Corneal Ulcer - Ophthalmology Notes

Definition

General Principles

Risk Factors

• Contact lens wear (most important) - especially extended-wear soft lenses; poor hygiene, but even meticulous care does not eliminate risk; daily disposable lenses are not immune
• Trauma (including LASIK)
• Ocular surface disease (dry eye, neurotrophic cornea, trichiasis)
• Long-term topical steroids
• Systemic immunosuppression / diabetes
• Prior corneal surgery / transplant

Key Rule

The causative organism cannot be reliably determined from the morphological appearance of the ulcer alone - empirical broad-spectrum treatment is usually initiated before microscopy results.

Investigations - Corneal Scraping

1. Instil preservative-free topical anaesthetic (proxymetacaine 0.5%)
2. Use No. 11 scalpel blade, 20/21-gauge needle bent tip, or Kimura spatula
3. Remove loose mucus and necrotic tissue first
4. Scrape margins and base of lesion
5. Thin smear onto glass slides for microscopy (Gram stain)
6. Re-scrape for each culture medium

Stains

1. Bacterial Keratitis

Pathogens

• Pseudomonas aeruginosa - Gram-negative rod; most common in contact lens wearers (>60% of contact lens-related keratitis); typically aggressive
• Staphylococcus aureus - Gram-positive, coagulase-positive; focal, fairly well-defined white/yellow-white infiltrate
• Streptococcus spp. - often aggressive
• Special pathogens that can penetrate intact epithelium: N. gonorrhoeae, N. meningitidis, C. diphtheriae, H. influenzae (usually with severe conjunctivitis)

Clinical Features

• Pain, photophobia, discharge, blurred vision
• White/yellow-white stromal infiltrate with overlying epithelial defect
• Surrounding stromal oedema and haze
• Anterior chamber reaction, hypopyon possible

Treatment

• Discontinue contact lenses (mandatory)
• Consider hospital admission for aggressive disease, poor compliance, or only eye
• Clear plastic eye shield if significant thinning/perforation

• Initiate empirical broad-spectrum coverage
• Fluoroquinolone monotherapy (ciprofloxacin or ofloxacin) is usual first choice - as effective as duotherapy, less surface toxicity
• Newer fluoroquinolones (moxifloxacin, gatifloxacin, besifloxacin) for resistant organisms
• Fortified antibiotics (combined Gram-positive + Gram-negative): e.g. cefuroxime 5% + gentamicin 1.5% (duotherapy), or fortified tobramycin/gentamicin + cephalosporin
• Initial: hourly instillation day and night for 24-48 hours, then taper by clinical response
• Daily follow-up until response noted

• Controversial; do NOT start until clinical improvement on antibiotics (typically 24-48 h)
• Avoid if significant thinning or delayed epithelial healing
• Can precipitate corneal melting
• Options: dexamethasone 0.1% q2h or prednisolone 0.5-1% qid

• N. meningitidis: IM benzylpenicillin or ceftriaxone (life-saving)
• H. influenzae: oral amoxicillin-clavulanate
• N. gonorrhoeae: 3rd-generation cephalosporin (ceftriaxone)
• Severe thinning/threatened perforation: oral ciprofloxacin + doxycycline 100 mg bd (anticollagenase effect)
• Scleral involvement: oral/IV treatment

TIP: Fluoroquinolones have limited activity against Gram-positives, especially Streptococcus.

