Diagnostic Considerations

Autosomal-recessive bestrophinopathy

Autosomal-recessive bestrophinopathy results from a homozygous or compound heterozygous BEST1 mutation. The age of onset is between 4 and 40 years, and the condition results in vision deterioration to below 20/70 within a few years. Fundus examination reveals irregular RPE and white subretinal deposits in the macula and midperiphery. Affected individuals may not have vitelliform lesions. EOG is severely reduced, and the pattern ERG is markedly abnormal.^[19]

Autosomal-recessive bestrophinopathy: Atrophic central lesion and white subretinal deposits along the vascular arcades in a 14-year-old female with 20/70 vision and no family history of Best macular dystrophy.

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Differential Diagnoses

Adult-Onset Vitelliform Macular Dystrophy (Pattern Dystrophy)
Autosomal-Recessive Bestrophinopathy
Basal Laminar Drusen
Central Serous Chorioretinopathy With Subretinal Fibrin
Exudative (Wet) Age-Related Macular Degeneration (AMD)
Fundus Flavimaculatus (Stargardt Disease)
Resolving Subretinal Hematoma

Workup

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Berkley WL, Bussey FR. Heredodegeneration of the macula. Am J Ophthalmol. 1949. 32:361-5.
Deutman AF. The Hereditary Dystrophies of the Posterior Pole of the Eye. Assen: Van Gorcum; 1971. 198.
Kinnick TR, Mullins RF, Dev S, Leys M, Mackey DA, Kay CN, et al. Autosomal recessive vitelliform macular dystrophy in a large cohort of vitelliform macular dystrophy patients. Retina. 2011 Mar. 31(3):581-95. [QxMD MEDLINE Link].
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Zhao L, Grob S, Corey R, Krupa M, Luo J, Du H, et al. A novel compound heterozygous mutation in the BEST1 gene causes autosomal recessive Best vitelliform macular dystrophy. Eye (Lond). 2012 Jun. 26(6):866-71. [QxMD MEDLINE Link]. [Full Text].
Marquardt A, Stohr H, Passmore LA, Kramer F, Rivera A, Weber BH. Mutations in a novel gene, VMD2, encoding a protein of unknown properties cause juvenile-onset vitelliform macular dystrophy (Best's disease). Hum Mol Genet. 1998 Sep. 7(9):1517-25. [QxMD MEDLINE Link].
Stone EM, Nichols BE, Streb LM, Kimura AE, Sheffield VC. Genetic linkage of vitelliform macular degeneration (Best's disease) to chromosome 11q13. Nat Genet. 1992 Jul. 1(4):246-50. [QxMD MEDLINE Link].
Stohr H, Marquardt A, Rivera A, Cooper PR, Nowak NJ, Shows TB, et al. A gene map of the Best's vitelliform macular dystrophy region in chromosome 11q12-q13.1. Genome Res. 1998 Jan. 8(1):48-56. [QxMD MEDLINE Link]. [Full Text].
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Wajima R, Chater SB, Katsumi O, Mehta MC, Hirose T. Correlating visual acuity and electrooculogram recordings in Best's disease. Ophthalmologica. 1993. 207(4):174-81. [QxMD MEDLINE Link].
Glybina IV, Frank RN. Localization of multifocal electroretinogram abnormalities to the lesion site: findings in a family with Best disease. Arch Ophthalmol. 2006 Nov. 124(11):1593-600. [QxMD MEDLINE Link].
Patrinely JR, Lewis RA, Font RL. Foveomacular vitelliform dystrophy, adult type. A clinicopathologic study including electron microscopic observations. Ophthalmology. 1985 Dec. 92(12):1712-8. [QxMD MEDLINE Link].
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Andrade RE, Farah ME, Costa RA. Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in best disease. Am J Ophthalmol. 2003 Dec. 136(6):1179-81. [QxMD MEDLINE Link].
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Media Gallery

