Herpes Keratitis

Definition: An infection of the cornea caused by the herpes simplex virus (HSV).

Epidemiology:

• Most frequent cause of corneal blindness in the United States
• Most common source of infectious blindness in the Western world. Approximately 2 million people worldwide have impaired vision from herpetic eye disease (Farooq 2012)

Pathophysiology:

• Primary infection: occurs most commonly in the mucocutaneous or ocular distribution of the trigeminal nerve, and can present as a non-specific upper respiratory infection
• Latency: the virus spreads from the infected epithelial cells to the cell body in the trigeminal ganglion where the virus persists indefinitely in a latent state
• Reactivation: interneuronal spread of HSV within the ganglion allows patients to develop subsequent ocular disease without ever having had primary ocular HSV infection
  

  Corneal Layers – emaze.com

• HSV keratitis can be divided into 3 types: epithelial, stromal, and endothelial (White 2014)
  • Epithelial: caused by actively replicating virus and occurs in the outermost layer of the cornea
  • Stromal: caused by immune mechanisms and occurs in deeper layers
  • Endothelial: caused by chronic inflammation and occurs in deeper layers
• Sequelae: Recurrent HSV keratitis can cause corneal scarring, ulceration, and perforation, ultimately leading toastigmatism and permanent vision loss.

Symptoms:

• Eye pain
• Corneal injection
• Visual changes (blurry vision, decreased visual acuity)
• Tearing
• Discharge
• Photophobia

Physical exam:

• Visual acuity should be performed in all patients
• Fluorescein staining
  • May reveal dendritic lesions (linear branching patterns with terminal bulbs)
  • If the lesion enlarges, it can form a geographic ulcer
• Slit lamp exam
  

  Geographic Ulcer – lasereyeconsultant.co.uk

  • Used to identify disease in deeper (stromal + endothelial) layers
  • Stromal disease shows up primarily as an inflammatory infiltrate with stromal edema, vascularization, and scarring

Diagnostics:

• The diagnosis of HSV keratitis is based on clinical eye exam.
• In the absence of dendritic lesions, decreased corneal sensation should increase concern for herpetic keratitsis (Weiner 2013)
• Viral culture
  • Gold standard test
  • Impractical in the ED: expensive, delayed
• Ophthalmology may perform additional testing, such as viral culture/PCR and Tzanck smear, to confirm the diagnosis but these are not routinely recommended (Welder 2012)

• Pitfalls: these tests are only positive when live virus is present, and cannot be used to diagnose stromal keratitis (White 2014)

Management:

• Most cases of HSV epithelial keratitis resolve spontaneously within 3 weeks. However, the American Academy of Ophthalmology recommends treatment of epithelial keratitis to prevent recurrence and progression to stromal or endothelial keratitis.
• Epithelial keratitis:
  • Trifluridine 1% solution: 1 drop Q2hours for 7 days OR
  • Ganciclovir 0.15% gel: five times per day
  • Oral antiviral agents (not FDA approved, but equal efficacy in studies) (Wilhelmus 2010)
  • Corneal debridement
• Stromal and endothelial keratitis:
  • Urgent referral to ophthalmology
  • Topical corticosteroid
  • Oral antiviral agents for 10 weeks as prophylaxis reduces the rate of recurrent herpetic keratitis (Wilhelmus 1999)

Take Home Points:

• Fluorescein is an essential tool in the diagnosis of HSV keratitis
• Identifying the type of HSV keratitis is crucial, as it will guide treatment
• Update tetanus vaccination
• Consult ophthalmology if there is concern for HSV keratitis as these patients require close and frequent follow-up

References:

Farooq AV et al. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol 2012; 57(5):448-462. PMID: 3652623

Wilhelmus KR et al. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial     keratitis. Cochrane Database Syst Rev 2010; (12): CD002898. PMID: 4739528

Weiner et al. Demystifying the ocular herpes simplex virus. American Academy of Ophthalmology. Link

McDonald et al. Management of epithelial herpetic keratitis: an evidence based algorithm. Link

Welder et al. Herpes simplex keratitis. University of Iowa Health Care. Link

Wilhelmus KR et al. Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthamology 1999; 101(12):1883-1896. PMID: 7997324

Chan RV et al. Herpes simplex keratitis – Latin America. American Academy of Ophthalmology. Link

White et al. Herpes simplex keratitis: A treatment guideline – 2014. Link