Statin use in relation to intraocular pressure, glaucoma, and ocular coherence tomography parameters in the UK Biobank

Objective: To evaluate the relationship between statin use and various glaucoma-related traits. Design: Cross-sectional analysis of UK Biobank data. Participants: We included 118,153 participants (mean age (SD)=56.8 (8.0) years) with data on statin use (5 statin types - 2006-2010) and corneal-compensated IOP measured in 2009-2013). Also, we included 192,283 participants (with 8,982 self-reported glaucoma cases as of 2006-2010) for the glaucoma analyses. After excluding participants with neurodegenerative diseases, 41,638 participants with global macular retinal nerve fiber layer thickness (mRNFL) and 41,547 participants with ganglion cell inner plexiform layer thickness (mGCIPL) measurements in 2009-2010 were available for analysis. Method: We examined associations with statin use utilizing multivariable-adjusted linear regression models for IOP, mRNFL, and mGCIPL and logistic regression models for glaucoma. We assessed whether a 2,673-member polygenic risk score (PRS) identified from a glaucoma multi-trait analysis of genome wide association study (MTAG) modified associations. We performed Mendelian randomization (MR) experiments using 5 gene variants as proxies for the cholesterol-altering effect of statins to investigate associations with various glaucoma-related outcomes. Main Outcome and Measures: IOP; glaucoma; mRNFL; mGCIPL. Results: Statin users had higher unadjusted mean IOP ± SD (16.3 ± 3.9 mm Hg; n = 20,593 participants) than non-users (15.9 ± 3.8 mm Hg; n = 97,560 participants), but in a multivariable-adjusted model, IOP did not differ by statin use (difference = 0.05 mm Hg; 95% CI: -0.02, 0.13; p=0.17). Similarly, statin use was not associated with prevalent glaucoma (OR = 1.05; 95% CI: 0.98, 1.13). Statin use was weakly associated with thinner mRNFL (difference = -0.15 microns; 95% CI: -0.28, -0.01; p=0.03) but not with mGCIPL thickness (difference = -0.12 microns; 95% CI: -0.29, 0.05; p=0.17). Among statins, simvastatin and atorvastatin, the two most commonly used statins, were not associated with any glaucoma outcome measures. No association was modified by the glaucoma MTAG PRS (Pinteraction≥0.16). MR experiments showed no evidence for a causal association between the cholesterol-altering effect of statins and various glaucoma outcomes (inverse weighted variance p≥0.14). Conclusions: Statin use was not associated with lower IOP, lower glaucoma prevalence, thicker mRNFL or thicker mGCIPL in the UK Biobank.