Best Disease

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Disease Entity

Best disease, or Vitelliform dystrophy, is a hereditary retinal dystrophy involving the retinal pigment epithelium (RPE), and leads to a characteristic bilateral yellow “egg-yolk” appearance of the macula. This disease tends to present itself in childhood or early adulthood, and usually portends a good visual prognosis. The disease was initially described by Franz Best in 1905.

Etiology

Best disease is inherited in an autosomal dominant pattern, although there can be wide phenotypic variance. The responsible mutation is in the VMD2, or “bestrophin” gene, located on chromosome 11, which encodes a transmembrane chloride channel localized in basolateral membrane of the RPE.

Risk Factors

Best disease is autosomal dominant, so children of affected parents have a 50% chance of receiving the gene. However, there is phenotypic variability.

General Pathology and Pathophysiology

The abnormal chloride channel in the RPE leads to a buildup of lipofuscin, a retinal breakdown pigment, between the outer retina and the retinal pigment epithelium. This buildup leads to the appearance of the typical subretinal vitelliform lesion often described as an “egg-yolk” lesion, and eventually leads to slow, mild to moderate vision deterioration. However, choroidal neovascularization (CNV) may occur and can cause rapid, significant visual loss.

Primary prevention

There are no recognized preventative measures.

Diagnosis

The diagnosis of Best disease is primarily made based on clinical appearance, however family history and adjunvant testing can help confirm the diagnosis.

History

Early on, patients with Best disease may be asymptomatic. As the disease progresses, patients may experience a slow, bilateral decrease in visual acuity, central scotoma, or metamorphosia.

Physical examination

The appearance of the vitelliform lesions is classically grouped into 5 stages:
  • Stage I (Previtelliform): normal vision, normal or only subtle RPE changes with abnormal EOG.
  • Stage II (Vitelliform): classic “egg-yolk” lesion. 30% have ectopic lesions. Normal vision or mild vision loss. 
  • Stage III (Pseudohypopyon): layering of lipufuscein. Vision similar to stage II.
  • Stage IV (Vitelleruptive): breakup of material gives “scrambled egg” appearance. Vision may be similar or mildly decreased from stage I/II.
  • Stage V (Atrophic): Central RPE and retinal atrophy. Vision may range from 20/30 – 20/200.
  • Stage VI (CNV): This complication occurs in about 20% of patients. Vision often decreased to 20/200 or worse.

Diagnostic Tests

Although Best disease can usually be diagnosed clinically, several tests may be helpful:

Electro-oculogram (EOG): Universally abnormal, with an Arden ratio (light:dark) of 1.5 or less.

Electro-retinogram (ERG): typically normal

Optical coherence tomography (OCT): can be used to evaluate for subretinal deposits or fluid associated with CNV.

Fluorescein angiogram (FA): hypofluorescence of typical vitelliform lesion, and as the disease progresses a mixed pattern of hyper and hypo fluorescence eventually gives way to hyperfluorescence of the atrophic stage.

Fundus Autofluorescense (FAF): during the earlier vitelliform stages, hyperautofluorescence predominates. This hyperfluoresecence settles with the pseduohypopyon stage, and becomes mottled with areas of hypoautofluorescence during the vitelleruptive stage, and eventually becomes hypofluorescent during the atrophic stage. Changes seen with FAF may precede or appear more striking than with ophthalmoscopy.

Laboratory test

Genetric testing for Best disease is available.

Differential diagnosis

The differential diagnosis of Best’s disease includes adult foveomacular vitelliform dystrophy (within the spectrum of pattern dystrophies), age related macular degeneration, dominant drusen, central serous retinopathy, solar retinopathy, macular hole, or other causes of central macular atrophy such as toxoplasmosis or myopic degeneration.

Of note, mutations in the VMD2 gene can lead to a wide spectrum of disease, including adult onset foveomacular vitelliform dystrophy, autosomal bestrophinopathy, autosomal dominant vitreoretinochoroidopathy, and the “microcornea, retinal dystrophy, cataract, and posterior staphyloma" syndrome. The EOG is universally abnormal in all of these conditions.

Management

There is no medical or surgical management for Best disease. CNV, however, can be a potentially devastating complication. Application of anti VEG-F therapy for CNV in the setting of Best disease has shown potential for improving outcomes, and photodynamic therapy has been attempted as well.

Additional Resources

http://www.bestdisease.net/

http://www.blindness.org/pdfs/science/registry.pdf

http://www.retina-international.org/sci-news/vmd2mut.htm

References

  1. Ryan SJ.  Retina, 4th edition.  Volume II; Medical Retinal, editor Schachat AP.  Elsevier Inc, 2006.
  2. Retina and Vitreous, Section 12. Basic and Clinical Science Course, AAO, 2009-10.
  3. Best's vitelliform dystrophy. Blodi CF, Stone EM. Ophthalmic Paediatr Genet. 1990 Mar;11(1):49-59.
  4. Choroidal neovascularisation secondary to Best's disease in a 13-year-old boy treated by intravitreal bevacizumab. Leu J, Schrage NF, Degenring RF. Arch Clin Exp Ophthalmol. 2007 Nov;245(11):1723-5.
  5. Intravitreal bevacizumab and triamcinolone treatment for choroidal neovascularization in Best disease. Cakir M, Cekiç O, Yilmaz OF. J AAPOS. 2009 Feb;13(1):94-6.
  6. Combined photodynamic therapy and intravitreal triamcinolone injection for choroidal neovascularization in Best disease,  M. Nobrega, C. Bortolotto and M. Farah, Can J Ophthalmol 42 (2007), pp. 761–762.
  7. Functional and clinical data of Best vitelliform macular dystrophy patients with mutations in the BEST1 gene. Querques G, et al. Mol Vis. 2009 Dec 31;15:2960-72.
  8. Phenotypic variability due to a novel Glu292Lys variation in exon 8 of the BEST1 gene causing best macular dystrophy. Sohn EH, et al. Arch Ophthalmol. 2009 Jul;127(7):913-20.
  9. Querques, M.C. Bocco, G. Soubrane and E.H. Souied, Intravitreal ranibizumab (Lucentis) for choroidal neovascularization associated with vitelliform macular dystrophy, Acta Ophthalmol. 86 (2008), pp. 694–695.
  10. Andrade RE, Farah ME, Costa RA. Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in best disease. Am J Ophthalmol 2003;136:1179–1181. 
  11. Clinical and molecular genetic analysis of best vitelliform macular dystrophy. Boon CJ, et al. Retina. 2009 Jun;29(6):835-47.
  12. Photodynamic therapy for childhood choroidal neovascular membrane associated with Best's vitelliform dystrophy.  Rishi et al. Retinal cases and Brief Reports. 3:288-292, 2009.
Original article contributed by: Hart Moss, M.D.
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