Medication Summary
The antifungal agents used include polyenes (eg, natamycin, amphotericin B), azoles (eg, ketoconazole, miconazole, fluconazole, itraconazole), and fluorinated pyrimidines (eg, flucytosine). Amphotericin B is the drug of choice in fungal keratitis caused by yeasts. Natamycin has a broad-spectrum of activity against filamentous organisms. Oral fluconazole and ketoconazole should be considered in the management of deep fungal keratitis.
Antifungal agents
Class Summary
Their mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.
Natamycin (Natacyn)
Initial drug of choice in Fusarium keratitis. 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 polyenesterol complex that alters membrane permeability, depleting essential cellular constituents. Activity against fungi is dose-related but 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, may help to reduce dosage gradually at 4- to 7-day intervals to ensure elimination of the organism.
Amphotericin B 0.1-0.25% (Amphocin, Fungizone)
Polyene antibiotic produced by a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols (eg, ergosterol) in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death. First agent of choice in corneal infections due to yeasts, such as Candida species.
Ketoconazole (Nizoral)
Fungistatic activity. Imidazole broad-spectrum antifungal agent; inhibits synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.
Often used systemically in the treatment of deep fungal infections. Studies have confirmed intraocular penetration in keratitis due to Fusarium, Aspergillus, Curvularia, and Candida species.
Fluconazole (Diflucan)
Alternative drug to ketoconazole in the treatment of deep fungal keratitis caused by a variety of fungi. Fungistatic activity. Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes.
Flucytosine 1% (Ancobon)
Converted to fluorouracil after penetrating fungal cells. Inhibits RNA and protein synthesis. Active against Candida and Cryptococcus and generally used in combination with amphotericin B. High incidence of acquired resistance has occurred; therefore, combined treatment with other agents is recommended.
In the treatment of fungal keratitis, polyenes and imidazoles have mostly replaced flucytosine.
Voriconazole (Vfend)
Voriconazole is the drug of choice for Aspergillus fumigatus, Aspergillus flavus, Fusarium species, Blastomyces dermatitidis, Coccidioides immitis, Curvularia species, Candida albicans, and Cryptococcus neoformans.
The mode of action is the inhibition of fungal cytochrome P-450, preventing fungal ergosterol biosynthesis, thus damaging the fungal cell wall. A 1% solution is used for local instillation, every hour during the day and every 2 hours during the night.
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Fungal corneal ulcer.
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Perforated fungal ulcer.
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Fungal infection under treatment.
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Perforated fungal corneal ulcer.
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Fungal ulcer in an elderly woman.
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Fungal ulcer.
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Fungal corneal ulcer, with excessive vascularization.
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Marginal ulcer, fungus positive.
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Healed fungal ulcer.
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Fungal keratitis.
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Corneal perforation, blocked by a crystalline lens and being covered by epithelium.
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Fungal keratitis, being controlled.
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Fungal infection.
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Fungal infection.
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Fungal abscess.
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Fungal corneal abscess/ulcer. A proven case of fungal infection, 5 days' duration. Intense infiltration around the abscess.
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Surgical trauma producing edema and striate keratitis. The corneal channels stand out in semiopaque corneal tissue, since they themselves are no-tissue spaces.
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Surgical trauma producing edema and striate keratitis. The corneal channels stand out in semiopaque corneal tissue, since they themselves are no-tissue spaces.
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A network of channels is visible in a case of megalocornea with faint opacification of stroma. The channels stand out as nonstructures.
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This kind of opacification is termed keratitis. Anatomically, it appears to be a microchannel structure.
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A network of corneal channels stands out inside the arcus senilis of an old patient. Whatever causes the opacification in the corneal tissue is not able to opacify the emptiness of corneal channels.
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Network of corneal channels in a 92-year-old patient.
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The corneal channels open in the lucid interval channel of Singh.
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Peripheral corneal channel network and canal of Singh in 3 dimensions.
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Optical section of corneal channels in a case of arcus senilis.
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The lucid interval in optical section clearly shows its triangular configuration and an anterior and posterior wall. The apex continues towards corneal channels in the stroma. The lucid interval channel is connected to limbal lymphatics.
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The lucid interval channel is connected to the lymphatics at the limbus and the corneal channels centrally.
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A blunt wire of 100 micrometers diameter has been pushed into the canal of Singh.
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A 230-micrometer blunt cannula in the canal of Singh.
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This networklike pattern of fungal corneal infection is explained only by the preferential path of spread through the corneal channel network.
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The fungal infection travels in various directions. Also seen are satellite lesions. Satellite lesions and other appearances are explained by the presence of channels in the cornea.
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Notice centrifugal, linear, circular, and satellitelike spread of fungal infection through the corneal channels.
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This patient presented with infection of the lucid interval of Singh without any evidence of corneal ulceration as a starting point, suggesting systemic spread. A satellite of infection is seen near the 6-o'clock position.
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Same patient with infection of the lucid interval of Singh without any evidence of corneal ulceration as a starting point, suggesting systemic spread. A big and a small satellite at the 6-o'clock position.
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The same eye showing the spread of fungal infection on the nasal side of the Singh canal. This patient showed no evidence of corneal injury, thus a systemic origin of infection is a distinct possibility.
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The whole of the infected lucid interval canal of Singh was opened. The scraping showed the presence of hyphae. The patient was treated by oral medication, local drops, and intracorneal antifungal voriconazole injections. Final vision was 6/6 uncorrected. There was no recurrence.
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Optical coherence tomography scans clearly showing the canal of Singh connected to the Schlemm canal.
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Optical coherence tomography scans clearly showing the canal of Singh connected to the Schlemm canal.
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Fungal keratitis under treatment. The infection has spread into the nearby lucid interval canal of Singh.
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The same case as in the previous photo. Optical coherence tomography scans shows the presence of exudates in the lucid interval canal of Singh and the adjoining trabecular meshwork.
