Best's disease

• vitelline macular dystrophy
  
  
  • vitelliform macular dystrophy or vitelliform dystrophy is a genetic eye disorder that can cause progressive vision loss
  • Best's disease is an autosomal dominant variant of vitelliform macular dystrophy, 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
• it is a bilateral disorder with different stages characterized by deposition of lipofuscin and macular atrophy
  • adult-onset foveomacular vitelliform macular dystrophy (AFVD), also known as pseudo-Best, pseudo-vitelliform, or Gass disease, and is a distinct aspect of Best disease, with which it shares phenotypic features (1,2)
  • since the description of the disease by Gass in 1974, AFVD raises the question of the continuum between some childhood macular dystrophies and the diseases of the macula in the adult
    • genetic inheritance is characterized by more sporadic cases than autosomal dominant ones
    • age of onset is between 30 and 50 years, and the visual acuity (VA) at onset usually ranges from 20/50 to 20/25
      • AFVD is a clinically heterogenous and pleomorphic disease displaying a variability in the size, shape, pigmentary changes, and distribution of the lesions, and frequently associated with drusen, where ophthalmoscopically visible changes often do not correspond with deterioration of visual function
        
        

• vitelliform macular dystrophy causes a fatty yellow pigment (lipofuscin) to build up in the retinal pigment epithelium (RPE)
  • lesions in this disease are restricted to the eye
  • no systemic associations
  • lipofuscin (periodic acid-Schiff [PAS] positive) accumulates within the RPE cells and in the sub-RPE space, particularly in the foveal area
    • lesion evolves through several stages over many years, with increasing potential for adverse visual outcome
      
      
• pathophysiology:
  • abnormality is in the retinal pigment epithelium, (RPE)
  • mutations in the RDS and VMD2 genes cause vitelliform macular dystrophy
    • mutations in the VMD2 gene are responsible for Best disease
    • mutations in either the VMD2 or RDS gene can cause the adult-onset form of vitelliform macular dystrophy (AFVD); however, less than a quarter of cases result from mutations in these two genes
      • in the majority of cases, the cause of the AFVD is unknown
        • VMD2 gene controls production of a protein called bestrophin
          • bestrophin is likely to act as a channel that controls the movement of negatively charged chloride ions into or out of cells in the retina
            • mutations in the VMD2 gene probably lead to the production of an abnormally shaped channel that cannot regulate the flow of chloride - it has not been determined how these malfunctioning channels are related to the buildup of lipofuscin RPE
        • RDS gene controls the production of a protein called peripherin
          • peripherin is essential for the normal function of light-sensing (photoreceptor) cells in the retina
          • unclear why RDS mutations affect only central vision in people with adult-onset vitelliform macular dystrophy
            
            
• clinical features:
  • the abnormal accumulation of this lipofuscin can lead to damage of the fovea
    • patients often lose their central vision and may experience blurry or distorted vision
    • optical coherence tomography (OCT) is provides a non-invasive technique, cross-sectional visualization of the retina (3)
    • this disorder does not affect peripheral or night vision
      • early-onset form (known as Best disease) usually appears in childhood; however, the onset of symptoms and the severity of vision loss vary widely
      • adult-onset form begins later, usually in middle age, and tends to cause relatively mild vision loss. The two forms of vitelliform macular dystrophy each have characteristic changes in the macula that can be detected during fundoscopy
        • age of onset is between 30 and 50 years, and the visual acuity (VA) at onset usually ranges from 20/50 to 20/25
        • AFVD is a clinically heterogenous and pleomorphic disease displaying a variability in the size, shape, pigmentary changes, and distribution of the lesions, and frequently associated with drusen, where ophthalmoscopically visible changes often do not correspond with deterioration of visual function
          • main early symptoms of the disease are a relative scotoma and metamorphopsia, or it may simply be discovered during a regular control for presbyopia
          • clinicopathologic studies show a massive accumulation of lipofuscin pigments within the macular retinal pigment epithelium (RPE) and loss of the RPE and photoreceptor cell layer with infiltration of pigment containing macrophages in the central area
            • only 4% of these individuals develop vision less than 20/200 in the better eye
              
              
• management:
  • no treatment exists for vitelliform macular dystrophy
  • laser treatment is used to manage secondary choroidal neovascularization
  • family screening is important in this condition

Reference:

• (1) Gass JDM. A clinicopathological study of a peculiar foveomacular dystrophy. Trans Am Ophthalmol Soc 1974; 72: 139-56
• (2) Vine AK, Schatz H. Adult-onset foveomacular pigment epithelial dystrophy. Am J Ophthalmol 1980; 89: 680-91
• (3) Andrade RE et al. Optical coherence tomography in choroidal neovascular membrane associated with Best's vitelliform dystrophy Acta Ophthalmologica Scandinavica 2002; 80 (2): 216-218.