Ocular manifestations of HSV or herpes zoster virus (HZV) infection typically occur much later in life, but disease in pediatric patients is often systemic and frequently accompanied by significantly more ocular inflammation and the complicating risk of amblyopia. Immunocompromised children are much more likely to have complex courses of disease, with persistence and recurrence, than immunocompetent children infected with HSV or HZV. The primary antiviral medications include trifluridine (Viroptic®, Monarch Pharmaceuticals, Inc., Bristol, TN), vidarabine (Vira-A®, Pfizer, New York, NY), acyclovir (Zovirax®, GlaxoSmithKline, Middlesex, United Kingdom), valacyclovir (Valtrex®, GlaxoSmithKline, Middlesex, United Kingdom), and foscarnet (Foscavir®, AstraZeneca, Wilmington, DE). After frequent (four to nine times daily) topical instillation, trifluridine 1% solution penetrates the cornea to produce therapeutic levels in the aqueous, making it particularly useful in treatment of herpes simplex stromal disease. Antiviral ointments include vidarabine (Vira-A®) and acyclovir 3%. Vidarabine is used less frequently for herpes simplex than trifluridine drops due to toxicity, hypersensitivity reactions and relative insolubility. It is occasionally useful to treat the rare patient with hypersensitivity reactions to trifluridine. By virtue of its selectivity, topical acyclovir 3% ointment causes significantly less toxicity than other antivirals even with long-term use.
Acyclovir is highly effective for treatment and prophylaxis of herpes simplex epithelial keratitis and immune stromal keratitis, and for prevention of recurrent infectious epithelial keratitis.[97,98] Oral acyclovir reaches therapeutic levels in both tears and aqueous, virtually eliminating the need for concurrent use of topical antivirals. It also avoids the problem of tear dilution as may occur with topical agents.
Treatment of HZV infections in the immunocompromised pediatric patient may require high doses of acyclovir. For patients older than 1 year of age, the recommended dosage is 30 mg/kg/day intravenously divided every 8 hours for 7-10 days or 250-600 mg/m2/dose given four to five times/day orally. The prodrugs famciclovir and valacyclovir, variants of penciclovir and acyclovir, respectively, have also been used in treatment of HZV, and have been found to offer superior acute pain relief in adults when compared to acyclovir.[100,101]
Results of the Epithelial Keratitis Trial performed by the Herpetic Eye Disease Study (HEDS) Group showed that adding oral acyclovir to topical antiviral medications when treating infectious epithelial keratitis did not prevent future episodes of stromal keratitis or iritis. However, in a study of 703 patients aged 12 years or over, they also found that long-term suppressive oral acyclovir therapy reduces the risk of recurrent HSV epithelial (9% versus 14%) and stromal (14% versus 28%) keratitis, with the greatest benefit for patients who have experienced prior HSV stromal keratitis (absolute benefit of treatment [risk in placebo group minus risk in acyclovir group] was 9% for patients with one prior episode, 11% for those with two to three prior episodes, and 17% for those with four or more episodes.)
In a 10-week study of three times daily oral acyclovir against placebo, pediatric patients with HSV stromal keratitis who were treated concomitantly with corticosteroids and topical trifluridine exhibited no statistically significant difference in success rate or in time to treatment failure. By 16 weeks, 38 of 51 children (75%) in the acyclovir group and 39 of 53 (74%) in the placebo group had failed treatment (i.e., experienced worsened symptoms, no change, or adverse events). However, visual acuity at 6 months was significantly better in the acyclovir group compared to the placebo group.
In a retrospective case series of seven children (aged 6 weeks to 5 years) with HSV epithelial keratitis, all symptoms resolved within 2 weeks of systemic acyclovir treatment. There were no recurrences of epithelial disease while undergoing treatment; however, four children had recurrences while tapering acyclovir or after discontinuation of treatment.
Famciclovir is converted enzymatically to penciclovir, which has a more extended half-life in infected cells than acyclovir. Fixed doses of valacyclovir, an oral acyclovir prodrug, reach similar serum concentrations to intravenous acyclovir by administration of a dose equivalent to 3.3 times the scheduled acyclovir dose in milligrams, and thus may be the preferred oral substitute for intravenous acyclovir therapy in children due to low and variable bioavailability of oral acyclovir, although only clinical studies of adults have been published on this matter.[106,107] Prepared oral liquids of valacyclovir are more suitable for children than large intact or bitter crushed tablets.
Toxicity associated with topical antivirals includes superficial punctate keratitis, chemical conjunctivitis, punctal occlusion, elevated introcular pressure, and rare hypersensitivity reactions. Normal renal function is required to excrete acyclovir. Therefore, patients on long-term acyclovir suppression therapy should have their renal function monitored. The principle adverse effect associated with intravenous foscarnet is nephrotoxicity as well.
Compr Ophthalmol Update. 2005;6(2):85-101. © 2005 Comprehensive Ophthalmology Update, LLC
Cite this: Ophthalmic Medications in Pediatric Patients - Medscape - Mar 01, 2005.