What is the recommended treatment for Herpes Simplex Virus (HSV) epithelial keratitis?

Treatment of HSV Epithelial Keratitis

Initiate combination therapy with both topical ganciclovir 0.15% gel (3-5 times daily) AND oral antiviral therapy (acyclovir 400 mg five times daily, valacyclovir 500 mg 2-3 times daily, OR famciclovir 250 mg twice daily) for HSV epithelial keratitis, as oral therapy alone is insufficient to prevent progression of corneal disease. 1

Primary Treatment Regimen

Topical Antiviral Therapy

• Ganciclovir 0.15% ophthalmic gel is the preferred first-line topical agent due to superior tolerability and less ocular surface toxicity compared to alternatives 1
• Dosing: 1 drop in the affected eye 5 times per day (approximately every 3 hours while awake) until the corneal ulcer heals, then 1 drop 3 times per day for 7 days 2
• Alternative topical agent: Trifluridine 1% solution 5-8 times daily if ganciclovir is unavailable 1
• The majority of dendritic ulcers heal within 7 days with ganciclovir therapy 1

Oral Antiviral Therapy (Mandatory Adjunct)

• Oral antivirals must be added to topical therapy—monotherapy with oral agents alone is inadequate for active epithelial keratitis 1, 3
• Options include:
  • Acyclovir 400 mg five times daily 1
  • Valacyclovir 500 mg 2-3 times daily 1
  • Famciclovir 250 mg twice daily 1
• Clinical evidence demonstrates that HSV blepharoconjunctivitis can progress to infectious epithelial keratitis despite oral acyclovir therapy, requiring topical antiviral addition 3

Critical Contraindications

Absolute Prohibition of Corticosteroids

• Topical corticosteroids are absolutely contraindicated in HSV epithelial keratitis as they potentiate viral replication and worsen infection 1
• Do not prescribe corticosteroids for epithelial disease, even if inflammation appears significant 1
• This is a common pitfall that can lead to devastating corneal complications 1

Comparative Effectiveness of Antiviral Agents

The evidence hierarchy for topical antivirals based on meta-analyses shows:

• Trifluridine and acyclovir are significantly more effective than older agents like idoxuridine (RR 1.31 and 1.23 respectively) 4
• Ganciclovir demonstrates similar or superior effectiveness to acyclovir (RR 1.40 compared to idoxuridine) 4
• Brivudine is at least as effective as acyclovir 4
• Vidarabine, while better than idoxuridine, is less effective than trifluridine or acyclovir 4

Adjunctive Therapies to Avoid

• Debridement alone without antiviral therapy increases risk of recrudescent epithelial keratitis 5
• Combination of debridement with antiviral therapy may accelerate healing but does not improve final outcomes compared to antiviral monotherapy 4
• Interferon combined with antivirals may speed healing but does not improve ultimate healing rates 4

Follow-Up Protocol

• Schedule follow-up within 1 week of initiating treatment 1
• Follow-up visit must include:
  • Visual acuity measurement 1
  • Slit-lamp biomicroscopy to assess epithelial healing 1
• Consider higher antiviral doses if apparent resistance to standard therapy develops 1

Contact Lens Prohibition

• Patients must not wear contact lenses if they have signs or symptoms of herpetic keratitis or during the entire course of therapy 2

Common Adverse Effects

The most frequent side effects with ganciclovir gel include:

• Blurred vision (60% of patients) 2
• Eye irritation (20%) 2
• Punctate keratitis (5%) 2
• Conjunctival hyperemia (5%) 2