Ophthalmic Medications in Pediatric Patients

Teresa M. Myers, MD; David K. Wallace, MD; Sandra M. Johnson, MD


Compr Ophthalmol Update. 2005;6(2):85-101. 

In This Article

Anti-Inflammatory Medications

Corticosteroids are used to treat inflammatory and allergic conditions affecting the eye. They are available as sterile ointments, solutions, and suspensions, usually in concentrations from 0.1 to 1%. Commonly used topical corticosteroid preparations are prednisolone acetate (Pred Forte®, Allergan, Irvine, CA) and prednisolone phosphate (Inflammase®, Novartis, Duluth, GA). Ointments, such as fluorometholone 0.1%, are usually used at night or for the treatment of inflammatory conditions of the eyelid as an adjunct to daytime drops; use of these viscous formulations can double the concentration of agent in the aqueous as compared to the same concentration provided as a solution, although the sustained release formulations may actually produce lower peak ocular concentrations of steroid when compared with drops.[55] When multiple medications are taken, drops should be administered first, as ointments can slow the entry of subsequent medications.

There are some case studies in the literature to support the efficacy of topical corticosteroid creams in certain cases to treat superficial periocular capillary hemangiomas, sometimes eliminating the need for intralesional steroid injections.[56,57,58] Topical corticosteroids may be required as frequently as every hour (for example, in severe cases of uveitis) and as infrequently as once daily or less.

Two modified corticosteroids, rimexolone (Vexol®, Alcon, Ft. Worth, TX) and loteprednoletabonate (Alrex® and Lotemax®, Bausch & Lomb, Rochester, NY), are indicated for short-term treatment and prophylaxis of severe allergic ocular surface disease, such as that caused by vernal keratoconjunctivitis. Rimexolone is a derivative of prednisolone that is metabolized to an inactive form in the anterior chamber, thus reducing the risk of increased intraocular pressure.[59]

Several undesirable side effects limit corticosteroid use: ocular hypertension (within 3-6 weeks in steroid-responsive patients),[60] reactivation of herpes infections, induction of posterior subcapsular cataracts, increased intraocular pressure and, rarely, systemic effects, such as headache and hypotension. Potent corticosteroids, such as prednisolone, dexamethasone, and betamethasone, tend to produce increased intraocular pressure more frequently than weaker corticosteroids, but formulation type can also produce variations in concentrations and side effects.[55] Symptoms generally remit a few weeks after discontinuation, but long-term use can cause corneal or scleral thinning or perforation, as well as optic nerve damage and visual field loss. Ophthalmic suspensions of prednisolone may contain sodium bisulfite, possibly causing allergic reactions in susceptible individuals. Lid ptosis and mydriasis are other possible local reactions. These drugs should be used with caution in patients with diabetes mellitus, hypertension, myopia greater than 5 D, or a Krukenberg spindle, who have a substantially increased risk of increased intraocular pressure during topical ophthalmic corticosteroid therapy.[61]

Systemic corticosteroids are used in the treatment of severe inflammatory conditions of the eye, such as posterior uveitis or scleritis. Systemic treatment can worsen diabetes and can lead to gastritis, stomach ulcers, and weight gain, and various psychiatric effects, including sleep disturbance and mood problems. Thus, dosage should be titrated for effect from the smallest possible dose and tapered as soon as possible, in most cases after no more than 2 weeks, at a rate of 10 mg/week over 6 weeks.

Corticosteroid injections (e.g., Kenalog®, Apothecon, a Bristol-Myers Squibb Company, Princeton, NJ) are used in the treatment of intermediate and posterior uveitis and capillary hemanigiomas. There have been reports of ophthalmic artery occlusion during intralesional injection of corticosteroids to treat eyelid capillary hemangioma with subsequent blindness.[62,63] The presumed mechanism was retrograde flow of the corticosteroid preparation through the feeder arteries to the hemangioma. A case of central retinal artery occlusion following injection in a 4-year-old child was reported and thought to be due to the force of injection and digital massage.[64]

