AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

Because of its potential to permanently impair vision or perforate the eye, a corneal ulcer is considered an ophthalmologic emergency. While corneal ulcers occasionally may be sterile, most are infectious in etiology. Ulcers due to viral infection occur on a previously intact corneal epithelium. Bacterial corneal ulcers generally follow a traumatic break in the corneal epithelium, thereby providing an entry for bacteria. The traumatic episode may be minor, such as a minute abrasion from a small foreign body, or it may result from such causes as tear insufficiency, malnutrition, or contact lens use. Increased use of soft contact lenses in recent years has led to a dramatic rise in the occurrence of corneal ulcer, particularly due to Pseudomonas aeruginosa. In addition, with the introduction of topical corticosteroid drugs in the treatment of eye disease, fungal corneal ulcers have become more common.

Peripheral ulcerative keratitis (PUK) is a complication of rheumatoid arthritis (RA) that can lead to rapid corneal destruction (corneal melt) and perforation with loss of vision.

Mooren ulcer is a rapidly progressive, painful, ulcerative keratitis, which initially affects the peripheral cornea and may spread circumferentially and then centrally. Mooren ulcer can only be diagnosed in the absence of an infectious or systemic cause.

For a CME activity, see AAO 2007: Cornea and External Disease.

Pathophysiology

Risk factors include contact lens use, trauma, ocular surface disease, and ocular surgery. Overnight contact lens wear has been shown to be associated with increased risk. Other identified risk factors include age, gender smoking, low socioeconomic class, and inadequate contact lens hygiene.

Common bacterial isolates cultured from patients with keratitis include Pseudomonas aeruginosa, coagulase-negative staphylococci, Staphylococcus aureus, Streptococcus pneumoniae, and Enterobacteriaceae (including Klebsiella, Enterobacter, Serratia, and Proteus). Klebsiella pneumoniae mucoid phenotype and its ability to form biofilm may be important in producing a corneal ulceration. Agents, such as N-acetylcysteine, may have a role in treatment because they inhibit biofilm formation. 

Fungi (Fusarium) and amoeba (Acanthamoeba) have been found in a small number of patients but frequently present with more severe symptoms.

Mooren ulcer is an idiopathic ulceration of the peripheral cornea, which may be due to an autoimmune reaction or it may be associated with the hepatitis C virus.

Frequency

United States

Approximately 25,000 Americans develop infectious keratitis annually. The annual incidence of microbial keratitis associated with contact lens use is approximately 2-4 infections per 10,000 users of soft contact lenses and 10-20 infections per 10,000 users of extended-wear contact lenses. Approximately 10% of these infections result in the loss of 2 or more lines of visual acuity.

International

A study from the United Kingdom reports factors associated with an increased risk of a corneal invasive event: wearing extended-wear hydrogel lenses, male gender, smoking, and the late winter months (March > July).¹

Authors from the United Kingdom also report an 8 times higher incidence of corneal invasive event in contact lens wearers who sleep in contact lenses compared with wearers who use lenses only during the waking hours.²

Mortality/Morbidity

Corneal scarring and vision loss are possible.

Sex

Studies from the United Kingdom suggest that males who wear extended-wear contact lenses are at increased risk of forming a corneal ulcer. 

Other studies suggest that males are at increased risk due to the higher probability of sustaining ocular trauma.

Age

Corneal injury or infection can affect people of all ages. A bimodal distribution exists. The age groups with a higher prevalence of disease are likely tied to risk factors, those in the first group (<30 y) who are more likely to be contact lenses wearers and/or sustain ocular trauma, and those in the second group (>50 y) who are more likely to undergo eye surgery.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

History

A number of questions can help make the diagnosis of keratitis.

• Current symptoms
• • Erythema of eyelid and conjunctiva
  • Mucopurulent discharge from eye
  • Foreign body sensation
  • Blurred vision
  • Light sensitivity
  • Pain
• Medication and contact lens use
• • Contact lens use
  • Type of contact lens (soft, hard, extended wear)
  • Type of contact lens solution
  • Contact lens hygiene
  • Current ocular medications, especially steroids
• Past medical history
• • History of ocular disease, eye surgery, or both
  • Diabetes mellitus
  • Exposure to sulphur mustard³
  • Collagen vascular disease (rheumatoid arthritis)
• Social history
• • Smoking history
  • Inquiry about the dietary habits of a patient with a corneal ulcer is important because vitamin A deficiency is associated with corneal ulcer formation.  
  • • Inadequate vitamin A can occur in a patient with an intentional diet deprivation or unintentional deprivation found in young children and pregnant women from Africa and Southeast Asia.
    • Secondary vitamin A deficiency may be found in a patient with celiac disease, sprue, cystic fibrosis, pancreatic disease, duodenal bypass, congenital partial obstruction of the jejunum, obstruction of the bile ducts, giardiasis, and cirrhosis.

