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Best Disease
Article Last Updated: Nov 26, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Michael Altaweel, MD, FRCS(C), Associate Professor, Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health
Michael Altaweel is a member of the following medical societies: American Academy of Ophthalmology and Association for Research in Vision and Ophthalmology
Editors: Andrew W Lawton, MD, Medical Director of Neuro-Ophthalmology Service, Section of Ophthalmology, Baptist Eye Center, Baptist Health Medical Center; Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles; Steve Charles, MD, Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine; Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri; Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Author and Editor Disclosure
Synonyms and related keywords:
Best’s disease, vitelliform macular dystrophy, vitelline dystrophy, vitelliruptive degeneration
Background
Best disease, also termed vitelliform macular dystrophy, is an autosomal dominant disorder, which classically presents in childhood with the striking appearance of a yellow or orange yolklike lesion in the macula. Dr Franz Best, a German ophthalmologist, described the first pedigree in 1905.1
The lesion evolves through several stages over many years, with increasing potential for adverse visual outcome. A hallmark of the disease is a markedly abnormal electro-oculogram (EOG) in all stages of progression and in phenotypically normal carriers.
Pathophysiology
Lesions in this disease are restricted to the eye. No systemic associations exist. Abnormalities in the eye result from a disorder in the retinal pigment epithelium (RPE). Lipofuscin (periodic acid-Schiff [PAS] positive) accumulates within the RPE cells and in the sub-RPE space, particularly in the foveal area. The RPE appears to have degenerative changes in some cases, and secondary loss of photoreceptor cells has been noted.
Frequency
United States
Rare
International
Rare
Mortality/Morbidity
Visual acuity is good in the previtelliform stage. Even with the egg-yolk appearance, visual acuity is maintained in the range of 20/20 to 20/50 (6/6 to 6/15) for many years. The breakup of the vitelliform stage, leading to the scrambled egg stage, may be accompanied by visual acuity deterioration. It is the final stages of geographic RPE atrophy with possible development of choroidal neovascular membrane that is associated with further deterioration in acuity. These changes usually occur in individuals older than 40 years. Various studies have shown that most individuals retain reading and driving vision in at least 1 eye into adulthood (88% have 20/40 or better vision). Only 4% of these individuals develop vision less than 20/200 in the better eye.
Race
Best disease is found in individuals of European, African, and Hispanic ancestry.
Sex
No known gender predilection exists.
Age
Usual onset is from 3-15 years, with an average age of 6 years. The condition often is not detected until much later in the disease because visual acuity may remain good for many years. The atrophic stage usually occurs after age 40 years.
History
Many individuals initially are asymptomatic, with fundus lesions noted on examination. Visual symptoms can include decreased acuity (blurring) and metamorphopsia. These symptoms may worsen if the disease progresses to the atrophic stage.
Physical
This disorder has variable clinical expression. Some carriers have a normal examination and remain asymptomatic. Findings are usually bilateral and can be asymmetric. - Visual acuity
- Previtelliform stage - 20/20
- Vitelliform stage - 20/20 to 20/50
- Pseudohypopyon stage - 20/20 to 20/50
- Vitelliruptive stage - 20/20 to 20/100
- Atrophic stage - Acuity may reduce to less than 20/200
- Several stages of fundus appearance are described. Not all individuals progress beyond the early stages. Other individuals can skip from the earliest stages to an atrophic-appearing macula. Unilateral findings and multifocal lesions have been described.
- Stage 1 (previtelliform) - Normal macula or subtle RPE pigment changes, EOG abnormal
- Stage 2 (vitelliform) - Well-circumscribed, 0.5-5 mm round, elevated, yellow or orange lesion; described as an egg-yolk appearance; usually centered on the fovea; can be multifocal; the rest of the fundus has a normal appearance.
- Stage 3 (pseudohypopyon) - Yellow material can break through the RPE and accumulate in the subretinal space in a cyst with a fluid level formed. The yellow material will shift with extended changes in position (60-90 min). This stage most often is found in the teenage years, but it has been described in individuals aged 8-38 years.
- Stage 4 (vitelliruptive) - Scrambled egg appearance is due to the breakup of the uniform vitelliform lesion. Pigment clumping and early atrophic changes may be noted. Visual acuity may deteriorate moderately.
- Stage 5 (atrophic) - As the yellow material disappears over time, an area of RPE atrophy remains. This appearance is difficult to distinguish from other causes of macular degeneration. Visual acuity can deteriorate more markedly at this stage.
- Stage 6 (choroidal neovascular/cicatricial) - Following the atrophic stage, choroidal neovascularization can develop, leading to a whitish subretinal fibrous scar.
- Hyperopia is common.
Causes
Best disease is autosomal dominant with variable penetrance. Genetic linkage has mapped the disease to the long arm of chromosome 11 (11q12-q13). The abnormality is in the RPE, as noted on histopathology and electrophysiology testing.