The corticosteroids rimexolone (Vexol®, Alcon, Ft. Worth, TX), medrysone (HMS® Liquifilm®, Allergan, Irvine, CA), loteprednol (Lotemax® and Alrex®, Bausch & Lomb, Rochester, NY) and fluorometholone (FML® Liquifilm®, Allergan, Irvine, CA; Eflone® and Flarex®, Alcon, Ft. Worth, TX) are claimed to have less effect on intraocular pressure; however, their anti-inflammatory effect is probably also limited.[65,66] In a study of 54 pediatric strabismus patients treated for 4 weeks postoperatively with rimexolone, a significantly higher mean intraocular pressure (19.7 [SD = 6.1] mmHg and mean net increase in intraocular pressure (5.9 [SD = 4.4] mmHg) was found in the 1%-rimexolone-treated eyes than in the fellow 0.1%-fluorometholone-treated eyes (17.6 [SD = 4.6] mmHg and 3.9 [SD = 4.1] mmHg) (P<.001). Six patients (11.1%) in the rimexolone-treated group had an increase in intraocular pressure of more than 10 mmHg compared with preoperative values.[67]

A prospective study of children randomized to different doses of fluorometholone for 4 weeks after strabismus surgery found that the ocular hypertensive response to fluorometholone was dose-dependent and was more profound than that observed in adults.[68] Such dose-dependent differences are of significance in situations, such as treatment of uveitis, when the course may be prolonged. Previous studies by the same authors found an even greater sensitivity to topical dexamethasone in children relative to adults.[69]

Nonsteroidal anti-inflammatory drugs show some efficacy treating uveitis, limited by their inability to modulate inflammatory cytokines other than those generated by arachidonic acid metabolism.[70] The most commonly used topical ocular preparations include ketorolac (Acular®, Allergan, Irvine, CA), diclofenac 0.1% (Voltaren Ophthalmic®, Novartis, Duluth, GA) and flurbiprofen 0.03% (Ocufen®, Allergan, Irvine, CA). Many studies of postoperative use of nonsteroidal anti-inflammatory medications include the concurrent administration of corticosteroids, and there is good evidence of their synergistic activity.[71,72] Although there are relatively less data on the use of nonsteroidal anti-inflammatory medications alone postoperatively, they are increasingly used for this purpose. In a study comparing diclofenac to dexamethasone in 40 pediatric patients undergoing strabismus surgery, diclofenac was superior in each of five postoperative outcome parameters measured: patient discomfort, conjunctival chemosis, inflammation, conjunctival gap, and intraocular pressure at 1, 2, and 4 weeks after surgery.[73] Flurbiprofen 0.03% is approved by the FDA for intraoperative use to inhibit excessive miosis during cataract surgery.

Ketorolac is the only approved topically effective nonsteroidal anti-inflammatory that is available in a preservative-free formulation (Acular® PF, Allergan, Irvine, CA) in the United States for the four times daily treatment of seasonal allergic conjunctivitis and double-blinded clinical trials have demonstrated its efficacy.[74] It has been found safe and effective for children 2 years of age and older. It has been reported to induce asthma in a patient with the triad of asthma, nasal polyposis, and aspirin sensitivity.[75]

Ophthalmic nonsteroidal anti-inflammatory agents may increase the risk of bleeding in ocular tissues following ophthalmic procedures (prescribing information, Volaten Ophthalmic, CIBA Vision, USA); postoperative bleeding, including hyphema, has been documented with flurbiprofen (package insert, Ocufen®, Allergan (US), 12/86 [received 1/87]). Like corticosteroids, they can also slow healing with prolonged treatment and the effect may be additive. Corneal thinning, erosion, and ulceration are possible in susceptible patients, including those with diabetes. Oral nonsteroidal anti-inflammatory agents are useful when tapering corticosteroids in many patients and they are an important treatment element in patients with chronic inflammation, such as that associated with juvenile rheumatoid arthritis.

Combination corticosteroid-antibiotic preparations, such as TobraDex® (tobramycin 0.3%/dexamethasone 0.1%) (Alcon, Ft. Worth, TX), and Maxitrol® (dexamethasone, neomycin, and polymyxin B) (Alcon, Ft. Worth, TX) are frequently used after ocular surgery, after superficial chemical or thermal burns, or in the treatment of inflammatory conditions of the ocular surface or eyelids.

