Topical ganciclovir ophthalmic gel, approved by the US Food and Drug Administration (FDA) in 2009, has the advantages of low corneal toxicity, less frequent applications, and gel formulation. Trifluridine solution and vidarabine ointment are also effective in treating HSV keratitis. However, epithelial toxicity is a frequent adverse effect, especially with prolonged use. Response to topical therapy usually occurs in 2-5 days, with complete resolution in 2 weeks. Topical therapy should be tapered rapidly after initial response and discontinued after complete healing, generally within 10-14 days. Failure of epithelial healing after 2-3 weeks of antiviral therapy suggests epithelial toxicity, neurotrophic keratopathy, or, rarely, drug-resistant strains of HSV. Vidarabine is often effective against HSV strains that are resistant to trifluridine and acyclovir.