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  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    2 Fundamentals and Principles of Ophthalmology

    Part V: Ocular Pharmacology

    Chapter 16: Ocular Pharmacotherapeutics*

    Anti-inflammatory Drugs

    Antiallergic Drugs: Mast-Cell Stabilizers and Antihistamines

    The human eye has approximately 50 million mast cells. Each cell contains several hundred granules that in turn contain preformed chemical mediators. Allergic conjunctivitis is an immediate hypersensitivity reaction in which triggering antigens couple to antibodies (IgE) on the cell surface of mast cells and basophils, causing the release of histamine, PG, leukotrienes, and chemotactic factors from secretory granules. The released histamine causes capillary dilatation and increased permeability and, therefore, conjunctival injection and swelling. It also stimulates nerve endings, causing pain and itching.

    Drugs treat ocular allergies by interfering at different points along this pathway. Corticosteroids are very effective, but adverse effects limit their application for this chronic condition. Mast-cell stabilizers and antihistamines (which block histamine receptor-1 [H1]) have fewer and less dangerous adverse effects and can be used singly or in combination. Table 16-19 lists drugs that relieve allergic conjunctivitis.

    Corticosteroids

    Corticosteroids are very effective for treating ocular allergies, especially in the acute phase, but they are prone to overuse and have a more dangerous adverse effect profile than other antiallergic drugs (see the section “Adverse effects” under Glucocorticoids). Loteprednol etabonate, 0.2%, a steroid designed to cause less IOP elevation, can be used for temporary treatment of ocular allergies. Recalcitrant cases of severe allergic, vernal, and atopic conjunctivitis may require the short-term use of stronger topical steroids, but these cases should be carefully monitored and patients switched to one of the previously mentioned drugs as soon as clinically prudent.

    Antihistamines

    Patients may achieve short-term relief of mild allergic symptoms with over-the-counter topical antihistamines such as antazoline and pheniramine, which are usually combined with the decongestant naphazoline. Specific H1-antagonists include emedastine and levocabastine.

    Emedastine difumarate, 0.05%, is a relatively selective H1-receptor antagonist indicated for temporary relief of signs and symptoms of allergic conjunctivitis. Dosing is 1 drop up to 4 times per day. The most common adverse effect reported is headache (11% of patients). Other adverse effects are unpleasant taste, blurred vision, burning or stinging, corneal infiltrates, dry eye, rhinitis, and sinusitis.

    Table 16-19 Drugs for Allergic Conjunctivitis

    Levocabastine hydrochloride, another H1-receptor antagonist, has an onset of action in minutes and lasts for at least 4 hours. It is as effective as cromolyn sodium for treating allergic conjunctivitis. The usual dosage of levocabastine, 0.05%, is 1 drop 4 times per day for up to 2 weeks. This drug has been discontinued in the United States.

    Mast-cell stabilizers

    Mast-cell stabilizers are thought to prevent calcium influx across mast-cell membranes, thereby preventing mast-cell degranulation and mediator release. Traditional mast-cell stabilizers such as cromolyn sodium, lodoxamide, and pemirolast prevent mast-cell degranulation but take days to weeks to reach peak efficacy. They have little or no antihistamine effect and do not provide immediate relief from allergic symptoms. Therefore, topical steroids or H1-antagonists may have to be used concurrently with mast-cell stabilizers for the first several weeks, until these drugs are fully effective.

    Lodoxamide stabilizes the mast-cell membrane 2500 times as effectively as cromolyn sodium does. In the treatment of allergic conjunctivitis, its onset of action is more rapid, with less stinging, than that of cromolyn sodium. In addition, a multicenter doublemasked study showed that lodoxamide was superior to cromolyn sodium in treating vernal keratoconjunctivitis. The usual dose of lodoxamide, 0.1%, for adults and children older than 2 years is 1 or 2 drops in the affected eye 4 times daily for up to 3 months. The most frequently reported adverse reactions are burning, stinging, and discomfort upon instillation (15% of patients).

    CLINICAL PEARL

    Comparisons between different mast-cell stabilizers and antihistamines are limited, and no clinical evidence indicates that any particular product is superior to others in treating ocular allergies. Mast-cell stabilizers and antihistamines are used for allergic, vernal, and atopic conjunctivitis.

    Combined antihistamine and mast-cell stabilizers

    Some drugs, including olopatadine, ketotifen, epinastine, azelastine, and alcaftadine, have a mast cell–stabilizing effect as well as H1-antagonism. These drugs provide immediate relief against released histamine and prevent the future degranulation of mast cells. Olopatadine hydrochloride, 0.1%, has a rapid onset, and its duration of action is at least 8 hours. Recommended dosing is 1 or 2 drops in the affected eye 2 times per day at an interval of 6–8 hours. This drug is now also available for once-a-day dosing as olopatadine, 0.2%. Adverse reactions of ocular burning, stinging, dry eye, foreign-body sensation, hyperemia, keratitis, eyelid edema, pruritus, asthenia, cold syndrome, pharyngitis, rhinitis, sinusitis, and taste perversion were all reported at an incidence of less than 5% (for each adverse effect). For ketotifen fumarate, 0.025%, the recommended dosing is 1 drop every 8–12 hours. Conjunctival injection, headaches, and rhinitis were reported at an incidence of 10%–25% with use of this drug, which is now available without a prescription.

    • Greiner JV, Edwards-Swanson K, Ingerman A. Evaluation of alcaftadine 0.25% ophthalmic solution in acute allergic conjunctivitis at 15 minutes and 16 hours after instillation versus placebo and olopatadine 0.1%. Clin Ophthalmol. 2011;13(5):87–93.

    • La Rosa M, Lionetti E, Reibaldi M, et al. Allergic conjunctivitis: a comprehensive review of the literature. Ital J Pediatr. 2013;39:18.

    • Verin P. Treating severe eye allergy. Clin Exp Allergy. 1998;28(suppl 6):44–48.

    Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.

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