Fungal, amoebic and herpetic keratitis

4. Fungal Keratitis: Filamentous Moulds vs Yeasts

Fungal keratitis accounts for a significant proportion of infectious keratitis in agricultural regions, tropical climates, and immunocompromised hosts.

Filamentous Keratitis (Fusarium, Aspergillus)

• Pathogenesis: Fungal hyphae penetrate vertically through intact collagen lamellae into deep stroma and Descemet membrane, explaining poor response to superficial debridement and high recurrence rates.
• Medical Therapy: Natamycin 5% ophthalmic suspension is the polyene drug of choice, superior to voriconazole for filamentous keratitis (Fusarium in particular, as demonstrated by the MUTT I trial). It binds fungal ergosterol, increasing cell membrane permeability. Topical voriconazole or systemic antifungal treatment may be selected by a specialist according to organism and extension. MUTT II did not show an overall benefit from routinely adding oral voriconazole in severe filamentous ulcers and found more adverse events; deep invasion alone is not an automatic oral-voriconazole prescription.

Yeast Keratitis (Candida albicans)

• Medical Therapy: Topical Amphotericin B 0.15% (polyene) is the first-line agent, supplemented by topical Voriconazole 1% or oral Fluconazole (200 mg daily).

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5. Acanthamoeba Keratitis

Acanthamoeba is a ubiquitous, free-living protozoan that exists in two forms: a motile, infective trophozoite and a dormant, highly resilient double-walled cyst (resistant to chlorine, desiccation, and freezing).

Clinical Presentation and Progression

• Risk Factors: Contact lens wearers who use domestic tap water for lens care, wear lenses in swimming pools or hot tubs, or use homemade saline solutions.
• Hallmark Symptom: Excruciating, severe ocular pain out of proportion to clinical signs, driven by perineural invasion.
• Clinical Staging:
  1. Early Phase: Punctate epithelial erosions, microcystic epitheliopathy, and pseudo-dendrites (frequently misdiagnosed as Herpes simplex virus).
  2. Intermediate Phase: Radial keratoneuritis (infiltrates tracking along corneal nerves, characteristic) and limbitis.
  3. Late Phase: Coalescence into a full-thickness ring infiltrate (annular stromal abscess), progressive stromal melting, sclerokeratitis, and persistent anterior uveitis.

Diagnostic Techniques

• In Vivo Confocal Microscopy (IVCM): Rapid non-invasive optical biopsy visualising bright, highly reflective, double-walled polygonal or spherical cysts ($10–25\,\mu\text{m}$) within the epithelial and stromal layers.
• Culture: Non-nutrient agar (NNA) seeded with a lawn of heat-killed E. coli; trophozoites leave clear migratory feeding tracks visible under low-power light microscopy within 2 to 7 days.

Medical Pharmacotherapy

Antiamoebic treatment is prolonged and specialist-led. The EU-authorised Akantior formulation contains polihexanide 0.8 mg/mL (0.08%) and uses a labelled intensive schedule followed by tapering. Other specialist protocols use biguanides such as PHMB or chlorhexidine, sometimes with a diamidine. Those concentrations and schedules are not interchangeable, and combination therapy is not required by every regimen.

Treatment intensity and duration depend on the selected preparation, clinical response and specialist monitoring. Recrudescence can occur because cysts persist; do not set one unverified minimum duration for all patients. Reassess persistent inflammation for active infection, toxicity and associated scleritis.

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6. Viral Keratitis: Herpes Simplex Virus (HSV)

Herpes simplex virus type 1 (HSV-1) establishes primary mucosal infection before undergoing retrograde axonal transport along sensory nerve branches to reside in lifelong latency within the sensory trigeminal (Gasserian) ganglion. Periodic viral reactivation travels anterograde to cause recurrent ocular disease.

1. Epithelial Keratitis (Active Replicative Infection)

• Biomicroscopy: True dendritic ulcer—an arborising, linear branching epithelial defect with swollen margins and characteristic terminal bulbs. Fluorescein stains the central ulcer bed where basement membrane is exposed; rose bengal or lissamine green stains the devitalised, virus-laden epithelial cells at the ulcer periphery.
• Geographic (Amoeboid) Ulcer: A broad, irregularly shaped epithelial ulcer with scalloped dendritic margins, classically precipitated by the inappropriate administration of topical corticosteroids.
• Treatment: Topical Ganciclovir 0.15% gel (5 times daily until healed, then 3 times daily for 7 days) or topical Aciclovir 3% ointment; or systemic oral Aciclovir 400 mg 5 times daily (or Valaciclovir 500 mg BD). Topical corticosteroids are strictly contraindicated in active epithelial keratitis!

2. Stromal Keratitis: Immune Disciform vs Necrotising

• Immune Stromal (Disciform) Keratitis: Stromal inflammation may be predominantly immune mediated, while endotheliitis can involve active viral infection. Distinguish epithelial, stromal and endothelial disease when selecting antiviral and steroid treatment. Biomicroscopy demonstrates a discrete, round/oval zone of stromal oedema with overlying intact epithelium, keratic precipitates (KPs) often beneath the area of oedema, and Descemet folds, without significant stromal necrosis. Management: use a specialist-selected topical corticosteroid with appropriate antiviral coverage and close epithelial/pressure review. The taper follows inflammatory response. Antiviral route and dose depend on epithelial disease, active endotheliitis versus suppression, renal function and local protocol; an oral suppressive dose is not a universal treatment for active infection.
• Necrotising Stromal Keratitis: Direct active viral invasion combined with destructive host immune response. Features dense, white, suppurative stromal infiltrates, severe tissue necrosis, ulceration, and rapid corneal thinning. Requires high-dose systemic antiviral therapy (oral aciclovir 800 mg 5 times daily or valaciclovir 1000 mg TDS) combined judiciously with topical steroids once epithelial closure is secure.

Summary of Herpetic Eye Disease Study (HEDS) Milestones

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7. Varicella Zoster Virus: Herpes Zoster Ophthalmicus (HZO)

Varicella zoster virus (VZV) reactivates from the ophthalmic division ($V_1$) of the trigeminal ganglion, producing a painful dermatomal vesicular eruption usually respecting the facial midline; atypical or disseminated presentations require broader assessment.

• Hutchinson's Sign: Vesicular involvement of the tip, ala, or side of the nose—innervated by the external nasal branch of the nasociliary nerve ($V_1$)—predicts a 3- to 4-fold elevated risk of ocular involvement (corneal inflammation, anterior uveitis, glaucoma).
• Corneal Pseudodendrites: Unlike HSV, HZO produces pseudodendrites (microdendrites): elevated, mucous epithelial plaques with blunt, tapered ends, lacking terminal end-bulbs, which stain minimally with fluorescein but intensely with rose bengal.
• Other Ocular Features: Nummular stromal keratitis, disciform keratitis, neurotrophic keratopathy (secondary to sensory denervation), lipid keratopathy, and post-herpetic neuralgia (PHN).
• Therapy: Oral Aciclovir 800 mg 5 times daily, Valaciclovir 1000 mg TDS, or Famciclovir 500 mg TDS for 7 to 10 days, started promptly, ideally within 72 hours of rash onset. Later treatment can still be appropriate with ongoing lesions, ocular involvement or immunosuppression. Antivirals do not guarantee prevention of post-herpetic neuralgia; adjust systemic dosing for renal function and the clinical context.

Sources: EMA Akantior, MUTT II and AAO bacterial keratitis.