Other Problems to be Considered
Vitelliform stage
Adult foveomacular dystrophy
Central serous retinopathy with fibrinous exudate
Pigment epithelial detachment/age-related macular degeneration
Coalescence of basal laminar drusen
Solar retinopathy
Stage 1 macular hole Atrophic stage
Age-related macular degeneration
Stargardt disease
Adult foveomacular dystrophy
Chronic central serous retinopathy
Imaging Studies
- Fluorescein angiogram reveals blockage of choroidal fluorescence by the vitelliform lesion. The angiogram is otherwise normal at this stage. In the atrophic stage, a transmission defect is noted. If a choroidal neovascular membrane develops, then a corresponding area of hyperfluorescence with leakage will be found.
- Fundus photography is useful for documentation and follow-up of fundus lesions.
Other Tests
- Electro-oculogram
- The EOG, which reflects RPE function, is the most diagnostic test for evaluating vitelliform macular dystrophy. In the majority of such individuals, a severe decrease occurs in light response, reflected by an Arden (light-peak/dark-trough) ratio of 1.1-1.5. (The normal Arden ratio is 1.8.) Carriers will also have an abnormal EOG result. No correlation exists between EOG result and disease stage, visual acuity, or patient age. EOG results are usually symmetric for both eyes.
- The EOG is very useful for distinguishing this diagnosis from its differential. The EOG result is usually normal in adult foveomacular dystrophy.
- The full-field electroretinogram (ERG) result is normal in this condition. A focal ERG or multifocal ERG, concentrating on macular function, may reveal some abnormality.
- Genetic testing: This disorder has been mapped to a genetic defect in chromosome 11 (region q12-q13.1).
Histologic Findings
This disease primarily affects the RPE. Lipofuscin accumulates within RPE cells and in the sub-RPE space. This material stains PAS-positive. The RPE can degenerate, and macrophages containing PAS-positive material have been found to migrate into the outer retina. The choriocapillaris is normal. Choroidal neovascularization has been demonstrated.
Staging
See Physical.
Medical Care
No treatment exists for vitelliform macular dystrophy. Secondary choroidal neovascularization can be managed with direct laser treatment. Treatment with an intravitreal injection of bevacizumab has also been described.
Evaluation of family members is important to identify carriers and individuals with vitelliform macular dystrophy. Both genetic counseling and career counseling are provided.
Consultations
- Consult a vitreoretinal disease specialist for the initial diagnosis, electrophysiology testing, and family assessment, as well as for the long-term follow-up care of patients to monitor disease progression and choroidal neovascularization.
- Consult a low vision specialist who can provide specialized equipment to assist individuals who have significant deterioration in visual acuity in both eyes.
- Occupational counseling is important. Although most patients retain reading vision in at least 1 eye throughout life, visual deterioration can occur, particularly beyond age 40 years. This knowledge may influence the choice of career.
Diet
Diet is not known to influence the progression of Best disease.
Activity
Physical activity does not influence the progression of Best disease.
No medications are used to treat Best disease.
Further Outpatient Care
- Examination of visual acuity and fundus lesions should be performed on a schedule dictated by the current stage of the disease. If visual changes occur at any stage, then an earlier visit should be scheduled.
- Previtelliform stage - Yearly
- Vitelliform/pseudohypopyon stage - Every 6 months
- Scrambled egg stage - Every 6 months
- Atrophic stage - Every 6 months to yearly
- Patients in the atrophic stage should routinely use an Amsler grid. Changes in the central visual field should prompt an early visit to evaluate for choroidal neovascularization.
- The electrophysiology test is usually only necessary once to establish the diagnosis. Initial results remain fairly stable during disease progression.
- Fluorescein angiography should be performed at any visit if choroidal neovascularization is suspected.
Complications
- Although uncommon, choroidal neovascularization can occur following the atrophic stage, and it can be responsible for further deterioration in visual acuity. A disciform scar may result.
- Plaques of white subretinal fibrous tissue can develop in conjunction with the atrophic stage. Visual acuity is often reduced to 20/100 or worse with this appearance.
Prognosis
- Prognosis for this disease is mixed. Some carriers will never phenotypically express their disorder. Some individuals will never have progression beyond the earliest stages of the disease and will maintain better than 20/40 vision in both eyes. In general, most people will maintain reading vision in at least 1 eye throughout life. In one study, 88% of patients retained 20/40 or better visual acuity, and only 4% of them had 20/200 or worse visual acuity in the better eye. The deterioration of vision usually is very slow and is not significant in most individuals until after age 40 years.
Patient Education
- Genetic inheritance: Provide an explanation of autosomal dominant inheritance to the patient and family members. In genetic counseling, discuss carrier state, variable penetrance and expressivity, and implications for offspring. Recommend familial evaluation.
- Occupational counseling: Discuss the patient's prognosis and the possible implications on career direction.
