Updated: Sep 15, 2008
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.
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.
Herpes simplex and varicella-zoster viruses can both cause a significant keratitis.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.
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.
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
Corneal scarring and vision loss are possible.
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.
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.
A number of questions can help make the diagnosis of keratitis.
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.
Herpes Zoster
Herpes Zoster Ophthalmicus
Corneal foreign body
Blepharitis
Mooren ulcer
Terrien degeneration
Herpes simplex keratitis
Perform the following for corneal ulcers:
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.
Corneal ulcers are considered an ophthalmologic emergency. Immediate ophthalmologic consultation is indicated.
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.
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.
Has a rapid onset of anesthesia that begins within 13-30 sec after instillation. Short duration of action (about 15-20 min). Since prolonged eye anesthesia can eliminate the patient's awareness of mechanical damage to the cornea, do not use outside of the ED. Frequent use of anesthetics may retard healing.
2-3 gtt q15-20min during ED examination
1-2 gtt q5-10min of 0.5% solution for 5-7 doses
Administer as in adults
None reported
Documented hypersensitivity
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Caution in cardiac disease or hyperthyroidism and with abnormal or reduced levels of plasma esterases
Therapy must cover all likely pathogens in the context of the clinical setting.
First-generation cephalosporin antibiotic for gram-positive bacterial coverage. Commonly used in combination with an aminoglycoside to achieve broad-spectrum coverage.
This 50-133 mg/mL solution must be compounded.
1-2 gtt q2-4h 50-133 mg/mL solution; not to exceed 2 gtt q1h for severe infections
Administer as in adults
None reported
Documented hypersensitivity; viral, mycobacterial, and fungal infections of the eye; use of steroid combinations after uncomplicated removal of corneal foreign body
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Not for use in ocular infections likely to become systemic; bacterial or fungal overgrowth of nonsusceptible organisms may occur with prolonged or repeated therapy
Aminoglycoside antibiotic used for gram-negative bacterial coverage. Commonly used in combination with a first-generation cephalosporin.
Ointment: 0.5-inch (1.25-cm) ribbon bid/tid to q3-4h to the affected eye
Solution: 1-2 gtt q2-4h; not to exceed q1h for severe infections
This preparation should be fortified to a concentration of 15 mg/mL, which must be compounded.
Administer as in adults
None reported
Documented hypersensitivity; viral, mycobacterial, and fungal infections of the eye; use of steroid combinations after uncomplicated removal of a corneal foreign body
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Do not use to treat ocular infections that may become systemic; prolonged or repeated antibiotic therapy may result in bacterial or fungal overgrowth of nonsusceptible organisms and may lead to secondary infections
Indicated for treatment of infections caused by susceptible strains of microorganisms and for prevention of corneal and conjunctival infections.
0.5-inch (1.25-cm) ribbon 2-8 times/d, depending on severity of infection
Administer as in adults
None reported
Documented hypersensitivity; viral, mycobacterial, and fungal infections of the eye; use of steroid combinations after uncomplicated removal of a corneal foreign body
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Do not use topical antibiotics to treat ocular infections that may become systemic; prolonged or repeated antibiotic therapy may result in bacterial or fungal overgrowth of nonsusceptible organisms and may lead to a secondary infection (take appropriate measures if superinfection occurs)
Bactericidal antibiotic that inhibits bacterial DNA synthesis, and consequently growth, by inhibiting DNA gyrase in susceptible organisms.
Indicated for pseudomonal infections and those due to multidrug-resistant gram-negative organisms.
1-2 gtt q1h while awake for 1 d; 1-2 gtt q4h while awake for another 7 d
Not established
None reported
Documented hypersensitivity; viral, mycobacterial, and fungal eye infections; use of steroid combinations after uncomplicated removal of a corneal foreign body
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
A white crystalline precipitate located in the superficial portion of corneal defect may occur (onset in 1-7 d); precipitate is usually cleared within 2 wk and does not adversely affect clinical course or outcome; do not use in ocular infections that may become systemic; superinfections may occur with prolonged or repeated antibiotic therapy
These agents are used in the treatment of rheumatoid arthritis associated corneal ulcer.
Chimeric anti-tumor necrosis factor alpha monoclonal antibody. Neutralizes cytokine TNF-alpha and inhibits its binding to TNF-alpha receptor. Mix in 250-mL normal saline for infusion over 2 h. Must use with low-protein-binding filter (1.2 micron or less). Indicated to reduce signs and symptoms of active ankylosing spondylitis.
5 mg/kg IV infusion at 0, 2, and 6 wk as induction regimen, then 5 mg/kg q6wk for maintenance
IV infusion must be administered over at least 2 h; must use infusion set with in-line, sterile, nonpyrogenic, low-protein-binding filter (pore size <1.2 microns)
Not established
None reported
Documented hypersensitivity
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
TNF-alpha modulates cellular immune responses; anti-TNF therapies, such as infliximab, may adversely affect normal immune responses and allow development of superinfections; more cases of lymphoma were observed in TNF alpha-blockers compared to controlled groups; may increase risk of reactivation of tuberculosis in patients with particular granulomatous infections
Instillation of a long-acting cycloplegic agent can relax any ciliary muscle spasm that can cause a deep aching pain and photophobia.
