Corneal Ulcers & Keratitis
Ophthalmology · Cornea · lean revision notes
Corneal Ulcers & Keratitis
Keratitis is inflammation of the cornea; when it is associated with epithelial loss and underlying stromal necrosis, it becomes a corneal ulcer — a sight-threatening ocular emergency. This is one of the highest-yield ophthalmology topics for NEET PG, tested heavily on etiology, slit-lamp morphology, scraping/stain pairings, and drug of choice.
Definition & Classification
A corneal ulcer is a discontinuity (break) in the corneal epithelium with necrosis of the surrounding tissue, usually due to infection. The cornea is avascular, so it depends on the tear film, limbal vessels, and aqueous for defence — making it both transparent and vulnerable.
Keratitis is broadly classified as:
- Infective (suppurative/microbial): bacterial, viral, fungal (keratomycosis), Acanthamoeba, chlamydial.
- Non-infective (non-suppurative): Mooren's ulcer, marginal (catarrhal) ulcer, neurotrophic/exposure keratitis, interstitial keratitis, peripheral ulcerative keratitis (PUK) of collagen vascular disease.
Anatomically, ulcers are central (usually infective, vision-threatening) or peripheral/marginal (often immunologic). A hypopyon ulcer is a central suppurative ulcer with a sterile collection of pus (leucocytes) in the anterior chamber.
High-yield: The hypopyon in a corneal ulcer is sterile (it is an inflammatory exudate from toxins, not organisms), EXCEPT in fungal keratitis and endophthalmitis where organisms may be present. Hypopyon shifts with head position (mobile) and has a smooth horizontal level.
| Type | Classic organism / cause | Predisposing factor |
|---|---|---|
| Bacterial | Pseudomonas aeruginosa, Staph aureus, Strep pneumoniae (pneumococcus) | Contact lens, trauma, ocular surface disease |
| Fungal | Aspergillus (commonest in India), Fusarium (contact lens), Candida | Vegetative trauma, agriculture, steroid use |
| Viral | Herpes simplex virus (HSV-1), Herpes zoster, adenovirus | Immunosuppression, stress, fever |
| Acanthamoeba | Acanthamoeba spp. (free-living protozoan) | Contact lens + contaminated water/swimming |
Etiology & Pathophysiology
The intact corneal epithelium is an excellent barrier — most organisms cannot invade an intact cornea. There are important exceptions that can penetrate intact epithelium: Neisseria gonorrhoeae*, Corynebacterium diphtheriae, Listeria, Haemophilus aegyptius (Koch–Weeks), and *Shigella.
Once a break occurs (trauma, contact lens, dry eye, exposure), pathogens invade. The sequence of a typical bacterial ulcer:
Stage of progressive infiltration → Stage of active ulceration → Stage of regression → Stage of cicatrisation (healing by scar)
Bacterial proteases and collagenases liquefy the stroma. Pseudomonas produces potent proteolytic enzymes causing rapid stromal melting (keratomalacia) within 48–72 hours, often with a greenish mucopurulent discharge.
Healing leaves scars graded by density:
- Nebula — faint, mild superficial scar.
- Macula — moderate density.
- Leucoma — dense white opacity. If iris adheres to the back, it is an adherent leucoma; if there is a bulge it becomes a keratectasia/anterior staphyloma.
High-yield: A descemetocele (herniation of Descemet's membrane through a thinned ulcer base) precedes perforation. Perforation may lead to iris prolapse, anterior synechiae, secondary glaucoma, or endophthalmitis.
Clinical Features
Common symptoms: pain, photophobia, lacrimation, blepharospasm, redness, foreign-body sensation, and diminished vision (especially central ulcers). Discharge type hints at cause (mucopurulent = bacterial; watery = viral).
Signs on examination: ciliary congestion (circumcorneal), an epithelial defect that stains with fluorescein, stromal infiltrate, and possibly hypopyon. The character of the ulcer edge and floor is the key discriminator.
Morphology by etiology
| Feature | Bacterial | Fungal | HSV | Acanthamoeba |
|---|---|---|---|---|
| Onset/course | Rapid, aggressive | Slow, indolent | Recurrent | Slow, very painful |
| Margin | Sharp, defined | Feathery / serrated margins | Branching dendrite | Ring infiltrate (later) |
| Surface | Wet, mucopurulent | Dry, raised, "dirty" | Linear branching | Radial keratoneuritis (early) |
| Special signs | Hypopyon, melt (Pseudomonas) | Satellite lesions, endothelial plaque, immune ring | Dendritic/geographic ulcer; reduced sensation | Pain out of proportion to signs |
| Sensation | Normal | Normal | Reduced (corneal anaesthesia) | Reduced |
High-yield (very frequently tested): The classic HSV epithelial ulcer is a dendritic ulcer — a branching figure with terminal end-bulbs that stains centrally with fluorescein and at the margins with rose bengal. If steroids are wrongly given, it enlarges into a geographic (amoeboid) ulcer.
