Association of systemic medication use with glaucoma and intraocular pressure: The European Eye Epidemiology Consortium

Joëlle E Vergroesen, Alexander K Schuster, Kelsey V Stuart, Nigus G Asefa, Audrey Cougnard-Grégoire, Cécile Delcourt, Cédric Schweitzer, Patrícia Barreto, Rita Coimbra, Paul J Foster, Robert N Luben, Norbert Pfeiffer, Julia V Stingl, Toralf Kirsten, Franziska G Rauscher, Kerstin Wirkner, Nomdo M Jansonius, Louis Arnould, Catherine P Creuzot-Garcher, Bruno H StrickerChristina Keskini, Fotis Topouzis, Geir Bertelsen, Anne E Eggen, Mukharram M Bikbov, Jost B Jonas, Caroline C W Klaver, Wishal D Ramdas, Anthony P Khawaja, European Eye Epidemiology (E3) Consortium

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Abstract

Purpose: To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population. Design: Meta-analysis of 11 population-based cohort studies of the European Eye Epidemiology Consortium. Participants: The glaucoma analyses included 143 240 participants and the IOP analyses included 47 177 participants. Methods: We examined associations of 4 categories of systemic medications—antihypertensive medications (β-blockers, diuretics, calcium channel blockers [CCBs], α-agonists, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers), lipid-lowering medications, antidepressants, and antidiabetic medications—with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Results of multivariable regression analyses of each study were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in participants with diabetes only. Main Outcome Measures: Glaucoma prevalence and IOP. Results: In the meta-analyses of our maximally adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.08 to 1.39). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR, 1.96; 95% CI, 1.23 to 3.12). No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with glaucoma. Use of systemic β-blockers was associated with a lower IOP (β coefficient, −0.33 mmHg; 95% CI, −0.57 to −0.08 mmHg). Monotherapy of both selective systemic β-blockers (β coefficient, −0.45 mmHg; 95% CI −0.74 to −0.16 mmHg) and nonselective systemic β-blockers (β coefficient, −0.54 mmHg; 95% CI, −0.94 to −0.15 mmHg) was associated with lower IOP. A suggestive association was found between use of high-ceiling diuretics and lower IOP (β coefficient, −0.30 mmHg; 95% CI, −0.47 to −0.14 mmHg) but not when used as monotherapy. No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with IOP. Conclusions: We identified a potentially harmful association between use of CCBs and glaucoma prevalence. Additionally, we observed and quantified the association of lower IOP with systemic β-blocker use. Both findings potentially are important, given that patients with glaucoma frequently use systemic antihypertensive medications. Determining causality of the CCB association should be a research priority. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Original languageEnglish
Pages (from-to)893-906
Number of pages14
JournalOphthalmology
Volume130
Issue number9
Early online date6 May 2023
DOIs
Publication statusPublished - Sept 2023

Bibliographical note

Funding Information:
The author(s) have made the following disclosure(s): A.K.S.: Consultant – AbbVie, Appelis; Financial support – AbbVie, Appelis, Novartis, Santen; Nonfinancial support – Heidelberg EngineeringK.V.S.: Financial support – Association for Research in Vision and Ophthalmology International Travel GrantC.D.: Consultant – Allergan, Bausch & Lomb, Laboratoires Théa, Novartis; Financial support – Fondation de France, Fondation Bordeaux Université; Lecturer – Appelis; Patent – W020210589914A1J.V.S.: Financial support – TransMed Clinical Research Fellowship, Association for Research in Vision and Ophthalmology Travel GrantT.K.: Financial support – LEUKO-Expert (Ministry of Health), TAG-White (Saxonian Ministry of Research), NFDI4Health (German Research Society), CODEX-PLUS (Ministry of Research), FAIR-DS (Ministry of Research)C.P.C.-G.: Consultant – AbbVie, Bayer, Novartis, Roche, Horus, Thea; Financial support – Novartis, Bayer, AbbVie; Lecturer – Thea, Novartis, Bayer, AbbVie; Nonfinancial support – NovartisF.T.: Consultant – Omikron, Thea; Financial support – Thea, Omikron, Pfizer, Alcon, Bausch & Lomb; Lecturer – Omikron, Allergan, Thea; President – European Glaucoma Society, Greek Glaucoma SocietyThe studies included in this meta-analysis were supported as follows. The Alienor Study was supported by Laboratoires Théa, Fondation Voir et Entendre, Agence Nationale de la Recherche (grant no.: ANR 2010-PRSP-011 VISA), French Ministry of Health (grant no.: PHRC 12_157, ECLAIR), CFSR Recherche (Club Français des Specialistes de la Retine). The Coimbra Eye Study was supported by Novartis. The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (grant nos.: MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK (grant no.: C864/A14136). K.V.S. is in receipt of a UCL Overseas Research Scholarship and is supported by grants from Fight for Sight (London) (1956A) and The Desmond Foundation. A.P.K. is funded by a UK Research and Innovation Future Leaders Fellowship, an Alcon Research Institute Young Investigators Award, and a Lister Institute for Preventative Medicine Fellowship. The Gutenberg Health Study is funded through the government of Rhineland-Palatinate (“Stiftung Rheinland-Pfalz für Innovation”; grant no.: AZ 961-386261/733), the research programs “Wissen schafft Zukunft” and “Center for Translational Vascular Biology (CTVB)” of the Johannes Gutenberg-University of Mainz, and its contract with Boehringer Ingelheim and PHILIPS Medical Systems, including an unrestricted grant for the Gutenberg Health Study. The LIFE-Adult-Study was supported by the Leipzig Research Centre for Civilization Diseases (LIFE), an organizational unit affiliated to the Medical Faculty of Leipzig University. LIFE is funded by means of the European Union, by the European Regional Development Fund (ERDF), and by funds of the Free State of Saxony within the framework of the excellence initiative (project nos: 713-241202, 14505/2470, and 14575/2470). F.G.R. is supported by a grant from German Research Foundation (grant no.: DFG 497989466). The glaucoma-related data-collection and analysis in Lifelines has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 661883. The Rotterdam Study was supported by the following foundations that contributed through Uitzicht: Stichting Glaucoomfonds, Landelijke Stichting voor Blinden en Slechtzienden (LSBS), and Oogfonds. Additional support was given by Rotterdamse Stichting Blindenbelangen (RSB), Stichting Lijf en Leven, Henkes stichting, Stichting voor Ooglijders, Stichting Blindenhulp, Erasmus Medical Center, Erasmus University, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The Thessaloniki Eye Study was supported in part by the International Glaucoma Association, London, UK; the UCLA Center for Eye Epidemiology, Los Angeles, California; the Health Future Foundation, Creighton University, Omaha, NE; the Texas Tech University Health Sciences Center, Lubbock, Texas; Pfizer, Inc., New York, New York; Merck and Co., Inc., Whitehouse Station, New Jersey; and Pharmacia Hellas, Athens, Greece. All grants were unrestricted. The main funding sources of the Tromsø Eye Study are UiT, The Arctic University of Norway, North Norwegian Regional Health Authority, Norwegian Ministry of Health and Care Services, University Hospital of North Norway, Troms County, and “Glaukomforskningsstiftelsen.” The sponsors or funding organizations had no role in the design or conduct of this research. F.G.R.: Financial support – German Federal Ministry of Education and Research. L.A.: Financial support – AbbVie. Obtained funding: N/A

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© 2023 American Academy of Ophthalmology

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