Blocks the action of acetylcholine at parasympathetic sites in the smooth muscle, producing pupillary dilation (mydriasis) and paralysis of accommodation (cycloplegia).
1-2 gtt qid
Not established
None reported
Documented hypersensitivity; primary glaucoma or initial stages of the disease
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Avoid excessive systemic absorption by compressing lacrimal sac, using digital pressure for 1-3 min after instillation; may produce drowsiness, blurred vision, or sensitivity to light (due to dilated pupils); observe caution while driving or performing other tasks requiring alertness, coordination, or physical dexterity
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).
Indicated as a topical idoxuridine or when toxic or hypersensitivity reactions to idoxuridine occur. Appears to interfere with the early steps of viral DNA synthesis.
If no signs of improvement are evident after 7 d or if complete reepithelialization has not occurred in 21 d, consider other forms of therapy. Some severe cases may require longer treatment. After reepithelialization has occurred, treat for an additional 7 d at a reduced dosage (eg, twice daily) to prevent recurrence.
0.5-inch (1.25-cm) ribbon q3h into lower conjunctival sac(s) 5 times/d
Administer as in adults
None reported
Documented hypersensitivity
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Viral resistance is possible but none reported
Used for epithelial infections (especially initial attacks). Infections characterized by the presence of a dendritic shape respond better to this medication than stromal infections.
Blocks the reproduction of HSV by producing incorrect DNA copies that prevent the virus from infecting or destroying the tissue.
1 gtt q1h during the day and q2h at night initially
Continue until a definite improvement occurs, usually within 7 d
Reduce dosage to 1 gtt q2h during the day and q4h at night
To minimize recurrences, continue therapy at this reduced dosage for 3-7 d after healing appears complete; maximum treatment period is approximately 21 d
Alternatively, 1 gtt/min for 5 min; repeat q4h, day and night
Not established
Coadministration with boric acid-containing solutions may result in a precipitate formation, which may cause irritation
Documented hypersensitivity
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Since some strains of herpes simplex seem resistant, undertake another form of therapy if there is no lessening of fluorescein staining in 14 d; do not exceed recommended frequency and duration of administration
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.
Predominantly fungicidal tetraene polyene antibiotic, derived from Streptomyces natalensis that possesses in vitro activity against a variety of yeast and filamentous fungi, including Candida, Aspergillus, Cephalosporium, Fusarium, and Penicillium species. Binds fungal cell membrane forming a polyene sterol complex that alters membrane permeability and depleting essential cellular constituents. Activity against fungi is dose related, but it is not effective in vitro against gram-negative or gram-positive bacteria. Generally, therapy should be continued for 14-21 d or until the fungal keratitis has resolved. In many cases, reducing the dosage gradually at 4-7 d intervals may help ensure that the organism has been eliminated.
1 gtt into conjunctival sac q1-2h
Frequency of application usually can be reduced to 1 gtt 6-8 times/d after the first 3-4 d
Not established
None reported
Documented hypersensitivity
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Since some strains of herpes simplex seem resistant, undertake another form of therapy if there is no lessening of fluorescein staining in 14 d; do not exceed recommended frequency and duration of administration
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.
Usually the DOC for treatment of mild to moderate pain, if no contraindications exist.
Inhibits inflammatory reactions and pain, probably by decreasing the activity of the enzyme cyclooxygenase, which results in prostaglandin synthesis.
200-400 mg PO q4-6h while symptoms persist; not to exceed 3.2 g/d
<6 months: Not established
6 months to 12 years: 10-70 mg/kg/d PO divided tid/qid
Start at lower end of dosing range and titrate upward to maximum of 2.4 g/d
>12 years: Administer as in adults
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy
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.
Drug combination indicated for the relief of moderate to severe pain.
1-2 tab or cap PO q4-6h prn
0.05-0.15 mg/kg/dose PO; not to exceed 5 mg/dose of oxycodone q4-6h prn
Phenothiazines may decrease analgesic effects; toxicity increases with coadministration of either CNS depressants or tricyclic antidepressants
Documented hypersensitivity
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Duration of action may increase in elderly persons; be aware of total daily dose of acetaminophen patient is receiving; do not exceed 4000 mg/d of acetaminophen; higher doses may cause liver toxicity
Morgan PB, Efron N, Brennan NA, et al. Risk factors for the development of corneal infiltrative events associated with contact lens wear. Invest Ophthalmol Vis Sci. Sep 2005;46(9):3136-43. [Medline].
Efron N, Morgan PB, Hill EA, et al. Incidence and morbidity of hospital-presenting corneal infiltrative events associated with contact lens wear. Clin Exp Optom. Jul 2005;88(4):232-9. [Medline].
Kehe K, Szinicz L. Medical aspects of sulphur mustard poisoning. Toxicology. Oct 30 2005;214(3):198-209. [Medline].
