Leukotriene receptor antagonists: do they work in allergic eye disease?

Published Online November 6, 2012

The term “allergic eye disease” encompasses a number of different conditions including allergic conjunctivitis (AC), vernal kerato-conjunctivitis (VKC), and atopic kerato-conjunctivitis (AKC). By far the most common of these conditions is allergic conjunctivitis.
The symptoms of this disease, which is caused by allergic antibodies against materials in the air, include itch, redness, and watering of the eyes in response to seasonal (e.g., pollen) or year-round (e.g., house dust mite or animal dander) airborne allergens. In general patients also suffer from nasal symptoms, such that the condition is referred to collectively as allergic rhino-conjunctivitis (ARC). Whilst the disease is not sight-threatening, gaining adequate symptom control can be challenging. VKC (in children) and AKC (in adults), whilst less common than AC, both carry a risk of visual impairment, and most cases require treatment with corticosteroids. Cysteinyl leukotrienes are inflammatory mediators which have been shown to play a role in all three conditions. One would expect therefore that drugs that block the effects of leukotrienes, such as leukotriene receptor antagonist (LTRA) drugs, may improve the symptoms of AC, VKC, and AKC and, should this prove to be the case, provide an alternative or additional treatment option for patients with these diseases.

In an article published in The Journal of Allergy and Clinical Immunology: In Practice, Gane and Buckley performed a systematic review and meta-analysis of the available evidence to attempt to address this important issue. A meta-analysis scientifically combines the results of multiple studies to be able to draw broader conclusions than one could from the individual studies. The authors used established systematic review methodology to identify and assess single or double-blind randomised controlled trials (RCTs) comparing LTRA to other common treatments for allergic eye diseases. Eighteen studies fulfilling the inclusion criteria were identified in adult and pediatric patients with ARC, studying 9017 patients in total. All 18 studies used the specific LTRA drug montelukast. No RCTs of LTRA use in VKC or AKC were identified. Six of the 18 studies were suitable for inclusion in one or more of 3 meta-analyses comparing 1) LTRA vs. placebo; 2) LTRA vs. oral antihistamine; and 3) LTRA and oral antihistamine vs. placebo. These large multi-centre trials were conducted in patients aged 15 years or older with mild to moderate seasonal ARC.

The six trials were meta-analysed and demonstrated that montelukast improved patients’ eye symptoms to a significantly greater extent than placebo Three trials were meta-analysed and found that oral antihistamine was superior to montelukast. Two trials compared montelukast and oral antihistamine against placebo. The improvement in symptom scores was three times greater than the improvement in the studies with montelukast alone.

The authors concluded from their results that there is good evidence to indicate that montelukast is more effective than placebo in controlling the eye symptoms of seasonal ARC but is less effective than oral antihistamines. The authors highlighted the paucity of high quality trials of LTRAs in all other categories of allergic eye disease and made suggestions for future research needs. As a result of the notable improvement in eye symptoms seen in the third meta-analysis (combination LTRA/oral antihistamine compared with placebo) they suggested further large studies comparing combination LTRA and oral antihistamine treatment against each medication alone to establish whether a synergistic effect of the two drug classes exists.

The Journal of Allergy and Clinical Immunology: In Practice, is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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