- Routine examination: Emphasize regular examinations because changes in fundus appearance over time may elucidate the eventual prognosis. Conduct evaluation for choroidal neovascularization.
- Amsler grid: Teach use of this tool to identify central visual field changes.
- Low vision aids: Assistive devices may be necessary if visual acuity deteriorates. Refer to a low vision specialist or organization.
- For excellent patient education resources, visit eMedicine's Eye and Vision Center. Also, see eMedicine's patient education article Macular Degeneration.
Medical/Legal Pitfalls
- Genetic counseling is important for the affected individual and extended family. Examination and EOG testing of the family can identify carriers who may then factor this disease into their career and family-planning decisions.
- EOG testing is highly diagnostic in this disease. Order this test if the diagnosis is in question.
- Follow-up care/Amsler grid education: If the atrophic stage has been reached, then it is important to teach Amsler grid use to help identify the growth of choroidal neovascular membranes at the earliest juncture.
Special Concerns
- Institute genetic counseling for the individual and the extended family.
| Media file 1:
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. |
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| Media file 2:
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. |
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| Media file 3:
The atrophic stage (stage 5) may be accompanied by the deposition of pigment or choroidal neovascularization, both of which can lead to visual deterioration. |
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| Media file 4:
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. |
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| Media file 5:
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. |
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| Media file 6:
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. |
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- Best F. Ubereine hereditare Maculaaffektion. Beitrage zur Vererbungslehre. Augenheilkd. 1905;13:199.
- Berkley WL, Bussey FR. Heredodegeneration of the macula. Am J Ophthalmol. 1949;32:361-5.
- Blodi CF, Stone EM. Best's vitelliform dystrophy. Ophthalmic Paediatr Genet. Mar 1990;11(1):49-59. [Medline].
- Deutman AF. Electro-oculography in families with vitelliform dystrophy of the fovea. Detection of the carrier state. Arch Ophthalmol. Mar 1969;81(3):305-16. [Medline].
- Deutman AF. The Hereditary Dystrophies of the Posterior Pole of the Eye. Assen: Van Gorcum; 1971:198.
- Epstein GA, Rabb MF. Adult vitelliform macular degeneration: diagnosis and natural history. Br J Ophthalmol. Oct 1980;64(10):733-40. [Medline].
- Falls HF. The polymorphous manifestations of Best's disease (vitelliform eruptive disease of the retina). Trans Am Ophthalmol Soc. 1969;67:265-82. [Medline].
- Krill AE, Morse PA, Potts AM, Klien BA. Hereditary vitelliruptive macular degeneration. Am J Ophthalmol. Jun 1966;61(6):1405-15. [Medline].
- Lanzetta P, Virgili G, Menchini U. Indocyanine green angiography in vitelliform macular lesions. Ophthalmologica. 1996;210(4):189-94. [Medline].
- Leu J, Schrage NF, Degenring RF. Choroidal neovascularisation secondary to Best's disease in a 13-year-old boy treated by intravitreal bevacizumab. Graefes Arch Clin Exp Ophthalmol. Nov 2007;245(11):1723-5. [Medline].
- 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. Sep 1998;7(9):1517-25. [Medline].
- Miller SA. Multifocal Best's vitelliform dystrophy. Arch Ophthalmol. Jun 1977;95(6):984-90. [Medline].
- Miller SA, Bresnick GH, Chandra SR. Choroidal neovascular membrane in Best's vitelliform macular dystrophy. Am J Ophthalmol. Aug 1976;82(2):252-5. [Medline].
- Mohler CW, Fine SL. Long-term evaluation of patients with Best's vitelliform dystrophy. Ophthalmology. Jul 1981;88(7):688-92. [Medline].
- Patrinely JR, Lewis RA, Font RL. Foveomacular vitelliform dystrophy, adult type. A clinicopathologic study including electron microscopic observations. Ophthalmology. Dec 1985;92(12):1712-8. [Medline].
- Pinckers A, Cuypers MH, Aandekerk AL. The EOG in Best's disease and dominant cystoid macular dystrophy (DCMD). Ophthalmic Genet. Sep 1996;17(3):103-8. [Medline].
- Stone EM, Nichols BE, Streb LM, Kimura AE, Sheffield VC. Genetic linkage of vitelliform macular degeneration (Best's disease) to chromosome 11q13. Nat Genet. Jul 1992;1(4):246-50. [Medline].
- Stöhr 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. Jan 1998;8(1):48-56. [Medline].
- 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. [Medline].
- Weingeist TA, Kobrin JL, Watzke RC. Histopathology of Best's macular dystrophy. Arch Ophthalmol. Jul 1982;100(7):1108-14. [Medline].
- Zhang K, Nguyen TH, Crandall A, Donoso LA. Genetic and molecular studies of macular dystrophies: recent developments. Surv Ophthalmol. Jul-Aug 1995;40(1):51-61. [Medline].
Best Disease excerpt Article Last Updated: Nov 26, 2007
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