Medication Summary
Pharmacologic management is a moderately effective adjunctive treatment when patients with giant papillary conjunctivitis (GPC) cannot or will not discontinue wearing contact lenses. GPC is a Gel-Coombs type 1 disease with degranulated conjunctival mast cells as the chief histologic feature; therefore, drugs that inhibit mast cell degranulation are effective. [35]
The most commonly used topical medications are combination, dual-acting H1 receptor antagonists and inhibitors of histamine release from mast cells (ie, olopatadine hydrochloride, ketotifen fumarate). These are more ideal for patient compliance because of their once-daily to twice-daily dosing.
Topical mast cell stabilizers were the original treatment for GPC. Topical sodium cromolyn 0.4% [4] is effective but does not promote compliance with the four-times-per-day dosing frequency. NSAIDs and antihistamines also are used.
Steroids can be useful for severe cases. [31, 32] Mild steroids such as loteprednol would be more ideal than stronger steroids because of their low risks of inducing glaucoma. More recently, topical immunomodulators have been used with results as efficacious as those of corticosteroids but without the adverse effects of corticosteroids. [33, 36]
Topical ophthalmic medications should be used cautiously with contact lens wear, because these medications are commonly preserved with benzalkonium chloride (BAK). BAK is associated with corneal epithelial toxicity episodes (a greater concern with hydrogel contact lenses).
If medication must be administered concomitantly with hydrogel contact lenses, application should be restricted to a maximum of 3 times a day (ie, one drop just prior to contact lens wear, one drop immediately upon contact lens removal, and one drop before going to bed). Once-daily and twice-daily ophthalmic medications are more ideal (eg, olopatadine ophthalmic, ketotifen, epinastine, alcaftadine ophthalmic) for increased patient compliance and convenience, especially for contact lens wearers. Patients should wait at least 10-15 minutes after medication instillation before contact lens insertion.
Antihistamines/Mast Cell Stabilizers
Class Summary
The dual-acting antihistamine and mast cell stabilizer makes them effective for the immediate itching and long-term management of GPC by controlling the degranulation of mast cells. Mast cell–stabilizing medications/antihistamine combination drops are most likely to achieve the therapeutic effect with minimal complications. The low dosing schedule of twice a day makes them practical for most patients. If patients are to wear contact lenses, have them wait 10-15 minutes before lens insertion.
Alcaftadine ophthalmic (Lastacaft)
Alcaftadine is an H1-receptor antagonist. It inhibits histamine release from mast cells, decreases chemotaxis, and inhibits eosinophil activation. Lastacaft is administered once a day to improve patient compliance.
Bepotastine (Bepreve)
Bepreve is a histamine H1 receptor antagonist indicated for the treatment of itching associated with allergic conjunctivitis. It is dosed twice a day in each eye.
Epinastine (Elestat)
Epinastine is a direct histamine-1 receptor antagonist. It is indicated for symptoms due to allergic conjunctivitis. Its recommended dosage is twice a day.
Olopatadine ophthalmic (Pataday 0.1%, Pataday 0.2%, Pataday 0.7%)
Olopatadine is a histamine H1 receptor antagonist that inhibits the release of histamine from mast cells and histamine-induced effects on conjunctival epithelial cells. Pazeo's recommended dosing is once a day, which can improve patient compliance.
Ketotifen, ophthalmic (Alaway, Zaditor, Zyrtec Itchy Eye)
Ketotifen is a relatively selective, non-competitive H1 receptor antagonist and inhibitor of histamine release from mast cells. This is an over-the-counter product. Its recommended dosage is twice a day.
Second-generation Antihistamines
Class Summary
These agents are used for the temporary relief of the signs and symptoms (itching) of allergic conjunctivitis. Compared to first-generation antihistamines, second-generation antihistamines do not sting and had longer durations of efficacy.
Azelastine ophthalmic (Optivar)
Azelastine ophthalmic is a selective H1-receptor competitor with H1-receptor sites on effector cells. It also exhibits H2-blocking properties. It inhibits the release of histamine and other mediators involved in the allergic response. Its recommended dosage is twice a day.
