Histopathology of Exfoliation Syndrome

Exfoliation syndrome (XFS) is characterized by light and electron microscopy by age-dependent gradual accumulation of whitish material of largely unknown composition and origin along both the anterior and posterior chambers and widely within the iris stroma. These deposits can be fairly specifically labeled with selected antibodies and lectins. Immunohistochemistry shows that intraocular exfoliation deposits share antigens with the microfibrillar elastic fiber system and several basement membrane components, including carbohydrate epitopes on glycosaminoglycans, proteoglycans, and cell adhesion molecules. The earliest histopathologic manifestation of XFS seems to be the deposition of characteristic fibers in various extraocular and anterior segment tissues, as observed by electron microscopy, and perivascular deposition of material within the iris stroma, which is antigenically typical of that found in classic intraocular exfoliation deposits. These findings precede the clinical diagnosis of XFS and likewise can be detected in the seemingly uninvolved fellow eyes of patients with clinically unilateral XFS. Indeed, histopathologic examination of capsulotomy, iridectomy, and trabeculectomy specimens can lead to a clinically unexpected diagnosis of XFS. Exfoliation fibers are additionally found widely distributed in extraocular connective tissues and visceral organs, but the matrix of these fibers seems to differ from that of intraocular deposits. In addition to this histopathologic discrepancy, both the frequent occurrence of clinically unilateral, histopathologically highly asymmetric exfoliation deposits, and the relationship between the early iris vasculopathy that not infrequently may be observed histopathologically for years before classic widespread exfoliation deposits appear along the anterior and posterior chambers remain to be resolved.