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Best disease: for patients

Overview

Best disease, alternatively known as Best vitelliform macular dystrophy (BVMD), is an eye condition associated with progressive degeneration of the macula, which is responsible for colour perception and recognition of fine visual details. Best disease is one of the most common inherited forms of macular degeneration, affecting 1 in 10,000 individuals.[1]

Individuals affected by Best disease usually start experiencing visual symptoms such as blurry vision around childhood or early adolescence, but some may only start experiencing symptoms later in life.[2] Along with the age of onset, the severity of symptoms is also highly variable. While some may be greatly affected, others may not even notice any visual problems and the typical macular features are only detected by chance on a routine eye check.[3] Furthermore, both eyes may not be affected to the same extent in some patients.

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The condition

Symptoms

Patients tend to be affected by the loss of central vision and reduction in visual sharpness (visual acuity). This can pose difficulties to patients in most daily tasks, such as reading print, watching TV, driving, seeing the screen of a phone or computer. Visual acuity tends to deteriorate gradually but without ever reaching the point of complete sight loss. It is often very difficult to predict future visual function in a particular individual as the rate of visual decline varies widely from patient to patient. In general, those with later onset of symptoms are usually less affected and have a slower rate of visual decline.[4-6] Despite progressive central visual loss, Best disease does not typically affect the outer parts of the retina and hence, patients are still able to retain useful peripheral (side) vision for navigation.

In addition to reduced visual acuity, patients may also experience some/all of the following symptoms:

  • Difficulty recognising colour
  • Straight objects (e.g lamp post or a door frame) appearing curvy or wavy (metamorphopsia)
  • Sensitivity to light (photophobia)

Some patients may not have any symptoms at all and the typical macular features are only detected by chance during a routine eye test.

How metamorphopsia looks from a patient's perspective. A pair of hands playing the piano. The piano keys appear distorted, along with the notes above the keys.
A patient’s perspective of metamorphopsia (B) compared to normal (A)

Cause

Best disease is caused by mutations in the BEST1 gene. The gene carries information for the production of the protein bestrophin-1, which can be found in the retinal pigment epithelium (RPE), a layer of cells that supports the light-sensing photoreceptors in the retina. Bestrophin-1 forms a channel between these two cell layers, allowing charged chloride ions to flow through, which is crucial in maintaining the normal functioning of the retina.[7-9] Mutations in the BEST1 gene can also cause other less common conditions, which together with Best disease are collectively termed bestrophinopathies. Researchers are still not sure why mutations in BEST1 gene predominantly affects the macula and cause Best disease, but studies are ongoing.

How is it diagnosed?

Best disease can be diagnosed by an ophthalmologist based on your symptoms and examination findings. During your eye clinic appointment, your ophthalmologist will perform a few tests to help with the diagnosis. An eye drop will be used to dilate the pupils so that the macula and the rest of the retina can be examined. Best disease typically appears as a vitelliform lesion on the macula that resembles an egg-yolk with the sunny side up. However, this characteristic appearance may not be seen in all patients and other features may be present instead. The doctor will also use specialised cameras to assess the health of the retina and macula in more detail. These cameras can pick up more subtle features of Best disease that may not be detected on examination. In addition, specialised electrodiagnostic tests called electro-oculogram (EOG) and electroretinogram (ERG) will also be arranged. Both tests are used to assess the overall health of the retina and RPE. In Best disease, the EOG reading is typically reduced when a light is shone at the tested eye. The ERG tends to be normal.

A photo of the retina of a patient with Best disease. The middle of the photograph has an egg-yolk-like yellowish lesion. This is the characteristic appearance of Best disease.
A patient with Best disease with a typical vitelliform lesion at the macula (green box). It is often described as having an egg-yolk-like appearance.

Given the variable clinical characteristics of Best disease, genetic testing is advised to confirm the diagnosis by identifying changes in the BEST1 gene.

How is it inherited?

1) Autosomal dominant (AD) inheritance

Best disease is inherited in this manner, meaning that only one faulty copy of the BEST1 gene (inherited from either parent) is enough to cause the condition. This means that each newborn of the patient has a 50% chance of inheriting the condition regardless of gender.

The faulty gene copy is present in the father while the mother is not affected. Each newborn of this couple has a 50% chance to be affected by the condition.
Autosomal dominant inheritance

As Best disease is an inherited condition, families can seek a genetic counsellor to obtain more information on inheritance and family planning options.

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Treatment

Is there any treatment?

1) Supportive visual measures

There is currently no treatment available for Best disease but researchers are exploring various approaches. Treatment is mainly focused on optimising remaining sight. These include:

  • Regular monitoring of visual function and prescribing glasses (if required)
  • Patching treatment may be required if a “lazy” eye is detected in children (usually involves patching of the better seeing eye)
  • Referral to low vision services
  • Utilising visual aids and assistive technology to improve quality of life
  • Having a healthy diet consisting of fresh fruits and green leafy vegetables
  • Using blue light screen protectors on mobile devices or computer screens*
  • Wearing hats/UV protected sunglasses and placing sunlight diffusers at the back window of cars

*Current available evidence shows that blue light emitted from screens do not damage the retina but it can disrupt our sleep cycle. The screen protectors are used as a precautionary measure.

