Vitelline Macular Dystrophy

Abstract

Vitelline macular dystrophy (also known as Best disease) is a progressive, chronic disease of the macula (central retina) at the back of the eye. Best disease is characterised by the development of a lesion in the retinal pigment epithelium and emerging as one of the leading causes of blindness in both juvenile and adult cases. This disease has an autosomal dominant pattern of inheritance with varied penetrance and expressivity. Diagnosis of this disease is delayed due to the fact that the individual may be asymptomatic for several years and the disease can be identified only after visual acuity reduces, during which the disease could have progressed to later stages. Mutations observed in the BEST1 and PRPH2 genes are involved in development of the disease. In this article, a review of the history, genetics and pathophysiology, diagnosis and treatment is outlined for further understanding of this disease.

Key Concepts:

  • Macular dystrophy is a rare, genetic condition of the eye, wherein the macula, which is the central part of the retina, is damaged due to successive buildup of eye pigments within the epithelial cells of the retina. There are two main types of this disease: Best disease, which is seen in juvenile cases, and adult‐onset macular dystrophy.

  • Best disease is also known as early‐onset or juvenile vitelliform macular dystrophy. It is an autosomal dominant disorder characterised by the accumulation of specific eye pigment material in the subretinal space, which leads to the formation of a lesion on the macula.

  • Adult‐onset vitelliform macular dystrophy is a disease of the retina wherein central vision loss occurs in the fourth or fifth decade of life. It is an autosomal dominant disorder. It is a dystrophy of the retinal pigment epithelium causing lesions on the macula.

  • VMD2 gene, also known as the BEST1 gene, codes for a protein called bestrophin. This protein functions as a chloride ion channel in the eye and its dysfunction leads to buildup of pigments and eventual loss of central vision.

  • PRPH2 gene codes for a protein called peripherin. This protein is essential for light sensing in the retina. Mutations in this gene lead to central vision loss.

Keywords: BEST1; macular dystrophy; vitelline macular dystrophy (VMD); PRPH2; retina; macula; yellow spot

Figure 1.

Best disease: appearance of a retinal lesion resembling an early egg yolk. Reproduced from Creel (). © Webvision.

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References

Andrade RE, Farah ME, Cardillo JA et al. (2002) Optical coherence tomography in choroidal neovascular membrane associated with Best's vitelliform dystrophy. Acta Ophthalmologica Scandinavica 80: 216–218.

Andréasson S (2006) Developments in molecular genetics and electrophysiology in inherited retinal disorders. Acta Ophthalmologica Scandinavica 84: 161–168.

Arndt C, Meunier IA, Ben Salah S et al. (2008) Three families with Best's disease and normal electro‐oculogram recordings. Acta Ophthalmologica 86(s243): 0. doi: 10.1111/j.1755-3768.2008.476.x

Baca W, Fishman GA, Alexander KR et al. (1994) Dark adaptation in patients with Best vitelliform macular dystrophy. British Journal of Ophthalmology 78: 430–432.

Best F (1905) Ubereine hereditare Maculaffection: beiträge zur Vererbungslehre. Z Augenheilkd 13: 199–212.

Blodi CF and Stone EM (1990) Best's vitelliform dystrophy. Ophthalmic Paediatrics and Genetics 11: 49–59.

Braley AE and Spivey BE (1964) Hereditary vitelline macular degenerationa clinical and functional evaluation of a new pedigree with variable expressivity and dominant inheritance. Archives of Ophthalmology 72: 743–762.

Brown M, Marmor M and Vaegan (2006) ISCEV standard for clinical electro‐oculography (EOG) 2006. Documenta Ophthalmologica 113(3): 205–212.

Ciardella AP, Kaufman SR and Yannuzzi LA (2009) The use of fluorescein angiography in acquired macular diseases. In: Tasman W and Jaeger EA (eds) Foundations of Clinical Ophthalmology, 15th edn, chap. 113F. Philadelphia, PA: Lippincott Williams & Wilkins.

Clemett R (1991) Vitelliform dystrophy: long‐term observations on New Zealand pedigrees. Australian and New Zealand Journal of Ophthalmology 19: 221–227.

Creel DJ (2011) The electroretinogram: clinical applications. Available at: http://webvision.med.utah.edu/book/electrophysiology/the-electroretinogram-clinical-applications/ (accessed on November 2008).

