Daily Aspirin Tied to Macular Degeneration

In a population-based study led by Paulus T.V.M. de Jong, MD, PhD, of the Netherlands Institute for Neuroscience and the Academic Medical Center, both in Amsterdam, researchers reported that, late-stage "wet" AMD was 2.22 times more likely among daily aspirin users (95% CI 1.61 to 3.05).

Daily aspirin use was also significantly elevated at earlier stages of the disease, although the association rose with AMD severity (P<0.001 for trend), de Jong and colleagues reported. But prior studies have yielded conflicting results on the connection between aspirin use and AMD, so further evaluation is needed, they noted.

De Jong said in a press release that, "If future studies support our results, then recommendations on aspirin may need to be modified for patients with age-related macular degeneration." "It's possible that increased AMD risk may outweigh aspirin's potential protective benefits for some patients, but we need to know more about the impacts of dose, length of use, and other factors before we can say for certain, or make specific recommendations."

His group's European Eye Study included 4,691 participants ages 65 or older randomly sampled from the population of seven European countries from Norway in the north to Italy in the south.

More than a third of these seniors (36.4%) showed early AMD on fundus photographs taken as part of the study, and late AMD was found in 3.3% of participants. Most participants reported at least some aspirin use: monthly for 41.2%, at least once a week for 7%, and daily for 17.3%.

Notably, one-third of individuals with wet AMD took aspirin daily compared with only 16% of those who did not have AMD. Adjustment for age, gender, and cardiovascular disease produced the 2.22-fold higher risk of wet AMD associated with daily aspirin.

Wet AMD risk rose with frequency of aspirin use (P<0.001).

For the "dry" form of advanced AMD, aspirin use didn't appear to correlate with prevalence. The lack of an association with dry AMD may in part have been because of the small sample size of only 49 cases, but the researchers noted that a prior study with substantially more dry AMD cases didn't find an association with aspirin use either.

Early AMD also showed a link to daily aspirin use, with 26% elevated risk of grade 1 AMD (OR 1.26, 95% CI 1.08 to 1.46) and 42% excess risk of grade 2 AMD (OR 1.42, 95% CI 1.18 to 1.70) compared with no use after adjustment for age, gender, and cardiovascular disease.

The association wasn't significant for grade 3 AMD, nor was any association with less than daily use of aspirin.

The researchers acknowledged the possibility of confounding by indication given that those with a history of cardiovascular disease are more likely to take daily aspirin and are also more likely to develop wet AMD.

"However, the odds ratios for aspirin use and wet AMD were virtually unchanged when cardiovascular disease was included in the analysis, indicating that the association of aspirin with AMD was independent of any association with cardiovascular disease and was not confounded by cardiovascular disease," they wrote.

Furthermore, the impact of daily aspirin use on AMD didn't differ between individuals with cardiovascular disease and those without it (P=0.06 for interaction).

More likely mechanisms are disruption of the fine balance in lipid oxidation and that aspirin's inhibition of cyclooxygenase 1 (COX-1) and prostaglandin-endoperoxide synthetase 2 may cut down on the vasodilator prostacyclin, leading to hypoxia and neovascularization, de Jong's group suggested.

• This European, cross-sectional, study found that frequent aspirin use was associated with early AMD and wet late AMD, and the association rose with increasing frequency of consumption.
• Although several studies suggested an association between aspirin use and AMD, other studies were unable to confirm this finding.

De Jong PTVM, et al "Associations between aspirin use and aging macula disorder: The European eye study" Ophthalmology 2012; DOI: 10.1016/j.ophtha.2011.06.025.