In ophthalmology, topical ketorolac tromethamine 0.5% is used for its anti-inflammatory effect in the symptomatic treatment of seasonal allergic (hay fever, pollinosis) conjunctivitis. Results from a limited number of controlled studies indicate that ketorolac tromethamine ophthalmic solution is more effective than vehicle in providing short-term relief of ocular itching associated with such conjunctivitis. Topically applied NSAIAs also may provide some relief of other ocular inflammatory manifestations of this condition but additional study and experience are needed to clarify the role of these agents in the management of seasonal allergic conjunctivitis.
Avoidance of allergen and other triggering factors (e.g., irritants) and application of cold compresses and lubricating eye drops are the initial means of managing allergic conjunctivitis. Drug therapy generally is reserved for use when such avoidance is not possible or is ineffective, and can include both prophylactic (e.g., topical mast-cell stabilizers such as cromolyn sodium, lodoxamide tromethamine) and symptomatic (e.g., topical and/or systemic antihistamines, topical vasoconstrictors, topical steroidal and nonsteroidal anti-inflammatory agents [NSAIAs]) therapy. The specific therapy(ies) employed will depend on the characteristics and severity of the allergic conjunctivitis. For patients with seasonal allergic conjunctivitis, prophylaxis with a mast-cell stabilizer often is initiated before and maintained throughout the pollen season, and symptomatic therapy with other agents (e.g., topical antihistamines, topical NSAIAs) generally is initiated as necessary to provide acute relief. Topical steroids usually are reserved for short-term use in patients with moderate to severe symptoms of allergic conjunctivitis.
While the efficacy of topical NSAIAs versus corticosteroids for the relief of inflammatory manifestations of allergic conjunctivitis remains to be established, NSAIAs generally are considered less toxic (e.g., absence of predisposition to superinfection, absence of adverse effect on IOP and cataract formation) than corticosteroids and therefore may be preferred as initial topical anti-inflammatory therapy in certain patients. An initial trial with topical NSAIA therapy may be particularly suited for mild to moderately severe conjunctivitis and when the risk of topical corticosteroid therapy, particularly prolonged therapy (which rarely is indicated), is of concern. However, because NSAIAs do not share the full range of anti-inflammatory and immunologic effects of corticosteroids, response may be limited. Regardless of the therapy employed (antihistamine, NSAIA, corticosteroid, vasoconstrictors), relief of all of the clinically important manifestations of allergic conjunctivitis may not be possible despite combined topical and/or systemic administration. In general, the least toxic therapy providing adequate relief should be employed.
Results from a limited number of controlled studies indicate short-term administration (up to 1 week) of ketorolac tromethamine 0.5% ophthalmic solution is more effective than vehicle in providing short-term symptomatic relief of seasonal allergic conjunctivitis. In these studies, administration of ketorolac tromethamine ophthalmic solution was associated with decreased conjunctival inflammation and ocular itching. In some patients, improvement in other ocular allergic manifestations (e.g., swollen eye, discharge or tearing, foreign body sensation) also was reported.
Topical NSAIAs also have been used for their anti-inflammatory activity in the symptomatic treatment of vernal or atopic keratoconjunctivitis and contact lens-associated giant papillary conjunctivitis. However, management of these ocular allergic conditions often is more complex than that of seasonal allergic conjunctivitis. Because of the severity of manifestations, topical corticosteroids, topical cromolyn sodium, and systemic antihistamines often are necessary for the management of acute episodes in patients with vernal or atopic keratoconjunctivitis. For patients with contact lens-associated giant papillary conjunctivitis, meticulous lens care, frequent replacement of lenses (e.g., switching to disposable lenses), changing the type of lens, and/or temporary or permanent discontinuance of contact lens use are the mainstay of management of this condition. However, despite the current paucity of efficacy data in either condition, a trial with topical NSAIA therapy may be attempted to provide some symptomatic relief since the risk of such therapy, at least in adults, appears minimal.
Postoperative and Posttraumatic Ocular Inflammation
In ophthalmology, topical ketorolac tromethamine 0.5% also has been used prophylactically after ocular surgery (e.g., cataract extraction, with or without implantation of an intraocular lens) to prevent or relieve postoperative ocular inflammation. Because NSAIAs inhibit prostaglandin formation rather than the effects of these autacoids once formed, efficacy of the drugs may be reduced if administration is delayed until inflammation is established. Therefore, some clinicians advocate that topical NSAIA therapy be initiated prior to surgery. However, optimal timing of such therapy remains to be established.