Daniele S, Carbonara A, Daniele C, Restagno G and Orcidi F (1996) Pattern dystrophies of the retinal pigment epithelium. Acta Ophthalmologica Scandinavica 74: 51–55.

Deutman AF (1969) Electro‐oculography in families with vitelliform dystrophy of the fovea. Detection of the carrier state. Archives of Ophthalmology 81: 305–316.

Epstein GA and Rabb MF (1980) Adult vitelliform macular degeneration: diagnosis and natural history. British Journal of Ophthalmology 64: 733–740.

Falls HF (1969) The polymorphous manifestations of Best's disease (vitelliform eruptive disease of the retina), Transactions of the American Ophthalmological Society 67: 265–282.

Felbor U, Schilling H and Weber BHF (1997) Adult vitelliform macular dystrophy is frequently associated with mutations in the peripherin/RDS gene. Human Mutation 10: 301–309.

Fishman GA (1990) Inherited macular dystrophies: a clinical overview. Australian and New Zealand Journal of Ophthalmology 18: 123–128.

Francois J, DeRouck A and Fernandez‐Sasso D (1967) Electro‐oculography in vitelliform degeneration of the macula. Archives of Ophthalmology 77: 726.

Gass JD (1974) A clinicopathologic study of a peculiar foveomacular dystrophy. Transactions of the American Ophthalmological Society 72: 139–156.

Glybina IV and Frank RN (2006) Localization of multifocal electroretinogram abnormalities to the lesion site: findings in a family with Best disease. Archives of Ophthalmology 124: 1593–1600.

Godel V, Chaine G, Regenbogen L and Lazar M (1986) Hereditary vitelliform macular dystrophy. Australian and New Zealand Journal of Ophthalmology 14: 221–228.

Greaves AH, Sarks JP and Sarks SH (1990) Adult vitelliform macular degeneration: a clinical spectrum. Australian and New Zealand Journal of Ophthalmology 18: 171–178.

Guymer R (2001) The genetics of age‐related macular degeneration. Clinical and Experimental Optometry 84: 182–189.

Krill AE, Morse PA, Potts AM and Klien BA (1966) Hereditary vitelliruptive macular degeneration. American Journal of Ophthalmology 61: 1405–1415.

Lotery AJ, Munier FL, Fishman GA et al. (2000) Allelic variation in the VMD2 gene in best disease and age‐related macular degeneration. Investigative Ophthalmology and Visual Science 41: 1291–1296.

Marchant D, Gogat K, Boutboul S et al. (2001) Identification of novel VMD2 gene mutations in patients with best vitelliform macular dystrophy. Human Mutation 17: 235.

Marquardt A, Stöhr H, Passmore LA et al. (1998) Mutations in a novel gene, VMD2, encoding a protein of unknown properties cause juvenile‐onset vitelliform macular dystrophy (Best's disease). Human Molecular Genetics 7: 1517–1525.

Mehta M, Katsumi O, Tetsuka S, Hirose T and Tolentino FI (1991) Best's macular dystrophy with a macular hole. Acta Ophthalmologica 69: 131–134.

Meunier I, Sénéchal A, Dhaenens CM et al. (2011) Systematic screening of BEST1 and PRPH2 in juvenile and adult vitelliform macular dystrophies: a rationale for molecular analysis. Ophthalmology 118: 1130–1136.

Michaelides M, Hunt DM and Moore A (2003) The genetics of inherited macular dystrophies. Journal of Medical Genetics 40: 641–650.

Miller SA (1977) Multifocal Best's vitelliform dystrophy. Archives of Ophthalmology 95: 984–990.

Miller SA, Bresnick GH and Chandra SR (1976) Choroidal neovascular membrane in Best's vitelliform macular dystrophy. American Journal of Ophthalmology 82: 252–255.

Modi G, Heckman JM and Saffer D (1992) Vitelliform macular degeneration associated with mitochondrial myopathy. British Journal of Ophthalmology 76: 58–60.

Mullins RF, Kuehn MH, Faidley EA, Syed NA and Stone EM (2007) Differential macular and peripheral expression of bestrophin in human eyes and its implication for best disease. Investigative Ophthalmology and Visual Science 48: 3372–3380.

Mullins RF, Oh KT, Heffron E, Hageman GS and Stone EM (2005) Late development of vitelliform lesions and flecks in a patient with best disease: clinicopathologic correlation. Archives of Ophthalmology 123: 1588.