Emedastine difumarate (Emadine)
Emedastine difumarate is a relatively selective H1 receptor antagonist that appears to be devoid of effects on adrenergic, dopaminergic, and serotonin receptors. It affects both the early and late phases of the ocular allergic reaction. Its recommended dosage is four times a day.
Mast cell stabilizers
Class Summary
GPC primarily appears to be a Gel-Coombs type 1 hypersensitivity disease. The primary pathological event is inappropriate degranulation of the conjunctival mast cells, which release many inflammatory mediators, such as histamine (resulting in itch). Pure mast cell stabilizers are indicated for long-term use after the acute phase of symptoms is abated. [35] They are well tolerated. Symptoms may include burning. Their four-times-a-day dosing decreases the rate of compliance and may result in treatment failure. [37]
Cromolyn sodium, ophthalmic
Cromolyn sodium is a mast cell stabilizer that inhibits histamine and SRS-A from mast cell. It was the first drug of its class. Its recommended dosage is four times a day.
Nedocromil ophthalmic (Alocril)
Nedocromil inhibits the release of various inflammatory cell mediators (mast cell stabilizer). It has greater efficacy than cromolyn sodium. Its recommended dosage is twice a day.
Pemirolast ophthalmic (Alamast)
Pemirolast is a mast cell stabilizer indicated for the prevention of itching due to allergic conjunctivitis. Its recommended dosage is four times a day.
Lodoxamide (Alomide)
Lodoxamide is a mast cell stabilizer indicated for the prevention of itching due to allergic conjunctivitis. Dosage is four times a day in each affected eye.
Corticosteroids
Class Summary
These agents inhibit many aspects of the inflammatory response from inciting agents: edema, capillary dilation and proliferation, leukocyte migration, and fibroblast proliferation.
Loteprednol etabonate (Lotemax, Alrex, Inveltys, Eysuvis)
Loteprednol modulates the activity of prostaglandins and leukotrienes. Placebo-controlled studies have demonstrated that loteprednol reduces the signs and symptoms of GPC after 1 week of treatment, continuing for up to 6 weeks while on treatment. It has a reduced risk of increasing intraocular pressure by rapidly converting into inactive metabolites after corneal penetration. It is available as a suspension in 0.2%, 0.25%, 0.5%, and 1% concentrations.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs), Ophthalmic
Class Summary
NSAIDs inhibit prostaglandin synthesis, which results in vasoconstriction, decreased vascular permeability, leukocytosis, and decreased intraocular pressure (IOP). However, these agents do not significantly affect IOP. Topical NSAIDs (especially a generic version of Voltarin) have been associated with rare corneal melting as a severe complication.
Bromfenac ophthalmic (Protensa)
Bromfenac ophthalmic solution is an ophthalmic that blocks prostaglandin synthesis by inhibiting cyclooxygenase 1 and 2. It is indicated to treat postoperative inflammation and to reduce ocular pain after cataract extraction.
Ketorolac ophthalmic (Acular, Acuvail)
Ketorolac inhibits prostaglandin synthesis by decreasing the activity of the enzyme cyclooxygenase, which results in decreased formation of prostaglandin precursors, which, in turn, results in reduced inflammation. Its recommended dosage is four times a day.
Topical immunomodulators
Class Summary
Immunomodulators are indicated for the treatment of severe and chronic ocular allergies without the adverse effects of corticosteroids.
Tacrolimus ointment (Protopic)
Tacrolimus binds to the FK506-binding proteins within the T lymphocytes and complexes with calcineurin-dependent proteins, inhibiting calcineurin activity. Calcineurin inhibition suppresses dephosphorylation of the nuclear factor of activated T cells and its transfer into the nucleus, which results in the suppressed formation of cytokines by T lymphocytes. Inhibition of T lymphocytes leads to the release of inflammatory cytokines and decreased stimulation of other inflammatory cells. Tacrolimus eyedrops have lower adverse effects of transient foreign body sensation, burning, and blurry vision compared to tacrolimus ointment. [31] Its recommended dosage is twice a day.
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Very large papillae in the everted upper lid of a patient who wears hydrogel (soft) contact lenses.
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Giant papillary conjunctivitis (GPC) response (slightly out of focus) seen in the upper lid of a young patient recovering from cataract extraction with an exposed suture barb (in focus).
