Clinicopathologic correlation of drusen and retinal pigment epithelial abnormalities in age-related macular degeneration

Background: Clinicopathologic studies of eyes lead to a better understanding of the nature of the ophthalmoscopic and fluorescein angiographic features of drusen. A study was conducted to provide clinicopathologic correlation of drusen and present a classification of drusen based on clinical and histopathologic features. Methods: The macular areas of three eyes from two patients were serially sectioned and studied, and features were depicted in a two-dimensional map and compared with clinical findings. Results: All three tyes had large drusen (>63 μm) with soft morphologic characteristics (poorly demarcated borders) documented on fundus photographs. In both eyes from one patient, these large drusen corresponded to areas of focal retinal pigment epithelium hypopigmentation overlying Bruch’s membrane, which was diffusely thickened throughout the macula. Similar findings were noted in another eye from a second patient, and additionally, where there was relatively marked fluorescein staining of large drusen on the late phase of an angiogram, the pathologic correlation demonstrated detachment of the thickened inner aspect of Bruch’s membrane from the remainder of Bruch’s membrane. Focal hyperpigmentation corresponded to areas of hypertrophy of the retinal pigment epithelium and to clusters of pigmented cells in the subretinal space and outer nuclear area. Conclusion: Diffuse thickening of the inner aspect of Bruch’s membrane is associated with retinal pigment epithelial hypopigmentation, focal atrophy, and soft (large) drusen formation.