In controlled studies, perioperative topical application to the eye of ketorolac tromethamine 0.5% reduced lid edema, conjunctival vasodilation, ciliary flush, and the number of anterior chamber cells and flare as determined by slit-lamp biomicroscopic or fluorophotometric evaluation. The drug also has reduced postoperative disruption of the blood-aqueous barrier. While topical corticosteroids were used concomitantly in some patients, the need for these drugs was less in ketorolac-treated patients than in those receiving placebo. In addition, there is evidence of ketorolac's efficacy from a placebo-controlled study in which concomitant corticosteroid therapy was not permitted. There also is some evidence that ketorolac tromethamine 0.5% may be at least as effective as dexamethasone sodium phosphate 0.1% (of dexamethasone phosphate) or prednisolone acetate 1% in the management of postoperative ocular inflammation and in restabilization of the blood-aqueous barrier, and evidence from studies with various NSAIAs suggests that the drugs actually may be more effective than corticosteroids in restabilizing the barrier. Additive or synergistic ocular anti-inflammatory activity may occur when a topical NSAIA and a corticosteroid are used concomitantly, and some patients may benefit from such combined therapy to the eye.
Postoperative Ocular Pain
In ophthalmology, topical ketorolac tromethamine 0.5% as a preservative-free solution is used after ocular incisional refractive surgery to reduce ocular pain and photophobia. Results from 2 double-blind, multicenter, placebo-controlled studies in over 300 patients indicate that short-term application (up to 3 days) of ketorolac tromethamine 0.5% (as a preservative-free solution) is more effective than vehicle in reducing ocular pain and photophobia following ocular incisional refractive surgery.
In ophthalmology, topical ketorolac tromethamine 0.4% is used following corneal refractive surgery to reduce ocular pain and burning/stinging. Ketorolac tromethamine 0.5% also provides analgesic and anti-inflammatory effects; however, use of the preparation is associated with ocular irritation, mainly burning and stinging on instillation. Ketorolac tromethamine 0.4% ophthalmic solution (Acular LS) is formulated with a lower concentration of the drug and certain inactive ingredients (i.e., benzalkonium chloride, edetate disodium) to reduce the incidence of adverse effects while maintaining clinical efficacy. Ketorolac tromethamine 0.4% ophthalmic solution has been evaluated for the treatment of ocular pain in patients undergoing photorefractive keratectomy (PRK), a procedure associated with severe postoperative ocular pain. In 2 multicenter, randomized, double-blind studies in over 300 patients undergoing PRK surgery, short-term therapy (up to 4 days) with ketorolac tromethamine 0.4% ophthalmic solution was more effective than placebo (vehicle) in reducing ocular pain and burning/stinging following surgery.
Cystoid Macular Edema
NSAIAs, including ketorolac tromethamine, also have been applied topically to the eye, with or without concomitant topical corticosteroid therapy, to prevent or relieve postoperative cystoid macular edema associated with cataract extraction. The drugs also have been used for the active treatment of chronic aphakic or pseudophakic cystoid macular edema. While prophylactic therapy with the drugs has effectively prevented or reduced angiographic evidence of cystoid macular edema for up to several months after cataract surgery, there is less evidence for improvement in visual acuity. The potential benefit on visual acuity of active treatment of cystoid macular edema also is unclear. There is limited evidence indicating that topical ketorolac therapy (without concomitant corticosteroid therapy) may improve distance acuity in many patients when used for the active treatment of chronic aphakic or pseudophakic cystoid macular edema but such improvement may not be permanent.
The comparative efficacy of topical NSAIAs, topical corticosteroids, topical NSAIAs combined with topical corticosteroids, or other agents for the prevention or active treatment of cystoid macular edema remains to be established. Most experience to date has involved combined therapy with a topical NSAIA and a topical corticosteroid. While there is limited evidence that NSAIAs alone can effectively prevent or relieve cystoid macular edema, there also is limited evidence that combined topical NSAIA and corticosteroid therapy may have an additive or synergistic effect in this condition. In addition, some clinicians state that the need for the development or identification of more effective therapy persists.
Inhibition of Intraoperative Miosis
In ophthalmology, NSAIAs also have been used prophylactically before ocular surgery (e.g., cataract extraction) to prevent or reduce intraoperative miosis, which may occur secondary to surgery-induced trauma despite preoperative induction of mydriasis. However, the clinical value of such therapy remains controversial, in part because of the variability and degree of the effect.
For systemic uses of ketorolac tromethamine,