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Abstract

Purpose
To test the association between use of calcium channel blocker (CCB) medications and the rate of visual field (VF) progression in a large cohort of patients from five glaucoma clinics.

Design
Retrospective, longitudinal case-control study.

Subjects
Patients attending five glaucoma clinics in the United Kingdom using the same Electronic Medical Record (EMR) system.

Methods
For the main analysis, we selected one eye of patients with at least 5 reliable (false positive errors < 15%) VFs over at least 4 years. The use of systemic medications was derived from the EMR system. CCB users were identified as cases. Propensity Score Matching (PMS) and multivariable analyses (MV) were used to adjust for confounders. A Directed Acyclic Graph (DAG) of the relevant variables guided the selection of covariates. Linear mixed effect models (LMMs) were used to test the effect on the rate of VF Mean Deviation (MD) associated with CCB use and other covariates (for the MV analysis). Sensitivity analyses were conducted with different inclusion criteria and cut-offs on the estimated duration of CCB use.

Main Outcome Measure
Mean difference in the rate of VF MD progression between CCB users and controls.

Results
The main analysis included 14,475 eyes (1,942 from CCB users) which met the selection criteria (one eye per patient). The Median [Interquartile Range] VF series length was 8 [6, 11] tests, with a follow-up of 8.6 [6, 11.5] and 8.2 [5.9, 11.2] years in CCB users and controls respectively. One-to-one PSM pairing with controls was achieved for all CCB users. The estimated rate of MD progression was -0.31 [-0.33, -0.28] dB/year (Mean [95%-Confidence Intervals]) in the CCB users and -0.35 [-0.37, -0.33] dB/year in the matched controls (p = 0.016). This significant difference was confirmed with the MV analysis, including all controls (p = 0.020). All sensitivity analyses confirmed the main results.

Conclusions
CCB use was statistically significantly associated with a slower rate of VF deterioration, after multivariable adjustment. The estimated difference was small and likely not clinically significant but may be influenced by the limited information on the duration of CCB exposure in this cohort.
Calcium channel blockers (CCBs) are some of the most commonly prescribed medications for cardiovascular conditions. Up to 40% of patients with systemic hypertension are prescribed a CCB1 to control their blood pressure. In the United Kingdom (UK), CCBs make up approximately 4% of all primary-care prescriptions2. Because the incidence of both systemic hypertension3 and glaucoma4 increases with age, and the known association between these two conditions5,6, many patients who are at risk of, or have, glaucoma are likely to be prescribed CCBs.
The effect of systemic CCBs on glaucoma is controversial. Many large observational investigations have consistently shown an association between CCB use and increased risk of receiving a glaucoma diagnosis7, 8, 9, 10, 11, replicating this result across different cohorts. Other studies have also shown an association between CCB use and glaucoma-related traits, such as thinner inner retinal layers on optical coherence tomography (OCT) imaging10,12. On the other hand, studies investigating the association between CCBs and disease progression in patients with glaucoma have shown either no association13 or a protective association14, 15, 16, 17, especially in normal tension glaucoma (NTG). Two of the studies showing a protective effect were small randomised clinical trials (RCTs)14,15.
However, well-powered studies of the association between CCB use and rate of glaucoma progression are still lacking. In this work, we analysed real-world data from more than 14,000 patients followed in five glaucoma clinics across the UK. We investigated the association between systemic CCB use and the rate of visual field (VF) progression, adjusting for multiple confounders. We further report on the association of the rate of VF progression with the use of systemic medication classes and multiple patient characteristics.

Publication Type:	Article
Additional Information:	This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Subjects:	R Medicine > RE Ophthalmology
Departments:	School of Health & Medical Sciences School of Health & Medical Sciences > Optometry & Visual Sciences
SWORD Depositor:	Symplectic Administrator

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