Risk Factors for Primary Open-Angle Glaucoma and Pseudoexfoliative Glaucoma in the Thessaloniki Eye Study FOTIS TOPOUZIS, M. ROY WILSON, ALON HARRIS, PANAYIOTA FOUNTI, FEI YU, ELEFTHERIOS ANASTASOPOULOS, THEOFANIS PAPPAS, ARCHIMIDIS KOSKOSAS, ANGELIKI SALONIKIOU, AND ANNE L. COLEMAN ● PURPOSE: To investigate risk factors for primary open- angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEXG) in the Thessaloniki Eye Study. ● DESIGN: Cross-sectional, population-based study. ● METHODS: Randomly selected subjects 60 years of age and older (n  2554) participated in the Thessaloniki Eye Study. Glaucomatous damage and presence of pseu- doexfoliation (PEX) were defined according to specific criteria. Open-angle glaucoma (OAG) subjects were compared with nonglaucoma subjects (controls), POAG subjects were compared with controls without PEX, and PEXG subjects were compared with controls with PEX for demographic, lifestyle, ophthalmic, and systemic fac- tors. Factors with P < .2 in the univariate analysis were retained for multivariate analyses. ● RESULTS: In multivariate analysis restricted to persons who participated in clinic visits and who had at least 1 phakic eye (n  2078), intraocular pressure (odds ratio [OR], 1.21 per 1 mm Hg; P < .001), PEX (OR, 2.81; P < .001), history of coronary artery bypass or vascular surgery (OR, 1.95; P  .017), and moderate-to-high myopia (> 3 diopters; OR, 2.40; P  .009) were associated with higher odds for OAG. In analysis includ- ing all clinic visits (n  2261), age became significantly associated (OR, 1.05; P  .004). In multivariate analy- sis for POAG (n  1840), associations were found for age (OR, 1.04 per year; P  .048), IOP (OR, 1.19 per 1 mm Hg; P < .001), history of coronary artery bypass or vascular surgery (OR, 2.09; P  .01), and history of diabetes treated with insulin (OR, 3.05; P  .045). In multivariate analysis for PEXG (n  238), the latter was associated with increased IOP (OR, 1.25 per 1 mm Hg; P < .001). ● CONCLUSIONS: IOP was the only factor associated with both POAG and PEXG, whereas moderate-to-high myopia showed borderline significance in both. Vascular systemic diseases and their treatment were associated only with POAG. The implications of these differences for the pathogenesis between the 2 common types of OAG should be explored further. (Am J Ophthalmol 2011;152:219 –228. © 2011 by Elsevier Inc. All rights reserved.) R ECENTLY, AN INCREASING AMOUNT OF DATA HAS been reported from population-based studies and randomized clinical trials on risk factors for open- angle glaucoma (OAG). 1–3 Identifying risk factors for a disease contributes substantially to our knowledge because it provides clues to the cause and enables the identification of groups at increased risk, which then can be targeted for early detection. 3 To date, although some risk factors for OAG have been established, the results have been incon- sistent. 1–3 This may be explained partly by differences in study designs, the variety of definitions used for glaucoma, and the fact that few variables have been included consis- tently in risk factors analyses across studies. However, these discrepancies also could reflect differences among populations in terms of genetic predisposition and expo- sure to environmental factors. Therefore, assessing risk factors in different populations is important, not only to verify previously published data, but also to identify new factors associated with increased OAG risk. Further, there is limited understanding of factors predis- posing to the development of pseudoexfoliative glaucoma (PEXG), 4 which represents one of the more common types of secondary OAG. 5 Although it has been reported that pseudoexfoliation (PEX) is the most common identifiable cause of OAG, 6 most subjects with PEX do not have glaucoma. 7–10 Also, based on a recent study by Arnarsson and associates, only a small proportion of subjects with PEX progressed to glaucoma over a 5-year period. 11 The known association of PEX with increased intraocular pressure (IOP) 5 may suggest that the increased risk of glaucoma in subjects with PEX is mediated through ele- Accepted for publication Jan 11, 2011. From the Department of Ophthalmology, School of Medicine, Aristo- tle University of Thessaloniki, American Hellenic Educational Progres- sive Association (AHEPA) Hospital, Thessaloniki, Greece (F.T., P.F., E.A., T.P., A.K., A.S.); the School of Medicine, University of Colorado Denver and Health Sciences Center, Denver, Colorado (M.R.W.); the Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana (A.H.); and the Center for Eye Epidemiology, Jules Stein Eye Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California (F.Y., A.L.C.). Inquiries to Fotis Topouzis, Aristotle University of Thessaloniki, A’ Department of Ophthalmology, American Hellenic Educational Progres- sive Association Hospital, St. Kiriakidi 1, 54636 Thessaloniki, Greece; e-mail: ftopouzis@otenet.gr © 2011 BY ELSEVIER INC.ALL RIGHTS RESERVED. 0002-9394/$36.00 219 doi:10.1016/j.ajo.2011.01.032