Long-Term Regular Use of Low-Dose Aspirin and Neovascular Age-Related Macular Degeneration

National Sample Cohort 2010–2015
Published:September 18, 2018DOI:


      The association between long-term cardioprotective aspirin use and neovascular age-related macular degeneration (AMD) is controversial. This study was undertaken to estimate the risk of neovascular AMD with long-term regular use of low-dose aspirin.


      Retrospective population-based study, using a nationwide cohort from a variety of clinics and hospitals in South Korea.


      Nonregular aspirin users and regular aspirin users under national health insurance, aged ≥45 years, who were followed from 2010 to 2015, were identified.


      Incidence per 10 000 person-years for neovascular AMD was estimated. Long-term regular use of low-dose aspirin was defined as sustained intake of ≤100 mg aspirin with ≥1044 days prescription between 2005 and 2009. Nonregular aspirin users included occasional users or nonusers. The analyses included a propensity score–adjusted analysis in a large, randomly selected, unmatched whole cohort (n = 482 613); propensity score–matched analysis in a matched cohort (n = 74 196); and maximally adjusted analysis in the unmatched whole cohort (n = 482 613).

      Main Outcome Measures

      Incidence of newly developed neovascular AMD using the registration code for intractable disease under national health insurance.


      Incidence of neovascular AMD was 3.5 among nonregular aspirin users and 7.2 among regular aspirin users per 10 000 person-years in the unmatched whole cohort. However, propensity score–adjusted analyses revealed no association between aspirin use and neovascular AMD (adjusted hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.73–1.30). Likewise, propensity score–matched analyses showed no association; incidences of neovascular AMD were 7.5 and 7.1 among nonregular aspirin users and regular aspirin users (crude HR, 0.94; 95% CI, 0.70–1.28), respectively. A maximally adjusted model, including age, sex, income, residential area, and history of 100 randomly selected types of generic drugs, showed no association (adjusted HR, 0.95; 95% CI, 0.71–1.28).


      We found no association between long-term regular use of low-dose aspirin for 5 years and future incidence of neovascular AMD. Thus, this large-scale study suggests that regular, long-term use of low-dose aspirin appears to be safe with respect to the new development of neovascular AMD.

      Abbreviations and Acronyms:

      AMD (age-related macular degeneration), CI (confidence interval), HR (hazard ratio), NHIS (National Health Insurance Service), NSC (National Sample Cohort)
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        • Klein B.E.
        • Howard K.P.
        • Gangnon R.E.
        • et al.
        Long-term use of aspirin and age-related macular degeneration.
        JAMA. 2012; 308: 2469-2478
        • Liew G.
        • Mitchell P.
        • Wong T.Y.
        • et al.
        The association of aspirin use with age-related macular degeneration.
        JAMA Intern Med. 2013; 173: 258-264
        • Rim T.H.
        • Kim D.W.
        • Han J.S.
        • Chung E.J.
        Retinal vein occlusion and the risk of stroke development: a 9-year nationwide population-based study.
        Ophthalmology. 2015; 122: 1187-1194
        • Rim T.H.
        • Han J.
        • Choi Y.S.
        • et al.
        Retinal artery occlusion and the risk of stroke development: twelve-year nationwide cohort study.
        Stroke. 2016; 47: 376-382
        • Lee J.
        • Lee J.S.
        • Park S.H.
        • et al.
        Cohort Profile: The National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea.
        Int J Epidemiol. 2017; 46: e15
        • Rim T.H.
        • Lee C.S.
        • Lee S.C.
        • et al.
        Intravitreal ranibizumab therapy for neovascular age-related macular degeneration and the risk of stroke: a National Sample Cohort Study.
        Retina. 2016; 36: 2166-2174
        • Park S.J.
        • Kwon K.E.
        • Choi N.K.
        • et al.
        Prevalence and incidence of exudative age-related macular degeneration in South Korea: a nationwide population-based study.
        Ophthalmology. 2015; 122: 2063-2070.e1
        • Rim T.H.
        • Kim D.W.
        • Cheng C.-Y.
        • Kim S.S.
        Protective effect of smoking against pterygium development in men: a nationwide longitudinal cohort study in South Korea.
        BMJ Open. 2017; 7e017014
        • Parsons L.S.
        Performing a 1: N case-control match on propensity score.
        in: Proceedings of the 29th Annual SAS Users Group International Conference. SAS Institute, Inc, Cary, NC2004 (165-29)
        • Kaul S.
        • Diamond G.A.
        Relationship of aspirin use with age-related macular degeneration: association or causation? Comment on “The association of aspirin use with age-related macular degeneration.”.
        JAMA Intern Med. 2013; 173: 264-266
        • Ye J.
        • Xu Y.F.
        • He J.J.
        • Lou L.X.
        Association between aspirin use and age-related macular degeneration: a meta-analysis.
        Invest Ophthalmol Vis Sci. 2014; 55: 2687-2696
        • Li L.
        • Li W.
        • Chen C.Z.
        • et al.
        Is aspirin use associated with age-related macular degeneration? A meta-analysis.
        J Clin Pharm Ther. 2015; 40: 144-154
        • Zhu W.
        • Wu Y.
        • Xu D.
        • et al.
        Aspirin use and risk of age-related macular degeneration: a meta-analysis.
        PLoS One. 2013; 8e58821
        • Kahawita S.K.
        • Casson R.J.
        Reprint of: Aspirin use and early age-related macular degeneration: a meta-analysis.
        Can J Ophthalmol. 2015; 50: S29-S33
        • de Jong P.
        • Chakravarthy U.
        • Rahu M.
        • et al.
        Associations between aspirin use and aging macula disorder. The Eureye Study.
        Invest Ophthalmol Vis Sci. 2010; 51: 1620
        • Christen W.G.
        • Glynn R.J.
        • Ajani U.A.
        • et al.
        Age-related maculopathy in a randomized trial of low-dose aspirin among US physicians.
        Arch Ophthalmol. 2001; 119: 1143-1149
        • Christen W.G.
        • Manson J.E.
        • Glynn R.J.
        • et al.
        Beta carotene supplementation and age-related maculopathy in a randomized trial of US physicians.
        Arch Ophthalmol. 2007; 125: 333-339
        • Blumenkranz M.S.
        • Russell S.R.
        • Robey M.G.
        • et al.
        Risk factors in age-related maculopathy complicated by choroidal neovascularization.
        Ophthalmology. 1986; 93: 552-558
        • DeAngelis M.M.
        • Lane A.M.
        • Shah C.P.
        • et al.
        Extremely discordant sib-pair study design to determine risk factors for neovascular age-related macular degeneration.
        Arch Ophthalmol. 2004; 122: 575-580
        • Douglas I.J.
        • Cook C.
        • Chakravarthy U.
        • et al.
        A case-control study of drug risk factors for age-related macular degeneration.
        Ophthalmology. 2007; 114: 1164-1169
        • Rim T.H.
        • Cheng C.-Y.
        • Kim D.W.
        • et al.
        A nationwide cohort study of cigarette smoking and risk of neovascular age-related macular degeneration in East Asian men.
        Br J Ophthalmol. 2017; 101: 1367-1373
        • Park S.M.
        • Yun Y.H.
        • Kim Y.A.
        • et al.
        Prediagnosis body mass index and risk of secondary primary cancer in male cancer survivors: a large cohort study.
        J Clin Oncol. 2016; 34: 4116-4124
        • Wong C.W.
        • Yanagi Y.
        • Lee W.K.
        • et al.
        Age-related macular degeneration and polypoidal choroidal vasculopathy in Asians.
        Prog Retin Eye Res. 2016; 53: 107-139