Best disease, also known as Best vitelliform macular dystrophy, is a rare genetic disease in which progressive macular degeneration leads to variable symptoms of impaired vision and visual acuity. The use of specialized ophthalmologic procedures, as well as genetic testing, is necessary to confirm the diagnosis.
Presentation
Best disease is a genetic disorder of macular degeneration that was described in the literature more than 100 years ago and is commonly termed Best vitelliform macular dystrophy [1] [2] [3]. The condition stems from mutations in genes that encode bestrophin-1, a calcium-sensitive chloride channel membrane protein in the retinal epithelium, and the clinical presentation depends on the degree of mutation penetrance [3] [4] [5]. Best disease is typically diagnosed in two age groups - in childhood and in late adolescence/early adulthood, while rare cases have extended the diagnostic window to the fifth decades of life [3] [5] [6]. The autosomal dominant mode of inheritance seen in this condition implies that a positive family history is the main risk factor [6]. Several studies have illustrated that Best disease follows a progressive clinical course starting with only minor changes in the retinal pigmented epithelium and the absence of symptoms, known as the previtelliform stage [3]. The second stage, termed vitelliform stage, is distinguished by the appearance of single or multiple well-demarcated yellow or orange "egg-yolk" macular lesions that cause symptoms of blurred vision, loss of central vision, and metamorphopsia [2] [6]. Further stages (pseudohypopyon, vitelliruptive stage, and atrophic stage) denote the progression of macular lesions that will resemble a "scrambled egg", and gradual loss of visual acuity usually ensues in the majority of cases [2] [6]. In the absence of an early diagnosis, complications such as subretinal hemorrhage and scarring may significantly affect long-term outcomes when it comes to vision [2].
Eyes
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Retinal Pigmentation
It is proposed that dysfunction of bestrophin results in abnormal fluid and ion transport by the retinal pigment epithelium, resulting in a weakened interface between the retinal pigment epithelium and photoreceptors. [ncbi.nlm.nih.gov]
Keywords Retinal Pigment Epithelium Macular Degeneration Retinal Pigment Epithelium Cell Bilateral Condition Central Scotoma These keywords were added by machine and not by the authors. [link.springer.com]
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Retinal Scar
RESULTS: An eye from a Best disease donor with a T6R mutation was found to have deposits containing lipid and glycoconjugates within the central retinal scar. These deposits may be remnants of the vitelliform lesion. [ncbi.nlm.nih.gov]
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Visual Acuity Decreased
acuity Decreased clarity of vision 0007663 Subretinal fluid 0031526 Visual impairment Impaired vision Loss of eyesight Poor vision This gene gives the body instructions for making a protein called bestrophin. [rarediseases.info.nih.gov]
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Retinal Scar
RESULTS: An eye from a Best disease donor with a T6R mutation was found to have deposits containing lipid and glycoconjugates within the central retinal scar. These deposits may be remnants of the vitelliform lesion. [ncbi.nlm.nih.gov]
Psychiatrical
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Type A Personality
• CSR typically presents unilaterally in males 25 to 50 years of age and is associated with conditions such as Type A personality, high stress situations, systemic hypertension, hypercortisolism or sleep apnea. 19,12 Although leakage from the choriocapillaris [reviewofoptometry.com]
Workup
To make the diagnosis of Best disease, it is necessary to perform a comprehensive clinical workup, starting with a thorough patient history that will note the course and progression of symptoms, as well as the time at which they appeared. Having in mind the autosomal dominant pattern of inheritance, the patient should be inquired about similar symptoms in siblings, parents, or grandparents. On the other hand, a detailed physical examination particularly focused on visual function and capacity, can significantly narrow the differential diagnosis. Specialized studies, however, are necessary to confirm Best disease as the underlying cause. Electrooculography (EOG) is a recommended procedure if clinical suspicion toward Best disease exists, as it reveals abnormally low light peak conductance, but the findings on an electroretinogram (ERG) are almost always within physiological limits [1] [6] [7]. EOG might be difficult to perform in children, as the procedure requires a high level of cooperation and patience [7]. Furthermore, optical coherence tomography (OCT) might be even more useful, as this non-invasive procedure provides a close view of the retina and its epithelium where pathological changes occur [3] [5]. Supplementary to ophthalmologic procedures, genetic studies should also be conducted, but their high cost and scarce availability reduce their role in general practice [6] [7].
