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Herpetic Disease of the Cornea

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Name: Austin D. Bohner, 2nd Year Medical Student, University of Utah, School of Medicine

Figure 1: A herpetic dendrite highlighted with a fluorescein stain.

Description:
Herpetic disease of the cornea from herpes simplex virus (HSV), also known as HSV keratitis, is a major cause of corneal scarring and blindness worldwide.1 Correct identification of HSV keratitis is important as misdiagnosis can result in a delay in treatment—or worse, inappropriate treatment with topical glucocorticoids which can exacerbate HSV infections.2

Diagnosis of HSV keratitis is based on clinical history and physical examination. Laboratory tests are usually not necessary, with slit lamp findings being typically sufficient. The exam findings include conjunctival injection near the limbus, a decrease in corneal sensation and characteristic dendritic lesions of the cornea that stain with fluorescein (see image 1).3 When deeper stromal tissue is involved corneal edema may also be found in addition to the above.

HSV-1 accounts for the majority of ocular HSV keratitis infections and is endemic in human populations, with the majority of people being exposed to the virus by middle age. The virus is transmitted through direct contact of mucosal membranes. The bulk of ocular disease is represented by reactivation of the virus from its latency in sensory neurons (usually the trigeminal nerve ganglion in ocular cases) rather than from primary infection. History of HSV infection and reactivation can be useful in making a clinical diagnosis. Most ophthalmic HSV cases occur unilaterally, with recurrences affecting the same eye. Ocular HSV reactivation has been associated with sun exposure, stress, ultraviolet laser treatment, topical ocular medication (epinephrine, beta-blockers and prostaglandins), and immunosuppression drugs such as glucocorticoids.

Treatment:
HSV Keratitis warrants prompt referral to an eye care specialist, as the treatment varies based on the depth of the involvement of the cornea as well as integrity of the overlying epithelium.  Topical and oral antiviral medications are frequently used and can shorten the duration of the disease though each has its limitations.4

Antiviral Dose Additional Notes
Trifluorothymidine 1% (trifluridine, Viroptic) One drop every two hours (8-9 doses daily) Treatment time is limited by epithelial toxicity
Topical Ganciclovir 0.15% gel (Zirgan) one drop five times daily until epithelial healing occurs and then three times daily for one week Less corneal epithelial toxicity, maybe better tolerated for long term use compared to trifluridine
Topical Acyclovir 3% Available in Europe but not in the US
Oral acyclovir 400mg five times daily. Avoids epithelial toxicity, though acyclovir resistant strains of HSV exist

References:

  1. Liesegang TJ. Herpes simplex virus epidemiology and ocular importance. Cornea. 2001;20(1):1-13.
  2. Benz MS, Glaser JS, Davis JL. Progressive outer retinal necrosis in immunocompetent patients treated initially for optic neuropathy with systemic corticosteroids. Am J Ophthalmol. 2003;135(4):551-553.
  3. Teng CC. Images in clinical medicine. Corneal dendritic ulcer from herpes simplex virus infection. N Engl J Med. 2008;359(17):e22.
  4. A controlled trial of oral acyclovir for iridocyclitis caused by herpes simplex virus. The Herpetic Eye Disease Study Group. Arch Ophthalmol. 1996;114(9):1065-1072.