Bang et al report that randomized treatment with simvastatin plus ezetimibe was associated with a 44% lower incidence of cataracts in the Simvastatin and Ezetimibe in Aortic Stenosis Study (SEAS) trial. Meta-analysis including the SEAS trial and previous studies indicates that the statin use is associated with a clinically and statistically significant decrease in the occurrence of cataracts. The findings of SEAS confirm the results of our previous meta-analysis, where a significant protective effect of statins was observed in 8 observational studies (odds ratio [OR] 0.81, 95% CI 0.70 to 0.93, p = 0.004), whereas an effect of similar magnitude was observed in the 6 randomized trials but did not reach statistical significance (OR 0.84, 95% CI 0.67 to 1.05, p = 0.119). When the SEAS trial was added to our meta-analysis of randomized trials, the effect became statistically significant (OR 0.78, 95% CI 0.63 to 0.95, p = 0.0165). Thus, statins exert a protective effect in preventing cataracts that is clinically and statistically significant and is primarily observed in younger subjects and with longer duration of statin therapy.

The protective effect of statins has been attributed to lower serum cholesterol or to pleotropic effects of statins on inflammation and oxidation. The relation of the effect with time varying serum low-density lipoprotein cholesterol in the SEAS trial suggests a protective effect of low cholesterol. In addition, this is supported by the low-density lipoprotein lowering in this trial which was due to ezetimibe that does not possess the pleotropic effect of statins. However, cholesterol is needed for maintaining the transparency of the lens, and low cholesterol could potentially promote the formation of cataracts. Reports of an increase or no effect on the rate of cataracts with statins are in agreement with the previously mentioned statement.

A definite way to settle the issue of the relation of statins to cataracts would be to perform a randomized clinical trial. Because such a study is unlikely to be performed because of the long duration of follow-up required, inclusion of data on cataract formation in studies using statins or newer agents such as PCSK9 antibodies may be advisable.