Physical

The physical examination should include a through physical examination, with additional focus on the eye examination. Visual acuity, gross examination of the eyelids, surface of the eye, pupils, extraocular muscles, and fundi, should be performed and documented. A slit lamp examination and ocular pressure measurements should also be obtained.

• Visual function is affected variably, depending on the location of the ulcer and whether associated corneal and uveal inflammation is present. Obtain visual acuities on all patients with ocular complaints.
• Examination of the lids and the conjunctiva may reveal associated inflammation in these locations.
• The eye is typically erythematous, and ciliary injection is often present. Pupillary constriction is usually present secondary to ciliary spasm and iritis.
• Purulent exudate may be seen in the conjunctival sac and on the surface of the ulcer, and infiltration of the stroma may result in a creamy opacity of the cornea. The ulcer often is round or oval, and the border generally is demarcated sharply, with the base appearing ragged and gray.
• Slit lamp examination may reveal findings of iritis, and hypopyon may be present. Hypopyon is an accumulation of inflammatory cells in the anterior chamber that produces a layered meniscus in the inferior anterior chamber.
• Fluorescein staining may reveal the characteristic dendritic ulcer of herpes simplex virus (HSV) infection.
• A Wood lamp may be useful, since the ulcer associated with P aeruginosa fluoresces in ultraviolet light.

Causes

• Viral infections
• • Herpes simplex virus (HSV) infection is the most common cause of corneal ulcer in the United States. Although not always present, the classic finding in HSV infection is a branching dendritic ulcer.
  • Infection with HSV may interfere with corneal sensation, resulting in corneal anesthesia.
  • Varicella-zoster virus (VZV) can cause a corneal ulcer. Although corneal involvement can occur in varicella (chickenpox), it is uncommon and typically benign. The form of zoster (shingles) involving the ophthalmic branch of the trigeminal nerve is a more common corneal infection caused by VZV.
  • When herpetic eruption occurs along the nose, the nasociliary branch of the ophthalmic nerve is involved, indicating that corneal involvement is likely. This is known as the Hutchinson sign.
  • The dendritic pattern seen in HSV infection is not seen with zoster infection, although pseudodendrites, which only vaguely resemble true dendrites, may be present. Loss of corneal sensation is a prominent feature of zoster infection.
  • In contrast to the usual benign course in varicella and HSV, corneal complications in ophthalmic zoster can be severe and blinding.
  • Superficial punctate keratitis is characterized by destruction of pinpoint areas in the outer layer of the corneal epithelium is associated with adenoviruses.
• Bacterial infections
• • Numerous bacteria have been reported to cause corneal ulcer, although staphylococcal species, P aeruginosa, Streptococcus pneumoniae, and Moraxella species are reportedly the most common causes in the United States.
  • Clinical characteristics of corneal ulcers caused by various bacteria are not sufficiently distinct to determine the causal bacterial agent, although a corneal ulcer having a bluish or green mucopurulent discharge is almost pathognomonic for P aeruginosa.
  • Most corneal ulcers are centered, but some occur at the periphery of the cornea (ie, marginal ulcers).
  • Although the location of the ulcer does not correlate well with the causative organism, a marginal ulcer is more likely to occur as a result of staphylococcal blepharoconjunctivitis. This ulcer is not due to direct bacterial infection but rather is an inflammatory reaction to staphylococcal bacterial antigens and toxins. The ulcer usually is self-limited and lasts from 7-10 days, but it is likely to recur unless the underlying blepharoconjunctivitis is treated.
• Fungal infections: Fungal ulcers are caused by Candida, Fusarium, Aspergillus, Penicillium, Cephalosporium, and mycosis fungoides species.
• Acanthamoeba keratitis
• Peripheral ulcerative keratitis, associated with rheumatoid arthritis, relapsing polychondritis, and Wegener granulomatosis
• Photokeratitis (snowblindness) is caused by excess exposure to UV light. This can occur with sunlight, suntanning lamps, or a welding arc.
• Sulphur mustard chemical keratitis

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

Corneal foreign body
Blepharitis
Mooren ulcer
Terrien degeneration
Herpes simplex keratitis

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

Perform the following for corneal ulcers:

• Culture the ulcer.
• Rheumatoid arthritis evaluation

Other Tests

• Scrapings of the ulcer may be necessary to identify the underlying organism. Place samples directly on culture media.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Emergency Department Care

Immediately obtain ophthalmologic consultation for all corneal ulcers, so that cultures may be taken and treatment initiated. Choice of medications should be left to the treating ophthalmologist but generally include broad-spectrum topical antibiotics and cycloplegic drops.

