EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.
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80 EW SECONDARY FEATURE February 2011 Retina October 2012 The status of statin use for ocular disease by Maxine Lipner Senior EyeWorld Contributing Writer How statins may hold possible sway for cataracts and AMD T hese days it seems as if statin use is practically ubiquitous for lowering cholesterol. But can this common agent also poten- tially help to combat ocular disease? Research suggests that there may be a role for statins in fighting cataracts as well as age-related macular degen- eration (AMD). Cataract connection For those of cataract age, statin use is extremely common, according to Donald S. Fong, M.D., Pasadena, Calif., who conducted a study on this subject. "Among patients who had an eye exam, about 58% were taking statins," Dr. Fong said. It was the fact that statin use was so common that helped spur Dr. Fong to take a closer look. "We wanted to figure out whether any medications could slow the develop- ment of cataracts," Dr. Fong said. "Statins are widely prescribed to lower cholesterol, and there have been suggestions that their use might have protective effects on other parts of the body." With that in mind, investigators undertook the study to see whether statin use might protect the lens against cataract development. For the study, investigators selected all patients enrolled with the Kaiser Permanente Southern California pre-paid health plan for more than 5 years. "We identified 13,982 patients who underwent cataract surgery in 2009 and 34,049 patients who had an eye examina- tion but did not undergo cataract surgery or have a diagnosis of cataract in their medical record," Dr. Fong said. "We then looked in their medical record to determine the use of the statin class of drug." In the February issue of the American Journal of Ophthalmology, investigators reported that for 50- to 64-year-olds, there appeared to be some benefit to prolonged statin use. "Recent longer-term statin use was protective against cataract surgery in younger patients, while shorter-term use was associated with an increased risk of surgery," Dr. Fong said. He theorized that cataracts might develop as a result of oxida- tive damage to the lens and that the protective effect seen might be be- cause of the antioxidant properties of statins. Dr. Fong also stressed that the statins were by no means caus- ing cataracts over the short term but that this was likely an indication that the treatment had just started and had only begun to control any metabolic imbalances. "The reason that only longer-term use is protec- tive against cataract surgery is that once cataracts have formed, it seems unlikely that treatment could then repair damaged proteins," Dr. Fong said. "It seems that statin use would need to be started earlier, when the patient is younger, and be taken for a longer time for any protective mechanism to work." At work on AMD Another area in which statin use is gaining ophthalmic ground is for combatting AMD, according to Robyn H. Guymer, Ph.D., deputy director, Centre for Eye Research Australia, East Melbourne, Australia. The idea of a possible statin AMD connection first arose about 10 years ago when the ApoE gene was linked to AMD. "It's involved in the lipid pathway," Dr. Guymer said. "It sug- gested that lipids were involved, thus if you could do something that would affect lipids, that would be a good idea." In addition, there was evidence that taking statins might slow the progression of Alzheimer's disease, a condition that implicated the same ApoE gene. "I thought that it would be a reasonable thing to try," Dr. Guymer said. Since that time, she pointed out it has become much more obvious that statins may work as an anti-in- flammatory agent. AMD, which has since been linked to the comple- ment factor H gene (CFH), is now considered an inflammatory disease. "The biggest genetic risk factor for AMD currently is the CFH gene, and it's involved in the inflammatory pathway," Dr. Guymer said. "Maybe statins work on not only altering lipids but also inflammation; it In early AMD cases, statins show potential for heading off progression Source: Robyn H. Guymer, Ph.D. seemed like a win/win situation that might work in both of those ways." Dr. Guymer's early research has been promising. In a 2011 Associa- tion for Research in Vision and Ophthalmology presentation, Dr. Guymer reported on the role that simvastatin may play in forestalling AMD. Included in the study were 114 high-risk AMD patients who were randomized to receive either 40 mg of simvastatin daily or placebo. At the 3-year mark, investigators determined that for those in the simvastatin group with early bilat- eral disease, progression of early diseased was slowed down by four times compared to placebo. Dr. Guymer is encouraged by these re- sults. "Early analysis suggests that perhaps there's a role in slowing the progression of early disease," she said. She is in the midst of further analysis on this and would also like to see more research. However, she acknowledged that this may not be easy. "Because a lot of people are on statins, because it's a well-tolerated, popular way to lower lipids, it's a difficult study to repeat," Dr. Guymer said. If these results are substantiated, however, Dr. Guymer sees enormous potential here. "If we show a positive slowing, it is a readily available, well-tolerated, relatively cheap treatment for this disease," she said. "If we could prove that this was true, then it's very quickly implemented." Going forward, Dr. Guymer thinks that it will be interesting to see whether statin outcomes in AMD are linked to the specific gene in- volved. "It will be interesting to see if there is a particular at-risk group that is better off," she said. EW Editors' note: Drs. Guymer and Fong have no financial interests related to this article. Contact information Guymer: 61-3 99298393, rh.guymer@unimelb.edu.au Fong: 626-564-5104, Donald.S.Fong@kp.org