Ocular and systemic pseudoexfoliation syndrome

PURPOSE: To provide an update on most recent developments regarding ocular and systemic manifestations and complications, clinical diagnosis and management, and molecular pathophysiology of pseudoexfoliation (PEX) syndrome, and to discuss future tasks and challenges in this field. DESIGN: Perspective. METHODS: Review of recent literature and authors' own clinical and laboratory studies. RESULTS: PEX syndrome is a common age-related generalized fibrotic matrix process of worldwide significance, which may not only cause severe chronic open-angle glaucoma and cataract, but also a spectrum of other serious spontaneous and surgical intraocular complications. Recent progress and advances have led to (1) improvements in clinical management by understanding the effects of the PEX process on ocular tissues, by refining diagnostic criteria, by applying new treatment regimes, and by developing preventive strategies to reduce surgical complications; (2) increasing evidence for systemic associations of PEX with cardiovascular and cerebrovascular morbidity; and (3) new insights into the molecular pathophysiology by analyzing the composition of PEX material, the differential gene expression of affected tissues, and key factors involved in pathogenesis. The current pathogenetic concept describes PEX syndrome as an elastic microfibrillopathy involving transforming growth factor-beta 1, oxidative stress, and impaired cellular protection mechanisms as key pathogenetic factors. CONCLUSIONS: Future tasks and challenges comprise epidemiologic prevalence and genetic studies of PEX syndrome, prospective randomized clinical and histopathological screening studies on its systemic manifestations and associations, and intensified basic research on differential protein and gene expression, animal and in vitro models, as well as potential biomarkers for PEX syndrome and its associated glaucoma.