Fungal Keratitis

Fungal keratitis.

Signs and Symptoms: Fungal keratitis shows no predilection for age, gender or race, although those with compromised immunity are especially prone. Risk factors include ocular trauma--particularly if organic vegetative matter is involved--topical steroid therapy and preexisting ocular or systemic immunosuppressive diseases. Those who work with plants may be at greater risk. Fungal infections are also more common in tropical environments. An altered epithelial barrier increases the threat. Pain is typically severe at first, but may diminish later as the corneal nerves become damaged.

In the cornea, filamentary fungal infections initially produce a feathery, branching pattern. The cornea takes on a dull gray appearance with possible heaping of epithelium and a dry, rough texture. Typically a severe anterior uveitis and plasmoid aqueous with hypopyon appears. The characteristic corneal appearance disappears later on as the fungal keratitis begins to resemble advanced bacterial keratitis. Misdiagnosis at this point is likely. Yeast infections, however, remain localized, with a "button appearance," an expanding stromal infiltrate and a relatively small epithelial ulceration.

Pathophysiology: There are two types of fungi, molds and yeasts. Molds (filamentary fungi) are further subdivided into septate (the most common causes of fungal keratitis) and non-septate organisms. They produce feathery colonies that join together to produce hyphae. Yeasts, however, form pseudohyphae. The non-septate filamentary fungi are responsible for orbital disease, but rarely infect the cornea. Of all possible fungal infections of the cornea, the vast majority is caused by Fusarium, Aspergillus (both filamentary fungi) and Candida (a yeast).

The Fluoroquinolone Advantage The fluorinated quinolones—Ciloxan (ciprofloxacin, Alcon Laboratories), Ocuflox (ofloxacin, Allergan), Quixin (levofloxacin, Santen) and Chibroxin (norfloxacin, Merck)--have revolutionized the standard of care for cases of infection or increased risk of infection of the conjunctiva, cornea, anterior segment and posterior segment. More potent and effective "off of the shelf" than previous antibiotics, they have all but eliminated the need for fortified compounds in treating moderate to severe infections, reducing expense, error and the risk of contamination during preparation.

Organic trauma is the major cause of filamentary fungal keratitis. Immunosuppression or a chronically compromised epithelial barrier usually causes yeast infection. A disrupted corneal defense system can allow for Candida infection, opportunistic yeast that is part of the normal human flora. Once fungi have colonized the stroma, they penetrate into the deeper layers and are inaccessible to diagnostic and therapeutic measures. The organisms' large size precludes complete ingestion by inflammatory cells from the host's immune response.

Management: Diagnosis of fungal keratitis begins with clinical suspicion; either culture or corneal biopsy confirms it. Diagnosis typically occurs late, as many frequently misdiagnose fungal keratitis as bacterial keratitis. Clinicians often consider fungal keratitis only after a presumed bacterial keratitis worsens during antibiotic therapy.

The standard corneal scraping performed in bacterial keratitis is acceptable; however, in addition to regular cultures with blood and chocolate agar incubated at 370° C for bacteria, inoculate additional blood and Sabouraud agar plates at room temperature. Anti-fungal sensitivity testing is unreliable and correlates poorly with clinical efficacy. Reserve corneal biopsy for cases where you suspect fungal infection yet cultures are negative, or in cases where ulceration persists despite aggressive antimicrobial therapy.

Treating fungal keratitis is difficult. Most antifungal medications are merely fungistatic, and require an intact immune system and prolonged therapeutic course. Except for Natacyn (natamycin 5%, Alcon), all antifungal medications must be adapted for ophthalmic use from systemic drugs. The result: considerable ophthalmic toxicity.

Drug classes used to treat fungal keratitis include the polyene antibiotics (nystatin, amphotericin B, natamycin); pyrimidine analogs (flucytosine); imidazoles (clortrimazole, miconozole, ketoconazole); triazoles (fluconazole, itraconazole); and silver sulfadiazine. Steroids are contraindicated; they will exacerbate the disease. For filamentary fungal infections, topical Natacyn is the first choice. Alternatives include amphotericin B 0.15% and flucytosine 1% 150 mg/kg--the same therapy for yeast infections. An alternative treatment in yeast infections is fluconazole 0.5% 200 mg and miconozole 1%. All therapies are indicated hourly around the clock.

Clinical Pearls:

• It is practically impossible to differentiate bacterial keratitis from fungal keratitis on clinical judgment alone, especially in advanced cases.
• A history of injury with vegetative matter is not necessary for a patient to develop fungal keratitis. Remember the strong role of immunosuppression in the development of Candida infections.
• In our combined experience, we have only once seen a case where a patient who actually underwent ocular trauma from vegetative matter progressed to fungal keratitis. We do not recommended that a patient receive prophylactic antifungal therapy in these instances.

Other reports in this section

• Terrien's Marginal Degeneration
• Acanthamoeba Keratitis
• Fungal Keratitis
• Filamentary Keratitis
• Bacterial Keratitis
• Understanding Corneal Topography