Several topical agents are available for the treatment and, to some degree, the prophylaxis of ocular allergic disease, such as seasonal allergic conjunctivitis and vernal keratoconjunctivitis. These include vasoconstrictors, antihistamines, mast-cell stabilizers, and anti-inflammatory agents. The antihistamines levocabastine 0.05% (Livostin®, Novartis, Duluth, GA) and emedastine 0.05% (Emadine®, Alcon, Ft. Worth, TX) are selective for the H1-receptor. The incidence of adverse effects associated with levocabastine therapy is low and is similar to that observed with placebo and sodium cromoglycate. Levocabastine provides prophylactic protection.[76] In one study levocabastine given twice daily and cromoglycate given four times daily were both well tolerated and proved equally effective, but patients deemed levocabastine to be more efficacious than cromoglycate.[77] In another study, levocabastine performed less effectively (P < .05) than ketorolac dosed four times daily in reducing mean itching scores, palpebral hyperemia, bulbar hyperemia, and edema.[78] In one 6-week environmental study emedastine was superior to levocabastine in reducing chemosis, eyelid swelling, and other symptoms of seasonal allergic conjunctivitis.[79] While the adverse effect of somnolence is much less likely with the second compared to first generation antihistamines, none of them are completely free of central nervous system effects, such as impaired concentration, dizziness, headache, and insomnia.

Several dual agents provide both mast-cell stabilizing effects and H1 receptor binding. In one randomized, double-masked clinical trial olopatadine 0.1% solution (Patanol®, Alcon, Ft. Worth, TX) was superior to cromolyn in reducing itching and redness and appeared to have better local tolerability in children aged less than 11 years.[80] An advantage of the 0.1% preparation is the twice-daily dosage. The next generation olopatadine is given once daily and is awaiting FDA approval.

Azelastine 0.05% solution (Optivar®, MedPointe Pharmaceuticals, Somerset, NJ) is a second-generation H1-receptor antagonist with an extensive array of anti-inflammatory mechanisms.[81] In the United States, azelastine has been approved as the only antihistamine nasal spray for the treatment of allergic conjunctivitis (Astelin® Nasal Spray, MedPointe Pharmaceuticals, Somerset, NJ), and its safety and effectiveness when dosed twice daily has been established down to age 3 years. The principal adverse effects of intranasal azelastine are local, but adverse systemic effects, including somnolence and headache can also occur. A randomized, multicenter trial of azelastine eye drops versus levocabastine versus placebo over 14 days found that both active treatments were equally effective in the treatment of allergic conjunctivitis, as measured by improvement of itching, conjunctival redness, and lacrimation, and by tolerability.[82]

Nedocromil (Alocril®, Allergan, Irvine, CA) and ketotifin 0.025% (Zaditor®, Novartis, Duluth, GA) both possess multiple actions, including mast cell stabilization, H1-receptor antagonism, and inhibitory effects on various allergic inflammatory cells.[64,83] Both are safe and effective for patients over 3 years of age when dosed twice daily.

Naphazoline 0.025%-pheniramine 0.3% (Naphcon-A®, Alcon, Ft. Worth, TX) and naphazoline-antazoline 0.05%/0/5% (Vasocon-A®, Novartis, Duluth, GA) both provide vasoconstrictor properties with H1-receptor binding. Both of the above medications are available over the counter. In a randomized antigen-challenge study, naphazoline-antazoline was more effective in alleviating the conjunctival inflammation and photophobia of allergic conjunctivitis than either agent alone or placebo.[84] Vasoconstrictors are ocular decongestants and should be used with caution in older children and avoided in those less than 6 years of age. Accidental oral ingestion can lead to central nervous system depression, coma, and marked hypothermia. The ocular side effects of vasoconstrictors include burning, stinging, and mydriasis, especially in those of lighter irides.

Mast cell inhibitors are effective in prophylaxis as well as treatment. Lodoxamide tromethamine 0.1% (Alomide®, Alcon, Ft. Worth, TX) has proved effective in treatment of vernal keratoconjunctivitis, for which it is labeled, although it is used off-label for seasonal allergic conjunctivitis as well. Several studies have found that lodoxamide was superior to cromolyn for relief of symptoms and signs of vernal keratoconjunctivitis when used up to four times daily in children.[85] It is indicated for use in children age 2 years or older for up to 3 months. Sodium cromoglycate 4% (Crolom®, Bausch & Lomb, Rochester, NY; Opticrom®, Allergan, Irvine, CA) is the prototypical mast cell mediator and was the first agent found to be effective for treatment of allergic conjunctivitis. Pemirolast is a mast cell stabilizer. Two randomized, double-masked, placebo-controlled trials conducted over 12-17 weeks found that pemirolast potassium 0.1% ophthalmic solution (Alamast®, Santen, Osaka, Japan) four times daily was superior to placebo in symptom relief as early as 3 minutes after ragweed antigen challenge and safety down to age 3 years has been established.


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