- 1.
What is a corneal ulcer?
Infections of the cornea involve the epithelium and/or stroma. Some infections may occur strictly within the epithelium (i.e., herpes simplex epithelial keratitis), whereas others manifest as an infiltrate in the corneal stroma. The term “corneal ulcer” refers to the loss of stroma associated with an overlying epithelial defect (that stains with fluorescein) ( Fig. 8-1 ). A corneal ulcer is usually considered infectious when accompanied by a stromal infiltrate, but may also have a noninfectious (or sterile) etiology.
Figure 8-1
Central Pseudomonas corneal ulcer.
- 2.
What clinical features distinguish an infectious corneal ulcer?
Infectious corneal ulcers may be caused by bacterial, fungal, viral, or parasitic microorganisms. They classically present with rapid onset of pain, conjunctival injection, photophobia (light sensitivity), and decreased vision. On slit lamp exam, a visible corneal infiltrate is surrounded by corneal edema. If the corneal inflammation is severe, then anterior chamber cell and flare, keratic precipitates, and/or a hypopyon may also develop. Bacterial corneal ulcers may also be associated with a mucopurulent discharge. Some corneal ulcers may be caused by slow-growing organisms, such as anaerobes or mycobacteria; These ulcers may present with a nonsuppurative infiltrate and intact epithelium.
- 3.
What clinical features distinguish a sterile corneal ulcer?
Sterile corneal ulcers are not due to infection with microorganisms. They may be caused by a large variety of etiologies, including dry eye, exposure, neurotrophic keratopathy (e.g., from previous corneal herpetic infections), autoimmune disorders (e.g., rheumatoid arthritis), a secondary immunologic response elicited by staphylococcal hypersensitivity, or hypoxia (e.g., from contact lens wear). These ulcers often present with mild conjunctival reaction, minimal or absent corneal infiltrate, and/or epithelial defect and a quiet anterior chamber ( Fig. 8-2 ). Patients may notice decreased vision but often do not complain of significant redness, pain, photophobia, or discharge.
Figure 8-2
Sterile corneal ulcer caused by rheumatoid arthritis.
- 4.
What conditions predispose to corneal infections?
Any condition that disrupts the corneal epithelial integrity may predispose to corneal infection, including:
- •
Contact lens wear (No. 1 risk factor, responsible for 19% to 42% of cases!)
- •
Trauma (e.g., corneal abrasion)
- •
Structural eyelid abnormalities (e.g., ectropion/entropion, trichiasis)
- •
Dry eye
- •
Chronic epithelial disease (e.g., recurrent erosions, bullous keratopathy)
- •
Topical medication toxicity
- •
Local or systemic immunosuppression (e.g., steroids, diabetes, HIV)
- •
Contaminated ocular medications
- •
- 5.
How can a contact lens wearer reduce the risk of infection?
Contact lens wear is associated with at least 30% of microbial keratitis cases (ranging from 19% to 42% in different studies), most commonly caused by Pseudomonas aeruginosa . The major risk factor identified for corneal infection with contact lens use is sleeping overnight in contact lenses, even if they are approved for extended wear. Patients need to know that disposable contact lenses are not any safer than conventional contact lenses and that lenses with higher oxygen permeability (“high DK” lenses) also increase the risk for infection. Proper contact lens cleaning and disinfection prior to reinsertion, in addition to proper cleaning of contact lens cases, are also of crucial importance in reducing the incidence of contact lens-related corneal infections.
- 6.
Describe classic presentations and associations of various types of corneal infections (e.g., bacterial, viral, fungal).
- •
History of trauma with any vegetable matter : Fungal keratitis
- •
Oral and eyelid vesicles or repeated problems in only one eye : Herpetic keratitis
- •
Contact lens wear : Pseudomonas or Acanthamoeba infection
- •
Gram-positive organisms : Focal, discrete infiltrate
- •
Gram-negative organisms : Spreading diffuse infiltrate
- •
Pseudomonas infections : Suppurative infection, stromal necrosis, anterior chamber (AC) reaction with hypopyon
- •
Herpes simplex keratitis : Epithelial dendrite
- •
Acanthamoeba keratitis : Ring infiltrate, pain out of proportion to exam
- •
Infectious crystalline keratopathy : dense white, branching infiltrate with minimal inflammatory response (due to α-hemolytic Streptococcus species)
- •
Fungal keratitis : Feathery, irregular borders with satellite lesions ( Fig. 8-3 )
Figure 8-3
Infectious ulcer caused by filamentous fungus. Note the indistinct, feathery borders.
