Corneal ulcer is an epithelial defect with underlying stromal inflammation, most commonly infectious in etiology, and represents an ophthalmologic emergency that can rapidly progress to corneal perforation, scarring, and permanent vision loss. [1-2] It is the primary cause of nontrachomatous corneal opacification and the fifth leading cause of blindness worldwide. [1]
1. History
- Onset and duration of eye pain, redness, tearing, discharge, photophobia, and blurred vision [3]
- Contact lens history — type, wearing schedule, overnight wear, hygiene practices, tap-water rinsing, swimming/hot tub use while wearing lenses [3]
- Trauma history — foreign body, organic matter, chemical/thermal injury [3]
- Prior ocular disease — HSV/VZV keratitis, previous corneal ulcer, recurrent erosions, dry eye, prior corneal or refractive surgery [3]
- Immunosuppression — diabetes, chronic topical steroid use, immunomodulatory therapy [2]
- Systemic conditions — rosacea, atopy, rheumatoid arthritis [3]
- Current and recent ocular/systemic medications, including recent fluoroquinolone use [3]
2. Alarm Features
- Hypopyon (layered white cells in the anterior chamber) [1][3]
- Central or large infiltrate (>2 mm, within 3 mm of corneal center) [3]
- Significant vision loss or rapidly declining visual acuity [4]
- Corneal thinning, descemetocele, or perforation [5]
- Severe pain with vomiting — rule out acute angle-closure glaucoma [4]
- Feathery edges, satellite lesions, ring infiltrate — suggest fungal or Acanthamoeba etiology, which carry worse prognosis [3][6]
- Pain out of proportion to findings — classic for Acanthamoeba keratitis [3]
Per the NEJM, severe ocular pain or a visual deficit with a red eye, a corneal infiltrate, or a hypopyon calls for immediate ophthalmology transfer — not simply a recommendation to see one. [4]
3. Medications
Empiric Treatment (ED initiation if ophthalmology not immediately available):
- Moxifloxacin 0.5% ophthalmic drops — loading dose: 1 drop q5min × 30 min → 1 drop q30min × 6 hrs → 1 drop q1hr until ophthalmology evaluation [5]
- Ofloxacin 0.3% (FDA-approved for corneal ulcer): Days 1–2: 1–2 drops q30min while awake; Days 3–7: q1hr while awake; then QID to completion [7]
- Cycloplegic (e.g., atropine 1% q8hr) for pain relief and synechiae prevention in severe cases [5]
Severe/Central Ulcers (ophthalmology-directed)
- Fortified antibiotics: vancomycin + ceftazidime or cefazolin + tobramycin [3][8]
- Systemic antibiotics for gonococcal keratitis or scleral extension [3]
Contraindicated/Cautions
- Never prescribe topical corticosteroids from the ED — may be considered by ophthalmology after 48 hrs of antibiotics with organism identification [3]
- Avoid corticosteroids entirely in suspected Acanthamoeba, Nocardia, or fungal keratitis [3]
- Never prescribe topical anesthetics for home use [4]
- Do not patch the eye in contact lens wearers or trauma patients — increases risk of secondary bacterial keratitis [3]
4. Diet
- No specific dietary triggers or restrictions
- Adequate hydration supports general healing
- In patients with vitamin A deficiency (rare in developed countries), supplementation may support corneal epithelial integrity
5. Review of Systems
- Ophthalmologic: visual acuity changes, photophobia, tearing, discharge character (purulent vs. watery)
- Dermatologic: rosacea, periocular vesicles (HSV/VZV), atopic dermatitis
- Rheumatologic: joint pain, dry mouth (Sjögren's), rash (SLE, vasculitis) — peripheral ulcerative keratitis may be autoimmune [3]
- Infectious: recent URI (adenoviral keratitis), oral/genital lesions (HSV), STI symptoms (gonococcal keratitis)
- Immunologic: HIV risk factors, immunosuppressive medications
6. Collateral History and Family History
- Collateral: contact lens care habits (often underreported by patients), compliance with prior ocular treatments, prior culture results
- Family history: generally not a major contributor; atopy and autoimmune conditions may have familial predisposition