High-yield: Pain out of proportion to clinical signs in a contact-lens wearer = think Acanthamoeba. Early sign is radial perineuritis (radial keratoneuritis); later a stromal ring infiltrate.
Special / Named Ulcers
- Mooren's ulcer: A chronic, painful, idiopathic peripheral ulcerative keratitis that starts at the limbus and progresses circumferentially and centrally with an overhanging undermined leading edge. It is autoimmune (against corneal stromal antigen). Two types: a benign unilateral type in the elderly and a malignant bilateral aggressive type in young (often African) patients. Treatment: topical steroids, immunosuppression, conjunctival resection; NOT primarily antimicrobial.
- Marginal (catarrhal) ulcer: A peripheral, hypersensitivity ulcer to Staphylococcus exotoxin, with a clear zone (lucid interval) of cornea between the ulcer and the limbus. Common with chronic staphylococcal blepharitis. Responds to topical steroids + antibiotic.
- Ring ulcer / ring abscess: Seen in Acanthamoeba, periarteritis nodosa, Pseudomonas.
- Serpiginous (creeping) ulcer: Classic pneumococcal (hypopyon) ulcer — a greyish-white ulcer that creeps over the cornea in one direction with hypopyon; often from dacryocystitis.
- Rodent ulcer is an older synonym used for Mooren's ulcer (do not confuse with the skin BCC "rodent ulcer").
High-yield mnemonic for HSV stains: "Centre = Fluorescein, Margin = Rose bengal" → CF, MR. Rose bengal stains devitalised/dead epithelial cells and is also used in dry eye.
Diagnosis & Investigation of Choice
Diagnosis is clinical (slit-lamp) plus corneal scraping before starting therapy. Scrapings are taken from the leading edge and base of the ulcer with a Kimura spatula/Bard-Parker blade No.15.
Stain → organism pairings (must memorise)
| Stain / medium | Detects |
|---|---|
| Gram stain | Bacteria, fungi (partially), Acanthamoeba |
| Giemsa stain | Fungi, Acanthamoeba cysts, chlamydial inclusions |
| KOH (10–20%) wet mount | Fungal hyphae — quickest, most sensitive bedside test for fungus |
| Calcofluor white (needs fluorescence microscope) | Fungi AND Acanthamoeba cysts (binds chitin/cellulose) — most sensitive |
| Blood agar / Chocolate agar | Most bacteria; chocolate for fastidious (Haemophilus, Neisseria) |
| Sabouraud dextrose agar (SDA) | Fungi (incubated at 25–27°C) |
| Non-nutrient agar with E. coli overlay | Acanthamoeba — confirmatory culture |
High-yield: KOH mount is the fastest investigation to demonstrate fungal filaments; calcofluor white is the most sensitive stain for both fungi and Acanthamoeba. Confocal microscopy is a non-invasive in-vivo tool that shows fungal hyphae and Acanthamoeba double-walled cysts.
HSV diagnosis is usually clinical; PCR of tear/corneal sample is most sensitive. Tzanck smear shows multinucleated giant cells.
Management & Drug of Choice
General principles: STOP steroids if fungal/HSV suspected, treat aggressively, hourly topical drops initially, cycloplegics (atropine/homatropine) for comfort and to prevent synechiae, and never pad an infected ulcer.
Stepwise approach to a suspected microbial keratitis
- Scrape → stain (Gram, KOH/calcofluor, Giemsa) → culture before therapy.
- Start empirical broad-spectrum therapy: fortified antibiotics or a 4th-gen fluoroquinolone (moxifloxacin/gatifloxacin) hourly.
- Cycloplegic (atropine 1%) to relieve pain and reduce iridocyclitis.
- Treat raised IOP if present; do NOT use topical steroids in the acute infective phase.
- Review at 48 hours → modify based on culture/response.
- Therapeutic penetrating keratoplasty (TPK) if impending/actual perforation or non-resolving melt.
Drug of choice by cause
| Cause | First-line drug |
|---|---|
| Bacterial (empirical) | Fortified cefazolin (5%) + tobramycin/gentamicin, OR monotherapy moxifloxacin / gatifloxacin |
| Pseudomonas | Fluoroquinolone or fortified aminoglycoside (ciprofloxacin/tobramycin) |
| Fungal (filamentous: Aspergillus, Fusarium) | Topical natamycin 5% (DOC) |
| Fungal (Candida/yeast) | Topical amphotericin B 0.15% or voriconazole |
| HSV epithelial keratitis | Topical acyclovir 3% ointment 5×/day, OR ganciclovir 0.15% gel; oral acyclovir 400 mg 5×/day |
| HSV stromal keratitis (disciform) | Oral acyclovir + topical steroid under cover |
| Acanthamoeba | PHMB (polyhexamethylene biguanide) 0.02% + propamidine isethionate (Brolene); or chlorhexidine |
High-yield: Natamycin 5% is the DOC for filamentary fungal keratitis (Fusarium/Aspergillus). Voriconazole (topical/oral/intrastromal) is used for resistant cases. For deep ulcers, intrastromal/intracameral voriconazole or amphotericin may be given.
