Cochrane for Clinicians

Putting Evidence into Practice

Topical Antihistamines and Mast Cell Stabilizers for Treating Allergic Conjunctivitis


Am Fam Physician. 2016 Jun 1;93(11):915-916.

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.

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Table 1.

Topical Treatments for Allergic Conjunctivitis

Drug classDosing scheduleCost*


Bepotastine (Bepreve)

Twice per day

NA ($180)

Emedastine (Emadine)

Four times per day

NA ($120)

Epinastine (Elestat)

Twice per day

$38 ($220)

Mast cell stabilizers

Lodoxamide (Alomide)

Four times per day

NA ($150)

Nedocromil (Alocril)

Twice per day

NA ($190)

Pemirolast (Alamast)

Four times per day

NA ($115)

Other formulations


Up to four times per day


Ketotifen (Zaditor)†

Twice per day

NA ($15)

Olopatadine (Patanol)

Twice per day

$50 ($250)

NA = not available.

*—Estimated retail cost for one month of therapy based on information obtained at (accessed April 13, 2016). Generic price listed first; brand price listed in parentheses.


Author disclosure: No relevant financial affiliations.


show all references

1. Williams DC, Edney G, Maiden B, Smith PK. Recognition of allergic conjunctivitis in patients with allergic rhinitis. World Allergy Organ J. 2013;6(1):4....

2. Ono SJ, Abelson MB. Allergic conjunctivitis: update on pathophysiology and prospects for future treatment. J Allergy Clin Immunol. 2005;115(1):118–122.

3. American Academy of Ophthalmology Conjunctivitis PPP–2013. Accessed August 5, 2015.

4. College of Optometrists. Clinical management guidelines: seasonal allergic conjunctivitis (hay fever conjunctivitis); perennial allergic conjunctivitis. Accessed April 12, 2016.

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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