corneal ulceration and ulcerative keratitis

8/13/2019 Corneal Ulceration and Ulcerative Keratitis

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Corneal Ulceration and Ulcerative Keratitis

Background

Because of its potential to permanently impair vision or perforate the eye, a corneal ulcer isconsidered 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 adramatic rise in the occurrence ofcorneal ulcer,particularly due toPseudomonas 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 leadto 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 bediagnosed in the absence of an infectious or systemic cause.

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

Pathophysiology

Risk factors include contact lens use, trauma, ocular surface disease, and ocularsurgery. 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 inadequatecontact lens hygiene.

Common bacterial isolates cultured from patients with keratitis includePseudomonasaeruginosa, coagulase-negative staphylococci, Staphylococcus aureus, Streptococcus

pneumoniae,andEnterobacteriaceae(includingKlebsiella, Enterobacter, Serratia,and

Proteus).Klebsiella pneumoniaemucoid phenotype and its ability to form biofilm may beimportant in producing a corneal ulceration. Agents, such asN-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 anautoimmune reaction or it may be associated with the hepatitis C virus.
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Frequency

United States

Approximately 25,000 Americans develop infectious keratitis annually. The annual incidence ofmicrobial 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 visualacuity.

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 latewinter months (March > July).

1

Authors from the United Kingdom also report an 8 times higher incidence of corneal invasiveevent 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(50 y) who are more likely to undergo eye surgery.

Clinical

History

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

Current symptoms


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o Erythema of eyelid and conjunctivao Mucopurulent discharge from eyeo Foreign body sensationo Blurred visiono Light sensitivityo Pain

Medication and contact lens useo Contact lens useo Type of contact lens (soft, hard, extended wear)o Type of contact lens solutiono Contact lens hygieneo Current ocular medications, especially steroids

Past medical historyo History of ocular disease, eye surgery, or botho Diabetes mellituso Exposure to sulphur mustard3o Collagen vascular disease (rheumatoid arthritis)

Social historyo Smoking historyo 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 deprivationor 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 whetherassociated 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 theselocations.

The eye is typically erythematous, and ciliary injection is often present. Pupillary constriction isusually present secondary to ciliary spasm and iritis.

Purulent exudate may be seen in the conjunctival sac and on the surface of the ulcer, andinfiltration 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.


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Slit lamp examination may reveal findings of iritis, and hypopyon may be present. Hypopyon isan 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 aeruginosafluoresces inultraviolet light.

Causes

Viral infectionso 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.

o Infection with HSV may interfere with corneal sensation, resulting in corneal anesthesia.o 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.

o When herpetic eruption occurs along the nose, the nasociliary branch of the ophthalmicnerve is involved, indicating that corneal involvement is likely. This is known as the

Hutchinson sign.

o The dendritic pattern seen in HSV infection is not seen with zoster infection, althoughpseudodendrites, which only vaguely resemble true dendrites, may be present. Loss of

corneal sensation is a prominent feature of zoster infection.

o In contrast to the usual benign course in varicella and HSV, corneal complications inophthalmic zoster can be severe and blinding.

o Superficial punctate keratitis is characterized by destruction of pinpoint areas in theouter layer of the corneal epithelium is associated with adenoviruses.

Bacterial infectionso Numerous bacteria have been reported to cause corneal ulcer, although staphylococcal

species, P aeruginosa, Streptococcus pneumoniae,and Moraxellaspecies are reportedly

the most common causes in the United States.

o Clinical characteristics of corneal ulcers caused by various bacteria are not sufficientlydistinct to determine the causal bacterial agent, although a corneal ulcer having a bluish

or green mucopurulent discharge is almost pathognomonic for P aeruginosa.

o Most corneal ulcers are centered, but some occur at the periphery of the cornea (ie,marginal ulcers).

o Although the location of the ulcer does not correlate well with the causative organism, amarginal 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
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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 withsunlight, suntanning lamps, or a welding arc.

Sulphur mustard chemical keratitisDifferential Diagnoses

Herpes ZosterHerpes Zoster Ophthalmicus

Other Problems to Be Considered

Corneal foreign body

BlepharitisMooren ulcer

Terrien degenerationHerpes simplex keratitis

Workup

Laboratory 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 samplesdirectly on culture media.