Management of Treatment Failure

• Do not confuse failed re-epithelialization with continued infection (drug toxicity can mimic this)
• If no improvement at 24-48 h: review antibiotic regimen; contact microbiology lab
• If no improvement after further 48 h: suspend treatment for 24 h, then re-scrape with broader media
• Corneal biopsy if cultures remain negative
• Consider PACK-CXL (photoactivated chromophore for corneal cross-linking) for suspected corneal melting or bacterial resistance
• Excisional keratoplasty (penetrating or deep lamellar) for medically resistant cases or perforation

Complications

• Corneal perforation: manage with bandage contact lens (small), tissue glue, or penetrating keratoplasty (large)
• Endophthalmitis (rare)
• Residual scarring - may require keratoplasty
• Irregular astigmatism - may need rigid contact lens (not before 3 months post re-epithelialization)
• Secondary cataract

2. Fungal Keratitis

Epidemiology/Pathogenesis

• Rare in temperate climates; major cause of visual loss in tropical/low-income countries
• Yeasts (e.g. Candida) - most common in temperate climates, immunocompromised hosts
• Filamentous fungi (Fusarium, Aspergillus) - most common in tropical climates; often follows trauma involving plant matter or agricultural tools; aggressive course
• Corneal perforation common; visual prognosis frequently poor

Predisposing Factors

• Chronic ocular surface disease
• Long-term topical steroids
• Prior corneal transplant
• Contact lens wear
• Systemic immunosuppression, diabetes
• Filamentous: trauma with vegetable/plant matter

Clinical Features

• Gradual onset: pain, grittiness, photophobia, blurred vision, watery/mucopurulent discharge
• Diagnosis frequently delayed; bacterial infection often initially presumed
• Candida: yellow-white, densely suppurative infiltrate
• Filamentous: grey or yellow-white stromal infiltrate with indistinct fluffy margins; satellite infiltrates; feathery edges; endothelial plaque
• Signs not reliably distinguishable from bacterial infection

Investigations

• Corneal scraping - same principles as bacterial
• PCR (highly sensitive, ~90%) - may be investigation of choice
• Confocal microscopy - identifies organisms in vivo (not widely available outside tertiary centres)
• Corneal biopsy if no improvement after 3-4 days or no growth from scrapings after 1 week (filamentous fungi tend to proliferate just anterior to Descemet membrane - need deep stromal specimen)
• Anterior chamber tap for resistant cases with endothelial exudate

Treatment

• Improvement slower than bacterial infection; hospital admission usually required
• Remove epithelium over lesion to enhance antifungal penetration
• Regularly debride mucus and necrotic tissue

• Candida: amphotericin B 0.15% or econazole 1% (alternatives: natamycin 5%, fluconazole 2%, voriconazole 1-2%)
• Filamentous: natamycin 5% or econazole 1% (alternatives: amphotericin B 0.15%, miconazole 1%, voriconazole 1-2%)
• Natamycin is the only FDA-approved topical agent for mycotic keratitis

• Voriconazole 400 mg bd day 1, then 200 mg bd
• Itraconazole 200 mg od (reduced to 100 mg od)
• Fluconazole 200 mg bd

• Broad-spectrum antibiotic to prevent/address bacterial co-infection
• Cycloplegia
• Doxycycline 100 mg bd for anticollagenase effect if significant thinning
• Subconjunctival fluconazole in severe cases
• Superficial keratectomy to debulk lesion
• Therapeutic keratoplasty (penetrating or DALK) if medically refractory or following perforation
• Anterior chamber washout + intracameral antifungal for unresponsive cases with enlarging endothelial exudation

3. Herpes Simplex Keratitis (HSK)

Epithelial HSK (Dendritic / Geographic Ulcer)

• Most common form; due to active viral replication
• Dendritic ulcer: branching epithelial ulcer with terminal bulbs; stains with fluorescein (bed) and rose Bengal / lissamine green (margins and surrounding cells)
• Geographic (amoeboid) ulcer: enlarged dendritic ulcer with irregular map-like margins (often follows steroid misuse)
• Reduced corneal sensation (corneal hypoaesthesia) is characteristic
• Mild subepithelial haze may persist after healing

• Topical antivirals: aciclovir 3% ointment 5 times/day, or ganciclovir 0.15% gel 5 times/day - usually continued until ulcer healed + 3 days
• Oral aciclovir 400 mg 5 times/day or valaciclovir 500 mg bd as alternative/adjunct
• Steroids are contraindicated in active epithelial disease (may exacerbate viral replication)
• Debridement of infected epithelium (gentle cotton swab) can reduce viral load - often combined with antivirals

