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OP4.3 | Infective Keratitis: Differential Diagnosis and Management — SDL Guide (Part 3)
Corneal Ulcer Complications and Management Outcomes
Untreated or inadequately treated infective keratitis progresses through a predictable series of complications, each more vision-threatening than the last. Understanding the complication sequence allows the clinician to recognise when to escalate urgency.
The sequential complications of progressive keratitis are: stromal thinning → descemetocele (forward bulging of the thin, stretched Descemet's membrane as the overlying stroma is destroyed — a dark, transparent bleb visible through the opaque surrounding tissue; an ophthalmological emergency) → corneal perforation (the ulcer breaks through Descemet's membrane and aqueous rushes out; the iris may plug the perforation — iris prolapse; the eye has effectively been decompressed and the patient faces endophthalmitis risk) → endophthalmitis (infection spreads into the vitreous cavity; devastating, with very poor visual prognosis despite treatment) → panophthalmitis (whole eye involved; may require evisceration).
Additional complications:
- Hypopyon uveitis: severe anterior chamber reaction accompanying keratitis; may require mydriatics and topical steroids once infection is controlled
- Corneal vascularisation: new vessels growing into the healing ulcer bed
- Corneal scar (leukoma): dense white opacity from fibrous healing of the ulcer bed; graded by location relative to visual axis
- Iris adhesions: anterior synechiae if the iris plugs a perforation; posterior synechiae from uveitis
- Secondary glaucoma: from anterior synechiae blocking the drainage angle
Management of complications: a descemetocele requires emergency therapeutic keratoplasty or tissue glue (cyanoacrylate glue can be applied to seal small perforations temporarily). A frank perforation may need emergency penetrating keratoplasty. Post-infective corneal scars are treated with keratoplasty after the infection is fully resolved and the eye is quiet — attempting keratoplasty in an active infection risks graft failure.
Clinical Decision-Making: Choosing the Right Treatment
The clinical decision-making algorithm for infective keratitis integrates history, slit-lamp pattern, and risk factors into a treatment choice BEFORE culture results are available — because a rapidly progressing bacterial or fungal ulcer cannot wait 48–72 hours.
The decision framework proceeds as follows:
Step 1 — Identify the danger signs: Is this an urgent or true emergency? Pain + photophobia + ciliary flush + stromal infiltrate + hypopyon = treat TODAY as sight-threatening. A descemetocele or perforation = refer immediately for emergency surgery.
Step 2 — Apply the pattern-recognition differential: Look for the distinguishing features outlined in the framework above. Ask specifically: (a) Is there a dendritic branching pattern with terminal bulbs? → HSV. (b) Is there vegetative trauma + feathery margins + satellite lesions? → Fungal. (c) Is there radial keratoneuritis + contact lens + tap water + severe pain? → Acanthamoeba. (d) Rapid onset in contact-lens wearer with creamy dense infiltrate? → Bacterial (Pseudomonas probable).
Step 3 — Scrape and culture: For all ulcers ≥1 mm or moderate-large in severity, scrape before starting treatment if it can be done within minutes. Do not delay >30 minutes waiting for scraping equipment if the patient is at high risk of rapid progression.
Step 4 — Start empirical treatment matched to the most likely organism category. The key drug-organism matching rules:
- Bacterial suspected → fluoroquinolone (ciprofloxacin, moxifloxacin) or fortified antibiotics (vancomycin + tobramycin for Gram-positive + Gram-negative cover). NEVER use these alone for fungal or HSV ulcers.
- Fungal suspected (vegetative trauma + feathery margins) → natamycin 5% (first-line for filamentous fungi); add oral voriconazole if severe. NEVER add steroids.
- HSV dendritic ulcer confirmed (terminal bulbs on fluorescein/rose bengal) → topical aciclovir 3% ointment 5 times daily. Do NOT add steroids to active epithelial disease. NEVER give antifungal or antibacterial as monotherapy for a dendritic ulcer.