Treatment

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 treatingophthalmologist but generally include broad-spectrum topical antibiotics and cycloplegic drops.

Consultations

Corneal ulcers are considered an ophthalmologic emergency. Immediate ophthalmologicconsultation is indicated.
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Medication

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 shorteraverage 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 prolongedfollowing 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 theinfected 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 alternativesinclude 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 thelens or cornea.

Topical corticosteroid use is controversial because its use in viral infections is relativelycontraindicated, 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

Anesthetics are indicated for pain relief and for conjunctival and corneal scrapings. Localanesthetics stabilize the neuronal membrane and prevent the initiation and transmission of nerve

impulses, thereby producing the local anesthetic action.

Proparacaine (Ophthetic, I-Paracaine)

Has a rapid onset of anesthesia that begins within 13-30 sec after instillation. Short duration ofaction (about 15-20 min). Since prolonged eye anesthesia can eliminate the patient's awarenessof mechanical damage to the cornea, do not use outside of the ED. Frequent use of anesthetics

may retard healing.


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Dosing Interactions Contraindications Precautions

Adult

2-3 gtt q15-20min during ED examination

1-2 gtt q5-10min of 0.5% solution for 5-7 doses

Pediatric

Administer as in adults

Dosing Interactions

Contraindications Precautions

None reported


Documented hypersensitivity


Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; mayuse if benefits outweigh risk to fetus

Precautions

Caution in cardiac disease or hyperthyroidism and with abnormal or reduced levels of plasmaesterases

Antibiotics

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


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Cefazolin (Ancef, Kefzol)

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.


Adult

1-2 gtt q2-4h 50-133 mg/mL solution; not to exceed 2 gtt q1h for severe infections

Pediatric



None reported


Documented hypersensitivity; viral, mycobacterial, and fungal infections of the eye; use of

steroid combinations after uncomplicated removal of corneal foreign body


Pregnancy



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Precautions

Not for use in ocular infections likely to become systemic; bacterial or fungal overgrowth ofnonsusceptible organisms may occur with prolonged or repeated therapy

Gentamicin (Genoptic)

Aminoglycoside antibiotic used for gram-negative bacterial coverage. Commonly used incombination with a first-generation cephalosporin.


Adult

Ointment: 0.5-inch (1.25-cm) ribbon bid/tid to q3-4h to the affected eyeSolution: 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 becompounded.

Pediatric



None reported


Documented hypersensitivity; viral, mycobacterial, and fungal infections of the eye; use of

steroid combinations after uncomplicated removal of a corneal foreign body



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Pregnancy


Precautions

Do not use to treat ocular infections that may become systemic; prolonged or repeated antibiotictherapy may result in bacterial or fungal overgrowth of nonsusceptible organisms and may lead

to secondary infections

Erythromycin (E-Mycin, E.E.S.)

Indicated for treatment of infections caused by susceptible strains of microorganisms and for

prevention of corneal and conjunctival infections.


Adult

0.5-inch (1.25-cm) ribbon 2-8 times/d, depending on severity of infection

Pediatric



None reported

Dosing

Interactions Contraindications Precautions

Documented hypersensitivity; viral, mycobacterial, and fungal infections of the eye; use ofsteroid combinations after uncomplicated removal of a corneal foreign body


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Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Do not use topical antibiotics to treat ocular infections that may become systemic; prolonged orrepeated 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)

Ciprofloxacin (Ciloxan)

Bactericidal antibiotic that inhibits bacterial DNA synthesis, and consequently growth, byinhibiting DNA gyrase in susceptible organisms.Indicated for pseudomonal infections and those due to multidrug-resistant gram-negative

organisms.


Adult

1-2 gtt q1h while awake for 1 d; 1-2 gtt q4h while awake for another 7 d

Pediatric

Not established


None reported

Dosing


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Documented hypersensitivity; viral, mycobacterial, and fungal eye infections; use of steroid

combinations after uncomplicated removal of a corneal foreign body


Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may

use if benefits outweigh risk to fetus

Precautions

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; superinfectionsmay occur with prolonged or repeated antibiotic therapy

Antirheumatic, disease-modifying agents

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

Infliximab (Remicade)

Chimeric anti-tumor necrosis factor alpha monoclonal antibody. Neutralizes cytokine TNF-alphaand 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.