X-Ray
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Bowel Distention
Hydro-MRI of the small bowel: effect of contrast volume, timing of contrast administration, and data acquisition on bowel distention. AJR. Am. J. Roentgenol. 187, W375–385 (2006). 100. Rimola, J. et al. [nature.com]
Other Test Results
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Electroretinogram Abnormal
Localization of multifocal electroretinogram abnormalities to the lesion site: findings in a family with Best disease. Arch Ophthalmol. 2006 Nov. 124(11):1593-600. [Medline]. Patrinely JR, Lewis RA, Font RL. [emedicine.com]
Localization of multifocal electroretinogram abnormalities to the lesion site: findings in a family with Best disease. Arch Ophthalmol. 2006; 124 :1593–600. [ PubMed : 17102007 ] Hartzell HC, Qu Z, Yu K, Xiao Q, Chien LT. [ncbi.nlm.nih.gov]
Treatment
Verteporfin therapy may be a viable treatment for subfoveal neovascular lesions in Best vitelliform macular dystrophy. [ncbi.nlm.nih.gov]
His condition remained stable for 1½ years after treatment. [wwe.eurekamag.com]
Click here for explanation of Inheritance pattern Additional information about Best Disease can be found here: TREATMENT Unfortunately there is no treatment for this eye condition at the moment. [rawa.com.au]
Prognosis
In this case, although VA was reasonably good in both eyes, it is difficult to assess the prognosis of surgically excised neovascularization vs natural history, also considering that nowadays photodynamic therapy and antiangiogenetic drugs are considered [ncbi.nlm.nih.gov]
Prognosis Prognosis for Best disease is mixed. Some carriers will never phenotypically express the disorder. [emedicine.com]
Prognosis BVMD may progress to geographic atrophy and in some cases is complicated by development of CNV. 7-9% of patients never experience vision loss, but have an aberrant EOG with normal ERG. [orpha.net]
Etiology
Etiology BVMD is characterized by atrophy of the retinal pigment epithelium (RPE) affecting photoreceptors with impaired central visual function. [orpha.net]
Etiology Best vitelliform dystrophy is inherited in an autosomal dominant pattern, with diminished penetrance and a highly variable expression. [eyewiki.aao.org]
Etiology Vitelliform Dystrophy. S disease, in our case. Onset foveomacular vitelliform dystrophy, Best. Giuseppe Querques1, 2, Vittorio Capuano1, Nathalie Puche1 and Eric H. The Retina Eye Center. Adult onset foveomacular vitelliform. [nuclear-borders.tk]
Diagnostics A battery of tests was performed to confirm the diagnosis of Best’s disease and establish a hereditary etiology in the mother and son. [reviewofoptometry.com]
One of the best uses of mfERGs is for distinguishing between retinal and central etiology of visual problems in patients with no apparent abnormalities in the ocular fundus. [webvision.med.utah.edu]
Epidemiology
Summary Epidemiology The prevalence is estimated to be between 1/5,000 and 1/67,000 in northern Sweden and Denmark respectively. Males are more affected than females (3:1). [orpha.net]
Diagnosis: Best Vitelliform Macular Dystrophy EPIDEMIOLOGY Autosomal Dominant Mutations in VMD2 gene Without family history, 25% will have new sporadic genetic mutation in VMD2. SIGNS Bilateral macular large yellow lesions with fried egg appearance. [webeye.ophth.uiowa.edu]
Ellie Paige, Research Associate in Epidemiology, University of Cambridge This article was originally published on The Conversation. Read the original article. [cam.ac.uk]
Epidemiology Frequency United States Best disease is rare. International Best disease is rare. Mortality/Morbidity Visual acuity is good in the previtelliform stage. [emedicine.com]
Pathophysiology
A vitrectomy surgery is effective to close the hole while further study is required to elucidate the pathophysiology of macular hole formation and the new vitelliform lesion in such a case. [ncbi.nlm.nih.gov]
General Pathology and Pathophysiology Currently, it is believed that Best disease represents a primary disturbance of the RPE. [eyewiki.aao.org]
Pathophysiology Lesions in Best disease are restricted to the eye. No systemic associations exist. Abnormalities in the eye result from a disorder in the retinal pigment epithelium (RPE). [emedicine.com]
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Prevention
The standard of care is treatment of the underlying disorder to prevent neovascularization (retinal or subretinal), vitreous hemorrhage, or subsequent retinal detachment. However, these complications may not present until late in the disease course. [ncbi.nlm.nih.gov]
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References
- Low S, Davidson AE, Holder GE, et al. Autosomal dominant Best disease with an unusual electrooculographic light rise and risk of angle-closure glaucoma: a clinical and molecular genetic study. Mol Vis. 2011;17:2272-2282.
- Zhang Q, Small KW, Grossniklaus HE. Clinicopathologic findings in Best vitelliform macular dystrophy. Graefes Arch Clin Exp Ophthalmol. 2011;249(5):745-751.
- Querques G, Zerbib J, Georges A, et al. Multimodal analysis of the progression of Best vitelliform macular dystrophy. Mol Vis. 2014;20:575-592.
- Frennesson CI, Wadelius C, Nilsson SE. Best vitelliform macular dystrophy in a Swedish family: genetic analysis and a seven-year follow-up of photodynamic treatment of a young boy with choroidal neovascularization. Acta Ophthalmol. 2014;92(3):238-242.
- Kay DB, Land ME, Cooper RF, et al. Outer Retinal Structure in Best Vitelliform Macular Dystrophy. JAMA Ophthalmol. 2013;131(9):1207-1215.
- Cohn AC, Turnbull C, Ruddle JB, et al. Best’s macular dystrophy in Australia: phenotypic profile and identification of novel BEST1 mutations. Eye (Lond). 2011;25(2):208-217.
- Ferrara DC, Costa RA, Tsang S, Calucci D, Jorge R, Freund KB. Multimodal fundus imaging in Best vitelliform macular dystrophy. Graefes Arch Clin Exp Ophthalmol. 2010;248(10):1377-1386.