Cyclosporine May Be an Option in Allergic Conjunctivitis

Norra MacReady

July 08, 2013

Topical cyclosporine relieves the symptoms of allergic conjunctivitis and may help patients reduce their dependency on steroids, according to a new meta-analysis published online June 4 in Ophthalmology.

Allergic conjunctivitis is estimated to affect 20% to 30% of the world's population, lead author Kelvin Ho-Nam Wan, MBChB, and colleagues write. Symptoms include tearing, itching, discharge, and photophobia. Topical corticosteroids are considered the mainstay of treatment for severe allergic conjunctivitis, but "prolonged use can result in elevated intraocular pressure with subsequent glaucoma, cataract, and increased susceptibility to microbial infection, leading to associated visual morbidity," and leading to a search for an effective and safe alternative treatment.

Cyclosporine (CSA) seemed like a good candidate because it inhibits T-cell activation, which is an important component of ocular surface inflammation. However, so far the randomized controlled trials of cyclosporine for this condition have been small and yielded conflicting results, so Dr. Wan, from the Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China, and coauthors performed a review and meta-analysis to gain a clearer perspective on the role of CSA in the management of allergic conjunctivitis.

Using the Cochrane highly sensitive search strategy, they combed the MEDLINE and EMBASE databases plus selected Web sites (such as clinicaltrials.gov) to search for randomized controlled trials comparing CSA with placebo in patients of all ages with seasonal or perennial allergic conjunctivitis. The authors looked for studies that examined the composite signs score, derived by averaging the scores for hyperemia, swelling, tarsal conjunctival papillae and giant papillae, hyperemia or edema of the bulbar conjunctiva, or corneal involvement; the composite symptoms score, calculated by averaging the scores for redness, tearing, burning, discharge, discomfort, photophobia, and foreign body sensation; use of steroid eye drops; or occurrence of adverse events such as stinging or burning. Ultimately, they found 7 RCTs including 153 patients and 306 eyes that met their inclusion criteria.

At 2 weeks' follow-up or longer, CSA was associated with a lower composite signs score, with a pooled standardized mean difference compared with placebo of −1.21 (95% confidence interval [CI], −1.80 to −0.62), and a lower composite symptoms score (−0.84; 95% CI, −1.51 to −0.16). The authors used the I 2 statistic to calculate the percentage of variation that results from heterogeneity among studies in a meta-analysis, rather than chance, with larger values showing more heterogeneity. In this analysis, the I 2 values were 71% and 80%, respectively, suggesting substantial heterogeneity among the studies included.

Of 3 studies that enrolled patients with steroid-dependent conjunctivitis, 2 reported a decrease in the use of steroid eyedrops associated with CSA, with a pooled mean difference of −61.16 (95% CI, −101.61 to −20.72) eyedrops per week. Topical CSA also was not associated with a significantly higher rate of adverse events than placebo (odds ratio, 2.56; 95% CI, 0.19 - 35.06).

"It was interesting to see that CSA had an effect on allergic conjunctivitis compared to placebo, irrespective of the dosage or regimen," senior author Alvin L. Young, MMedSc(Hons), told Medscape Medical News. Having established the efficacy of CSA compared with placebo, a head-to-head comparison with corticosteroids would be a logical next step. "Implications of the research based on our meta-analysis may include evaluating the long-term efficacy and safety of CSA, as well as comparison with other immunomodulators," said Dr. Young, from the Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, and the Alice Ho Miu Ling Nethersole Hospital and Prince of Wales Hospital.

"This was a good study: the meta-analysis and Cochrane method of selecting the most scientifically valid papers is probably the best method available," said George Cioffi, MD, chairman of the Department of Ophthalmology, Columbia Medical School, and New York Presbyterian Hospital, New York City. He emphasized that the patients in these trials were suffering from severe allergic conjunctivitis and "not your garden-variety pinkeye — that's a very important distinction." He does not recommend CSA for infectious or milder cases of allergic conjunctivitis. However, given the results of this analysis, "I think in short order we'll see a randomized controlled trial comparing cyclosporine with steroids or other anti-inflammatory agents" for people with severe allergic conjunctivitis.

Limitations of the analysis include the considerable heterogeneity between the studies, the use only of studies published in indexed journals and trial registers, and the inclusion of patients who used different doses and concentrations of CSA and who had various forms of allergic conjunctivitis, such as vernal conjunctivitis and atopic keratoconjunctivitis. However, these are both "subsets of allergic conjunctivitis with similar pathophysiologic features," the authors write. "Thus, we believe that the heterogeneity that resulted from their pooling had a minimal impact on the outcomes."

However, these very limitations point to the need for more research, other experts say. "Since meta-analyses pool the results of various prior studies, the patients studied and treatments given may vary, limiting the conclusions we can draw about the efficacy and safety of cyclosporine for the treatment of allergic conjunctivitis," Kenneth Chang, MD, MPH, an ophthalmologist at the Massachusetts Eye and Ear Infirmary, and Gelareh Homayounfar, BS, a student at Harvard Medical School, Boston, Massachusetts, told Medscape Medical News.

The findings support the use of CSA for treating allergic conjunctivitis, the authors conclude. "I do not see cyclosporine drops replacing corticosteroids per se," said Dr. Young. "But they certainly should be considered when a steroid-sparing agent is needed."

The authors, Dr. Cioffi, Dr. Chang, and Homayounfar have disclosed no relevant financial relationships.

Ophthalmology. Published online June 4, 2013. Abstract

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