- •
- 7.
When should smears and cultures be performed?
Corneal scrapings for smears and cultures should be obtained on most corneal ulcers suspected of being infectious. Small, peripheral corneal infiltrates (less than 1 mm in diameter) do not necessarily have to undergo scraping prior to the initiation of intensive empiric broad-spectrum antibiotic therapy. However, corneal smears and cultures should be performed in all sight-threatening ulcers (>1 mm), in any case in which an atypical organism is suspected or in any corneal ulcer that is unresponsive to antimicrobial therapy. Of particular importance, corneal infections that do not improve on therapy should undergo scraping or rescraping, and documentation of current antibiotic medication should be given to the laboratory.
- 8.
How should smears and cultures be performed?
Corneal smears and cultures should be performed at the slit lamp after the patient has been given topical anesthetic drops. Corneal scrapings should be obtained using a sterile Kimura spatula, resterilized over a flame between each scraping, or with sterile calcium alginate swabs. Of note, a sterile needle or surgical blade can also be used to scrape corneal ulcers. Separate slides should be used for each smear (e.g., Gram’s stain, potassium hydroxide (KOH)). Separate plates should be used for each culture and for Giemsa or calcofluor white stains. For viral cultures, Dacron swabs can be used to obtain viral-infected cells from the cornea. Of note, calcium alginate and cotton swabs should be avoided when obtaining viral cultures, as both can inhibit viral growth.
- 9.
What smears and cultures should be obtained? What culture plates should be used?
See Table 8-1 .
Table 8-1
Smears and Cultures for Infectious Keratitis
Routine Test
Tests for
Gram stain (smear)
Bacteria
KOH or Giemsa stain (smear)
Fungi/yeasts
Sabaroud’s dextrose agar culture plate (without cycloheximide)
Fungi
Chocolate agar culture plate
Hemophilus and Neisseria species
Thioglycolate culture broth
Aerobic and anaerobic bacteria
Optional Test (as needed based on clinical suspicion)
Tests for
Gomori methenamine silver stain (smear)
Acanthamoeba , fungi
Acid fast stain (smear)
Mycobacteria
Calcofluor white stain (smear)
Acanthamoeba , fungi
Löwenstein-Jensen agar culture plate
Mycobacteria, Nocardia spp.
Nonnutrient agar culture plate with Escherichia coli overlay
Acanthamoeba
- 10.
What is the diagnostic yield for smears and cultures performed prior to the initiation of therapy?
Although Gram’s stain smears may provide early insight into the causative organism, they may be negative (with a highly variable positivity range of 0% to 57%). Smears must not be relied on too heavily because their correlation with culture results is low as a result of contamination by normal flora and improper staining/processing technique. On the other hand, cultures grow organisms in approximately 50% to 75% of suspected infectious ulcers. Though cultures performed prior to starting antibiotics have higher yield, clinical evidence suggests that the yield is not significantly diminished by antibiotic treatment if the infection is not responding.
- 11.
What are the most common organisms that cause bacterial keratitis?
The most common organisms that cause bacterial keratitis are P. aeruginosa (most common organism in contact lens wearers), Staphylococcus aureus , Staphylococcus epidermidis , Streptococcus pneumonia , Proteus , Enterobacter , and Serratia .
- 12.
What is the recommended initial therapy for suspected infectious ulcers? How does one determine whether single-agent, broad-spectrum antibiotics or combination-fortified antibiotics should be used?
In general, initial therapy for corneal ulcers must cover a broad range of gram-positive and gram-negative bacteria and be administered frequently (every 15 to 30 minutes). Previous multicenter studies have shown that monotherapy with topical fluoroquinolones may be as effective as fortified antibiotics in many cases. It is our practice to treat small, peripheral ulcers with a single, fourth-generation fluoroquinolone antibiotic, such as besifloxacin, gatifloxacin, or moxifloxacin, which has shown improved coverage of gram-positive organisms such as streptococcal and staphylococcal species. We reserve combination-fortified antibiotics for more severe, sight-threatening infections. For ulcers that are >1 mm or sight-threatening, it is recommended to start initial broad-spectrum therapy. Once culture results are available, antibiotic therapy tailored to the offending microorganism should be initiated.
- 13.
How does the presence of a hypopyon affect the management of infectious keratitis?
