Herpes Simplex Keratitis

Signs and Symptoms

The keratitis caused by the herpes simplex virus (HSV) typically presents as a unilateral "red eye" with a variable degree of pain or ocular irritation. Photophobia and epiphora are common; however, vision may or may not be affected, depending upon the location and extent of the corneal lesion. You may see a vesicular skin rash and follicular conjunctivitis with the initial infection, but these are less common with recurrent HSV. A more common sign is secondary uveitis. A dendritic corneal ulcer is the hallmark sign of HSV infection, accompanied by stromal keratitis in more severe presentations. These ulcers may begin as nondescript punctate keratopathies, but quickly coalesce to form the familiar branching patterns which stain brightly with sodium fluorescein dye. Because the virus invades and compromises the epithelial cells surrounding the ulcer, the leading edges (the so-called "terminal end-bulbs") will stain with rose bengal or lissamine green.

Pathophysiology
Herpes simplex is actually the most common virus found in humans. It is transmitted via bodily fluids, usually saliva, and may affect the skin and mucous membranes of the host. Primary infections occur most often in children between the ages of 6 months and 5 years. It typically manifests as a vesicular rash, sometimes affecting the skin of the lids but more commonly resulting in a "fever blister" or "cold sore" in or around the mouth. After resolution, the virus remains dormant in the body of the host and can be reactivated in as many as 25 percent of cases by fever, trauma, stress, immunosuppressive agents or exposure to ultraviolet radiation. In recurrent attacks, the virus invades and replicates within the corneal epithelium. As the cells die, an ulcerative keratitis results. Disciform stromal scarring, conjunctivitis and uveitis are common sequelae.

Management
Corneal epithelial disease secondary to HSV infection must be managed aggressively and quickly to prevent deeper penetration. The treatment of choice is topical trifluridine 1% given at two hour intervals, nine times daily. As the dendrites begin to regress, taper the dosage to q3-4h until the lesion resolves completely (usually in seven to 10 days). At this point, however, have the patient continue the medication t.i.d. for another week to ensure suppression of the virus. Some practitioners recommend debriding the ulcer bed to remove active virus cells, but this has not been definitively proven to hasten resolution or improve the final visual outcome. You may also need to prescribe a cycloplegic (homatropine 2% t.i.d.-q.i.d. or scopolamine 0.25% b.i.d.-q.i.d.), again depending upon the severity of the uveitic response. Avoid topical steroids in cases of active epithelial HSV keratitis. Studies show that the virus replicates more rapidly in the presence of steroids, prolonging the course of the disease. The use of oral acyclovir (400mg 5x/day) or another oral antiviral for recalcitrant ulcers has yet to be proven clinically significant. However, it has been shown recently that the use of oral acyclovir 400mg q.d. significantly reduces the recurrence of herpes simplex keratitis in imunocompetent patients. At this point, consider using oral prophylaxis therapy only in patients with confirmed recurrent HSV keratitis or patients on initial presentation who request it after being thoroughly educated. A new development in the management of herpes simplex keratitis has come in the form of topical acyclovir ointment (Zovirax). Place the ointment in the lower cul-de-sac five times per day at four hour intervals. At this point, toxicity seems to be low.

Clinical Pearls

Suspect HSV in cases of unilateral adult-onset red eye that is inconsistent with the symptoms (i.e., the patient seems to be in far less discomfort than the appearance of the eye would indicate), particularly if the individual has a previous history of similar "infections." Each recurrent attack induces greater damage to the corneal nerves, leading to hypoesthesia (reduced corneal sensitivity). The cotton-wisp test for corneal sensitivity is invariably positive in cases of HSV keratitis; use it whenever in doubt. Also, consider a history of prolonged sun exposure or extreme psychological stress to be significant in diagnosing HSV.