- Social context: occupation (agricultural workers at higher risk for fungal keratitis from organic matter trauma), swimming/hot tub use (Acanthamoeba risk) [3][6]
7. Risk Factors
- Contact lens wear — #1 risk factor in the US; overnight wear and poor hygiene are major contributors [1][3]
- Ocular trauma, especially with organic/vegetable matter (fungal risk) [1][6]
- Prior corneal disease — HSV keratitis, recurrent erosions, dry eye, epithelial basement membrane dystrophy [3]
- Prior ocular surgery — refractive surgery, corneal transplant [3]
- Immunosuppression — diabetes, chronic topical steroids, systemic immunomodulators [2]
- Ocular surface disease — severe dry eye, lagophthalmos, neurotrophic keratopathy [1]
- Decorative/cosmetic contact lenses purchased without prescription [3]
8. Differential Diagnosis
- Corneal abrasion — superficial epithelial defect without stromal infiltrate; no white opacity on penlight [5]
- HSV keratitis — dendritic ulcer on fluorescein staining; may have decreased corneal sensation [3]
- Fungal keratitis — feathery edges, satellite lesions, dry elevated slough, endothelial plaque; subacute onset; 5–6× higher perforation rate than bacterial [6]
- Acanthamoeba keratitis — ring infiltrate, radial keratoneuritis, pain out of proportion; contact lens + water exposure history [3]
- Sterile (contact lens-associated) infiltrate — typically small, peripheral, less symptomatic; no anterior chamber reaction [3]
- Autoimmune peripheral ulcerative keratitis — associated with RA, GPA, PAN; peripheral location, may have scleritis [3]
- Acute angle-closure glaucoma — mid-dilated fixed pupil, elevated IOP, corneal edema without infiltrate [4]
- Anterior uveitis/iritis — cell and flare without corneal infiltrate
- Gonococcal keratitis — hyperacute, copious purulent discharge; can perforate rapidly [3]
Pearl: Even cornea specialists correctly differentiate bacterial from fungal keratitis clinically in <70% of cases — cultures are essential. [3]
9. Past Medical History
- Prior episodes of keratitis or corneal ulcer (recurrent disease more likely S. aureus) [3]
- History of HSV/VZV ocular disease
- Prior corneal or refractive surgery (LASIK, PRK, corneal transplant)
- Diabetes, autoimmune disease, immunosuppression
- MRSA colonization or prior multidrug-resistant infection [3]
- Chronic topical steroid use
10. Physical Exam
Vital Signs: Generally normal; fever may suggest systemic infection (gonococcal)
Focused Eye Exam
- Visual acuity — document in each eye; decreased acuity is a red flag [1]
- Penlight/slit lamp: White or gray corneal infiltrate with epithelial defect is the hallmark finding [3][5]
- locationsizedepthshapemargins[3]
- Fluorescein staining with Wood's lamp or cobalt blue: epithelial defect will uptake stain; look for dendrites (HSV) [3]
- Anterior chamber: assess for cell/flare, fibrin, hypopyon [3]
- Eyelids: evaluate for lagophthalmos, entropion/ectropion, trichiasis, blepharitis [3]
- Conjunctiva: injection pattern, discharge character, foreign body, evert upper lid [3]
- Pupil: rule out fixed mid-dilated pupil (glaucoma)
- IOP: if safe to measure (avoid in suspected perforation)
- Contralateral eye: examine for bilateral disease or clues to etiology [3]
11. Lab Studies
- Corneal cultures and smears — indicated for central/large infiltrates (>2 mm), hypopyon, prior surgery, atypical features, or poor response to empiric therapy [3]
- Use proparacaine 0.5% (avoid tetracaine — antimicrobial effect) [3]
- Scrape base and edges of ulcer with sterile blade/spatula
- Inoculate directly onto culture media (blood agar, chocolate agar, Sabouraud's, thioglycolate broth) [3]
- Gram stain, Giemsa stain, KOH prep for smears [3]
- PCR — increasingly available for HSV, Acanthamoeba, fungi; cannot distinguish live organisms from antigenic material [3]
- Culture contact lenses, case, and solution if applicable [3]
- STI testing if gonococcal keratitis suspected
Most small, noncentral, community-acquired ulcers resolve with empiric therapy and do not require cultures. [3]
12. Imaging