Stromal HSK

• Central disc-shaped stromal oedema with Descemet folds
• Wessely immune ring (antigen-antibody precipitate at periphery)
• Mild keratic precipitates
• Treatment: topical steroids + antiviral cover (prednisolone 1% or dexamethasone 0.1% qid, taper over ≥4 weeks); IOP monitoring; cycloplegia if needed

• Difficult to distinguish from severe disciform
• Requires antivirals; steroids used cautiously

Prophylaxis

• Long-term oral aciclovir 400 mg bd or valaciclovir 500 mg od reduces recurrence frequency (HEDS trial)

4. Herpes Zoster Ophthalmicus (HZO) / VZV Keratitis

• Reactivation of VZV in ophthalmic division of trigeminal nerve (V1)
• Hutchinson's sign (tip/side of nose vesicles - nasociliary nerve involvement) predicts ocular involvement
• Corneal manifestations: epithelial keratitis (pseudodendrites - lack terminal bulbs), stromal keratitis, neurotrophic keratitis, disciform keratitis
• Pseudodendrites distinguished from HSV dendrites: coarser, do not have true terminal bulbs, mucus plaques

• Systemic antivirals within 72 hours of rash onset (reduces severity, duration, post-herpetic neuralgia, and late ophthalmic complications by ~50%)
• Aciclovir 800 mg 5 times/day for 7-10 days, OR valaciclovir 1 g tds or famciclovir 250-500 mg tds (more convenient, equally effective)
• IV aciclovir 5-10 mg/kg tds: for severe disease, encephalitis, moderate-severe immunocompromise
• Systemic steroids (prednisolone 60 mg od tapering over 12 days): for moderate-severe disease + neurological complications; only with antiviral cover; avoid in immunodeficiency
• Topical steroids for stromal/disciform keratitis with antiviral cover
• Do NOT use IDU or adenine arabinoside (not effective for VZV)

5. Acanthamoeba Keratitis (Protozoan Keratitis)

Epidemiology

• Strongly associated with contact lens wear (particularly with use of tap water for lens care, homemade saline)
• Also following ocular trauma with soil or contaminated water

Clinical Features - Key Signs

• Severe pain out of proportion to signs (disproportionate pain)
• Perineural infiltrates (radial keratoneuritis) - pathognomonic if present; fine grey infiltrates tracking along corneal nerves
• Ring infiltrate - classic but late sign (stromal ring abscess)
• Epithelial irregularity early; pseudodendrites (mimics HSV - common cause of initial misdiagnosis)
• Can be associated with scleritis

Investigations

• Confocal microscopy - visualises cysts in vivo
• Calcofluor white stain or acridine orange - highly specific for Acanthamoeba cysts
• PCR - highly sensitive
• Culture on non-nutrient agar seeded with E. coli

Treatment

• Prolonged (often 12 months or more)
• Polyhexamethylene biguanide (PHMB) 0.02% + propamidine isethionate (Brolene) 0.1% is the standard dual therapy
• Chlorhexidine 0.02% is an alternative to PHMB
• Hourly instillation initially, then taper
• Oral voriconazole may be added for severe/resistant cases
• Penetrating keratoplasty for medically resistant cases (risk of re-infection in graft)

6. Interstitial Keratitis (Syphilitic)

• Congenital syphilis (Treponema pallidum): presents age 5-25 years; bilateral in 80%
• Deep stromal vascularization + cellular infiltration + 'salmon patch' appearance (limbitis + still-perfused vessels)
• Granulomatous anterior uveitis
• After months: vessels become non-perfused ('ghost vessels')
• Healed stage: ghost vessels, feathery deep stromal scarring
• Treatment: topical steroids + cycloplegics + systemic penicillin (genitourinary/ID specialist)

Complications of Corneal Ulcer (General)

Prognosis

Quick Differential Summary