What is the appropriate treatment for herpes simplex keratitis (herpes eye involvement)?

Treatment of Herpes Simplex Keratitis

For herpes simplex keratitis, initiate immediate combination therapy with topical ganciclovir 0.15% gel 3-5 times daily PLUS oral antiviral therapy (valacyclovir 500 mg 2-3 times daily or acyclovir 400 mg five times daily), and never use topical corticosteroids in epithelial disease as they potentiate viral replication and worsen outcomes. 1

Initial Treatment Algorithm

First-Line Combination Therapy

• Start dual therapy immediately upon diagnosis or strong clinical suspicion of HSV keratitis 1

• Topical antiviral options:

  • Ganciclovir 0.15% gel: 3-5 times daily (preferred due to less ocular surface toxicity) 2, 3
  • Trifluridine 1% solution: 5-8 times daily (alternative, but causes inevitable epithelial toxicity if used >2 weeks) 2

• Oral antiviral options (choose one):

  • Valacyclovir 500 mg 2-3 times daily 2
  • Acyclovir 200-400 mg five times daily 2
  • Famciclovir 250 mg twice daily 2

Critical Treatment Principles

The combination of topical AND oral antivirals is essential because oral antivirals alone may not adequately prevent progression of HSV blepharoconjunctivitis, but adding topical treatment has proven effective 2. This represents a shift from older monotherapy approaches.

Topical ganciclovir is superior to trifluridine for longer-term use because it causes significantly less ocular surface toxicity 2. Trifluridine should be avoided beyond 2 weeks due to inevitable epithelial damage 2.

Absolute Contraindications

Never Use Topical Corticosteroids in Epithelial HSV

• Topical corticosteroids potentiate HSV epithelial infections and must be avoided 2, 1
• Steroids enhance viral replication in active epithelial disease, leading to geographic ulceration and worse visual outcomes 2
• This is the most critical pitfall to avoid in HSV keratitis management

Follow-Up Protocol

• Schedule follow-up within 1 week of initiating treatment 2, 1
• Each visit must include:
  • Interval history
  • Visual acuity measurement
  • Slit-lamp biomicroscopy with fluorescein staining 2
  • Intraocular pressure measurement if any corticosteroids are being considered for stromal disease 2

Treatment-Resistant Cases

When Standard Therapy Fails

• Consider higher doses of oral antivirals based on anecdotal experience showing effectiveness in resistant cases 2
• Oral valganciclovir 900 mg twice daily for 10 days (treatment dose), then 900 mg daily for prophylaxis, has shown success in patients unresponsive to conventional therapy 4
• Valganciclovir achieved corneal epithelial healing within 2 weeks in all reported treatment-failure cases, with no recurrences during 6-12 months of prophylaxis 4

Long-Term Prophylaxis

Preventing Recurrences

• Lower doses of oral antivirals are recommended for long-term prophylaxis against recurrent HSV conjunctivitis and keratitis 2
• Long-term suppressive oral acyclovir therapy reduces the incidence of recurrent HSV keratitis 5
• Prophylaxis is particularly important given that HSV establishes latent infection in the trigeminal ganglion with potential for reactivation triggered by stress, illness, immunosuppression, or trauma 6

Special Populations

Neonates

• Require prompt consultation with pediatrician or primary care physician because systemic HSV infection is life-threatening 2
• Neonatal HSV represents a medical emergency requiring immediate systemic antiviral therapy

Immunocompromised Patients

• May require more aggressive treatment regimens 2
• Bilateral presentation can occur in atopic, pediatric, or immunocompromised patients 1

Diagnostic Confirmation When Uncertain

• Clinical diagnosis is based on characteristic dendritic or geographic corneal ulcers on slit-lamp examination with fluorescein staining 1
• Laboratory confirmation using immunofluorescence assay (IFA) or PCR when diagnosis is uncertain, with IFA showing 78.6-85.7% sensitivity and 85.3-95% specificity 1
• Look for excavated ulcers with true epithelial defects penetrating Bowman's layer (pathognomonic for HSV) 1, 7