Aspirin Benefits Outweigh Risks in Macular Degeneration

Laird Harrison; July 16, 2015

VIENNA — Patients can continue to take aspirin as recommended by their primary care physicians without fear of worsening their macular degeneration, researchers say.

"Taking patients off aspirin can cause premature morbidity and mortality," said Kent Small, MD, from Los Angeles, California.

He presented a meta-analysis on aspirin, cardiovascular disease, and age-related macular degeneration here at the American Society of Retina Specialists (ASRS) 2015 Annual Meeting.

Dr Small explained that he got interested in the topic when he realized that his patients were reacting to reports in the media of studies linking macular degeneration to aspirin use.

"My patients were coming into my office having taken themselves off aspirin without having any discussion with their primary doctors or me," he said.

He conducted a literature review and found 197 cardiovascular studies with 167,582 subjects and four ophthalmologic studies with 13,175 subjects.

Randomized placebo-controlled trials provide strong evidence that aspirin can reduce the risk for cardiovascular disease, he reported.

My patients were coming into my office having taken themselves off aspirin without having any discussion with their primary doctors or me.Dr Kent Small A previous meta-analysis by the Antithrombotic Trialists Collaboration demonstrated that aspirin reduces vascular mortality by 15%, total mortality by 10%, and stroke by 25%, but increases the risk for extracranial bleeds ( Lancet. 2009;373:1849-1860).

In contrast, the studies of macular degeneration were epidemiologic, Dr Small explained. Although three of them suggested the risk for macular degeneration increased in patients taking aspirin, two suggested the risk decreased.

In the Blue Mountains Eye Study, 257 of the 2389 participants used aspirin, and 63 developed wet macular degeneration during a 15-year period ( JAMA Intern Med. 2013;173:258-264). In fact, the rate of degeneration was 2.5 times higher in aspirin users than in nonusers, and the risk increased over time.

However, the Blue Mountains Eye team drew no conclusions about the correlation. They pointed out that the results did not reach statistical significance when adjusted for body mass index, blood pressure, diabetes mellitus, blood total cholesterol level, or fish consumption, Dr Small reported.

In the European Eye Study, researchers analyzed data on 4691 participants older than 65 years ( Ophthalmology. 2012;119:112-118). They found that aspirin was associated with early — grades 1 and 2 — macular degeneration and wet late degeneration. However, there was no association between aspirin and late macular trouble in people older than 85 years. And in this study, the potential influence of cardiovascular deaths or angina was not eliminated.

The Beaver Dam Eye Study looked at 4926 people 43 to 86 years of age ( JAMA. 2012;308:2469-2478). The risk for wet macular degeneration was elevated in people who had used aspirin 10 years before examination, but not in those who used aspirin 5 years before examination. However, in this study, factors such high cholesterol were not controlled for.

In contrast, the Physicians' Health Study, a randomized placebo-controlled trial, demonstrated that people taking aspirin were less likely to develop macular degeneration than those taking placebo ( Arch Ophthalmol. 2001;119:1143-1149).

Likewise, the Age-Related Eye Disease Study showed that the use of anti-inflammatory medications, including aspirin, seem to have a protective effect on dry macular degeneration.

Well-Established Cardiovascular Benefit

In the meta-analysis of all these studies, the possible risk for macular degeneration was outweighed by the well-established cardiovascular benefits, Dr Small explained.

"The ophthalmologic data are somewhat mixed," he concluded. "I think the jury is still out. And I think patients should continue to use their aspirin, despite the perceived risks of exacerbating macular degeneration."

After Dr Small's presentation, a member of the audience asked whether any of the studies looked specifically at the risk for hemorrhagic macular degeneration with aspirin use. Dr Small reported that the studies did not show an increased risk.

I think the jury is still out.Dr Kent Small However, the meta-analysis doesn't go very far in clarifying that question, said session moderator Susanne Binder, MD, from the Rudolf Foundation Clinic at the Boltzmann Institute for Retinology and Biomicroscopic Laser Surgery in Vienna.

"It's a big concern among patients," she told Medscape Medical News. "As soon as these patients have a subretinal hemorrhage and a severe drop in vision, then they are frightened to continue aspirin. And their internists tell them to stop it because they are also frightened."

Forty percent of patients with macular degeneration also have cardiovascular disease, so it is not surprising that many people taking aspirin also have eye problems, she pointed out. The patients who are taking aspirin also tend to be the sickest patients.

The fact that three studies showed an increased risk for macular degeneration with aspirin use and two others showed a decreased risk does not provide any guidance for physicians, she said.

In her institution, clinicians stop aspirin in patients who have suffered a subretinal hemorrhage, she explained. They treat the patients for the hemorrhage, then try to get them back on a reduced dosage after 2 or 3 weeks.

However, Dr Binder acknowledged that this approach is "totally unproven," and that most patients are afraid to resume aspirin. In particular, "those who have lost the sight in one eye are afraid they will lose the sight in the other eye," she said.

Dr Small has disclosed no relevant financial relationships. Dr Binder reports that she has consulted for Carl Zeiss.


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