June 2014
Volume 55, Issue 6
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Letters to the Editor  |   June 2014
Aspirin Use and Risk of Age-Related Macular Degeneration
Author Notes
  • Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, People's Republic of China. 
Investigative Ophthalmology & Visual Science June 2014, Vol.55, 3954. doi:10.1167/iovs.14-14203
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    • Get Citation

      Wei Wang, Xiulan Zhang; Aspirin Use and Risk of Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(6):3954. doi: 10.1167/iovs.14-14203.

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We read with great interest the article by Ye et al. 1 titled “Association Between Aspirin Use and Age-Related Macular Degeneration: A Meta-Analysis,” published online in February of 2014 in Investigative Ophthalmology and Visual Science. In this meta-analysis, Ye et al. 1 analyzed the association between aspirin use and age-related macular degeneration (AMD). The analysis included data from 2 randomized trials, 4 case-control studies, and 3 cohort studies. The authors concluded that aspirin use is not associated with AMD but that it increased the risk of neovascular AMD. We congratulate and applaud their interesting and important work on this topic; however, there are some issues we feel need to be addressed. 
  1. 1.  
    The authors have not focused specifically on the issue of the completeness of the search strategy report for the databases. They provide a list of terms they used to search the 4 databases but no search strategy. We suggest that the authors provide details of the retrieval strategy.
  2. 2.  
    Although the authors evaluated the methodological quality of the included studies, they did not provide the details of the methodological assessment. The Downs and Black checklist only produced a summary quality score, which may be misleading. Instead, the results of the quality assessment should have incorporated an investigation of individual quality items.
  3. 3.  
    The definition of aspirin use was different across the studies (the most common definition was “ever use” aspirin). However, there did not appear to be any attempt to standardize the definition across the studies. The authors have included studies with the exposure to aspirin as “ever/never.” Aspirin is an over-the-counter drug, and as such, how can an individual be considered an aspirin “user” if they only used aspirin once or twice in a lifetime? It would seem prudent to exclude these studies from the analysis.
  4. 4.  
    Given the studies presented, it appears that the most reasonable interpretation of the data is in the data from the randomized controlled trials (RCTs), the study design best suited to control the known (and unknown) confounders. However, the pooled estimate of the two RCTs showed a moderately protective effect, whereas the results of the case-control and cohort studies demonstrated slightly harmful effects, although that was not statistically significant at the P level of <0.05. The authors should explain why the protective effects were noted in the RCTs, whereas most of the observational studies showed hazardous effects.
  5. 5.  
    Although the authors used a quality assessment method in an attempt to rank the various studies according to the 27 criteria (the two RCTs were ranked highest), there is still concern that the inherent limitations in the case-control and cohort study designs have not been overcome. For example, there is a concern that even after the risk factor adjustment, unadjusted and residual confounding remains in case-control and cohort studies, such that the participants who self-select for aspirin use remain at an elevated risk of AMD (independent of aspirin use). In other words, although aspirin use may be causally associated with neovascular AMD, it is also possible that aspirin use is simply a marker for underlying factors or conditions more closely associated with the development of AMD. Indeed there are reports of significant associations between stroke, angina, myocardial infarction, hypertension, alcohol intake, and AMD. 2,3 People who regularly use aspirin are usually patients with cardiovascular disease or those at high risk of these diseases. Thus, a subgroup analysis according to these variables should be included.
  6. 6.  
    The aspirin dose has only been documented in 2 RCTs and 1 cohort study. Differences in the aspirin dose could have an effect on the association. Furthermore, the duration of aspirin use in the included studies varied considerably. This should also be discussed.
We agree that currently there is insufficient evidence for patients with AMD to stop aspirin use. However, further high-quality RCTs based on larger sample sizes and long-term population-based prospective studies are still needed. We believe that our remarks will contribute to a more accurate elaboration of the results presented by Ye et al. 
References
Ye J Xu Y He J Lou L. Association between aspirin use and age-related macular degeneration: a meta-analysis [published online ahead of print February 7, 2014]. Invest Ophthalmol Vis Sci . doi:10.1167/iovs.13-13206 .
Fraser-Bell S Wu J Klein R Cardiovascular risk factors and age-related macular degeneration: the Los Angeles Latino Eye Study. Am J Ophthalmol . 2008; 145: 308–316. [CrossRef] [PubMed]
Hyman L Schachat AP He Q Leske MC; for the Age-Related Macular Degeneration Risk Factors Study Group. Hypertension, cardiovascular disease, and age-related macular degeneration. Arch Ophthalmol . 2000; 118: 351–358. [CrossRef] [PubMed]
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