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Am Fam Physician. 2016;93(11):915-916

Author disclosure: No relevant financial affiliations.

Clinical Question

Are topical antihistamines and mast cell stabilizers, used alone or in combination, effective and safe in treating patients with seasonal and perennial allergic conjunctivitis?

Evidence-Based Answer

Topical antihistamines and mast cell stabilizers, either alone or in combination, are safe and effective for reducing the symptoms of seasonal and perennial allergic conjunctivitis. (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.) There is insufficient evidence to compare the effectiveness of specific topical medications. No serious adverse effects are associated with these medications.

Practice Pointers

Patients with seasonal allergic conjunctivitis and perennial allergic conjunctivitis often report itching, tearing, swollen eyelids, and redness mediated by the release of histamine from mast cells, resulting in conjunctival inflammation.1,2 Itching is the most common symptom, occurring in more than 75% of patients. The authors of this Cochrane review evaluated the effectiveness of topical mast cell stabilizers and antihistamines for this common condition.

This review included 30 randomized controlled trials with 4,344 participants four to 85 years of age who had seasonal or perennial allergic conjunctivitis. Studies of patients with vernal keratoconjunctivitis, atopic keratoconjunctivitis, or giant papillary conjunctivitis were excluded, as were studies that analyzed oral or nasal antihistamines. Within the 30 trials, 17 different drug or treatment comparisons were conducted in North and South America, Asia, Europe, Africa, and Australia; the duration of the studies ranged from one to eight weeks. The primary outcomes were participant reports of photophobia and ocular itching, irritation, and watering. Secondary outcomes included adverse effects; the duration of acute symptoms; the incidence of acute episodes per year; and signs of hyperemia, chemosis, or tarsal papillae on examination. The risk of bias was judged to be low.

Overall, the results favor topical antihistamines and mast cell stabilizers, alone or in combination, vs. placebo for short-term relief of the symptoms of allergic conjunctivitis (Table 1). Eight studies comparing the mast cell stabilizers nedocromil (Alocril) or cromolyn sodium vs. placebo favored the mast cell stabilizers. Trials comparing the antihistamines azelastine (nine studies) and levocabastine (not available in the United States; five studies) vs. placebo all favored the antihistamines. Because of heterogeneity between studies, meta-analysis was possible only for four studies with 204 patients that compared the effect of olopatadine (Patanol) with ketotifen (Zaditor) on itching and tearing at 14 days. In this analysis, olopatadine was superior to ketotifen overall in reducing itching (mean difference = −0.32; 95% confidence interval, −0.59 to −0.06) but equivalent in reducing tearing. The evidence was insufficient to make any other drug comparisons. There were no serious adverse effects related to treatment with topical medications.

Drug classDosing scheduleCost*
Bepotastine (Bepreve)Twice per dayNA ($180)
Emedastine (Emadine)Four times per dayNA ($120)
Epinastine (Elestat)Twice per day$38 ($220)
Mast cell stabilizers
Lodoxamide (Alomide)Four times per dayNA ($150)
Nedocromil (Alocril)Twice per dayNA ($190)
Pemirolast (Alamast)Four times per dayNA ($115)
Other formulations
AzelastineUp to four times per day$40
Ketotifen (Zaditor)Twice per dayNA ($15)
Olopatadine (Patanol)Twice per day$50 ($250)

Clinical guidelines from the American Academy of Ophthalmology 3 and the College of Optometrists4 (England) for the management of allergic conjunctivitis support the use of topical antihistamines and topical mast cell stabilizers, either alone or as combined formulations.


The practice recommendations in this activity are available at

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the U.S. Air Force Medical Service or the U.S. Air Force at large.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at

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