eMedicine Specialties > Ophthalmology > Cornea

Herpes Simplex

Robert H Graham, MD, Senior Associate Consultant, Department of Ophthalmology, Mayo Clinic, Scottsdale, Arizona
Kerry Assil, MD, Medical Director and CEO, The Sinskey Eye Institute
Contributor Information and Disclosures

Updated: Jun 18, 2006

Introduction

Background

Herpes simplex virus (HSV), a large complex DNA virus, commonly infects the skin and the mucous membranes in the regions of the mouth, genitalia, and eye. Two antigenically related strains of HSV can be distinguished, type 1 and type 2. Type 1 most commonly is associated with infections of the orofacial area and the ocular surface, while type 2 causes genital disease.

Pathophysiology

Infection is spread by direct contact of skin or mucous membranes to infected secretions. The initial attack generally is self-limited and often is subclinical. However, herpetic disease is recurrent, and a wide range of clinical manifestations can result from an infection with this agent. The most common site of primary infection in humans is the skin and the mucous membrane innervated by the trigeminal nerve. The virus is transported via the nerve axon to its cell body in the sensory ganglion where it persists in a latent state until reactivation. Some indication exists that the human cornea also may harbor latent virus. Recurrent disease is the result of reactivation of this latent virus.

Frequency

United States

Of adults in the US, 50-90% have antibodies to HSV type 1, indicating previous exposure to the virus. Incidence of ocular HSV infection is approximately 0.15%.

Mortality/Morbidity

HSV keratitis is the most frequent cause of corneal blindness in the US, with reports of any visual disability as high as 40%.

Sex

This condition has a slightly higher male predominance.

Age

The mean age of presentation is in the late fifth to early sixth decade of life.

Clinical

History

• Patients may present with the following:
  • Red eye
  • Pain
  • Photophobia
  • Tearing
  • Decreased vision
  • Skin (eg, eyelid) rash
• History of previous episodes
• History of corneal abrasion; contact lens wear; or previous nasal, oral, or genital sores

Physical

Primary herpes infection of the eye typically is a unilateral blepharoconjunctivitis, characterized by vesicles on the skin of the lids, follicular conjunctivitis, preauricular adenopathy, and, sometimes, punctate keratitis. After primary infection, recurrent disease may involve any or all layers of the cornea. Since both infectious and immune responses are responsible for ocular disease, it is better to classify the keratitis based upon both the anatomical location (ie, epithelial, stromal, endothelial) and on the pathophysiology (ie, infectious, immune, neurotrophic). Based on this mechanism of classification, 4 major categories of herpes simplex keratitis exist.

• Infectious epithelial keratitis
  • Corneal vesicles: These are minute, raised, clear vesicles in the corneal epithelium that correspond to the vesicles on the skin surface. Within a few hours, these vesicles coalesce and erupt to form a dendritic or geographic ulcer. In immunocompromised individuals, they may coalesce without eruption, forming a raised dendrite without ulceration that shows reverse staining with fluorescein.
  • Dendritic ulcer: This is the most common presentation. The lesion reveals a linear branching pattern with terminal bulbs and heaped borders that contain live virus.
  • Geographic ulcer: As the dendritic ulcer widens, it looses its linear pattern and assumes a geographic form, with scalloped edges and heaped borders. This tends to occur in patients immunocompromised by the use of topical steroids or diseases (eg, HIV).
  • Marginal ulcer: When a dendrite develops close to the limbus its anterior stroma gets infiltrated by leukocytes from the limbal blood vessels, resulting in a dendritic lesion overlying an anterior stromal infiltrate. This often can be mistaken for a marginal staphylococcal ulcer.
• Neurotrophic keratopathy: This is neither infectious nor immune in nature, but the result of abnormal corneal innervation and poor tear production. A nonhealing, oval epithelial defect develops. This defect has smooth borders in contrast to geographic ulcers, which have scalloped borders. Over time, stromal ulceration and opacification develop under the epithelial defect. Corneal perforation can occur.
• Stromal keratitis develops in 25% of patients with epithelial disease.
  • Necrotizing stromal keratitis presents as necrosis and dense infiltration of the stroma, with an overlying epithelial defect. This is a result of direct stromal invasion by the virus. This entity may resemble bacterial or fungal keratitis. The use of topical corticosteroids without antiviral coverage is a risk factor in developing necrotizing keratitis.
  • Nonnecrotizing stromal keratitis also is called immune stromal keratitis and interstitial keratitis. An antigen antibody inflammatory response is believed to be triggered by retained viral antigens in the corneal stroma. Stromal infiltration with or without neovascularization occurs. The overlying epithelium is intact, unless a concomitant infectious or neurotrophic keratitis is present.
• Endotheliitis is an immune reaction at the level of the endothelium that may occur months to years after an episode of infectious keratitis. Characteristic findings include keratic precipitates (KP), overlying stromal and possibly epithelial edema, and iritis. Unlike stromal edema from primary stromal keratitis, no stromal infiltrates or neovascularization is present. Patients present with pain, photophobia, and injection. Based on the distribution of the KP, 3 recognized forms of endotheliitis can be identified.
  • Disciform endotheliitis presents as a round area of central or paracentral stromal edema overlying an area of KP.
  • Diffuse endotheliitis presents with scattered KP and diffuse edema.
  • Linear endotheliitis: Keratic precipitates develop in the peripheral cornea and proceed centrally. Associated corneal edema is isolated to the peripheral corneal stroma and epithelium.

Causes

Primary herpes keratitis is a ubiquitous disease with no apparent risk factors. Recurrent infection due to reactivation, and occasionally reinfection, can be triggered by many events, including the following:

• Stress
• Sunlight
• Fever
• Menstruation
• Trauma including surgical trauma (eg, lamellar keratoplasty, peripheral iridectomy)
• Antiglaucoma medication latanoprost, a prostaglandin analogue because of its ability to induce release of endogenous prostaglandins in the iris and ciliary muscles can induce reactivation of HSV keratitis

References

• Chlamydia
• Conjunctivitis, Allergic
• Conjunctivitis, Viral
• Contact Lens Complications
• Corneal Abrasion
• Corneal Graft Rejection
• Herpes Zoster
• Keratitis, Bacterial
• Keratitis, Fungal
• Keratitis, Interstitial
• Keratoconjunctivitis, Epidemic
• Ocular Manifestations of Syphilis

• Sexually Transmitted Diseases Center
• Teeth and Mouth Center
• Genital Herpes Overview
• Genital Herpes Causes
• Genital Herpes Symptoms
• Genital Herpes Treatment
• Oral Herpes Overview