Ozdek S, Ozmen MC, Tufan HA, Gurelik G and Hasanreisoglu B (2012) Photodynamic therapy for best disease complicated by choroidal neovascularization in children. Journal of Pediatric Ophthalmology and Strabismus 49: 216–221.

Petrukhin K, Koisti MJ, Bakall B et al. (1998) Identification of the gene responsible for Best macular dystrophy. Nature Genetics 19: 241–247.

Rakoczy P and Constable IJ (1998) Pathogenesis of macular degeneration: is there any progress? Australian and New Zealand Journal of Ophthalmology 26: 67–70.

von Rückmann A, Fitzke FW and Bird AC (1997) In vivo fundus autofluorescence in macular dystrophies. Archives of Ophthalmology 115: 609–615.

Saleem R and Walter M (2002) The complexities of ocular genetics. Clinical Genetics 61: 79–88.

Schatz P, Abrahamson M, Eksandh L et al. (2003) Macular appearance by means of OCT and electrophysiology in members of two families with different mutations in RDS (the peripherin/RDS gene). Acta Ophthalmologica Scandinavica 81: 500–507.

Spaide RF (2003) Fundus autofluorescence and age‐related macular degeneration. Ophthalmology 110: 392–399.

Stone EM, Nichols BE, Streb LM, Kimura AE and Sheffield VC (1992) Genetic linkage of vitelliform macular degeneration (Best's disease) to chromosome 11q13. Nature Genetics 1: 246–250.

Sun H, Tsunenari T, Yau KW and Nathans J (2002) The vitelliform maculardystrophy protein defines a new family of chloride channels. Proceedings of the National Academy of Sciences of the USA 99: 4008–4013.

Swann PG, Collin HB and Livanes A (2000) Pattern dystrophies of the retinal pigment epithelium. Clinical and Experimental Optometry 83: 274–278.

Tiu AL and Duane BM (1992) Adult vitelliform macular degeneration. Clinical and Experimental Optometry 75: 56–61.

Vail D and Shoch D (1965) Hereditary degeneration of the macula. II. Follow‐up report and histopathologic study. Transactions of the American Ophthalmological Society 63: 51.

Voxuan L (2010) Recognizing Best's disease. Two cases of this rare condition, involving a mother and son, demonstrate an assortment of diagnostic challenges. Chilton's Review of Optometry 147: 87.

Weber BH, Walker D and Müller B (1994) Molecular evidence for non‐penetrance in Best's disease. Journal of Medical Genetics 31: 388–392.

White K, Marquardt A and Weber BHF (2000) VMD2 mutations in vitelliform macular dystrophy (Best disease) and other maculopathies. Human Mutation 15: 301–308.

Wrigley JD, Ahmed T, Nevett CL and Findlay JB (2000) Peripherin/rds influences membrane vesicle morphology: implications for retinopathies. Journal of Biological Chemistry 275: 13191– 13194.

Yoder FE, Cross HE, Chase GA et al. (1988) Linkage studies of Best's macular dystrophy. Clinical Genetics 34: 26–30.

Zhang K, Nguyen TH, Crandall A and Donoso LA (1995) Genetic and molecular studies of macular dystrophies: recent developments. Survey of Ophthalmology 40: 51–61.

Further Reading

Aggarwal A (2011) Gass. Atlas of Macular Disease, 5th edn., vol. 1. Philadelphia: Elsevier Health Sciences.

Gass JDM (1997) Best's disease. In: Stereoscopic Atlas of Macular Disease. Diagnosis and Treatment, pp. 304–331. St.Louis‐London‐Philadelphia‐Sydney‐Toronto: Mosby.

King RA, Oetting WS, Summers CG, Creel DJ and Hearing V (2007) Abnormalities of pigmentation. In: Edinburgh (ed.) Emory and Rimoin's Principles and Practice of Medical Genetics, 5th edn, pp. 3396–3413. Churchhill Livingston.

Weingeist TA, Kobrin JL and Watzke RC (1982) Histopathology of Best's macular dystrophy. Archives of Ophthalmology 100: 1108.

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Priya Doss, C George, Kumar, Aditi S, and Narayan, Vaishnavi(Feb 2014) Vitelline Macular Dystrophy. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0025491]