Fungal Keratitis

Overview

Fungal keratitis is an aggressive, sight-threatening corneal infection and a leading cause of corneal blindness in tropical and subtropical regions.² It is often caused by filamentous fungi such as Fusarium and Aspergillus species, or by yeasts, particularly Candida species, and is notoriously difficult to diagnose because clinical signs are frequently non-specific and overlap substantially with bacterial keratitis.¹

Epidemiology & Risk Factors

Fungal keratitis occurs particularly in contact lens wearers and in patients with systemic disease such as diabetes or immunosuppression.¹ Filamentous fungal keratitis (Fusarium, Aspergillus) is classically associated with vegetative or plant-matter trauma, especially in agricultural workers, and is more common in warm, humid climates. Candida keratitis tends to occur on a compromised ocular surface (chronic epithelial disease, prior herpetic keratitis, long-term topical steroid use) rather than after trauma. Rare and emerging organisms, such as Corynespora cassiicola, have also been reported, typically following agricultural trauma.³

Pathophysiology

Fungal organisms invade the corneal stroma following an epithelial breach (trauma) or on a chronically compromised ocular surface. Filamentous fungi characteristically penetrate deeply along stromal lamellae, often extending beyond the visible extent of the surface infiltrate — a key reason fungal ulcers are notoriously difficult to eradicate medically and often require deeper tissue sampling or surgical intervention. Fungal cell walls and secreted proteases contribute to progressive stromal necrosis.

Clinical Presentation

Patients present with pain, photophobia, redness, discharge, and decreased vision, often with a preceding history of vegetative trauma (branch, plant matter), contact lens wear, or chronic ocular surface disease. Onset and progression are often more indolent than bacterial keratitis, sometimes leading to delayed presentation or diagnosis.

Exam Findings

• Corneal infiltrate with feathery, fuzzy, or delicate branching (filamentous) margins — a suggestive but not definitive sign
• Satellite lesions (smaller infiltrates surrounding the main ulcer) — supportive of a fungal etiology
• Elevated, dry-appearing infiltrate surface (compared with the more mucoid appearance of bacterial infiltrates)
• Hypopyon, often disproportionately large relative to the size of the surface infiltrate given deep stromal extension
• Ring infiltrate in some cases
• Endothelial plaque may indicate deep stromal/endothelial extension

Differential Diagnosis

• Bacterial keratitis (often more acute, more mucoid infiltrate, but substantial clinical overlap)
• Acanthamoeba keratitis (radial perineural infiltrates, disproportionate pain, contact lens or contaminated water exposure)
• Herpetic stromal keratitis
• Sterile inflammatory infiltrates

Management

Diagnosis is challenging because clinical signs are often non-specific; a combination of in vivo confocal microscopy, fungal cultures, and corneal scraping with histopathological/microscopic examination (KOH prep, calcofluor white staining) is used, with cultures on specific fungal media held for at least 1–2 weeks given slower fungal growth compared with bacteria.¹ PCR-based and molecular sequencing methods are increasingly used for atypical or slow-growing/rare organisms.³

Treatment is based on topical antifungal agents, most commonly natamycin (particularly effective for filamentous fungi such as Fusarium) and voriconazole (effective against a broad range of filamentous fungi and yeasts, with good corneal penetration).¹ Treatment is prolonged, often for many weeks, and requires close monitoring for response.

For refractory or deep/severe cases, intracameral amphotericin B has emerging evidence of benefit as an adjunctive therapy: a systematic review and meta-analysis found improved ulcer healing rates, shortened healing time, reduced hypopyon duration, and a decreased need for therapeutic keratoplasty, without clear evidence of ICAMB-attributable ocular toxicity at commonly used doses — though the underlying evidence is primarily observational rather than from randomized trials.² In refractory cases unresponsive to medical therapy, therapeutic penetrating keratoplasty may be required.¹

Complications

• Deep stromal or endothelial extension leading to corneal perforation
• Endophthalmitis from intraocular fungal extension
• Need for therapeutic keratoplasty in medically refractory cases
• Permanent corneal scarring and significant visual loss

Clinical Pearls

• Suspect fungal keratitis after any vegetative/plant-matter trauma, especially with an indolent course not responding to standard antibacterial therapy
• Satellite lesions and a disproportionately large hypopyon relative to the surface infiltrate both suggest a fungal (rather than bacterial) cause
• Natamycin is often preferred for filamentous fungal keratitis; voriconazole has broader-spectrum activity against both filamentous fungi and yeasts¹
• Fungal cultures grow slowly — hold cultures for at least 1–2 weeks before calling them negative
• Intracameral amphotericin B is an emerging, promising adjunct for refractory disease, though evidence is still primarily observational²

Common Pitfalls

• Treating an indolent, slowly progressive corneal ulcer with antibacterial therapy alone without considering a fungal cause
• Stopping fungal cultures too early, before slow-growing organisms have had time to grow
• Underestimating the depth of fungal stromal invasion based on the visible surface infiltrate alone
• Using topical corticosteroids empirically in suspected infectious keratitis before a fungal cause has been excluded, which can worsen fungal infections
• Failing to consider rare/emerging fungal organisms in atypical presentations following agricultural trauma³