- Acanthamoeba suspected → PHMB 0.02% + chlorhexidine 0.02% hourly. Long treatment course; refer to tertiary centre.
Step 5 — Review at 24–48 hours: if improving, continue treatment; if worsening, consider broadening cover (add natamycin if bacterial empirical treatment not working, to cover possible fungal), repeat scraping, refer to cornea specialist.
SELF-CHECK
A 22-year-old woman presents with a branching epithelial lesion in the right cornea with terminal bulbs visible on fluorescein staining. She has a history of recurrent lip cold sores. Corneal sensation is reduced. Her GP had prescribed topical dexamethasone 0.1% four times daily two days ago for 'inflammation.' She is worse today with a larger, irregular, map-shaped epithelial defect. What happened and what is the correct treatment now?
A. Bacterial superinfection occurred; add topical ciprofloxacin to the dexamethasone
B. The steroid converted an HSV dendritic ulcer to a geographic ulcer by allowing HSV replication without antiviral cover; stop steroid and start topical aciclovir 3% ointment five times daily
C. Fungal superinfection occurred; add topical natamycin and continue the steroid
D. Acanthamoeba infection; start PHMB and chlorhexidine
Reveal Answer
Answer: B. The steroid converted an HSV dendritic ulcer to a geographic ulcer by allowing HSV replication without antiviral cover; stop steroid and start topical aciclovir 3% ointment five times daily
This is the classic HSV geographic ulcer trap. Topical steroids applied to an active HSV dendritic ulcer — without antiviral cover — suppress the local immune response while the virus replicates freely, expanding the dendritic into a large, irregular geographic (amoeboid) ulcer. The treatment is to stop the steroid immediately and start topical aciclovir 3% ointment five times daily (or topical ganciclovir 0.15%). Once the epithelial disease is controlled, a carefully titrated steroid may be considered if there is significant stromal involvement — but not before.
Self-Assessment: Infective Keratitis Differentials
Work through these clinical scenarios as you would during an OSCE or viva.
Scenario 1: A 50-year-old sugarcane cutter presents with a 7-day history of right eye pain after a cane leaf struck his eye. Slit-lamp: 4 mm × 3 mm grey-white infiltrate with feathery margins, two satellite lesions at 6 o'clock and 8 o'clock, endothelial plaque, and 1 mm hypopyon. KOH mount: not yet available. What is your working diagnosis and empirical treatment? (Answer: fungal keratitis — vegetative trauma + feathery margins + satellite lesions + endothelial plaque. Start natamycin 5% hourly immediately. Do not start antibiotics as first-line or add steroids.)
Scenario 2: A 19-year-old woman has worn monthly contact lenses for 2 years. She presents with 3 days of severe right eye pain, worse at night, with minimal redness visible to her. Slit-lamp: early ring infiltrate in stroma, radial whitish infiltrates along nerve tracks. She admits rinsing lenses under the tap. What diagnosis do you suspect, what specific investigation confirms it, and what treatment do you start? (Answer: Acanthamoeba keratitis. Scraping for Giemsa stain (cysts) and culture on non-nutrient agar with E.coli overlay. Start PHMB 0.02% + chlorhexidine 0.02% hourly. Refer to cornea specialist. Warn about prolonged treatment course.)
Scenario 3: A 35-year-old man has a 4-day history of painful eye with a white spot. He had a similar episode 3 years ago that was 'treated and resolved.' Slit-lamp with fluorescein shows a branching lesion with terminal bulbs at each branch tip. Rose bengal also stains the perimeter of the lesion. Sensation is reduced. The GP prescribed ciprofloxacin 4 times daily 3 days ago; there is no improvement. Why hasn't the ciprofloxacin worked, and what do you prescribe? (Answer: HSV dendritic ulcer — the branching pattern with terminal bulbs and rose bengal positivity at the margins are diagnostic. Ciprofloxacin is an antibiotic; it has no activity against HSV. Stop ciprofloxacin; start topical aciclovir 3% ointment 5 times daily.)