Araki-Sasaki K, Nishi I, Yonemura N, et al. Characteristics of Pseudomonas corneal infection related to orthokeratology. Cornea. Oct 2005;24(7):861-3. [Medline].
Clewes AR, Dawson JK, Kaye S, et al. Peripheral ulcerative keratitis in rheumatoid arthritis: successful use of intravenous cyclophosphamide and comparison of clinical and serological characteristics. Ann Rheum Dis. Jun 2005;64(6):961-2. [Medline].
Frith P, Gray R, MacLennan S. The Eye in Clinical Practice. 1994:77-95.
Goldberg DF, Negvesky GJ, Butrus SI, et al. Ulcerative keratitis in mycosis fungoides. Eye Contact Lens. Sep 2005;31(5):219-20. [Medline].
Höfling-Lima AL, de Freitas D, Sampaio JL, et al. In vitro activity of fluoroquinolones against Mycobacterium abscessus and Mycobacterium chelonae causing infectious keratitis after LASIK in Brazil. Cornea. Aug 2005;24(6):730-4. [Medline].
Int Ophthalmol Clin. Contact lenses and external disease. Int Ophthalmol Clin. 1986;26(1):1-166. [Medline].
Khanal B, Deb M, Panda A, et al. Laboratory diagnosis in ulcerative keratitis. Ophthalmic Res. May-Jun 2005;37(3):123-7. [Medline].
Krachmer JH, Mannis MJ, Holland EJ. Cornea: Fundamentals of Cornea and External Disease. 1997:403-407.
Leibowitz HM. Corneal Disorders: Clinical Diagnosis and Management. 1984:353-372.
Mirza SH. Fungal keratitis due to fusarium solani. J Coll Physicians Surg Pak. Sep 2005;15(9):576-7. [Medline].
O'Donnell C, Efron N. Contact lens wear and diabetes mellitus. Cont Lens Anterior Eye. 1998;21(1):19-26. [Medline].
Pichare A, Patwardhan N, Damle AS, et al. Bacteriological and mycological study of corneal ulcers in and around Aurangabad. Indian J Pathol Microbiol. Apr 2004;47(2):284-6. [Medline].
Pinna A, Sechi LA, Zanetti S, et al. Detection of virulence factors in a corneal isolate of Klebsiella pneumoniae. Ophthalmology. May 2005;112(5):883-7. [Medline].
Seino JY, Anderson SF. Mooren's ulcer. Optom Vis Sci. Nov 1998;75(11):783-90. [Medline].
Servat JJ, Ramos-Esteban JC, Tauber S, et al. Mycobacterium chelonae-Mycobacterium abscessus complex clear corneal wound infection with recurrent hypopyon and perforation after phacoemulsification and intraocular lens implantation. J Cataract Refract Surg. Jul 2005;31(7):1448-51. [Medline].
Thomas JW, Pflugfelder SC. Therapy of progressive rheumatoid arthritis-associated corneal ulceration with infliximab. Cornea. Aug 2005;24(6):742-4. [Medline].
Vaughan D, Asbury T, Riordan-Eva P. General Ophthalmology. 1995:124-133.
Velasco Cruz AA, Attie-Castro FA, Fernandes SL, et al. Adult blindness secondary to vitamin A deficiency associated with an eating disorder. Nutrition. May 2005;21(5):630-3. [Medline].
Verhelst D, Koppen C, Van Looveren J, et al. Clinical, epidemiological and cost aspects of contact lens related infectious keratitis in Belgium: results of a seven-year retrospective study. Bull Soc Belge Ophtalmol. 2005;7-15. [Medline].
Zaher SS, Sandinha T, Roberts F, et al. Herpes simplex keratitis misdiagnosed as rheumatoid arthritis-related peripheral ulcerative keratitis. Cornea. Nov 2005;24(8):1015-7. [Medline].
corneal ulceration, ulcerative keratitis, corneal ulcer, peripheral ulcerative keratitis, PUK, corneal infiltrative events, CIEs, corneal ulcer disease, Mooren's ulcer, Mooren ulcer, corneal melt
Trevor John Mills, MD, MPH, Chief of Emergency Medicine, Veterans Affairs Northern California Health Care System; Associate Professor of Emergency Medicine, Louisiana State University Health Sciences Center
Trevor John Mills, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Public Health Association, Society for Academic Emergency Medicine, Southern Medical Association, and Wilderness Medical Society
Disclosure: Nothing to disclose.
William K Chiang, MD, Associate Professor, Department of Emergency Medicine, Department of Emergency Medicine, New York University School of Medicine; Consulting Staff, Bellevue Hospital Center
William K Chiang, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Medical Toxicology, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.
Douglas Lavenburg, MD, Clinical Professor, Department of Emergency Medicine, Christiana Care Health Systems
Douglas Lavenburg, MD is a member of the following medical societies: American Society of Cataract and Refractive Surgery
Disclosure: Nothing to disclose.
John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Barry E Brenner, MD, PhD, FACEP, Program Director, Professor, Department of Emergency Medicine, Professor, Internal Medicine, University Hospitals, Case Western Reserve School of Medicine
Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
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.
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