Some Chronic Medications Affect IOP, May up Glaucoma Risk

By Marilynn Larkin

January 19, 2017

NEW YORK (Reuters Health) - Use of commonly prescribed medications for chronic conditions can alter intraocular pressure (IOP), a major risk factor for the development of glaucoma, researchers from Singapore say.

Drs. Ching-Yu Cheng and Henrietta Ho of Singapore National Eye Center told Reuters Health, "IOP is the only modifiable risk factor for glaucoma, the leading cause of irreversible blindness in the older people. Altered IOP is also important in the progression of this disease."

"With an aging population, the prevalence of glaucoma and chronic diseases such as diabetes that require medication is on the rise," they said by email. "Understanding how medication use influences IOP in co-existing comorbidities is paramount to understanding its potential risk in disease progression."

To investigate, the coauthors and their colleagues analyzed data from an age-stratified random sample of participants in the Singapore Epidemiology of Eye Diseases study, a population-based study of more than 10,000 individuals from three ethnic groups.

A total of 8,063 adults with a mean age of 57 (50% women) were included in the current study, with about equal representation from Chinese, Malay and Indian individuals.

As reported in JAMA Ophthalmology, online January 12, after adjusting for age, gender, body mass index, ethnicity and the conditions for which medications were taken (for example, statins adjusted for lipids, insulin adjusted for glycosylated hemoglobin), systemic beta-blocker use was independently associated with an IOP of 0.45 mmHg lower (P<0.001).

By contrast, higher mean IOP was associated with use of angiotensin converting enzyme inhibitors (0.33 mmHg higher, P=0.008), angiotensin receptor blockers (0.40 mmHg higher, P=0.02), statins (0.21 mmHg higher, P=0.03) and sulfonylureas (0.34 mmHg higher, P=0.02).

All associations were "modest at best," according to the authors, and no additive, synergistic or antagonist effects of medications on IOP were identified. Further, "only the associations with systemic hypoglycemic agents were greater than 1 mmHg, a threshold that has translated to a 14% greater risk of incident glaucoma across five years in other studies."

Drs. Cheng and Ho said, "Although diabetes itself could partly account for the higher IOP in patients taking sulfonylureas, it is not likely to be causative, given the negative results in those who are using the other hypoglycemic agents that we reviewed. Our findings suggest that sulfonylureas should be used with caution in persons with known glaucoma risk factors, such as a positive family history, or examination findings like a greater cup-to-disc ratio."

"At this point, it is unclear if our findings will be reproducible in glaucoma patients, in whom a change in IOP would potentially have greater consequences for the patients," they added. "Future research examining this relationship in glaucoma patients is needed and will provide further insights to our findings."

Dr. Anthony Khawaja of University College London Institute of Ophthalmology, coauthor of an accompanying commentary, told Reuters Health, "Examining the relationship between systemic medication use and an unrelated disease or trait is an exciting method to identify novel biological pathways that cause disease. This may in turn lead to new treatments for disease."

"Additionally, many of our glaucoma patients have comorbidities and we remain uncertain how these comorbidities, or the treatments for them, affect glaucoma and its management," he said by email.

"A challenge with this hypothesis-generating approach, however, is the chance of false positive results due to the large number of statistical tests," he observed. "This means the findings . . . need to replicated in an independent study before we can use the results to inform our practice."

Dr. Khawaja added that the relationship between diabetes and glaucoma "remains controversial." Although systematic reviews support an increased risk of glaucoma in diabetic patients, the studies used in these reviews "are biased," he said. "Diabetic patients have regular eye screening, meaning they have a higher chance of glaucoma detection."

"Longitudinal population-based studies suggest there may no association between diabetes and glaucoma," he noted, "and it has been suggested that higher blood sugar may help protect the optic nerve from damaging effects of intraocular pressure."

Dr. Melissa Yao of the Department of Ophthalmology and Visual Sciences at Montefiore Medical Center in New York City, told Reuters Health, "Most of our patients have multiple concomitant, systemic diseases that they are receiving treatment for. Therefore, it will not be surprising to find many of them taking the exact systemic medications that this study has identified."

"The likelihood of the associated small increases in IOP causing visual morbidity is very low, whereas the benefits of the systemic medications in preventing diabetic and hypertensive associated morbidity may outweigh the risk," she said by email.

Dr. Alex B. Theventhiran, also of Montefiore, agreed, and added, "the complexity of optimizing control of one of these conditions at the potential expense of another is a very difficult question to answer . . . The article provides evidence that this area will have to be studied further and that the future care of our glaucoma patients will likely involve even closer interaction with our primary care colleagues."


JAMA Opthalmol 2017.