Herpes Simplex Keratitis

Herpes simplex keratitis is a recurrent corneal infection or immune reaction caused by reactivation of herpes simplex virus type 1 (rarely type 2) from latency in the trigeminal ganglion. It is the leading infectious cause of corneal blindness in developed countries.

• Primary ocular infection is a follicular blepharoconjunctivitis, often with vesicular lid lesions, in a child or young adult.
• Recurrent disease occurs in about 25 percent within 2 years and up to 50 percent over longer follow up, triggered by stress, fever, ultraviolet light, trauma, surgery, immunosuppression, and menstruation.
• Forms: epithelial (infectious), neurotrophic, stromal (immune or necrotising), endothelial (disciform keratitis, endotheliitis, and linear endotheliitis), and combined.

• Redness, tearing, photophobia, foreign body sensation, and blurred vision; pain is mild if sensation is reduced.
• Epithelial: branching dendritic ulcer with terminal bulbs (swollen epithelial edges stain with rose Bengal and the base with fluorescein) or a larger geographic ulcer; reduced corneal sensation.
• Stromal: necrotising (cheesy infiltrate and melt, vascularisation) or immune (interstitial keratitis, ring infiltrate, scarring).
• Endothelial: disc shaped stromal oedema with keratic precipitates beneath the lesion (disciform), anterior chamber inflammation, and raised intraocular pressure.
• Neurotrophic: persistent epithelial defect with smooth rolled edges that fails to heal.
• Recurrent scarring, vascularisation, thinning, and visual loss.

• Mostly clinical. Fluorescein shows a dendritic ulcer; test corneal sensation (decreased in herpetic disease).
• Confirmation when needed (atypical, steroid treated, or neonatal disease): PCR of scrapings or swabs, viral culture, or immunofluorescence.
• Measure intraocular pressure and examine for iritis; consider HIV testing in atypical, bilateral, or severe disease in young adults.
• Differential diagnosis: herpes zoster keratitis (dermatomal rash, pseudodendrites), healing abrasion, Acanthamoeba and bacterial or fungal keratitis, toxic keratopathy from drops, and contact lens complications.

• Epithelial keratitis (dendritic or geographic):
  • Topical ganciclovir 0.15 percent gel five times daily until healed (about 7 to 10 days), then three times daily for 1 week; or aciclovir 3 percent ointment five times daily; or trifluridine 1 percent drops 9 times daily until healed then reduced, with a maximum of 2 to 3 weeks (toxicity).
  • Oral aciclovir 400 mg five times daily for 7 to 10 days or valaciclovir 500 mg twice daily is an alternative or addition (equal efficacy), and is preferred in children, in those who cannot use drops, in immunocompromised patients, and when both eyes are involved.
  • Gentle debridement of the epithelium with a cotton bud shortens the course.
  • Avoid topical corticosteroids in active epithelial disease.
• Stromal keratitis without ulceration: topical corticosteroid (prednisolone acetate 1 percent 4 to 6 times daily) with antiviral cover (aciclovir 400 mg twice daily or valaciclovir 500 mg once daily), tapered slowly over 10 to 12 weeks or longer; with an epithelial defect, give full dose antivirals first.
• Endothelitis and disciform keratitis: topical steroid with oral aciclovir 400 mg three to five times daily (or valaciclovir 500 mg three times daily) for 7 to 10 days, then reduce; treat raised pressure with timolol 0.5 percent twice daily (avoid prostaglandin analogues).
• Necrotising stromal keratitis: oral antiviral plus steroid under close observation, and consider keratoplasty for perforation.
• Neurotrophic ulcer: preservative free lubricants, bandage lens, autologous serum drops, topical recombinant nerve growth factor (cenegermin 20 micrograms/mL six times daily for 8 weeks), amniotic membrane, and tarsorrhaphy.
• Cycloplegic (cyclopentolate 1 percent twice daily) for iritis and pain.
• Prophylaxis against recurrence: oral aciclovir 400 mg twice daily or valaciclovir 500 mg once daily for at least 12 months after any recurrent disease; this halves the recurrence rate. Review need yearly; stop and observe after a trial.
• Keratoplasty after 6 to 12 months of quiescence for scars, with continued antiviral prophylaxis (graft failure and recurrence are risks); Cross linking and rigid lenses are used for irregular scars.
• Complications: scarring, neovascularisation, perforation, secondary bacterial or fungal infection, glaucoma, cataract, and amblyopia in children.