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Aspirin intake may increase chances of developing early and wet late AMD

Paulus T.V.M. de Jong

The European Eye Study suggested an association between aspirin use and early and wet late age-related macular degeneration, with a positive correlation between more frequent consumption and increased risk.

“People should be aware that aspirin, often bought over the counter without prescription, may have adverse effects apart from gastrointestinal issues and other bleeds,” study author Paulus T.V.M. de Jong, MD, PhD, told OSN Retina.

A population-based, cross-sectional analysis across seven centers in Europe, the trial lends further support to growing concern over complications associated with aspirin use.

 “I would advise persons who have early or late AMD not to take aspirin regularly as a pain killer. In light of our findings and those of the meta-analysis published by the Antithrombotic Trialists’ Collaboration in 2009, I would also advise people with AMD who take small amounts of aspirin for primary prevention (ie, those with no past history of cardiac or vascular problems and no elevated risk factors for these diseases) to discuss with their doctor if it is wise to continue doing so,” Dr. de Jong said.

For those with elevated risks or disorders, the benefits of daily aspirin use as secondary prevention outweighs its risks, he said.

Results, related studies

The study included 4,691 participants aged 65 years or older who were recruited between 2000 and 2003 through random sampling. A structured questionnaire determined aspirin intake and possible AMD confounders, and logistic regression analysis discerned potential associations.

Early and late AMD occurred in 36.4% and 3.3% of participants, respectively. Monthly aspirin use was reported by 41.2% of participants, at least once weekly use by 7% and daily use by 17.3%. Odds ratios, adjusted for potential confounders including cardiovascular disease and angina, showed a steady increase with increasing severity of early AMD grade, excluding grade 3, and wet late AMD for daily aspirin users.

The Age-Related Eye Disease Study (AREDS) demonstrated similar associations between aspirin intake and early but not late prevalent AMD. Additionally, a retrospective, cross-sectional analysis published in Retina in 2010 showed three types of anti-platelet or anti-coagulant medications, aspirin included, to be associated with increased risk for intraocular hemorrhage in patients with wet late AMD.

According to the study authors, aspirin may inhibit cyclooxygenase 1 and prostaglandin-endoperoxide synthetase 2, which could decrease synthesis of an endothelium-derived vasodilator in blood vessels known as prostacyclins. This in turn might lead to hypoxia and subsequent neovascularization. Aspirin might also disrupt the delicate balance of lipid oxidation through direct action and its own metabolites that protect against such oxidation.

Aspirin and dry late AMD

No association between aspirin intake and dry AMD was established, but the study authors noted the small sample size of dry AMD patients (49 of the 157 participants with late AMD).

“Given the association between daily aspirin use and early AMD stage 1 and 2 but not stage 3, and wet AMD but not dry late AMD, I would think that the most likely explanation is a lack of statistical power due to smaller numbers of cases in stage 3 early AMD and dry late AMD,” Dr. de Jong said.

However, in AREDS, which featured a significantly larger number of dry AMD cases, an association was not found.

Other limitations of the analysis included the possibility that participants took aspirin following visual complications, a lack of data on the amount of aspirin used, potential recall error, and other potential confounders that were not analyzed, such as arthritis.

“Future randomized trials will be necessary to confirm our observational findings and to find out if there is a critical dose of aspirin in relation to the risk of AMD,” Dr. de Jong said. – by Michelle Pagnani

References:

• Age-Related Eye Disease Study Research Group. Risk factors associated with age-related macular degeneration. A case-control study in the age-related eye disease study: Age-related Eye Disease Study Report Number 3. Ophthalmology. 2000;107(12):2224-2232.
• Antithrombotic Trialists’ (ATT) Collaboration, Baigent C, Blackwell L, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomized trials. Lancet. 2009; 373(9678):1849-1860.
• de Jong PTVM, Chakravarthy U, Rahu M, et al. Associations between aspirin use and aging macula disorder. Ophthalmology. 2012;119(1):112-118.
• Kiernan DF, Hariprasad SM, Rusu IM, et al. Epidemiology of the association between anticoagulants and intraocular hemorrhage in patients with neovascular age-related macular degeneration. Retina. 2010;30(10):1573-1578.

• Paulus T.V.M. de Jong, MD, PhD, can be reached at the Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences, 47 Meibergdreef, 1105BA Amsterdam, the Netherlands; email: p.dejong@nin.knaw.nl.
• Disclosure: Dr. de Jong has no relevant financial disclosures.