The presence of a hypopyon ( Fig. 8-4 ) is indicative of corneal inflammation severe enough to cause a marked anterior chamber response. Therefore, the treatment should be intense, including frequent combined fortified antibiotics in most cases as well as cycloplegic agents to help stabilize the blood–aqueous barrier. For the most part, hypopyons associated with infectious corneal ulcers are sterile and do not require evaluation and treatment for endophthalmitis.
Figure 8-4
Hypopyon associated with infectious corneal ulcer.
- 14.
When should an anterior chamber and/or vitreous tap be performed?
An anterior chamber and/or vitreous tap should be done whenever endophthalmitis is suspected. Endophthalmitis must be considered when there is severe inflammation after intraocular surgery or perforating trauma, especially when vitreous inflammatory cells are present. Once diagnosed, topical antibiotics are inadequate and intravenous antibiotics are unnecessary; antibiotics must be injected directly into the vitreous cavity after taking samples for culture (with vitrectomy indicated in severe cases). Endophthalmitis secondary to infectious keratitis in the absence of perforation is uncommon, and a sterile inflammatory response in the vitreous that resolves with the clearing of the corneal infection may be present.
- 15.
When should patients with corneal ulcers be hospitalized?
- •
If the patient lacks the ability or support to administer drops as frequently as every 30 minutes around the clock
- •
If the patient lives too far away to be followed on a daily basis
- •
For any condition requiring intravenous antibiotics or possible surgery (e.g., Neisseria infections involving the cornea and perforated corneal ulcers)
- •
- 16.
When are systemic medications indicated?
Systemic antibiotics are seldom indicated in bacterial corneal ulcers. However, oral antibiotics are used with impending or existing scleral involvement. Parenteral antibiotics play an important role in the treatment of aggressive infections from Neisseria and Hemophilus species with corneal involvement and impending perforation.
Systemic antifungal agents are used in some cases of fungal keratitis in which the infiltrate involves deep corneal stroma or in cases that worsen on topical therapy alone. Oral acyclovir is the primary mode of therapy for patients with ocular herpes zoster and is also used by some physicians to treat primary herpes simplex infection.
- 17.
Other than antibiotics, what adjunctive therapy may be necessary in the treatment of corneal ulcers?
Topical cycloplegic agents are often indicated to help relieve photophobia and pain from ciliary spasm and to help prevent posterior synechiae.
Severe anterior chamber inflammation may cause the intraocular pressure to increase, often necessitating the use of antiglaucoma medications. Pilocarpine should be avoided because of the phenomenon of blood–aqueous breakdown with subsequent increase in anterior chamber inflammation. In the case of impending or frank perforated corneal ulcer, cyanoacrylate tissue glue can be useful in temporarily and sometimes permanently sealing the open wound.
The role of topical corticosteroids in the management of bacterial keratitis is controversial, but they may be used as well (see below).
- 18.
How should the smear and culture results be used to modify treatment?
Smears may provide a quick means of telling the clinician the general type of infection (e.g., bacterial, fungal, protozoan) and can help start the appropriate empiric therapy. However, we recommend that broad-spectrum antibiotics be continued until culture results are available.
Culture results identify the organism, help to target therapy, and eliminate extraneous medication. Sensitivities can be useful for guiding treatment, but must be interpreted with caution as they are based on drug levels attainable in the serum and not on drug concentrations in the cornea.
- 19.
What are the important immediate and delayed sequelae of corneal ulcers?
The immediate concern with corneal ulcers is progressive thinning and perforation. Management and prognosis change considerably with perforation, and the concern for intraocular infection (i.e., endophthalmitis) rises dramatically. Perforated corneal ulcers can result in the loss of the eye. The delayed sequelae of corneal ulcers deal mainly with corneal scarring, which can severely limit visual acuity and function.
- 20.
How should impending and frank corneal perforations be managed?
Corneal infections can be associated with corneal perforation. One study showed that outdoor occupation, trauma with vegetative matter, a central location of corneal ulcer, monotherapy with fluoroquinolone, and lack of corneal neovascularization, as well as delay in starting management with antimicrobial therapy in infectious keratitis, led to an increased risk of corneal perforation. In this study, S. epidermidis was the most commonly isolated organism in cases of perforated corneal ulcers.
Any corneal infection associated with marked thinning or perforation ( Fig. 8-5 ) should be protected with an eye shield without a patch. When the cornea becomes thinned to the point of imminent or existent corneal perforation, certain steps need to be taken. If the affected area is small, cyanoacrylate glue can be used to help seal the defect. However, most cases of perforation will eventually need patch grafting or therapeutic corneal transplantation if the eye has visual potential.
