summary

  • Best disease is an autosomal dominant macular dystrophy caused by BEST1.
  • Five stages: normal fundus with an abnormal EOG → egg yolk → yolk settles with a level → scrambled egg → atrophy.
  • The yellow material is bright on FAF and sits under the retina on OCT. Atrophy is dark on FAF.
  • The EOG is usually abnormal at every stage, while the ERG is normal. Genetic testing confirms the diagnosis.
  • There is no treatment for the dystrophy, but CNV is treated with anti-VEGF injections.

Figure credits

Vitelliform stage: reproduced from the 49th National Examination for Certified Orthoptists (Japan), morning session, question 69, published by the Ministry of Health, Labour and Welfare. Rotated and cropped from the original.

Pseudohypopyon stage: Figure 8 from de Souza CPR, Mello LGM, Gomez F, Morizot E. Int J Retina Vitreous 2019;5:6 (https://doi.org/10.1186/s40942-019-0156-0), licensed under CC BY 4.0. Unchanged.

Stages on OCT and autofluorescence: Figure 1 from Jauregui R, Parmann R, Nuzbrokh Y, Tsang SH, Sparrow JR. Sci Rep 2021;11:14300 (https://doi.org/10.1038/s41598-021-93316-3), licensed under CC BY 4.0. Cropped to remove the OCT angiography column (C, F, I, L).

EOG curves: drawn by the author.

References

[1] Salmon JF. Kanski’s Clinical Ophthalmology: A Systematic Approach. 10th ed. Elsevier; 2025. Chapter 15, Inherited retinal degenerations: Best vitelliform macular dystrophy.

[2] Laich Y, Georgiou M, Fujinami K, et al. Best vitelliform macular dystrophy natural history study report 1: clinical features and genetic findings. Ophthalmology. 2024;131(7):845-854. PMID 38278445.

[3] Jauregui R, Parmann R, Nuzbrokh Y, Tsang SH, Sparrow JR. Stage-dependent choriocapillaris impairment in Best vitelliform macular dystrophy characterized by optical coherence tomography angiography. Sci Rep. 2021;11(1):14300. PMID 34253754.

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