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Study: Statin users may be at lower risk for uveitis
Statins may help reinforce the blood-retinal barrier by decreasing formation of oxygen-free radicals and increasing levels of nitric oxide.
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The odds of statin users developing uveitis were approximately half that of non-statin users in one study, according to one of the study’s authors.
“After adjusting for the effects of age, sex, race and autoimmune disease, we found that, using the general population control, the odds of a statin user developing uveitis were 48% less than the odds of developing uveitis for a patient not taking statins (P = .03),” senior author Nisha R. Acharya, MD, told Ocular Surgery News. “Results were similar when using the ophthalmology control group, although the P value was not statistically significant for that comparison.”
Study design
The retrospective case-control study, which appeared in the American Journal of Ophthalmology and was part of the Pacific Ocular Inflammation Study, reviewed the medical records of 108 patients with a new diagnosis of uveitis in the Kaiser Permanente Hawaii health plan between January 2006 and December 2007. Two control groups were also randomly selected at a 5:1 ratio to cases: 540 controls in the general Kaiser population (patients who were seen within the whole health system during the study period) and 540 controls seen in the Kaiser ophthalmology clinic during the same period.
Acharya said the study results were not surprising. “[However,] it is nice to confirm a clinical suspicion,” she said. “It makes sense from a scientific standpoint that statins could modulate the inflammatory process and impact the development of conditions such as uveitis.”
Benefits of statins
Numerous studies have shown additional anti-inflammatory and immunomodulatory benefits of statins in a variety of systemic diseases, including multiple types of cancer, inflammatory bowel disease and rheumatoid arthritis, the authors noted.
“Some studies have shown a protective effect of this class of medications for ocular diseases, such as age-related macular degeneration,” Acharya said. Multiple laboratory studies also suggest anti-inflammatory properties of statins in animal models with experimental autoimmune uveitis (EAU).
Furthermore, one clinical case-control study found a nonsignificant protective association between statin use and all types of ocular inflammatory disease, Acharya said.
Supported by data in these studies, the authors wanted to further study whether statin use was associated with uveitis.
“There was plausibility based on other clinical and animal studies, and there is a need to identify treatments that can modulate the onset or severity of uveitis,” Acharya said.
Statins have demonstrated the ability to reduce levels of key inflammatory cytokines, such as interleukins 6 and 8, TNF-alpha and C-reactive protein.
“Additionally, this class of medications has been shown to decrease interactions between leukocytes and endothelial cells via the intercellular adhesion molecule-1 pathway,” Acharya said. “This can prevent leukocyte migration across the blood-retinal barrier, thus decreasing intraocular inflammation.”
Likewise, statins can help bolster the blood-retinal barrier by decreasing the formation of oxygen-free radicals and increasing levels of nitric oxide.
“Many of these mechanisms have been demonstrated in prior studies using animal models of EAU,” Acharya said.
Smoking has been shown to be associated with the development of uveitis, but a sensitivity analysis to evaluate the effect of current smoking status did not impact the link between statin use and uveitis.
The authors also raised the question of whether there may be a therapeutic benefit of statins after diagnosis of uveitis, in terms of severity and course of disease, notably because of the “relatively benign side effect profile” of statins compared with systemic immunosuppressant therapies.
Although the authors are not involved in a follow-up study at this time, they hope to further investigate the association between statin use and uveitis in other populations.
“We are also interested in looking further to see if the effect of statins varies by race,” Acharya said. – by Bob Kronemyer
Reference:
Borkar DS, et al. Am J Ophthalmol. 2015;doi:10.1016/j.ajo.2015.01.009.For more information:
Nisha R. Acharya, MD, can be reached at F.I. Proctor Foundation, Room S309, 513 Parnassus Ave., UCSF, San Francisco, CA 94143-0412; email: nisha.acharya@ucsf.edu.Disclosure: Acharya reports no relevant financial disclosures.