Calcium Channel Blocker Use and Associated Glaucoma and Related Traits Among UK Biobank Participants
Authors: Kastner Alan , Stuart Kelsey V. , Montesano Giovanni , De Moraes C. Gustavo , Kang Jae H. , Wiggs Janey L. , Pasquale Louis R. , Hysi Pirro , Chua Sharon Y. L. , Patel Praveen J. , Foster Paul J. , Khaw Peng T. , Khawaja Anthony P. ,   UK Biobank Eye and Vision Consortium, Allen Naomi , Aslam Tariq , Atan Denize , Balaskas Konstantinos , Barman Sarah , Barrett Jenny , Bishop Paul , Black Graeme , Braithwaite Tasanee , Carare Roxana , Chakravarthy Usha , Chan Michelle , Chua Sharon , Day Alexander , Desai Parul , Dhillon Bal , Dick Andrew , Doney Alexander , Egan Cathy , Ennis Sarah , Foster Paul , Fruttiger Marcus , Gallacher John , Garway-Heath David , Gibson Jane , Guggenheim Jeremy , Hammond Chris , Hardcastle Alison , Harding Simon , Hogg Ruth , Hysi Pirro , Keane Pearse , Khaw Peng , Khawaja Anthony , Lascaratos Gerassimos , Littlejohns Thomas , Lotery Andrew , Luben Robert , Luthert Phil , MacGillivray Tom , Mackie Sarah , Madhusudhan Savita , McGuinness Bernadette , McKay Gareth , McKibbin Martin , Moore Tony , Morgan James , O'Sullivan Eoin , Oram Richard , Owen Chris , Patel Praveen , Paterson Euan , Peto Tunde , Petzold Axel , Pontikos Nikolas , Rahi Jugnoo , Rudnicka Alicja , Sattar Naveed , Self Jay , Sergouniotis Panagiotis , Sivaprasad Sobha , Steel David , Stratton Irene , Strouthidis Nicholas , Sudlow Cathie , Sun Zihan , Tapp Robyn , Thomas Dhanes , Trucco Emanuele , Tufail Adnan , Viswanathan Ananth , Vitart Veronique , Weedon Mike , Williams Katie , Williams Cathy , Woodside Jayne , Yates Max , Zheng Yalin 
Published: September 2023

Importance

Calcium channel blocker (CCB) use has been associated with an increased risk of glaucoma in exploratory studies.

Objective

To examine the association of systemic CCB use with glaucoma and related traits among UK Biobank participants.

Design, Setting, and Participants

This population-based cross-sectional study included UK Biobank participants with complete data (2006-2010) for analysis of glaucoma status, intraocular pressure (IOP), and optical coherence tomography (OCT)–derived inner retinal layer thicknesses. Data analysis was conducted in January 2023.

Exposure

Calcium channel blocker use was assessed in a baseline touchscreen questionnaire and confirmed during an interview led by a trained nurse.

Main Outcomes and Measures

The primary outcome measures included glaucoma status, corneal-compensated IOP, and 2 OCT-derived inner retinal thickness parameters (macular retinal nerve fiber layer [mRNFL] and macular ganglion cell–inner plexiform layer [mGCIPL] thicknesses). We performed logistic regression and linear regression analyses to test for associations with glaucoma status and IOP and OCT-derived inner retinal thickness parameters, respectively.

Results

This study included 427 480 adults. Their median age was 58 (IQR, 50-63) years, and more than half (54.1%) were women. There were 33 175 CCB users (7.8%). Participants who had complete data for glaucoma status (n = 427 480), IOP (n = 97 100), and OCT-derived inner retinal layer thicknesses (n = 41 023) were eligible for respective analyses. After adjustment for key sociodemographic, medical, anthropometric, and lifestyle factors, use of CCBs (but not other antihypertensive agents) was associated with greater odds of glaucoma (odds ratio [OR], 1.39 [95% CI, 1.14 to 1.69]; P = .001). Calcium channel blocker use was also associated with thinner mGCIPL (−0.34 μm [95% CI, −0.54 to −0.15 μm]; P = .001) and mRNFL (−0.16 μm [95% CI, −0.30 to −0.02 μm]; P = .03) thicknesses but not IOP (−0.01 mm Hg [95% CI, −0.09 to 0.07 mm Hg]; P = .84).

Conclusions and Relevance

In this study, an adverse association between CCB use and glaucoma was observed, with CCB users having, on average, 39% higher odds of glaucoma. Calcium channel blocker use was also associated with thinner mGCIPL and mRNFL thicknesses, providing a structural basis that supports the association with glaucoma. The lack of association of CCB use with IOP suggests that an IOP-independent mechanism of glaucomatous neurodegeneration may be involved. Although a causal relationship has not been established, CCB replacement or withdrawal may be considered should glaucoma progress despite optimal care.