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Adult

5 mg/kg IV infusion at 0, 2, and 6 wk as induction regimen, then 5 mg/kg q6wk for maintenanceIV infusion must be administered over at least 2 h; must use infusion set with in-line, sterile,

nonpyrogenic, low-protein-binding filter (pore size


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Scopolamine (Isopto Hyoscine)

Blocks the action of acetylcholine at parasympathetic sites in the smooth muscle, producingpupillary dilation (mydriasis) and paralysis of accommodation (cycloplegia).

Dosing


Adult

1-2 gtt qid

Pediatric

Not established


None reported


Documented hypersensitivity; primary glaucoma or initial stages of the disease


Pregnancy


Precautions

Avoid excessive systemic absorption by compressing lacrimal sac, using digital pressure for 1-3min after instillation; may produce drowsiness, blurred vision, or sensitivity to light (due to


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dilated pupils); observe caution while driving or performing other tasks requiring alertness,

coordination, or physical dexterity

Antivirals

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

vidarabine, idoxuridine, trifluridine).

Vidarabine (Vira-A)

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 longertreatment. After reepithelialization has occurred, treat for an additional 7 d at a reduced dosage(eg, twice daily) to prevent recurrence.


Adult

0.5-inch (1.25-cm) ribbon q3h into lower conjunctival sac(s) 5 times/d

Pediatric



None reported




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Pregnancy



Precautions

Viral resistance is possible but none reported

Idoxuridine (Herplex)

Used for epithelial infections (especially initial attacks). Infections characterized by the presenceof 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.


Adult

1 gtt q1h during the day and q2h at night initiallyContinue until a definite improvement occurs, usually within 7 dReduce 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 dAlternatively, 1 gtt/min for 5 min; repeat q4h, day and night

Pediatric

Not established



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Coadministration with boric acid-containing solutions may result in a precipitate formation,

which may cause irritation




Pregnancy



Precautions

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

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, andketoconazole. Topical application of these drugs, however, is somewhat limited because most of

them must be compounded.

Natamycin (Natacyn)

Predominantly fungicidal tetraene polyene antibiotic, derived from Streptomyces natalensisthat

possesses in vitro activity against a variety of yeast and filamentous fungi, including Candida,

Aspergillus, Cephalosporium, Fusarium,andPenicilliumspecies. Binds fungal cell membraneforming 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 oruntil 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.


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Adult

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

Pediatric

Not established

Dosing Interactions

Contraindications Precautions

None reported




Pregnancy


Precautions

Since some strains of herpes simplex seem resistant, undertake another form of therapy if there isno lessening of fluorescein staining in 14 d; do not exceed recommended frequency and duration

of administration


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Nonsteroidal anti-inflammatory agents (NSAIDs)

Mechanism of action is believed to be through inhibition of the cyclooxygenase enzyme that isessential 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.

Ibuprofen (Ibuprin, Motrin, Advil)

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.


Adult

200-400 mg PO q4-6h while symptoms persist; not to exceed 3.2 g/d

Pediatric

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 effectof 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



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Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal

insufficiency; high risk of bleeding


Pregnancy

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

Precautions

Caution in congestive heart failure, hypertension, and decreased renal and hepatic function;caution in anticoagulation abnormalities or during anticoagulant therapy

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 severepain.

Oxycodone and acetaminophen (Percocet)

Drug combination indicated for the relief of moderate to severe pain.


Adult

1-2 tab or cap PO q4-6h prn

Pediatric

0.05-0.15 mg/kg/dose PO; not to exceed 5 mg/dose of oxycodone q4-6h prn


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Follow-up

Further Inpatient Care

For patients with corneal ulcers, the emergency physician should contact an ophthalmologistwhile the patient is still in the emergency department. Timely consultation can be arranged atthis time.

Complications

The complications of corneal ulcer can be devastating. Corneal perforation, although rare, canoccur. 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'sEye and Vision Center.Also, seeeMedicine's patient education articlesAnatomy of the Eye,Corneal Ulcer,andIritis.

Miscellaneous

Medicolegal Pitfalls

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