Treatment of viral (herpes simplex) stromal keratitis

1. Stromal keratitis with intact epithelium (immune/disciform type)

• Topical steroid: prednisolone acetate 1% (or dexamethasone 0.1%), 4 to 8 times daily at the start. Taper slowly over weeks to months, and often longer. Some patients need low-dose maintenance indefinitely (- Wills Eye Manual, p. 227).
• Antiviral cover: oral acyclovir 400 mg twice daily, valacyclovir 500 mg once or twice daily, or famciclovir 250 mg once or twice daily (- Wills Eye Manual, p. 227). Kanski suggests topical antiviral cover given in parallel with the steroid.
• Tapering (Kanski):
  • Reduce steroid and antiviral together over at least 4 weeks.
  • Prednisolone 0.5% once daily is usually a safe point to stop antiviral cover.
  • Some patients need weaker steroids long term, such as fluorometholone 0.1% or loteprednol 0.2% on alternate days.
  • Try periodically to stop the steroid altogether (- Kanski's Clinical Ophthalmology, 10th ed., p. 238).
• Keep steroid intensity and duration to the minimum that controls the inflammation, and monitor IOP.

2. Stromal keratitis with epithelial ulceration

• Limited topical steroid: prednisolone acetate 1% twice daily.
• Therapeutic oral antiviral for 7 to 10 days:
  • Acyclovir 800 mg 3 to 5 times daily, or
  • Valacyclovir 1 g 2 to 3 times daily, or
  • Famciclovir 500 mg 2 to 3 times daily.
• Then reduce to the prophylactic dose for as long as the topical steroid continues (- Wills Eye Manual, p. 227).
• Kanski suggests keeping the steroid as low as possible and using a more frequent antiviral regimen, for example a topical antiviral 5 times daily with steroid 2 to 3 times daily. Oral antivirals may help, but their efficacy here is not established.

3. Necrotizing stromal keratitis

4. Endothelial keratitis

Adjuncts and special points

• Cycloplegic (for example cyclopentolate 1%) for comfort and when uveitis is present.
• Raised IOP: use aqueous suppressants. Avoid prostaglandin analogues, which are associated with HSV recurrence and uveitis. Steroid response can contribute to the rise.
• Topical ciclosporin 0.05% can help when there is epithelial ulceration, and it helps taper steroids, for example with steroid-related IOP rise (- Kanski, p. 238).
• Oral steroids are occasionally used as an adjunct in severe stromal inflammation.
• Antibiotic ointment (for example erythromycin) if an epithelial defect is present.
• Non-healing ulcer: think of antiviral toxicity, bacterial or fungal coinfection, Acanthamoeba, or neurotrophic keratopathy. Stop the topical antiviral if it is toxic. A persistent ulcer with stromal keratitis is commonly due to the underlying inflammation, which needs cautious steroid therapy (- Wills Eye Manual, p. 227).
• Perforation: tissue adhesive or keratoplasty.
• Scarring and neovascularization: fine needle diathermy or laser for established corneal neovascularization. Optical keratoplasty later, once the eye has been quiet.
• Prophylaxis: long-term oral antivirals reduce recurrences, including keratouveitis.
• Contraindication: topical steroids are contraindicated in infectious epithelial disease unless antiviral-covered, as in the ulcerated regimen above.

Recent evidence

• Steroid plus acyclovir worked better than acyclovir alone.
• Oral and topical acyclovir resolved disease in a similar time.
• Steroid benefit was greater with a tapered course lasting at least 10 weeks.
• Ciclosporin A, tacrolimus, and flurbiprofen looked like safe and effective alternatives, but the evidence is limited.