Corneal Ulcer

A corneal ulcer (microbial keratitis) is an infection of the corneal stroma representing an ophthalmic emergency, most commonly caused by bacterial infection in contact lens wearers, requiring urgent assessment and intensive topical antibiotic therapy.

PLAB 1UKMLA0 questions

Key Facts

Microbial keratitis is the most serious complication of contact lens wear, with incidence 1.2 per 10,000 daily-wear soft lens users per year Pseudomonas aeruginosa is the most common cause in contact lens wearers; Staphylococcus aureus in non-lens wearers Acanthamoeba keratitis is associated with contact lens wear and exposure to contaminated water, causing severe pain disproportionate to signs Presents with painful red eye, photophobia, tearing, reduced visual acuity, and visible white corneal infiltrate/ulcer Corneal scrape for microscopy, culture, and sensitivity before starting treatment (if available within 1 hour) Intensive topical fluoroquinolone monotherapy (ofloxacin 0.3% or levofloxacin 0.5%) hourly, or dual fortified antibiotics (cefuroxime 5% + gentamicin 1.5%) for severe ulcers Fungal keratitis should be suspected with agricultural/organic matter injury; treated with natamycin 5% or voriconazole 1% drops Never prescribe topical steroids without specialist ophthalmology input in corneal infection

Overview

Key Facts

A corneal ulcer (microbial keratitis) is an infectious process involving loss of corneal epithelium with underlying stromal infiltration and necrosis. It is an ophthalmic emergency requiring prompt diagnosis and treatment to prevent corneal perforation and permanent visual loss.

Epidemiology

  • Incidence: 27,000-30,000 cases per year in the UK
  • Contact lens-related keratitis: 1.2 per 10,000 daily-wear soft lens users per year
  • Risk increases 5-15× with overnight lens wear
  • Agricultural workers at risk of fungal keratitis

Aetiology

  • Bacterial (most common): Pseudomonas aeruginosa (contact lens), Staphylococcus aureus, Streptococcus pneumoniae, Moraxella
  • Viral: Herpes simplex keratitis (dendritic ulcer), Herpes zoster ophthalmicus
  • Fungal: Fusarium, Aspergillus (tropical, agricultural injury)
  • Protozoal: Acanthamoeba (contact lens, contaminated water)
  • Risk factors: contact lens wear (especially extended wear, poor hygiene), corneal trauma, dry eye, corneal surgery (LASIK), immunosuppression, topical steroid use

Pathophysiology

  • Disruption of corneal epithelial barrier allows organism entry
  • Microbial invasion of corneal stroma triggers inflammatory response
  • Neutrophil infiltration causes stromal necrosis and ulceration
  • Proteolytic enzymes (from organisms and neutrophils) cause stromal melting
  • Endotoxins (Pseudomonas) cause rapid corneal destruction
  • Untreated, leads to corneal perforation, endophthalmitis, and loss of eye

Clinical Presentation

Typical Presentation

  • Acute painful red eye (often severe)
  • Photophobia
  • Tearing and discharge (mucopurulent in bacterial)
  • Reduced visual acuity
  • Foreign body sensation
  • Contact lens wearer history

Examination Findings

  • White/grey corneal infiltrate with overlying epithelial defect (stains with fluorescein)
  • Conjunctival injection (often marked)
  • Anterior chamber reaction (cells and flare)
  • Hypopyon (layered white cells in anterior chamber) in severe cases
  • Lid oedema

Organism-Specific Features

  • Pseudomonas: rapidly progressive, large ulcer, green-yellow mucopurulent discharge, ring infiltrate
  • Acanthamoeba: severe pain disproportionate to signs, perineural infiltrates (radial keratoneuritis), ring infiltrate
  • Herpes simplex: dendritic or geographic ulcer pattern, reduced corneal sensation
  • Fungal: feathery margins, satellite lesions, slow progression

Red Flags

  • Rapidly enlarging ulcer
  • Hypopyon
  • Corneal thinning or descemetocoele
  • Central/paracentral location threatening visual axis
  • Failed initial treatment