Classic egg-yolk appearance in the second (vitelliform) stage of vitelliform macular dystrophy. The 0.5-6 mm diameter yellow or orange lesion results from an accumulation of lipofuscin beneath and within the retinal pigment epithelium. This lesion is usually noted in individuals aged 3-15 years. Visual acuity is most often preserved in the 20/20 to 20/40 range.
The pseudohypopyon (stage 3) lesion is found in the teenage or later years. It results from a break in the retinal pigment epithelium, allowing accumulation of the yellow substance in the subretinal space with the formation of a fluid level. This fluid can shift over 60-90 minutes with positioning.
The atrophic stage (stage 5) may be accompanied by the deposition of pigment or choroidal neovascularization, both of which can lead to visual deterioration.
The scrambled egg appearance of stage 4 results from a deterioration of the uniform cystic lesion noted in stage 2 (egg-yolk appearance). At this point, the visual acuity can begin to worsen.
Adult vitelliform macular dystrophy resembles Best disease, but it can be differentiated by its later age of onset, smaller lesion, and normal electro-oculogram testing.
The fluorescein angiogram of the latter lesion reveals a transmission defect consistent with atrophic changes in the retinal pigment epithelium. This appearance also can be found in the later stages of Best disease.
Spectral domain optical coherence tomography demonstrates subretinal lesion with adjacent cystoid macular edema.
Autosomal-recessive bestrophinopathy: Atrophic central lesion and white subretinal deposits along the vascular arcades in a 14-year-old female with 20/70 vision and no family history of Best macular dystrophy.

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Author

Paige J Richards, MD Resident Physician, Department of Ophthalmology, University of Wisconsin School of Medicine and Public Heatlh

Paige J Richards, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, Wisconsin Academy of Ophthalmology, Women in Ophthalmology, Inc

Disclosure: Nothing to disclose.

Coauthor(s)

Samuel A Whittier, MD Resident Physician, Department of Ophthalmology and Visual Sciences, University of Wiconsin School of Medicine and Public Health

Disclosure: Nothing to disclose.

Michael Altaweel, MD, FRCSC Professor, Fellowship Director for Vitreoretinal Surgery, Department of Ophthalmology and Visual Science, University of Wisconsin School of Medicine and Public Health

Michael Altaweel, MD, FRCSC is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Association for Research in Vision and Ophthalmology, Macula Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, American Glaucoma Society

Disclosure: Nothing to disclose.

Steve Charles, MD Founder and CEO of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine

Disclosure: Received royalty and consulting fees for: Alcon Laboratories.

Chief Editor

Donny W Suh, MD, MBA, FAAP, FACS Professor, Department of Ophthalmology, Chief of Pediatric Ophthalmology and Adult Strabismus, Medical Director of Eye-Mobile, Gavin Herbert Eye Institute, UC Irvine Health, University of California, Irvine, School of Medicine; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Chief Medical Officer, Suh Precision Syringe, LLC; Medical Staff, Children’s Hospital of Orange County

Donny W Suh, MD, MBA, FAAP, FACS is a member of the following medical societies: American Academy of Ophthalmology, American Academy of Pediatrics, American Association for Pediatric Ophthalmology and Strabismus, American College of Healthcare Executives, American College of Surgeons, American Medical Association, Section on Ophthalmology, American Ophthalmological Society, International Strabismological Association, Iowa Medical Society, Metro Omaha Medical Society, National Eye Care Project, Nebraska Chapter of American Academy of Pediatrics, ORBIS, Surgical Eye Expeditions (SEE) International

Disclosure: Nothing to disclose.

Additional Contributors

Andrew W Lawton, MD Neuro-Ophthalmology, Ochsner Health Services

Andrew W Lawton, MD is a member of the following medical societies: American Academy of Ophthalmology, Arkansas Medical Society, Southern Medical Association

Disclosure: Nothing to disclose.

Paul S Boeke, MD Fellow in Vitreoretinal Surgery, Department of Ophthalmology, University of Wisconsin Health Care

Disclosure: Nothing to disclose.

Kathleen R Schildroth, MD Assistant Professor, Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health

Disclosure: Nothing to disclose.

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Best Disease Differential Diagnoses

Diagnostic Considerations

Autosomal-recessive bestrophinopathy

Differential Diagnoses

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