[Drusen in Bruch's membrane. Their significance for the pathogenesis and therapy of age-associated macular degeneration]

Abstract

The drusen found in Bruch's membrane represent precursors for the development of age-related macular degeneration. The pathogenetic concepts are summarized: 1. As a result of aging changes in the metabolism of the pigment epithelium with age, the normal structure of Bruch's membrane is destroyed. This process is associated with lipid accumulation and the development of drusen. The lipids deposited are predominantly phospholipids or neutral lipids. 2. The clinical appearance of drusen can also vary from one person to another, but individually a significant symmetry of drusen characteristics can be seen, demonstrating that drusen are the results of specific metabolic dysfunctions rather than non-specific aging products. 3. The development of specific forms of age-related macular degeneration corresponds with different drusen. Larger, more confluent and hypofluorescent drusen are associated with the development of pigment epithelium detachments. In eyes with smaller, scattered and hyperfluorescent drusen, choroidal neovascularizations are more likely. 4. Histochemically, larger, hypofluorescent drusen contain predominantly neutral lipids. In contrast, smaller, hyperfluorescent drusen consist predominantly of phospholipids. 5. The accumulation of neutral lipids in Bruch's membrane is therefore associated with Pigment epithelium detachments. These apolar lipids may produce a hydrophobic barrier in Bruch's membrane for the water transport from the retina towards the choroid. A pigment epithelium detachment can develop. 6. The deposition of polar phospholipids predisposes to the development of choroidal neovascularization. These lipids in association with the changed structure of Bruch's membrane may induce an inflammation--like reaction, resulting in the in-growth of choroidal capillaries under the pigment epithelium. The analysis of the relationship between subclinical aging changes in Bruch's membrane and different forms of age-related macular degeneration may help to identify specific risk factors and to predict the future outcome in individual eyes. This may result in differentiated treatment concepts adapted to the specific aging changes in each person.