Treatment of HSV Epithelial Keratitis
Initiate combination therapy with both topical ganciclovir 0.15% gel (3-5 times daily) AND oral antiviral therapy (valacyclovir 500 mg 2-3 times daily, acyclovir 400 mg five times daily, OR famciclovir 250 mg twice daily) for all patients with HSV epithelial keratitis. 1
Primary Treatment Regimen
Topical antiviral therapy is mandatory and cannot be replaced by oral therapy alone, as oral antivirals are insufficient to prevent progression of corneal disease. 1 The preferred topical agents include:
- Ganciclovir 0.15% ophthalmic gel 3-5 times daily is the first-line topical agent due to superior tolerability and less ocular surface toxicity, with healing of dendritic ulcers within 7 days in the majority of patients 1
- Trifluridine 1% solution 5-8 times daily is an alternative topical agent that demonstrates significantly better healing than older agents like idoxuridine (RR 1.30; 95% CI 1.18 to 1.43) 2
- Topical acyclovir is equally effective to trifluridine, with both agents showing superior outcomes compared to vidarabine or idoxuridine 3, 2
Oral antiviral therapy must be added to topical treatment, using one of these regimens 1:
- Valacyclovir 500 mg 2-3 times daily
- Acyclovir 400 mg five times daily
- Famciclovir 250 mg twice daily
Critical Contraindications
Topical corticosteroids are absolutely contraindicated in HSV epithelial keratitis as they potentiate viral replication and worsen infection. 1 This prohibition applies even when inflammation appears significant, as steroids should only be considered for HSV stromal keratitis (not epithelial disease) and must always be combined with prophylactic antiviral therapy. 4, 5
Adjunctive Therapies
The combination of topical interferon with an antiviral agent significantly accelerates epithelial healing at 7 days (OR 13.49; 95% CI 7.39-24.61), though the benefit diminishes by 14 days. 6 This combination may be considered to expedite healing but is not essential for successful outcomes. 3, 2
Corneal debridement combined with antiviral therapy improves healing outcomes (RR 1.21; 95% CI 1.04 to 1.42) compared to antiviral monotherapy, though debridement alone without antiviral coverage risks recrudescent epithelial keratitis. 3, 6
Follow-Up Protocol
Schedule follow-up within 1 week to assess treatment response, including visual acuity measurement and slit-lamp biomicroscopy. 1 For patients not improving after 2-3 weeks, re-evaluation should include interval history, visual acuity measurement, and slit-lamp examination. 4
Common Pitfalls to Avoid
- Never use oral antivirals as monotherapy for active epithelial keratitis, as topical therapy is essential for corneal disease control 1
- Never prescribe corticosteroids for epithelial disease, even if inflammation appears significant, as this represents a fundamental treatment error 1
- Consider higher antiviral doses in cases demonstrating apparent resistance to standard therapy 1
- Avoid using antibiotics in viral keratitis management due to potential adverse treatment effects without therapeutic benefit 4
Comparative Effectiveness
Among the nucleoside antivirals, trifluridine, acyclovir, brivudine, and ganciclovir demonstrate similar therapeutic effectiveness and are all significantly superior to older agents like idoxuridine. 3, 2 Brivudine (RR 1.34; 95% CI 1.18 to 1.51) and ganciclovir (RR 1.40; 95% CI 1.25 to 1.57) show at least equivalent efficacy to acyclovir. 3
The combination of two topical antivirals does not improve outcomes (RR 1.00; 95% CI 0.89 to 1.12) compared to monotherapy and is not recommended. 3