Perspective
Ocular and Systemic Pseudoexfoliation Syndrome

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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-β1, 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.

Section snippets

Ocular manifestations relevant to clinical management

The hallmark of PEX syndrome is the pathologic production and accumulation of an abnormal fibrillar extracellular material in anterior segment tissues. As suggested by ultrastructural indications, the characteristic PEX fibrils appear to be multifocally produced by various intraocular cell types including the preequatorial lens epithelium, nonpigmented ciliary epithelium, trabecular endothelium, corneal endothelium, vascular endothelial cells, and virtually all cell types of the iris.4 The

Open questions and future challenges

Despite its clinical significance and many new insights in recent years, much remains to be learned about the clinical ocular and systemic manifestations, the epidemiologic and genetic characteristics, and the cause and pathogenesis of PEX syndrome. Last but not least, it would be desirable to have a universally applied nomenclature for this disease reflecting its true underlying pathophysiology. From a pathologist’s viewpoint, the process does not represent a true exfoliation of the lens

Conclusions

PEX syndrome is a common age-related generalized fibrotic matrix process, which may not only cause severe chronic open-angle glaucoma and cataract, but also a spectrum of other serious, potentially disastrous ocular and surgical complications. In view of the multitude of clinical complications, this entity is of relevance to all ophthalmologists including subspecialists in glaucoma, cataract, cornea, retina, uveitis, and neuroophthalmology. In view of a rising mean age of populations, we shall

Ursula Schlötzer-Schrehardt, PhD, is a Professor of Experimental Ophthalmology and a Chief Scientist in the Department of Ophthalmology at the University of Erlangen-Nürnberg, Erlangen, Germany. Apart from being dedicated to the subject of pseudoexfoliation syndrome and glaucoma, her research interests relate to corneal epithelial stem cells and ophthalmic pathology.

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    Ursula Schlötzer-Schrehardt, PhD, is a Professor of Experimental Ophthalmology and a Chief Scientist in the Department of Ophthalmology at the University of Erlangen-Nürnberg, Erlangen, Germany. Apart from being dedicated to the subject of pseudoexfoliation syndrome and glaucoma, her research interests relate to corneal epithelial stem cells and ophthalmic pathology.

    Gottfried O. H. Naumann, MD, is an Emeritus of the Department of Ophthalmology at the University of Erlangen-Nürnberg, Erlangen, Germany, has been President of the International Council of Ophthalmology (ICO) from 1998 to 2006. His textbook “Pathology of the Eye” is available in German, English, and Japanese languages. Dr Nauman clinical and research interests focus on microsurgery of the anterior segment and on Ophthalmic Pathology.

    Supported in part by grant SFB-539 from the German Research Foundation.

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