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Herpes Simplex Keratitis Clinical Presentation

  • Author: Jim C Wang (王崇安), MD; Chief Editor: Hampton Roy, Sr, MD  more...
 
Updated: Dec 07, 2015
 

History

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.

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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 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; 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.

Endotheliitis

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.
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Contributor Information and Disclosures
Author

Jim C Wang (王崇安), MD Vitreo-Retinal and Cornea/Anterior Segment Subspecialist, Department of Ophthalmology, Kaiser Permanente Fontana Medical Center

Jim C Wang (王崇安), MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, American Society of Cataract and Refractive Surgery

Disclosure: Nothing to disclose.

Coauthor(s)

David C Ritterband, MD, FACS Assistant Director of Cornea Service, New York Eye and Ear Infirmary; Clinical Professor of Ophthalmology, Icahn School of Medicine at Mount Sinai

David C Ritterband, MD, FACS is a member of the following medical societies: Alpha Omega Alpha, Association for Research in Vision and Ophthalmology, American Academy of Ophthalmology, American College of Surgeons, International Society of Refractive Surgery

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Acknowledgements

Kerry Assil, MD Medical Director and CEO, The Sinskey Eye Institute

Kerry Assil, MD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, Association for Research in Vision and Ophthalmology, and Contact Lens Association of Ophthalmologists

Disclosure: Nothing to disclose.

Kilbourn Gordon III, MD, FACEP Urgent Care Physician

Kilbourn Gordon III, MD, FACEP is a member of the following medical societies: American Academy of Ophthalmology and Wilderness Medical Society

Disclosure: Nothing to disclose.

Robert H Graham, MD Consultant, Department of Ophthalmology, Mayo Clinic, Scottsdale, Arizona

Robert H Graham, MD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, and Arizona Ophthalmological Society

Disclosure: Medscape/WebMD Salary Employment

Anisha Judge, MD Consulting Staff, Department of Ophthalmology, Kaiser Permanente at West Los Angeles Medical Center

Disclosure: Nothing to disclose.

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Christopher J Rapuano, MD Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Institute

Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Cornea Society, Eye Bank Association of America, and International Society of Refractive Surgery

Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; Alcon Honoraria Speaking and teaching; RPS Ownership interest Other; Bausch & Lomb Honoraria Speaking and teaching; Merck Consulting fee Consulting; Bausch & Lomb Consulting; Merck Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Jack L Wilson, PhD Distinguished Professor, Department of Anatomy and Neurobiology, University of Tennessee Health Science Center College of Medicine

Jack L Wilson, PhD is a member of the following medical societies: American Association of Anatomists, American Association of Clinical Anatomists, and American Heart Association

Disclosure: Nothing to disclose.

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Herpes simplex virus dendritic ulcer stained with rose bengal.
Herpes simplex virus dendritic ulcer stained with fluorescein.
Large paracentral herpes simplex virus dendritic ulcer.
Recurrent herpes simplex virus dendritic ulcer with an adjacent stromal scar.
Healing herpes simplex virus dendritic ulcer.
Herpes simplex virus geographic ulcer.
Neurotrophic keratopathy.
Large neurotrophic ulcer.
Active immune stromal keratitis.
Inactive immune stromal keratitis.
Disciform endotheliitis with secondary stromal ulceration.
 
 
 
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