More Frequent Aspirin Use Associated With More Severe AMD

Daniel M. Keller, PhD

January 05, 2012

January 5, 2012 — The risks for early age-related macular degeneration (AMD) and wet late AMD are associated with frequent aspirin use, and the risk increases with greater aspirin consumption, European researchers reported in an article published in the January 2012 issue of Ophthalmology.

The results, from the large, population-based, cross-sectional European Eye Study, suggest caution in recommending aspirin to patients with early or late AMD who may take it for other conditions, such as prevention of cardiovascular disease (CVD).

When adjusted for all potential confounders of age, sex, education, smoking, body mass index, diabetes, CVD, angina, cholesterol, and systolic blood pressure, daily aspirin users had a greater than 2-fold increased risk for wet AMD when compared with participants who never consumed aspirin.

The research, led by Paulus T.V.M. de Jong, MD, PhD, emeritus professor of ophthalmic epidemiology at the Academic Medical Center and a member of the Netherlands Institute of Neuroscience in Amsterdam involved 4691 participants aged 65 years or older who were chosen by taking a random sampling from population registers in 7 countries.

Field workers interviewed the participants about sociodemographic, health, and lifestyle factors. Aspirin use was quantified as never (n = 2760), monthly or less (n = 766), weekly but not daily (n = 326), or daily (n = 839). Digitized color fundus images were recorded at each participating center and sent to Rotterdam, the Netherlands, where 2 staff members graded them according to the International Classification and Grading System for Age-Related Maculopathy and AMD.

Grades 1, 2, and 3 corresponded to early AMD, and grade 4 corresponded to late AMD, which was subdivided into dry or wet AMD. Wet AMD was defined as serous or hemorrhagic detachment of the retinal pigment epithelium, a subretinal neovascular membrane, subretinal hemorrhage, or other signs. Participants with grade 0 (macula free of drusen or pigmentary irregularities or with hard drusen) were the control patients. The main outcome measure was the odds ratio (OR) for AMD in aspirin users.

Daily aspirin users were older, were less likely to smoke, and had lower blood pressure and cholesterol levels, but more CVD and angina.

Among all participants, 36.4% had early AMD, and 3.3% had late AMD, of whom about two thirds had wet and one third dry AMD. More frequent aspirin use was associated with higher grades of AMD. One third of the individuals with wet AMD consumed aspirin daily compared with only 16% of control participants.

Table. Association of Aspirin Use and Wet Late AMD*

Aspirin Use OR (95% Confidence Interval)
Never 1
Monthly or less 0.85 (0.42 - 1.72)
At least weekly but less than daily 1.30 (0.59 - 2.87)
Daily 2.26 (1.66 - 3.08)
Pvalue for trend <.001

*Adjusted for all potential confounders.

Similar trends in ORs were seen when investigators adjusted only for age and sex, or for age, sex, and CVD (both P < .001 for the trends). There was no significant association for aspirin with wet AMD according to the presence or absence of CVD or angina (ie, AMD was independent of CVD or angina).

For the 42 cases of dry AMD with information on aspirin use and potential confounders, dry AMD was not associated with aspirin use after adjustment for age and sex.

Significant trends for aspirin use and early AMD for grade 1 (n = 1652) and grade 2 (n = 463) AMD were also seen when adjusted for all potential confounders (P = .001 and P < .001, respectively, for trends). However, no such association was seen for grade 3 (n = 114; P =.9).

Limitations of the study include its cross-sectional and retrospective nature, with the possibility of recall error about aspirin use and possible confounders. In addition, there were no data on the doses of aspirin or the use of other antiplatelet or anticoagulant drugs.

Dr. de Jong told Medscape Medical News that "people should be aware that aspirin, often just bought over the counter without prescription, may have adverse effects — apart from major gastrointestinal and other bleeds, also for AMD." He said future randomized trials will be necessary to find out whether there is a critical dose of aspirin in relation to the risk for AMD.

On the basis of this study and the body of literature, he said, he would advise people who have early or late AMD not to take aspirin for pain, and if they are taking it for primary prevention of CVD to discuss with their physicians whether it is wise to continue doing so. "For secondary prevention...the benefits of daily aspirin outweigh the risks," Dr. de Jong said.

George Williams, MD, chairman of the Department of Ophthalmology and director of the Beaumont Eye Institute at William Beaumont Hospital in Royal Oak, Michigan; clinical professor of ophthalmology and biomedical sciences at Oakland University William Beaumont School of Medicine; and an expert correspondent for the American Academy of Ophthalmology, commented to Medscape Medical News that the study "raises some interesting questions" but "does not provide a definitive answer on the role of aspirin in the development of AMD."

There has not been a consistent trend among studies looking at this question, and differing inclusion criteria and definitions of AMD severity make it difficult to compare studies.

"The strength of this study is that they have photographic documentation of the status of the macular degeneration," Dr. Williams said. "In some of the other studies, we know exactly how much aspirin people were on because they were randomized to aspirin. However, in those studies we are relying upon less robust data to determine the degree of macular degeneration."

Another potential confounder is that aspirin is a component of many over-the-counter medications that people do not recognize as containing the drug.

Dr. Williams said he is concerned that although the study started with almost 4700 patients, in the end there were only 36 patients in the wet AMD group who had been taking daily aspirin. He said he would want to see larger numbers before becoming more comfortable with an association of aspirin with wet AMD.

He noted that the value of prophylactic aspirin for the prevention of CVD is coming under increasing scrutiny. "It's going to require physicians to take the time to talk to their patients about the possibility that there may be an association [of aspirin with the development of AMD]," he said. "So patients who are on aspirin should discuss with their prescribing physician the reasons why they're on aspirin, what the benefits are, and then make a decision as to whether they wish to continue. But at this point I certainly see no definitive reason for people to stop aspirin when it's indicated for their overall health."

A disadvantage for primary care physicians is that most will not have a comprehensive knowledge of the status of their patients' macular degeneration, "so it will require communication between primary care providers and ophthalmologists to come up with the best solution for a specific patient," Dr. Williams advised.

Dr. de Jong has disclosed no relevant financial relationships. Dr. Williams is a consultant/advisor to Alcon Laboratories, Allergan, Neurotech, OptiMedica, Pfizer, and Thrombogenics. He also has received grant support from Alcon Laboratories, Allergan, Genentech, and Neurotech, is an equity owner of Nu-Vue Technologies, OptiMedica, and Thrombogenics, and has patent/royalty income from Nu-Vue Technologies.

Ophthalmology. 2012;119:112-118. Abstract


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