Regular coffee intake ups risk of primary open-angle glaucoma

Genetic evidence from a recent study suggests that habitual coffee drinkers have an increased risk of primary open-angle glaucoma (POAG).

“Given that coffee is widely consumed, our findings provide new insights into potential strategies to prevent and manage POAG,” the researchers said.

This study employed two-sample Mendelian randomization (MR) and selected single-nucleotide polymorphisms (SNPs) associated with coffee consumption (including phenotypes 1 and 2) from a genome-wide association study (GWAS) that included 121,824 individuals of European descent.

The researchers used coffee intake data obtained from the MRC-IEU UK Biobank to identify instruments for coffee intake. They also acquired summary-level data for POAG from the largest publicly available meta-analyses involving 16,677 POAG patients and 199,580 controls.

Inverse variance-weighted (IVW) method was applied for the main MR analysis. For the sensitivity analysis, the researchers used weighted-median, weighted mode-based estimate (MBE), MR Pleiotropy RESidual Sum and Outlier (PRESSO) test, and MR-Egger regression. They evaluated the causal association between coffee intake and POAG risk using three sets of instrumental variables.

Genetically predicted higher coffee consumption phenotype 1 (cups/day) significantly correlated with a higher likelihood of developing POAG (odds ratio [OR], 1.241, 95 percent confidence interval [CI], 1.041‒1.480; p=0.016). [Ophthalmology 2022;129:1014-1021]

Likewise, genetically predicted higher coffee consumption phenotype 2 (high vs no/low) significantly correlated with a higher POAG risk (OR, 1.155, 95 percent CI, 1.038‒1.284; p=0.008, using the IVW method). Genetically predicted higher coffee intake from the MRC-IEU UK Biobank OpenGWAS was also a significant predictor of higher POAG risk (OR, 1.727, 95 percent CI, 1.230‒2.425; p=0.002).

These findings were robust to possible pleiotropy in sensitivity analyses.

“Many studies regarding coffee consumption revealed its inverse correlation with the incidence of diabetes mellitus, various cancer lines, Parkinsonism, and Alzheimer’s disease,” the researchers said. [Crit Rev Food Sci Nutr 2011;51:363-373]

“With regard to the relationship between coffee consumption and glaucoma, intraocular pressure (IOP) levels, retrobulbar vessel haemodynamics, and other risk factors have been discussed extensively,” they added.

Earlier studies have examined the relationship between coffee or caffeine consumption and IOP levels, given the known association of IOP with the death of retinal ganglion cells and optic nerve fibres in POAG patients. [Lancet 2004;363:1711-1720]

Some of these studies reported that coffee intake increases the risk of glaucoma associated with elevated IOP. [Eye 2012;26:1122-1130; Psychopharmacology 2019;236:811-819; Graefes Arch Clin Exp Ophthalmol 2020;258:613-619; Ann Pharmacother 2002;36:992-995]

On the other hand, the Blue Mountains Eye Study found no association between habitual caffeine intake and IOP among healthy participants. [J Glaucoma 2005;14:504-507]

Of note, a study by Terai and colleagues revealed a significant vasoconstrictor response of the retinal vessels 1 hour after caffeine intake in young healthy individuals. [Acta Ophthalmologica 2012;90:e524-e528]

“Therefore, considering the non-negligible ischemia-hypoxia effect of coffee consumption, it is more sensible to investigate the causal effect of coffee consumption on POAG than [to assess] the causal effect of coffee consumption on IOP as done in a previous study,” the researchers said. [Ophthalmology 2021;128:866-876]