Differential Diagnosis

DiagnosisKey FeaturesInvestigation
Herpes simplex keratitisDendritic ulcer, reduced corneal sensationFluorescein staining, PCR
Marginal keratitisPeripheral, small, associated blepharitis, less painfulClinical, response to steroids
Corneal abrasionHistory of trauma, epithelial defect without infiltrateFluorescein staining
Anterior uveitisPain, photophobia, cells/flare, no corneal defectSlit lamp examination
Contact lens-related sterile infiltrateSmaller, less symptomatic, no organisms on cultureCorneal scrape
Corneal foreign bodyVisible FB, surrounding rust ringSlit lamp examination

Diagnosis / Investigation

Bedside

  • Visual acuity
  • Slit lamp biomicroscopy: ulcer size, depth, location, anterior chamber activity
  • Fluorescein staining: epithelial defect
  • Corneal sensation testing (reduced in HSV, Acanthamoeba)

Corneal Scrape

  • Corneal scrape for microscopy (Gram stain), culture (blood agar, chocolate agar, Sabouraud for fungi), and sensitivity
  • Perform before starting antibiotics if specialist available within 1 hour
  • Consider confocal microscopy for Acanthamoeba
  • PCR for HSV, Acanthamoeba in atypical cases

Bloods

  • Not routinely required
  • Consider HbA1c if recurrent infections (diabetes screening)
  • HIV test if atypical or recurrent

Imaging

  • B-scan ultrasound if posterior segment view obscured (exclude endophthalmitis)
  • Anterior segment OCT: assess ulcer depth

Management

Non-pharmacological

  • Cease contact lens wear immediately
  • Frequent review (daily initially)
  • Protect eye from further trauma

Pharmacological

  • Bacterial keratitis (non-sight-threatening):
    • Ofloxacin 0.3% drops hourly (day and night for first 24-48 hours), then reduce frequency
    • OR Levofloxacin 0.5% drops hourly
  • Bacterial keratitis (sight-threatening, large, central, hypopyon):
    • Dual fortified drops: cefuroxime 5% + gentamicin 1.5% (or tobramycin 1.5%) hourly alternating
  • Acanthamoeba keratitis: polyhexamethylene biguanide (PHMB) 0.02% + propamidine isethionate 0.1% (Brolene) hourly, for months
  • Fungal keratitis: natamycin 5% hourly or voriconazole 1% drops; systemic antifungals may be needed
  • HSV keratitis: topical aciclovir 3% ointment 5×/day for 2 weeks
  • Cyclopentolate 1% for pain relief (ciliary spasm) and to prevent posterior synechiae
  • Do NOT use topical steroids without specialist input

Surgical

  • Therapeutic corneal transplant (penetrating keratoplasty) for corneal perforation or non-resolving disease
  • Amniotic membrane transplant for persistent epithelial defects
  • Tissue adhesive (cyanoacrylate) for impending perforation

Referral Criteria

  • All suspected microbial keratitis requires same-day ophthalmology assessment
  • Urgent corneal specialist referral for non-responding cases, Acanthamoeba, fungal keratitis
  • Emergency referral if perforation or hypopyon >1mm

Prognosis

  • Bacterial keratitis with prompt treatment: good visual outcome in >70% of peripheral ulcers
  • Central ulcers carry worse visual prognosis due to scarring in visual axis
  • Pseudomonas ulcers: poor outcome in 20-30% despite treatment
  • Acanthamoeba: prolonged treatment (3-6 months); visual outcome poor in 25-30%
  • Fungal keratitis: often poor response, 40-50% require surgical intervention
  • HSV keratitis: good prognosis for epithelial disease; stromal disease may recur and scar
  • Complications: corneal scarring, perforation, endophthalmitis, phthisis bulbi

Other Relevant Information

Corneal Scrape Protocol

MediumOrganisms Targeted
Blood agarBacteria (aerobic)
Chocolate agarFastidious organisms (Haemophilus, Neisseria)
Sabouraud agarFungi
Non-nutrient agar with E. coliAcanthamoeba
Brain-heart infusion brothEnrichment

Intensive Topical Antibiotic Regimens

SeverityRegimenFrequency
Non-sight-threateningOfloxacin 0.3% monotherapyHourly for 48h, then 2-hourly
Sight-threateningCefuroxime 5% + gentamicin 1.5%Alternating hourly day and night
Pseudomonas suspectedAdd ciprofloxacin 0.3%Hourly
MRSA suspectedVancomycin 5% fortified dropsHourly