2) Optimisation of development

As vision is important in normal childhood development and education, children with visual impairment due to Best disease should be referred to developmental paediatricians and advisory teaching services for children/adolescents with visual impairment (e.g. sensory support services within local authority). This will enable provisions to be made within the educational and home settings so that the child can reach his/her developmental potential and develop skills to achieve independence.

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Current research in Best disease

1) Gene therapy

Gene therapy works by introducing a healthy copy of the gene into the appropriate cells to compensate for the faulty gene copy that is not producing enough functional protein. While it has shown promising results in animal models, more work is still required before human clinical trials can commence for Best disease.[10]

The normal gene copy is packaged into a harmless virus. The virus then breaches the target cells and delivers the normal gene copy to the cell's DNA mechanism. As a result, the cell is now making normal and functional protein.
Principles of gene therapy

2) Stem cells

Stem cells have the ability to self-replicate continuously and also differentiate into many different cell types. Stem cells derived from patients affected by Best disease will help researchers gain better understanding about the genetic mechanisms of the condition and to efficiently screen for potential therapies.[11,12] There are currently two trials underway aiming to establish RPE stem cell lines derived from skin and hair cells of patients with bestrophinopathies (NCT 02162953 and NCT 01432847).

Related links

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Practical advice

Living with Best disease

Patients are still able to lead independent lives through maximising their available vision and having access to social support. Here are some ideas:

  • Attending the low vision clinic which provides access to low vision specialists, Eye Clinic Liaison Officers (ECLOs), visual aids and visual rehabilitation services
  • Utilising visual aids and assistive technology that may improve quality of life
  • Getting in touch with the local education authority for access to qualified teachers for children with visual impairment (QTVI) and special educational needs co-ordinator (SENCO)
  • Registering your child as sight impaired (SI) or severely sight impaired (SSI) if eligible for access to social support and financial concessions
  • Getting in touch with national or local charities for advice and peer support

Related links

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Referral to a specialist centre

If you are based in the UK and would like to be seen in the nearest specialist centre for your eye condition, either to receive a more comprehensive genetic management or just to find out more about current research, you can approach your GP to make a referral or alternatively arrange for a private appointment. 

More information can be found in our “How to see a genetic eye specialist?” page.

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Further information and support

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References

  1.  Rahman N, Georgiou M, Khan KN, Michaelides M. Macular dystrophies: clinical and imaging features, molecular genetics and therapeutic options. Br J Ophthalmol. Apr 2020;104(4):451-460. doi:10.1136/bjophthalmol-2019-315086
  2.  Renner AB, Tillack H, Kraus H, et al. Late onset is common in best macular dystrophy associated with VMD2 gene mutations. Ophthalmology. Apr 2005;112(4):586-92. doi:10.1016/j.ophtha.2004.10.041
  3.  Renner AB, Tillack H, Kraus H, et al. Morphology and functional characteristics in adult vitelliform macular dystrophy. Retina. Dec 2004;24(6):929-39. doi:10.1097/00006982-200412000-00014
  4.  Kramer F, White K, Pauleikhoff D, et al. Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular dystrophy (Best disease) and adult vitelliform macular dystrophy but not age-related macular degeneration. Eur J Hum Genet. Apr 2000;8(4):286-92. doi:10.1038/sj.ejhg.5200447
  5.  Boon CJ, Theelen T, Hoefsloot EH, et al. Clinical and molecular genetic analysis of best vitelliform macular dystrophy. Retina. Jun 2009;29(6):835-47. doi:10.1097/IAE.0b013e31819d4fda
  6.  Khan KN, Islam F, Moore AT, Michaelides M. THE FUNDUS PHENOTYPE ASSOCIATED WITH THE p.Ala243Val BEST1 MUTATION. Retina. Mar 2018;38(3):606-613. doi:10.1097/iae.0000000000001569
  7.  Singh R, Shen W, Kuai D, et al. iPS cell modeling of Best disease: insights into the pathophysiology of an inherited macular degeneration. Hum Mol Genet. Feb 1 2013;22(3):593-607. doi:10.1093/hmg/dds469
  8.  Marmorstein AD, Kinnick TR, Stanton JB, Johnson AA, Lynch RM, Marmorstein LY. Bestrophin-1 influences transepithelial electrical properties and Ca2+ signaling in human retinal pigment epithelium. Mol Vis. 2015;21:347-59
  9.  Milenkovic A, Brandl C, Milenkovic VM, et al. Bestrophin 1 is indispensable for volume regulation in human retinal pigment epithelium cells. Proc Natl Acad Sci U S A. May 19 2015;112(20):E2630-9. doi:10.1073/pnas.1418840112
  10.  Guziewicz KE, Cideciyan AV, Beltran WA, et al. BEST1 gene therapy corrects a diffuse retina-wide microdetachment modulated by light exposure. Proc Natl Acad Sci U S A. Mar 20 2018;115(12):E2839-e2848. doi:10.1073/pnas.1720662115
  11.  Singh R, Kuai D, Guziewicz KE, et al. Pharmacological Modulation of Photoreceptor Outer Segment Degradation in a Human iPS Cell Model of Inherited Macular Degeneration. Mol Ther. Nov 2015;23(11):1700-1711. doi:10.1038/mt.2015.141
  12.  Johnson AA, Guziewicz KE, Lee CJ, et al. Bestrophin 1 and retinal disease. Prog Retin Eye Res. May 2017;58:45-69. doi:10.1016/j.preteyeres.2017.01.006

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Updated on November 29, 2020
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