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.