Herpes Simplex Keratitis Clinical Presentation

Updated: Dec 15, 2016
  • Author: Jim C Wang (王崇安), MD; Chief Editor: Andrew A Dahl, MD, FACS  more...
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Patients with herpes simplex virus (HSV) keratitis may report the following:

  • Pain
  • Photophobia
  • Blurred vision
  • Tearing
  • Redness

A history of prior episodes in patients with recurrent disease may exist. Patients with ocular HSV who have previous stromal involvement have a significantly higher risk of subsequent stromal keratitis; in contrast, patients with epithelial keratitis alone have no increased rate of recurrent HSV disease.


Physical Examination

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. [14, 15] After primary infection, recurrent disease may involve any or all layers of the cornea.

Since infectious responses and immune responses are responsible for ocular disease, it is better to classify the keratitis based on the anatomic location (ie, epithelial, stromal, endothelial) and the pathophysiology (ie, infectious, immune, neurotrophic). As a result, the following 4 major categories of HSV keratitis exist [16] :

  • Infectious epithelial keratitis
  • Neurotrophic keratopathy
  • Stromal keratitis
  • Endotheliitis

Infectious epithelial keratitis

Infectious epithelial keratitis is characterized by the following lesions:

  • Corneal vesicles
  • Dendritic ulcers
  • Geographic ulcers
  • Marginal ulcers

Corneal vesicles

The earliest sign of active viral replication in the corneal epithelium is the development of small, raised, clear vesicles that are analogous to the vesicular eruptions seen in mucocutaneous herpes infection elsewhere in the body. These infectious epithelial vesicles are rarely seen or recognized during a patient's first presentation. However, in patients with a known history of HSV keratitis, infectious epithelial vesicles may be observed even in the absence of any clinical symptoms.

Within several hours, the corneal vesicles coalesce into a dendritic pattern. In some patients, particularly patients who are immunocompromised, the recurring infection may be arrested at the vesicle stage. As the disease progresses, a central epithelial defect develops. The resultant dendritic ulcer is the most common presentation of HSV keratitis.

Dendritic ulcers

This is the most common presentation of HSV keratitis. Prominent features of a dendritic ulcer include a linear branching pattern within the corneal epithelium with terminal bulbs, swollen epithelial borders that contain live viruses, and central ulceration through the basement membrane. (See the images below.)

Herpes simplex virus dendritic ulcer stained with Herpes simplex virus dendritic ulcer stained with rose bengal.
Herpes simplex virus dendritic ulcer stained with Herpes simplex virus dendritic ulcer stained with fluorescein.
Large paracentral herpes simplex virus dendritic u Large paracentral herpes simplex virus dendritic ulcer.
Recurrent herpes simplex virus dendritic ulcer wit Recurrent herpes simplex virus dendritic ulcer with an adjacent stromal scar.
Healing herpes simplex virus dendritic ulcer. Healing herpes simplex virus dendritic ulcer.

Geographic ulcers

If the infectious ulcer enlarges, its shape is no longer linear. It is then referred to as a geographic ulcer. The swollen epithelial cells and the scalloped or geographic borders differentiate this infectious lesion from the smooth borders of a neurotrophic ulcer. (See the image below.)

Herpes simplex virus geographic ulcer. Herpes simplex virus geographic ulcer.

Marginal ulcers

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

The earliest signs of neurotrophic keratopathy include an irregular corneal surface and punctate epithelial erosions. These erosions may progress to a persistent epithelial defect and eventual stromal ulceration.

In contrast to the irregular shape and scalloped borders of an infectious geographic ulcer, a neurotrophic ulcer is typically oval with smooth borders and often lies within the interpalpebral fissures, located in the central or inferior paracentral area of the cornea. Decreased corneal sensitivity helps confirm the diagnosis.

Complications of neurotrophic keratopathy include stromal scarring, neovascularization, necrosis, and perforation. (See the images below.)

Neurotrophic keratopathy. Neurotrophic keratopathy.
Large neurotrophic ulcer. Large neurotrophic ulcer.

Stromal keratitis

Corneal stromal inflammation may be the primary manifestation of HSV keratitis, or it may be seen secondary to infectious epithelial keratitis, neurotrophic keratopathy, or endotheliitis. [17] Stromal keratitis develops in 25% of patients with epithelial disease. [18]

The 2 forms of primary stromal involvement are necrotizing stromal keratitis and immune stromal keratitis (ISK).

Necrotizing stromal keratitis

Necrotizing stromal keratitis, characterized by dense stromal infiltrate, ulceration, and necrosis, is believed to result from viral replication in stromal keratocytes and severe host inflammatory response. This destructive intrastromal inflammation may lead to thinning and perforation within a short period.

Immune stromal keratitis

ISK, also known as nonnecrotizing stromal keratitis and interstitial keratitis, is a common manifestation of chronic, recurrent ocular HSV disease; ISK may present clinically with focal, multifocal, or diffuse cellular infiltrates; immune rings; neovascularization of the corneal stroma; or ghost vessels at any level of the cornea. (See the images below.)

Active immune stromal keratitis. Active immune stromal keratitis.
Inactive immune stromal keratitis. Inactive immune stromal keratitis.


The inflammation directed at the endothelium may cause endothelial decompensation and overlying stromal and epithelial edema.

Clinical signs of endotheliitis include keratic precipitates (KP), overlying stromal and epithelial edema, and absence of stromal infiltrate or neovascularization. A mild to moderate iritis is frequently seen. Patients present with pain, photophobia, and injection.

HSV endotheliitis can be classified as follows:

  • Disciform endotheliitis - Presents with a round area of corneal edema in a central or paracentral region with a clear demarcation between involved and uninvolved cornea (see the image below)
  • Diffuse endotheliitis - Shows scattered KP and may stem from a previous disciform area of involvement
  • Linear endotheliitis - Appears as a line of KP progressing centrally from the limbus, with peripheral corneal edema trailing the migrating line of KP; the line of KP can be sectoral or circumferential and may take on either a straight or serpiginous pattern
    Disciform endotheliitis with secondary stromal ulc Disciform endotheliitis with secondary stromal ulceration.