Drusen in age-related macular degeneration: Pathogenesis, natural course, and laser photocoagulation-induced regression

Drusen are subretinal pigment epithelial deposits that are characteristic o f but not uniquely associated with age-related macular degeneration (AMD). Age-related macular degeneration is associated with two types of drusen tha t have different clinical appearances and different prognoses. Hard drusen appear as small, punctate, yellow nodules and can precede the development o f atrophic AMD. Areolar atrophy of the retinal pigment epithelium (RPE), ch oriocapillaris, and outer retina develop as the drusen disappear, but druse n can regress without evidence of atrophy. Soft drusen appear as large (usu ally larger than 63 mu m in diameter), pale yellow or grayish-white, dome-s haped elevations that can resemble localized serous RPE detachments. They t end to precede the development of clinically evident RPE detachments and ch oroidal neovascularization. Drusen characteristics correlated with progress ion to exudative maculopathy include drusen number (five or more), drusen s ize (larger than 63 mu m in diameter), and confluence of drusen. Focal hype rpigmentation in the macula and sptemic hypertension also are associated wi th an increased risk of developing choroidal new Vessels (CNVs). Large drus en are usually a sign of diffuse thickening of Bruch's membrane with basal linear deposit, a vesicular material that probably arises from the RPE, con stitutes a diffusion barrier to water-soluble constituents in the plasma, r esults in lipidization of Bruch's membrane, and creates a potential cleavag e plane between the RPE basement membrane and the inner collagenous layer o f Bruch's membrane through which CNVs can grow. Disappearance of drusen spo ntaneously and in areas adjacent to laser photocoagulation scars was first noted by Gass (Gass JD: Arch Ophthalmol 90:206-217, 1973; Trans Am Acad Oph thalmol Otolaryngol 75:580-608, 1971). Subsequent reports have confirmed th ese observations. Photocoagulation-induced drusen regression might prevent patients with drusen from developing exudative maculopathy. The mechanism f or spontaneous drusen regression probably involves RPE atrophy. The mechani sm for photocoagulation-induced drusen regression is unknown. If photocoagu lation-induced drusen regression is anatomically similar to atrophy-associa ted drusen regression, then the former will be associated with dissolution of basal linear deposit and a residuum of basal laminar deposit. Sarks and coworkers (Sarks JP, Sarks SH, Killingsworth MC: Eye 11:515-522, 1997) prop osed that this in turn will eliminate the potential cleavage plane between the RPE basement membrane and inner collagenous layer of Bruch's membrane t hrough which CNVs grow, thus retarding the growth of CNVs. (C) 1999 by Else vier Science Inc. All rights reserved.