What is the treatment and secondary prophylaxis for Herpes Simplex Virus (HSV) keratitis?

HSV Keratitis Treatment and Secondary Prophylaxis

Acute Treatment: Combination Therapy is Essential

For acute HSV keratitis, you must use combination therapy with both topical AND oral antivirals—oral antivirals alone are insufficient to prevent progression of corneal disease. 1, 2

Topical Antiviral Options (Choose One):

• Ganciclovir 0.15% gel: 5 times daily (approximately every 3 hours while awake) until corneal ulcer heals, then 3 times daily for 7 days 3

  • This is the preferred first-line topical agent due to superior tolerability and less ocular surface toxicity compared to trifluridine 4
  • FDA-approved specifically for acute herpetic keratitis (dendritic ulcers) 3

• Trifluridine 1% solution: 5-8 times daily 1, 2

  • Effective but inevitably causes epithelial toxicity if used beyond 2 weeks 1
  • Reserve for cases where ganciclovir is unavailable

Oral Antiviral Options (Choose One):

• Valacyclovir 500 mg orally 2-3 times daily for 7-14 days until epithelial healing is complete 2
• Acyclovir 200-400 mg orally 5 times daily 1, 2
• Famciclovir 250 mg orally twice daily 1, 2

Critical Treatment Principles:

• Avoid topical corticosteroids during active epithelial disease—they potentiate HSV infection and worsen outcomes 1, 2
• Patients should not wear contact lenses during active infection or treatment 3
• Follow-up within 1 week with visual acuity measurement and slit-lamp biomicroscopy to assess epithelial healing 1, 2
• Adjust oral antiviral doses in patients with impaired renal clearance 2

Why Combination Therapy Matters:

The evidence is clear that oral antivirals by themselves fail to prevent progression of HSV blepharoconjunctivitis to keratitis 1, 5. In a case series, three patients developed HSV infectious epithelial keratitis despite therapeutic doses of oral acyclovir, but responded rapidly to topical antivirals within 3-10 days 5. This demonstrates that topical therapy is essential for corneal involvement, not optional.

Secondary Prophylaxis: Long-Term Suppression

For patients with recurrent HSV keratitis, use lower-dose oral antivirals for long-term prophylaxis to reduce recurrence rates. 1, 6

Prophylactic Dosing Options:

• Valacyclovir 500 mg daily (lower than acute treatment dose) 2
• Acyclovir 400 mg twice daily (lower than acute treatment dose) 6
• Famciclovir 250 mg daily (lower than acute treatment dose)

The landmark Herpetic Eye Disease Study demonstrated that long-term suppressive oral acyclovir significantly reduces the incidence of recurrent HSV keratitis 6. Prophylaxis is particularly important for patients with a history of HSV stromal keratitis or iritis, who have a 23% recurrence rate compared to 9% in those without such history 7.

Special Considerations for Stromal Keratitis:

If HSV stromal keratitis develops, topical corticosteroids can be used BUT only in conjunction with prophylactic oral antiviral therapy. 1, 6 This combination shortens the duration of active stromal disease while preventing viral replication 6. Use the minimum effective corticosteroid dose and taper slowly 1.

Resistant or Refractory Cases:

For patients unresponsive to conventional antivirals or with documented allergies, oral valganciclovir 900 mg twice daily for 10 days, followed by 900 mg daily for prophylaxis has shown success 8. In a case series, all four patients with treatment-refractory HSV keratitis achieved epithelial healing within 2 weeks and remained recurrence-free during 6-12 months of prophylaxis 8.

Common Pitfalls to Avoid:

• Never use oral antivirals alone for active keratitis—this is inadequate and allows disease progression 1, 5
• Never use topical corticosteroids during active epithelial disease—reserve for stromal involvement only, and always cover with oral antivirals 1, 2
• Don't use trifluridine beyond 2 weeks—it causes inevitable epithelial toxicity 1
• Don't forget renal dosing adjustments for oral antivirals in patients with impaired kidney function 2