October 10, 2014
3 min read

Systemic beta-blockers, nitrates may be independently linked with lower IOP

Conversely, study finds that statins and aspirin do not lower IOP by themselves.

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The use of systemic beta-blockers or nitrates was found to significantly lower IOP in an older British population, according to a study.

“We still know relatively little about the pathogenesis of primary open-angle glaucoma,” lead author Anthony P. Khawaja, MB BS, MA(Cantab), MPhil, FRCOphth, said. “Higher intraocular pressure is the most important risk factor for POAG, and understanding why some people have higher IOP than others may offer new targets for treatment.”

Anthony Khawaja, MB BS, MA(Cantab), MPhil, FRCOphth

Anthony P. Khawaja


Many older people take systemic medication; hence, “looking for associations between medication classes and IOP offers a powerful method for examining whether certain biological processes are important for pathophysiological processes underlying IOP,” Khawaja told Ocular Surgery News.

Beta-blockers and nitrates

All 7,093 participants in the observational study, published in Ophthalmology, were from the European Prospective Investigation into Cancer-Norfolk Eye Study. The mean age of participants was 68 years, and exclusion criteria included a history of glaucoma therapy.

Four classes of medication were associated with lower IOP: beta-blockers, nitrates, statins and aspirin.

“But only two of these classes — beta-blockers and nitrates — had independent effects on lowering IOP,” Khawaja, a senior resident at Moorfields Eye Hospital who is pursuing doctoral research at the University of Cambridge, where the study was conducted at Strangeways Research Laboratory, said.

The use of beta-blockers was associated with 0.92 mm Hg lower IOP, and nitrate medication was associated with 0.63 mm Hg lower IOP.

“These two differences in IOP are quite large on a population level and, based on longitudinal eye studies, would translate into roughly 15% and 10% risk reductions of incident glaucoma over a 5-year period, respectively,” he said.

Although the association between beta-blockers and IOP did not surprise the authors, “it served as an excellent internal control for our study,” Khawaja said. “The fact we saw that patients taking systemic beta-blockers had lower IOP meant our methodological approach was valid.”

On the other hand, the finding of lower IOP in participants using nitrates “was a surprise and an exciting finding,” Khawaja said. “This relatively novel finding potentially offers the basis for exploring nitrate medication as a new IOP-lowering treatment, for example, topically. It also confirms basic science research, suggesting an important role of nitric oxide in aqueous dynamics.”

Systemic medication use

The authors were intrigued that the lower IOP observed in patients using statins was due solely to the fact that these patients were more likely to also use systemic beta-blockers.

“Statins have been reported as being protective against the development of glaucoma,” Khawaja said. “However, we should now be cautious that these reported associations may have been due to confounding by the concurrent use of beta-blockers, rather than due to any biological effect of statins on glaucoma risk.”

Additionally, the study shed light on the management of glaucoma patients with comorbidity. For instance, for patients being treated for ischemic heart disease or hypertension, “it is worth considering the role of their systemic medication,” Khawaja said. “If a patient stops a systemic beta-blocker or nitrate, it may be worthwhile to check IOP and monitor for progression more closely.”

Likewise, for a patient taking beta-blockers or nitrates for the first time, “it is worth remembering that his IOP was likely higher for the period prior to him starting systemic medication,” Khawaja said. “I think our findings also reinforce what we already know about the likely negligible effect of prescribing topical beta-blockers to a patient already taking systemic beta-blockers.”

Going forward, Khawaja anticipates more research into new IOP-lowering medications that make use of the nitric oxide-donating mechanism. Meanwhile, he and his colleagues are investigating systemic medication and glaucoma-related quantitative traits, such as retinal nerve fiber layer thickness.

“For this, the analysis method has to be different from the IOP study,” Khawaja said. “Rather than looking for a cross-sectional association, we need to look at cumulative dosage over a longer period, given the slow, unidirectional changes that occur in structural parameters.” – by Bob Kronemyer


Khawaja AP, et al. Ophthalmology. 2014;doi:10.1016/j.ophtha.2014.02.009.

For more information:

Anthony P. Khawaja, MB BS, MA(Cantab), MPhil, FRCOphth, can be reached at Strangeways Research Laboratory, 2 Worts’ Causeway, Cambridge CB1 8RN, U.K.; 44-1223-335995; email: anthony.khawaja@gmail.com.

Disclosure: Khawaja has no relevant financial disclosures.