What is the diagnosis and treatment approach for a patient presenting with keratitis, considering their medical history and potential for infectious or fungal causes?

Diagnosis and Treatment of Keratitis

Immediate Diagnostic Approach

For suspected bacterial keratitis, begin empiric broad-spectrum antibiotic therapy immediately while simultaneously obtaining corneal cultures if the infiltrate is central, large (≥2mm), or associated with significant stromal involvement. 1, 2

Critical History Elements

• Contact lens details: wearing schedule, overnight wear, lens type, hygiene protocol, tap-water exposure, swimming/hot tub use while wearing lenses 1, 2
• Symptom characteristics: severity of pain, redness, discharge, photophobia, blurred vision, and exact duration 1, 2
• Risk factors: previous keratitis, HSV/VZV history, trauma, dry eye, recent ocular surgery (including refractive procedures), immunosuppression, diabetes, rosacea, MRSA history 1, 2
• Medication history: current/recent topical and systemic medications, allergies 1

Essential Physical Examination Findings

Slit-lamp biomicroscopy is mandatory and should specifically document:

• Infiltrate characteristics: location (central vs peripheral), size in millimeters, depth (superficial vs mid-stromal vs deep), margin definition (bacterial typically shows indistinct/feathery edges), density 1, 3
• Epithelial defect: presence, size, and shape using fluorescein staining 1, 3
• Surrounding stromal changes: edema, white cell infiltration, thinning, melting, neovascularization 1, 3
• Anterior chamber reaction: cell and flare, hypopyon (usually sterile in bacterial keratitis), fibrin 1, 3
• Eyelid assessment: lagophthalmos, trichiasis, meibomian gland dysfunction, blepharitis 1
• Facial examination: rosacea, herpes zoster 1, 2

When to Obtain Cultures and Smears

Cultures are NOT needed for most community-acquired cases that respond to empiric therapy. 1, 2

Mandatory culture indications:

• Central infiltrate or infiltrate ≥2mm 1, 2, 3
• Significant stromal involvement or corneal melting 1, 2
• Chronic or unresponsive to broad-spectrum antibiotics 1, 2
• History of corneal surgery 1, 2
• Atypical features suggesting fungal, amoebic, or mycobacterial infection 1, 2
• Multiple infiltrate locations 1

Culture technique:

• Obtain before initiating antibiotics when possible 1
• Use heat-sterilized platinum spatula, blade, or jeweler's forceps under slit-lamp magnification 1
• Scrape advancing borders of infected area, not just purulent material 1
• Inoculate directly onto culture media at bedside for maximum yield 1, 4
• Obtain Gram stain and Giemsa stain 1
• For suspected fungal: add Calcofluor-KOH stain (most sensitive), potassium hydroxide preparation 4

Treatment Algorithm

Bacterial Keratitis (Most Common)

First-line empiric therapy: Fortified vancomycin + fortified tobramycin 5

• This combination covers the most common Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) organisms 5
• Bacteria account for 83.4% of positive cultures 5
• Initiate immediately for sight-threatening cases while awaiting culture results 1, 6

Treatment goals:

• Eradicate microorganisms from corneal tissues 1
• Reduce pain and discharge 1
• Resolve corneal and anterior chamber inflammation 1
• Minimize stromal infiltration, tissue loss, and scarring 1
• Heal epithelial defect and restore corneal integrity 1
• Optimize visual function 1

Fungal Keratitis

Suspect fungal etiology when infiltrate shows feathery, finger-like projections with indistinct elevated margins—this appearance is pathognomonic. 4

However, clinical appearance alone is insufficient: cornea specialists correctly differentiate bacterial from fungal keratitis in less than 70% of cases based on appearance. 1, 4

Treatment for fungal keratitis:

• Natamycin 5% ophthalmic suspension is the FDA-approved first-line agent 7
• Initial dosing: one drop hourly or every 2 hours 7
• After 3-4 days, reduce to 6-8 times daily 7
• Continue for 14-21 days or until resolution 7
• Indicated for Fusarium solani keratitis, fungal blepharitis, and conjunctivitis 7

Diagnostic confirmation:

• Calcofluor-KOH stain is most sensitive for fungal elements 4
• Confocal microscopy shows high sensitivity (66-74% for fungal, 80-100% for Acanthamoeba) and specificity (78-100% for fungal, 84-100% for Acanthamoeba) 8
• Most common filamentous fungi: Fusarium, Aspergillus, Dematiaceous fungi 4

Viral Keratitis

Herpesviruses are the predominant cause of viral keratitis and a leading cause of corneal opacity. 9

• Diagnosis requires recognition of characteristic dendritic or geographic epithelial defects 9
• Immunosuppressed patients display recurring disease with pronounced severity 9
• Early diagnosis is beneficial for disease management and treatment response 9

Critical Pitfalls to Avoid

• Never perform aqueous or vitreous taps for hypopyon in bacterial keratitis unless there is high suspicion of endophthalmitis (post-surgery, perforating trauma, sepsis)—hypopyon is usually sterile 1, 2
• Do not empirically use corticosteroids before ruling out fungal infection, as this worsens fungal keratitis outcomes 4
• Distinguish epithelial staining from pooling of stain in areas of corneal thinning by wicking away with cotton swab 2
• Avoid tetracaine for anesthesia before cultures due to antimicrobial effects; avoid preservative-containing anesthetics 1
• Do not delay treatment while awaiting culture results in sight-threatening cases 1, 6, 10
• Recognize that highly virulent organisms (Pseudomonas, Streptococcus pneumoniae, Neisseria gonorrhoeae) cause rapid tissue destruction requiring urgent intervention 1
• Consider polymicrobial infection in patients with multiple systemic risk factors 1

Emerging Diagnostic and Treatment Modalities

• Confocal microscopy aids in vivo identification of fungal and Acanthamoeba keratitis with high sensitivity and specificity 4, 8
• PCR and metagenomic deep sequencing are promising but cannot distinguish viable organisms from antigenic material 4, 5
• PACK-CXL (photoactivated chromophore corneal collagen cross-linking) may benefit patients with corneal melting 5
• Rose Bengal photodynamic antimicrobial therapy (RB-PDAT) shows promise for fungal keratitis 5