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48 EW RETINA June 2013 Questioning the link between aspirin and AMD by Vanessa Caceres EyeWorld Contributing Writer New study shows a small connection with aspirin and neovascular, late AMD A recently released study is stirring the pot over the topic of aspirin use and age-related macular degeneration (AMD). The latest study to touch on this topic appeared in the December 2012 issue of JAMA, led by researchers with the Beaver Dam Eye Study in Wisconsin.1 The wellknown Beaver Dam Eye Study has provided previous insight into a number of AMD and other health and visual correlations. In this investigation, researchers examined the association between regular aspirin use and AMD. Like the general public, a number of study participants were using aspirin for cardioprotective benefits. In the JAMA study, there were 4,926 participants who had a baseline eye exam between 1988 and 1990. Participants had eye exams every five years for 20 years. The study tracked participants' frequency of aspirin use. Regular aspirin use was defined as at least twice a week for more than three months. The study examined the incidence of early AMD, late AMD, as well as neovascular AMD and geographic atrophy. Investigators used retinal photographs assessed with the Wisconsin Age-Related Maculopathy Grading System. The results The study found a small but statistically significant increased risk for late and neovascular AMD associated with aspirin use. There were 512 cases of early AMD and 117 cases of late AMD. Regular aspirin use 10 years before the retinal examination was connected with late AMD. Additionally, regular aspirin use 10 years before the retinal examination had a significant association with neovascular AMD. Investigators did not find a connection between early AMD and aspirin use five or 10 years prior to the retinal exam. The study also did not find a link between the number of aspirin milligrams taken per day and early or late AMD. As the study tracked other medications that participants used, they analyzed if there was a link between nonsteroidal anti-inflammatory drugs and AMD as well as warfarin and AMD. Again, no significant connection emerged. "If our finding is borne out in other studies, it suggests that the effect of aspirin on mechanisms leading to AMD may be different, at least partially, from aspirin's immediate effects on clotting, which seem to be responsible for cardioprotection," the investigators wrote. Investigators noted that their results are similar to those in a 2012 European study that linked aspirin use and AMD. That research, published in the January 2012 issue of Ophthalmology, included 4,691 participants over the age of 65.2 They found an association between frequent aspirin use with early AMD and wet late AMD. The odds ratios increased with frequency of consumption. The Beaver Dam Eye Study investigators noted that their study limitations include limited data from some participant visits regarding aspirin use details. They also pointed out that their study was almost all whites (99%) of European ancestry. Future studies should further explore the link between aspirin and AMD to see if the same results occur, the investigators concluded. "If confirmed, defining the causal mechanisms may be important in developing methods to block this effect to prevent or retard the development of neovascular AMD in persons who use aspirin, especially to prevent [cardiovascular disease]," they wrote. Now here's the twist Although the results do not point to a change that should occur in aspirin regimens, physicians who treat AMD say part of the battle with a study like this is quelling patients' fears. "This gets into the lay press, and some patients ask about it," said James M. Maisel, MD, Retina Group of New York, Hempstead, N.Y. The information may get misinterpreted either by the lay press or by the patients themselves, he said. "It's a big burden to deal with this. Sometimes people stop taking aspirin who really need to take it … This study tells us that there is no risk or a very low risk to our patients who require aspirin for systemic reasons." Dr. Maisel said that aspirin use is very common in his patients, especially for carotid disease or valve disease associated with retinal vascular disease. He also sees patients with retinal vascular occlusions associated with some thrombotic risk factors. These patients are sometimes treated with aspirin. "My concern with this study is that it may scare individuals into stopping their aspirin use, which had been recommended to reduce the risk of stroke and cardiac events," said Paul Sternberg Jr., MD, G.W. Hale professor and chairman, Vanderbilt Eye Institute, Nashville, Tenn. "The protective effect of aspirin versus cardiovascular disease appears stronger than the risk of blindness from wet AMD related to the aspirin use." Dr. Sternberg also pointed out that two previous randomized studies, the Women's Health Study and the Physician's Health Study, found no beneficial or harmful effect of aspirin use on the risk for AMD.3,4 Further study of the connection between aspirin and AMD would be helpful, perhaps looking at a subset analysis of bilateral progressive AMD, Dr. Maisel said. EW References 1. Klein BE, Howard KP, Gagnon RE, Dreyer JO, Lee KE, Klein R. Long-term use of aspirin and age-related macular degeneration. JAMA. 2012;308:2469-2478. 2. de Jong PT, Chakravarthy U, Rahu M, et al. Associations between aspirin use and aging macula disorder: the European Eye Study. Ophthalmology. 2012;119:112-118. 3. Christen WG, Glynn RJ, Ajani UA, et al. Age-related maculopathy in a randomized trial of low-dose aspirin among U.S. physicians. Arch Ophthalmol. 2001;119:1143-1149. 4. Christen WG, Glynn RJ, Chew EY, Buring JE. Low-dose aspirin and medical record–confirmed age-related macular degeneration in a randomized trial of women. Ophthalmology. 2009;116:2386-2392. Editors' note: The physicians interviewed have no financial interests related to this article. Contact information Maisel: 516-939-6100, zydocmd@gmail.com Sternberg: 615-322-5000, paul.sternberg@vanderbilt.edu