FEB 2014

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Page 59 of 114

E W FEATURE 5 7 A new retrospective analysis suggests oral azithromycin may be beneficial A ccording to the recent International Workshop on Meibomian Gland Dysfunction (MGD), "terms such as 'meibomi- tis' or 'meibomianitis' describe a s ubset of disorders of MGD associ- ated with inflammation of the mei- bomian glands," but inflammation is not always associated with MGD and therefore, the terms are not in- terchangeable. 1 Further, the etiology of mei- bomitis "has not been fully sorted out," said Todd P. Margolis, MD, professor of ophthalmology, Wash- ington University, St. Louis, adding there may be an inflammatory aspect within the lipids. An issue for clinicians is simply the definition of meibomitis, and there has yet to be a universally ac- cepted method on how to describe it—or how to treat it, said Joseph Tauber, MD, in private practice, Kansas City, Mo. MGD itself is generally recog- nized as a common disease and one of the most common causes of dry eye disease, said Michael Lemp, MD, clinical professor of ophthal- mology, Georgetown University, Washington, D.C., and chief medical officer, TearLab Corp., San Diego. "But we have to consider what causes it. Is it an infectious disease? What role does inflammation play? We still do not have all the an- swers." If MGD persists for a long enough time, it will stimulate in- flammatory activity in the lacrimal glands, he said. Azithromycin is a macrolide antibiotic that also has anti-inflam- matory properties, Dr. Margolis said. In its topical form, the compound is approved for the treatment of bacterial conjunctivitis and has been studied for the treatment of blephar- itis. "There was some logic behind evaluating the oral version of azithromycin for lid disorders," Dr. Margolis said, who, with colleagues, retrospectively evaluated oral azithromycin in patients with refrac- tory meibomitis, dosed at 1 g orally once a week for three weeks. 2 The analysis found about 70% of the patients had improved symptoms. With no real guidelines on how to uniformly define or evaluate these disorders, "we're in unchar- tered waters in how to be objective," Dr. Tauber said. "It's not unusual to hear that someone is using oral azithromycin in some of these refractory cases." Using a systemic drug to treat an ocular disorder has potential, but physicians should still start with the established care routines that in- clude lid massage, lid hygiene, and topical antibiotics, said James McCulley, MD, chair of ophthal- mology, UT Southwestern Medical Center, Dallas. "If a patient fails standard therapy, then I'd consider oral azithromycin," Dr. McCulley said, who added the study has "thrown out an interesting thought, but there's no good data to support the hypothesis. It's objectively weak support for oral azithromycin; most clinicians should read the study and come to the reasonable conclusion that the findings are interesting, but not that they should overhaul their current treatment regimens." Agreed Gary Foulks, MD, emer- itus professor of ophthalmology, University of Louisville School of Medicine: "The study remarks only on improvement in symptoms and not the objective features of MGD. I believe topical azithromycin works, but I suspect oral azithromycin also would work." Dr. Foulks added that the American Academy of Ophthal- mology guidelines on blepharitis "carry a strong warning about use of oral azithromycin due to cardiac deaths reported with its use for other conditions." Role of oral azithromycin in ocular surface disorders "As clinicians, we can't be against any potential treatment," Dr. Lemp said. "This analysis gets into one of the issues about ensuring what it is you're treating. Is there a difference between meibomitis and MGD?" The original intent of the retrospective study (n=32) was to show possible evidence that oral azithromycin may be a useful ad- junct in patients who were not re- sponding to other treatments, said Bennie H. Jeng, MD, professor and chair, Department of Ophthalmol- ogy and Visual Sciences, University of Maryland School of Medicine, Baltimore, and one of the co-authors of the analysis. "When we looked at patients who had failed previous topical ther- apy—antibiotics, steroids, or some combination—they still improved after oral azithromycin," Dr. Jeng said. Patients were receiving three weeks of azithromycin at therapeu- tic levels, Dr. Margolis said, ensuring that any bacterial component would be eradicated. "Patients were coming in saying they felt better. It was irrelevant what the previous treatments had been—on oral azithromycin and a t opical agent for the lid margins, we achieved tremendous success rates," he said. Dr. McCulley said the finding is "something short of a proof of con- cept, but it is a very interesting thought and results are prelimi- nary," mainly because the analysis was not controlled and there were no details on what, if any, standard previous failed therapies had been. "The benefits reported were only for a few weeks," Dr. McCulley said. "It's an interesting observation that needs further investigation in an appropriately controlled clinical trial." Oral azithromycin should "ab- solutely" be considered as a poten- tial treatment for meibomitis, Dr. Tauber said, as the compound has both anti-inflammatory and antimi- crobial properties. Dr. Jeng said the analysis eluci- dated the long-lasting effects of azithromycin, although he contin- ues to recommend initiating treat- ment with lid hygiene (e.g., mechanical scrubbing). "Once failure happens with con- servative treatment, then I used to invoke tetracycline derivatives," he said, primarily doxycycline. "But that has to be taken twice daily for an extended period of time; oral azithromycin is dosed once a week for three weeks. The catch, of course, is the potential for it to create irregu- larities in heart rhythm." There has been some clinical efficacy with pulsed dosing of oral azithromycin in the treatment of posterior blepharitis, 3 with all clini- cal outcomes and most subjective symptoms statistically improved after the 500 mg/day for three February 2011 by Michelle Dalton EyeWorld Contributing Writer Treating meibomitis AT A GLANCE • Oral azithromycin may be useful in t reating meibomitis, even after failed topical azithromycin therapy. • Randomized and controlled clinical studies are necessary to prove e fficacy of oral azithromycin. • Oral tetracyclines remain a viable t reatment option in refractory cases. Meibomitis associated with evaporative dry eye Source: John D. Sheppard, MD continued on page 58 February 2014 Corneal infections 56-68 Feature_EW February 2014-DL2_Layout 1 1/30/14 10:44 AM Page 57

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