title: Drusen maculopathy: a risk factor for visual deterioration.
abstract: Age-related macular degeneration (AMD), the most common cause of visual loss after the age of 65, displays a degeneration of the retinal pigment epithelial (RPE) cells and photoreceptors in the retinal centre (macula). The central macula (fovea) that contains mostly cone photoreceptors mediates the high visual acuity. Drusen maculopathy may lead to visual deterioration. Drusen are extracellular deposits of debris that accumulate on Bruch's membrane. Drusen attract inflammatory, immunological and vasoactive stimuli. RPE and photoreceptor cells overlying drusen exhibit biochemical and morphological signs of degeneration. Strong and intermittent light exposure (photons) induces the formation of free radicals in the very high oxygen tension milieu of the retina. The negative effects of irradiation stimulate accumulation of lipofuscin in RPE and photoreceptor cells leading to mitochondrial dysfunction and apoptotic cell death. A hydrophobic barrier is built up in Bruch's membrane reducing diffusion to the choroid. Hereditary and inflammatory factors modify the risk for AMD. There is a genetic dysregulation of the complement system leading to inappropriate complement activation. The genetic polymorphism of complement factor H (CFH) and age-related maculopathy susceptibilty 2 (ARMS2) increase the risk of progression to advanced AMD. The photoelectric effect creates free radicals, resulting in a continuous increase of lipofuscin formation and impairing mitochondrial activity. In addition, inflammation and complement dysregulation contribute to the formation of drusen and vasoproliferative reactions with neovascularization. Antioxidants neutralize reactive oxygen species and reduce lipofuscin accumulation in RPE and photoreceptor cells. For prophylactic treatment of drusen maculopathy, high doses of antioxidants such as vitamins C and E, lutein, zeaxanthine and zinc are used according to the Age-Related Eye Disease Study 2 (AREDS 2). The risk of developing advanced AMD was reduced by 27% at 10 years follow-up. No adverse events were noted.
authors.affiliation: Karolinska Institute, St Erik Eye Hospital, Stockholm, Sweden.
authors.forename: Peep V
authors.initials: PV
authors.lastname: Algvere
authors.affiliation: Karolinska Institute, St Erik Eye Hospital, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Kvanta
authors.affiliation: Karolinska Institute, St Erik Eye Hospital, Stockholm, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Seregard
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use; D006801:Humans; D008268:Macular Degeneration / Q000209:etiology* / Q000517:prevention & control; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D015593:Retinal Drusen / Q000150:complications* / Q000188:drug therapy; D055213:Retinal Pigment Epithelium / Q000473:pathology; D012307:Risk Factors; D014786:Vision Disorders / Q000209:etiology* / Q000517:prevention & control
chemical_list: D000975:Antioxidants
keywords: age-related eye disease study; age-related maculopathy; antioxidants; drusen; lipofuscin; pathogenetic features; photoelectric effect; reactive oxygene species