Excerpt from Keratitis, Herpes Simplex

Synonyms, Key Words, and Related Terms: herpetic keratitis, HSV keratitis, neurotrophic ulcer, metaherpetic ulcer, trophic ulcer, interstitial keratitis, stromal keratitis, disciform keratitis, keratouveitis, herpetic endotheliitis

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Background: Herpes simplex virus (HSV) keratitis encompasses a variety of disease processes that HSV can cause in the human cornea. A variety of clinical manifestations of both infectious disease and immunologic disease, such as infectious epithelial keratitis, neurotrophic keratopathy, necrotizing stromal keratitis, immune stromal keratitis (ISK), and endotheliitis, can affect all levels of the cornea. Although more common as a manifestation of recurrent HSV infection, HSV keratitis may also be seen during a primary infection.

Pathophysiology: HSV is a DNA virus that commonly infects humans. Infection is spread by direct contact of infectious secretions with epidermis or mucous membrane. HSV type 1 (HSV-1) is primarily responsible for orofacial and ocular infections, and HSV type 2 (HSV-2) generally is transmitted sexually and causes genital infections. HSV-2 may rarely infect the eye by means of direct contact with infectious genital secretions and occasionally is transmitted to neonates as they pass through the birth canal of a mother with genital HSV-2 infection.

Primary HSV-1 infection occurs most commonly in the mucocutaneous distribution of the trigeminal nerve. After the primary infection, the virus spreads from the infected epithelial cells to nearby sensory nerve endings and is transported along the nerve axon to the cell body located in the trigeminal ganglion. Then, the virus genome enters the nucleus of a neuron, where it persists indefinitely in a latent state. Primary infection of any of the 3 branches (ie, ophthalmic, maxillary, mandibular) of cranial nerve V can lead to latent infection of nerve cells in the trigeminal ganglion. Interneuronal spread of HSV within the ganglion allows patients to develop ocular disease without ever having had primary ocular HSV infection.

Recurrent HSV infection traditionally has been thought of as reactivation of virus in the sensory ganglion, which migrates down the nerve axon to produce a lytic infection in ocular tissue. Recent evidence suggests that the virus may subsist latently within corneal tissue, serving as a potential source of recurrent disease and also donor-derived HSV in transplanted corneas.

Frequency:

In the US: Approximately 20,000 new cases of ocular HSV occur in the United States annually, and more than 28,000 reactivations occur in the United States annually. Of the US population, a history of external ocular HSV infection is present in 0.15%. HSV keratitis is one of the most frequent causes of corneal blindness in the United States with 500,000 people experiencing HSV-related ocular disease.

Mortality/Morbidity: HSV keratitis is one of the most frequent causes of corneal blindness in the United States and a leading indication for corneal transplantation.

Age: Most HSV recurrent eye disease occurs in adults. However, herpetic keratitis in children almost always involves the corneal epithelium and is marked by a disproportionate risk of binocular disease, a high recurrence rate, and amblyopia as a complication.