High-yield: In HSV, topical corticosteroids are CONTRAINDICATED in active epithelial (dendritic) disease — they cause geographic spread and worsen ulceration. Steroids are used (with antiviral cover) only in stromal/disciform keratitis where the pathology is immune-mediated.
High-yield: For HSV prophylaxis against recurrence (HEDS study), oral acyclovir 400 mg twice daily reduces recurrence. The HEDS trial established the role of oral antivirals and steroids in stromal keratitis.
Complications
- Corneal perforation → iris prolapse, anterior synechiae.
- Descemetocele, anterior staphyloma, adherent leucoma.
- Secondary glaucoma and complicated cataract.
- Endophthalmitis / panophthalmitis (intraocular spread) → phthisis bulbi (end-stage shrunken eye).
- Corneal scarring/opacity — a leading cause of avoidable blindness in India (corneal blindness is 2nd commonest cause of blindness in India after cataract).
- Choroidal/retinal detachment in severe disease.
Key Differentials
When confronted with a "red painful eye with corneal involvement," distinguish:
| Condition | Discriminating feature |
|---|---|
| Bacterial vs fungal ulcer | Fungal = feathery margins, satellite lesions, hypopyon with intact epithelium over it, vegetative trauma |
| HSV vs HZ ophthalmicus | HZ: dermatomal V1 rash, Hutchinson's sign (nasociliary/tip-of-nose involvement → likely eye involvement), pseudodendrites without true end-bulbs |
| Acanthamoeba vs HSV | Acanthamoeba: contact lens, pain >> signs, ring infiltrate, radial keratoneuritis |
| Marginal ulcer vs Mooren's | Marginal = lucid interval, self-limiting; Mooren's = limbus-contiguous, undermined edge, progressive |
| Sterile infiltrate (CLARE) vs microbial | Sterile = small, peripheral, multiple, minimal anterior chamber reaction |
High-yield: Hutchinson's sign = vesicles on the side/tip of the nose in herpes zoster (nasociliary branch of V1) predicts ocular involvement. Pseudodendrites of HZ are raised mucous plaques without true terminal bulbs (unlike HSV true dendrites).
Recently asked / exam angle
- Stain–organism matching is a perennial favourite: KOH → fungus; calcofluor white → fungus + Acanthamoeba; non-nutrient agar with E. coli → Acanthamoeba; Giemsa → chlamydial inclusions.
- "Pain out of proportion to signs + contact lens" → Acanthamoeba; investigation = confocal microscopy / non-nutrient agar.
- "DOC for fungal corneal ulcer" → Natamycin 5%.
- "Organisms that penetrate intact corneal epithelium" → Neisseria, Corynebacterium diphtheriae, Listeria, Haemophilus (Koch-Weeks), Shigella.
- "Dendritic ulcer treatment / contraindicated drug" → acyclovir is DOC; steroids contraindicated (geographic ulcer).
- Mooren's ulcer characteristics (overhanging undermined edge, autoimmune, NOT treated with antibiotics).
- Serpiginous ulcer = pneumococcus, often associated with chronic dacryocystitis (always check the lacrimal sac / regurgitation test before intraocular surgery).
- Rose bengal vs fluorescein staining of HSV dendrite.
- MYCOTIC ulcer clue images: feathery margin + satellite lesions + immune ring + endothelial plaque.
Rapid revision
- Corneal ulcer = epithelial break + stromal necrosis; an ocular emergency.
- Commonest bacterial causes: Pseudomonas, Staph aureus, pneumococcus; Pseudomonas melts cornea fast.
- Hypopyon in corneal ulcer is sterile (except fungal/endophthalmitis) and mobile.
- Fungal ulcer = feathery margins + satellite lesions + immune ring; commonest fungus in India = Aspergillus.
- KOH mount = fastest for fungus; calcofluor white = most sensitive (fungus + Acanthamoeba).
- Natamycin 5% = DOC for filamentary fungal keratitis; voriconazole for resistant.
- HSV dendritic ulcer: terminal end-bulbs, centre stains with fluorescein, margins with rose bengal; reduced corneal sensation.
- Steroids are contraindicated in active HSV epithelial keratitis (causes geographic ulcer).
- Acanthamoeba: contact lens + pain >> signs + ring infiltrate + radial keratoneuritis; culture on non-nutrient agar with E. coli; treat with PHMB + propamidine.
- Mooren's ulcer = autoimmune peripheral ulcer with undermined overhanging edge; treat with steroids/immunosuppression, not antibiotics.
- Serpiginous ulcer = pneumococcal, linked to chronic dacryocystitis.
- Organisms penetrating intact cornea: N. gonorrhoeae, C. diphtheriae, Listeria, Haemophilus, Shigella; corneal opacity is the 2nd leading cause of blindness in India.