Demographics

While keratomycosis may affect either sex, there seems to be a higher incidence in men, especially in farm workers and other outdoorsmen. In the southern United States, there is a bimodal distribution of occurrence with greater frequencies in the spring and late fall to early winter.

Incidence is estimated to be approximately 1,500 cases per year in the United States, accounting for up to 5% to 10% of all corneal infections.

Significant History

The history should cover the known risk factors associated with fungal keratitis. The following information should be obtained:

• Has the patient sustained corneal trauma, especially with organic material? (Infection usually occurs 36 to 48 hours after trauma, often slowly progressive.)
  
• Is the patient systemically or topically immunocompromised?
  
• Does the patient have any chronic systemic diseases, especially diabetes mellitus?
  
• Does the patient wear extended contact lenses or a therapeutic bandage lens? (Fungal infection has been reported in contact lens wearers, but bacterial keratitis is more common in these patients.)
  
• Does the patient have a chronic preexisting ocular surface disorder that may compromise the epithelium (e.g., exposure keratitis, keratitis sicca, herpes simplex keratitis, prior keratoplasty, etc.)?

Ancillary Tests

Diagnosing keratomycosis is often difficult. The primary obstacle in many cases is a failure to suspect a fungal etiology. It is therefore important for a clinician to perform a prompt and thorough laboratory investigation. One should complete the same culture procedure as previously described in the section on bacterial keratitis; however, several points should be emphasized.

1. Scraping the cornea with a sharpened Kimura spatula or a No. 15 scalpel blade is required to enhance the retrieval of fungal elements. The base and leading edge of the infiltrate should be vigorously scraped and then incubated on blood agar, thioglycolate broth, and Sabouraud’s agar (without cyclohexamide) without breaking the surface of the media. (Cyclohexamide is an inhibitant of saprophytic fungi, which are considered contaminants elsewhere in the body, but can be potential pathogens of the cornea.)

2. Scrapings should also be used to make thin smears for Gram, Giemsa, or Gomori methenamine silver stains. Gram stains may help to identify yeast forms of fungi (e.g., Candida), while Giemsa stain is more likely to define filamentous fungi (e.g., Fusarium, Aspergillus, Cephalosporium). Occasionally, specialized stains (i.e., potassium hydroxide with calcofluor white; acridine orange; etc.) and media (i.e., brain-heart infusion broth) are required to identify the more fastidious organisms.
    Note: Diagnosis requires laboratory confirmation and should never be made solely on the basis of the history or the appearance of the cornea. DNA amplification using polymerase chain reaction–based assay is a useful method for rapid and sensitive diagnosis of fungal keratitis, although specificity and availability may be an issue.

• Confocal microscopy may also be used to facilitate the diagnosis.

3. Sensitivities of isolated fungi to various antifungal agents can only be performed in a few specialized laboratories, such as the CDC in Atlanta. It is recommended that isolated organisms should not be discarded so that additional studies could be performed at one of these sites in the event the patient does not respond to therapy.

The Treatment

Typically, most infectious corneal infiltrates and ulcers are treated empirically with broad spectrum antibacterial therapy unless fungal elements are seen on smears or fungi are isolated on cultures. Interestingly, certain topical antibiotics (i.e., chloramphenicol, moxifloxacin, and tobramycin) as well as BAK have a modest effect on Fusarium and Aspergillus. Antifungal therapy of a corneal ulcer is usually not used until a definitive diagnosis is made.

Specific medical therapy for keratomycosis is somewhat limited by FDA-approved topical antifungal agents and by the poor penetration into ocular tissues. If studies verify a fungal etiology, typical management often includes the following measures:

2. Epithelial debridement and debulkment of necrotic tissue often aids drug penetration into the cornea. However, excessive scraping may be associated with worse outcomes in regards to BCVA following resolution of the infection.

3. Cycloplegics (e.g., scopolamine 0.25% t.i.d.) are used to prevent synechiae formation, reduce inflammation, and increase patient comfort.

4. Intraocular pressures should be monitored and secondary glaucoma controlled as needed (see glaucoma section).

5. Topical corticosteroids are contraindicated during early therapy of a fungal ulcer as they may exacerbate the infection, cause an inflammatory rebound, and ultimately worsen the prognosis. Topical antifungal agents are typically fungistatic and efficacy may vary. After several weeks of effective antifungal therapy and documented clinical improvement, topical steroids are sometimes judiciously employed to decrease corneal inflammation and scarring with the continued use of antifungal agents. However, most clinicians would agree that steroids are best avoided in a confirmed case of fungal keratitis, unless the benefits clearly outweigh the substantial risks.

• Clinical signs of response to treatment are initially an arrest of progression, decreasing infiltrate size and opacity, blunting of the leading edge of the infiltrate, and resolution of a hypopyon.
  
• Unfortunately, even with early, appropriate, and aggressive treatment, patients with fungal keratitis sometimes proceed to corneal perforation or develop keratoscleritis or endophthalmitis. Since these patients have a higher risk of graft rejection than patients with corneal opacification due to noninflammatory conditions, keratoplasty should be considered early in patients not responding to aggressive medical therapy to try and prevent these sight-threatening complications.
  
• Lamellar keratoplasty (LK) may be an option if the ulcer does not involve all corneal layers. Penetrating keratoplasty (PK) is indicated when there is a full-thickness corneal infection, corneal perforation, or recurrence after LK. If PK is performed, the excision should encompass the entire infiltrate plus 1 mm of clear cornea.

Note: Cyclosporine A (Restasis) has been shown to possess antifungal activity and may allow some degree of steroid-free inflammation control in a patient with a sight-threatening fungal keratitis. Topical cyclosporine may also help prevent allograft rejection in patients incurring corneal transplant after mycotic infections.