PSEUDOEXFOLIATION SYNDROME: PATHOBIOLOGY AND CLINICAL-HISTOPATHOLOGIC CORRELATIONS

U. Schloetzer-Schrehardt and G. O. H. Naumann

Department of Ophthalmology, University of Erlangen-Nuernberg, Germany

Pseudoexfoliation (PEX) syndrome has recently been acknowledged as a generalized disorder of the extracellular matrix characterized by the production and progressive accumulation of an abnormal fibrillar extracellular material in many intra- and extraocular tissues. Its ocular manifestations affect all structures of the anterior segment and lead to a wide spectrum of spontaneous and intraoperative ocular complications, such as lens dislocation, zonular ruptures, blood-aqueous barrier breakdown, melanin dispersion, formation of posterior synechiae, corneal endothelial decompensation, and open-angle as well as angle-closure glaucomas. Secondary open-angle glaucoma may develop in patients with PEX syndrome due to active and local production of PEX material by trabecular cells, the progressive accumulation of the material in the juxtacanalicular tissue, and subsequent degenerative structural changes.

The characteristic fibrillar PEX material is composed of microfibrillar subunits surrounded by an amorphous matrix. The material has a complex glycoprotein/proteoglycan structure composed of a protein core surrounded by glycoconjugates, e.g. glycosaminoglycans. The material appears to be multifocally produced by various cell types, e.g. the nonpigmented ciliary epithelium, the iris pigment epithelium, the preequatorial lens epithelium, corneal endothelium, trabecular cells, vascular endothelia and smooth muscle cells of the iris. Immunohistochemical evidence of elastic fiber epitopes in PEX material as well as molecular biologic data showing overexpression of elastic fiber components have led to the current pathogenetic concept which explains PEX syndrome as a type of elastosis affecting especially elastic microfibrils. Significantly increased aqueous humor levels of TGF-ß1 in PEX patients suggest a role for this growth factor in the abnormal matrix formation.