Pathophysiology of age-related macular degeneration

The clinical and histopathological features of age-related macular degeneration (AMD) include a relationship with age, and the presence of pigmentary disturbances, drusen, thickening of Bruch's membrane, and basal laminar deposits. AMD is an advanced stage of a deteriorative process that takes place in all eyes. The primary lesion in AMD appears to reside in the retinal pigment epithelium (RPE), possibly resulting from its high rate of molecular degradation. Beginning early in life, and continuing throughout the life span, cells of the RPE gradually accumulate sacs of molecular debris. These residual bodies (lipofuscin) are remnants of the incomplete degradation of abnormal molecules which have been damaged within the RPE cells or derived from phagocytized rod and cone membranes. Progressive engorgement of RPE cells with these functionless residues is associated with the extrusion of aberrant materials which accumulate in Bruch's membrane and aggregate in the form of drusen and basal laminar deposits. These excretions contribute to the further deterioration of the RPE. Loss of vision results from death of visual cells due to degeneration of RPE cells, or the effects of leakage from neovascular membranes that invade the region of abnormal extracellular deposits.