Duration of Acyclovir After Corneal Transplantation
For patients undergoing corneal transplantation for herpes simplex keratitis, prophylactic oral acyclovir should be continued for a minimum of 12 months postoperatively at a dose of 400 mg twice daily, with strong consideration for indefinite continuation in patients with a history of recurrent HSV keratitis. 1, 2, 3, 4
Standard Prophylactic Regimen
Dosing and Duration
- Oral acyclovir 400 mg twice daily for at least 12 months is the evidence-based standard regimen following penetrating keratoplasty for HSV keratitis 3, 4
- Alternative oral antivirals include valacyclovir 500 mg 2-3 times daily or famciclovir 250 mg twice daily, though these are extrapolated from acute treatment guidelines rather than post-transplant prophylaxis studies 5
Evidence Supporting Extended Prophylaxis
- Prophylactic acyclovir reduces HSV recurrence risk by approximately 71% (RR 0.29,95% CI 0.13-0.64), preventing approximately 23 cases of recurrence per 100 corneal grafts 6
- Graft failure risk is reduced by 60% (RR 0.40,95% CI 0.16-0.97), preventing approximately 13 graft failures per 100 operations 6
- Studies demonstrate 0-8.3% recurrence rates with prophylaxis versus 33-50% without prophylaxis over 16-30 months of follow-up 1, 2, 3, 4
Risk-Stratified Approach
High-Risk Patients (History of Recurrent HSV Keratitis)
- Consider indefinite prophylaxis beyond 12 months in patients with multiple prior HSV episodes or those who underwent transplantation for necrotizing keratitis with perforation 3
- Recurrences may develop after cessation of acyclovir, particularly in high-risk patients (28.6% recurrence rate in necrotizing keratitis patients after stopping prophylaxis) 3
- One study documented that 2 of 3 recurrences occurred specifically after withdrawal of acyclovir therapy at one year 3
Standard-Risk Patients
- Minimum 12 months of prophylaxis is appropriate for patients with corneal scarring without perforation and no history of frequent recurrences 3, 4
- After 12 months, consider tapering with close monitoring rather than abrupt cessation 3
Renal Function Adjustments
Dose Modifications
- Acyclovir requires dose adjustment in renal impairment due to renal excretion 5
- For valacyclovir (if used as alternative), renal dosing adjustments are mandatory in patients with impaired creatinine clearance 5
- Monitor renal function periodically during long-term prophylaxis, particularly in elderly patients or those with baseline renal compromise 7
Specific Considerations
- The kidney transplant literature provides guidance: reduce immunosuppression temporarily if systemic HSV infection develops, though this principle applies differently to corneal transplant patients who are not systemically immunosuppressed 7
Critical Management Principles
Contraindications During Prophylaxis
- Topical corticosteroids must be used cautiously and only after epithelial healing is complete, as they potentiate HSV replication 8, 9, 5
- Never use corticosteroids for active epithelial disease even while on prophylactic antivirals 8, 9
Monitoring Requirements
- Schedule follow-up within 1 week initially, then regularly throughout the first year 8, 9
- Perform visual acuity measurement and slit-lamp biomicroscopy at each visit to detect early recurrence 8, 9
- Monitor for signs of graft rejection, which occurred in 15.8% of prophylaxis patients but was successfully treated medically 3
Common Pitfalls to Avoid
Treatment Errors
- Do not use oral antivirals as monotherapy for active epithelial keratitis if it develops during prophylaxis; combination with topical antivirals is mandatory 8, 9, 5
- Do not abruptly discontinue prophylaxis at 12 months in high-risk patients without careful consideration of extended therapy 3
- Do not assume prophylaxis provides complete protection; breakthrough infections can occur (8.3% even while on therapy) 3