What is the first-line topical antiviral agent for HSV keratitis?

• A. Trifluridine
• B. Acyclovir
• C. Ganciclovir
• D. Vidarabine

Answer: (A)

Treating HSV keratitis focuses on stopping viral DNA synthesis right where the virus is active—in the corneal epithelium. Trifluridine fits this goal best because it’s a potent antiviral that acts quickly when applied topically to the eye.

Mechanistically, trifluridine is a fluorinated pyrimidine nucleoside analog. Once applied, it’s phosphorylated by cellular kinases to an active triphosphate form. This active molecule competes with the normal building block in viral DNA synthesis and gets incorporated into viral DNA, causing faulty replication and chain termination. Because the infection is in the corneal epithelium, a drug that rapidly delivers its active form to the surface and inhibits HSV DNA polymerase is especially effective, leading to quicker control of epithelial disease.

Clinically, this translates to rapid improvement and healing of dendritic or epithelial ulcers, which is why trifluridine has traditionally been considered the first-line topical agent. It is typically used as a 1% ophthalmic solution with frequent dosing initially, then tapered as healing occurs.

Other antivirals like acyclovir or ganciclovir are certainly active against HSV and can be options, but they generally don’t provide the same combination of rapid corneal epithelial action and practical topical delivery as trifluridine, which is why it’s favored as the initial topical choice. Vidarabine is older and less commonly used due to tolerability issues and slower effect.