Best Disease - Stages, Diagnosis, Treatment, and Complications

Introduction

Best disease is an eye condition affecting the macula of the eye. It is a rare autosomal dominant disorder that occurs because of mutations of the BEST-1 or VMD-2 gene located on the long arm of chromosome no 11. However, it can be autosomal recessive also. Retinal pigment epithelium (RPE) is mainly affected, and the yellow-colored pigment is deposited. There is no sex predilection in Best disease. It is primarily seen between the age group of three to 15 years. The atrophic stage is usually seen in old age.

Dr. Friedrich Best, a German ophthalmologist, described the first case in 1907, and hence the name was given Best disease. Many patients suffering from Best disease are usually asymptomatic. The hallmark of the disease is an abnormal electrooculogram. Lesion goes through various stages and has variable visual outcomes according to the progression of the disease. Due to its rarest occurrence, it is too difficult to treat and manage the outcome of the disease. Therefore, interprofessional team members are required to treat the disease.

What Is the Pathophysiology of Best Disease?

Dysfunction of protein bestrophin results in abnormal ion and fluid transport by RPE. As a result, a yellow-colored pigment called lipofuscin is deposited in the retinal epithelium and foveal area. It can lead to macular degeneration and secondary loss of photoreceptor cells. As a result, there is a loss of central vision and the loss of ability to perceive colors and details. Peripheral vision remains unaffected. It mainly affects the eyes; no systemic manifestations are seen.

What Are the Stages of Best Disease?

1. Stage 1

• Pre Vitelliform Stage- Macula looks healthy, normal or slight changes can be seen in RPE, and vision is 20/20 in this stage.

2. Stage 2

• Vitelliform Stage- Blister formation occurs on the macula, and a classic egg yolk appearance can be seen. It is well circumscribed 0.5 to 5 mm elevated yellow or orange colored lesion on the center of the fovea. It is caught between three to 15 years of age. There can be slight changes in the vision, (20/50.)

3. Stage 3

• Pseudo-Hypopyon Stage- Cyst formation occurs because of the breakdown of yellow material through RPE, and a change in sight level may occur. It is usually seen in the teenage years. Visual acuity varies from 20/20 to 20/50.

4. Stage 4

• Vitelli Eruptive Stage- This Stage affects one or more layers of the retina, and patients may experience moderate changes in vision. Visual acuity ranges from 20/20 to 20/100.

5.Stage 5

• Atrophic Stage- This Stage is the final stage of the Best disease. The yellow material causes the lesions to start disappearing and leaves scarring behind. Vision is more markedly affected. Visual acuity may be reduced to 20/200. The atrophic stage usually occurs after 40 years of age.

6. Stage 6

• Choroidal Neovascularization (CNV)- This Stage develops following the atrophic stage when the eyes start fixing the macula's damage by creating new blood vessels. It occurs in 20 % of the population. Eventually, these blood vessels leak out and can form whitish subretinal fibrous scar tissue and further deterioration in visual acuity.

What Is the Diagnosis of Best Disease?

Genetic Testing

• Electro-Oculogram- The electrophysiologic test helps measure the electrical potential between the cornea and Bruch membrane. It is the hallmark of the Best disease and is abnormal, with a reduced Arden ratio of 1.5 or less.

• Electroretinogram- It is a diagnostic test that measures the retina's electrical activity and is entirely normal.

• Optical Coherence Tomography- It is a non-invasive imaging technique that creates pictures of the back of the eyes. The vitelliform stage demonstrates the thickening of the cone's outer segments. Subretinal hemorrhage may depict CNV.

• Fundus Fluorescein Angiogram- It uses a fundus camera and Fluorescein dye. Hypo fluorescence is seen in the vitelliform stage, and as the disease progresses, a mixed pattern of hyper and hypo fluorescence is seen. The atrophic stage shows a window defect.

• Fundus Autofluorescence (FAF)- It is also a non-invasive modality. The vitelliform stage is hyper autofluorescent and has a round shape predominating. This hyper fluorescence gets reduced with the atrophic phase.

• Visual Field- Visual field is the area from where objects can be seen from the side. There is no peripheral vision defect; only central vision is affected.

Is There Any Management of Best Disease?

• Usually, Best disease requires no treatment.

• Regular follow-up is essential for the CNV stage.

• Treatment with anti-vascular endothelial growth factor agents like Bevacizumab, Ranibizumab, or Aflibercept has been reported more recently.

• Laser and photodynamic therapy can also be used for the treatment of CNV.

• For patients suffering from cataracts, cataract surgery may lead to visual improvement.

• Amsler grid is a diagnostic tool to detect degenerative changes in the macula.

• Family assessment is essential for determining the carrier and the person suffering from Best disease.

• Magnifiers and telescopes may help to rehabilitate patients with poor visual acuity.

What Are the Complications Associated With Best Disease?

• The choroidal neovascular membrane (CNVM) is a membrane formed due to new blood vessels growing beneath the retina and causing leakage.

• Subretinal fibrosis can occur due to a wound healing response that follows the choroidal neovascular membrane.

• Macular holes can appear, and it blurs the central vision.

• Vitreous hemorrhage can occur, the extravasation of blood into the potential spaces formed within the vitreous body.

• Geographic atrophy is a chronic degeneration of the macula.

What About the Prognosis of Best Disease?

Best disease has a mixed prognosis. Usually, patients retain better visual acuity. However, metamorphopsia may occur in the atrophic stage.

What Is the Differential Diagnosis of Best Disease?

• Stargardt Disease- It is a rare genetic disorder characterized by the deposition of fatty material into the macula.

• Solar Retinopathy- It refers to photochemical toxicity and causes injury to retinal tissues.

• Macular Hole- It is defined as the central break in the retina.

• Basal Laminar Drusen- It can occur, and it is age-related macular degeneration.

• Retinal Pigment Epithelial Atrophy- Several structural changes are seen in the eyes.

• Retinal Pigment Epithelial Atrophy Fibrosis- Fibrosis is there along with retinal diseases.

Conclusion

There is no such treatment for the Best disease. Long-term follow-up is essential to monitor the Best disease's condition and progression. Visit an ophthalmologist if the patient notices a loss of vision. CNV can be treated with lasers and anti-vascular endothelial growth factor medications. Smoking can accelerate the disease process; avoiding tobacco and taking a healthy diet is advisable