Consultations

Corneal ulcers are considered an ophthalmologic emergency. Immediate ophthalmologic consultation is indicated.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The first-line regimen usually consists of alternating an aminoglycoside with a first-generation cephalosporin every 15-30 minutes. Frequently used, ciprofloxacin 0.3%, offers a shorter average time to healing and a reduced duration of therapy than conventional therapy. Obviously, the concern with this type of monotherapy is resistance.

Antibiotics may be administered by subconjunctival injection if compliance is a concern. To reduce the inhibition of corneal regeneration caused by concentrated antimicrobial solutions, the intervals between antimicrobial instillation and/or frequency of instillation should be prolonged following a decrease in purulence and a reduction in ulcer size.

If tests show that a viral infection is present, begin therapy with mechanical debridement of the infected rim along with a rim of the normal epithelium, followed by a topical instillation of the antiviral medications.

In fungal infections, a broad-spectrum antifungal drug usually is chosen. Some of the alternatives include natamycin, fluconazole, amphotericin B, miconazole, and ketoconazole. Natamycin is the first-line treatment in fungal infections of the cornea.

An adjunctive therapy may be required for conditions secondary to the ulcer. Atropine 1% or scopolamine 0.25% drops can be used to prevent formation of adhesions between the iris and the lens or cornea.

Topical corticosteroid use is controversial because its use in viral infections is relatively contraindicated, but it may prevent corneal scarring and perforation. Corticosteroids must be tapered to prevent rebound inflammation.

Hyperosmotics, carbonic anhydrase inhibitors, or beta-blockers can be administered if transient increases of intraocular pressure result from the keratitis.

Drug Category: Anesthetics

Anesthetics are indicated for pain relief and for conjunctival and corneal scrapings. Local anesthetics stabilize the neuronal membrane and prevent the initiation and transmission of nerve impulses, thereby producing the local anesthetic action.

Drug Category: Antibiotics

Therapy must cover all likely pathogens in the context of the clinical setting.

Drug Category: Antirheumatic, disease-modifying agents

These agents are used in the treatment of rheumatoid arthritis associated corneal ulcer.

Drug Category: Cycloplegics

Instillation of a long-acting cycloplegic agent can relax any ciliary muscle spasm that can cause a deep aching pain and photophobia.

Drug Category: Antivirals

Therapy of viral infections begins with mechanical debridement of the involved rim along with a rim of normal epithelium. This is followed by the topical instillation of antiviral medications (eg, vidarabine, idoxuridine, trifluridine).

Drug Category: Antifungals

Broad-spectrum antifungal agents that cause minimal pain and corneal irritation are recommended. Natamycin is the first-line treatment in fungal infections of the cornea. Candidal infections refractory to natamycin may respond to amphotericin B, miconazole, fluconazole, and ketoconazole. Topical application of these drugs, however, is somewhat limited because most of them must be compounded.

Drug Category: Nonsteroidal anti-inflammatory agents (NSAIDs)

Mechanism of action is believed to be through inhibition of the cyclooxygenase enzyme that is essential in the biosynthesis of prostaglandins. Inhibition of prostaglandin synthesis results in vasoconstriction and decreases in vascular permeability, leukocytosis, and intraocular pressure (IOP). These agents, however, have no significant effect on IOP.

Drug Category: Analgesics

Pain control is essential to quality patient care, ensuring patient comfort, promoting pulmonary toilet, and containing sedating properties that benefit patients who experience mild or severe pain.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Further Inpatient Care

• For patients with corneal ulcers, the emergency physician should contact an ophthalmologist while the patient is still in the emergency department. Timely consultation can be arranged at this time.

Complications

• The complications of corneal ulcer can be devastating. Corneal perforation, although rare, can occur. Corneal scarring may develop, resulting in partial or complete loss of vision. Anterior and posterior synechiae, glaucoma, and cataracts also can develop.

Prognosis

• Corneal ulcerations should improve daily and should heal with appropriate therapy.
• If healing does not occur or the ulcer extends, consider an alternate diagnosis and treatment.

Patient Education

• For excellent patient education resources, visit eMedicine's Eye and Vision Center. Also, see eMedicine's patient education articles Anatomy of the Eye, Corneal Ulcer, and Iritis.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical/Legal Pitfalls

• Attempting to treat in the ED and not obtaining an immediate ophthalmology consultation

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Jerome FX Naradzay, MD, and Wesley S Grigsby, MD, to the development and writing of this article.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

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Article Last Updated: Sep 15, 2008