- Imaging is generally not required for uncomplicated corneal ulcer
- B-scan ultrasonography — if fundus view is obscured, to rule out endophthalmitis or posterior segment involvement
- Anterior segment OCT — may help assess infiltrate depth and corneal thinning (ophthalmology setting)
- In vivo confocal microscopy — can identify Acanthamoeba cysts and fungal hyphae (specialized centers)
13. Special Tests
- Fluorescein staining — essential point-of-care test; epithelial defect uptakes fluorescein; dendrites suggest HSV [3]
- Seidel test — streaming fluorescein indicates corneal perforation (emergent finding)
- Corneal sensation testing (cotton wisp) — decreased sensation suggests HSV/VZV neurotrophic keratopathy [3]
- Corneal biopsy — reserved for culture-negative cases unresponsive to treatment; performed by ophthalmology [3]
- Special culture media — Löwenstein-Jensen for mycobacteria; non-nutrient agar with E. coli for Acanthamoeba [3]
14. ECG
- Not routinely indicated
- Consider if systemic fluoroquinolone therapy is initiated (QTc prolongation risk with moxifloxacin), particularly in patients with cardiac history or concurrent QT-prolonging medications
15. Assessment
Severity Stratification
- Typical presentation: Acute unilateral eye pain, redness, photophobia, tearing, decreased vision with visible white corneal opacity [1]
- Atypical presentations: Bilateral (autoimmune), painless (neurotrophic), subacute (fungal), indolent (Acanthamoeba early) [3][6]
- Complications: Corneal scarring, perforation, endophthalmitis, secondary glaucoma, vision loss, need for enucleation/evisceration (especially fungal) [6]
16. Treatment Plan
Initial Stabilization (ED)
- Discontinue contact lens wear immediately [5]
- Check and document visual acuity
- Perform fluorescein exam; if ulcer confirmed, do NOT patch [3]
Empiric Antibiotic Therapy (if ophthalmology not available within 1–3 hours):
- Moxifloxacin 0.5%: 1 drop q5min × 30 min → q30min × 6 hrs → q1hr ongoing [5]
- Alternative: Ofloxacin 0.3%: 1–2 drops q30min while awake (days 1–2) → q1hr (days 3–7) → QID [7]
- Cycloplegic (atropine 1% 1 drop q8hr) for severe cases [5]
Ophthalmology-Directed (Severe/Central Ulcers)
- Corneal cultures before antibiotics when feasible [3][5]
- Fortified antibiotics: vancomycin (25–50 mg/mL) + ceftazidime (50 mg/mL) or cefazolin (50 mg/mL) + tobramycin (14 mg/mL) — alternating q1hr [3]
- A 2025 Cochrane network meta-analysis found vancomycin + ceftazidime, moxifloxacin, and cefazolin + tobramycin had the shortest time to healing [8]
- Adjunctive topical corticosteroids may be considered after 48 hrs of antibiotics with identified organism and clinical response — never for suspected fungal, Acanthamoeba, or Nocardia [3]
- Systemic antibiotics for gonococcal keratitis or scleral extension [3]
- Surgical intervention (keratoplasty, amniotic membrane, corneal glue) for perforation or medically refractory cases [8]
17. Disposition
Emergent Ophthalmology Consultation/Transfer
- All corneal ulcers warrant urgent/emergent ophthalmology evaluation [4-5]
- Central or large ulcers, hypopyon, significant vision loss, suspected perforation → immediate transfer [4]
Admission Criteria
- Corneal perforation or impending perforation
- Need for hourly fortified antibiotic drops (adherence concerns)
- Gonococcal keratitis requiring systemic therapy
- Endophthalmitis
- Inability to self-administer drops (pediatric, elderly, cognitively impaired)
Discharge Criteria (with ophthalmology follow-up within 24 hours):
- Small, peripheral, non-vision-threatening ulcer
- Reliable patient who can adhere to intensive drop regimen
- No hypopyon, no significant anterior chamber reaction
- Stable or improving visual acuity
18. Follow Up / Return Precautions
Follow-Up Timing
- Severe ulcers: daily ophthalmology follow-up until stable or improving [3]
- Mild-moderate ulcers: ophthalmology within 24 hours of ED visit
- Therapy modification if no improvement within 48 hours [3]
Return Precautions — Instruct patients to return immediately for:
- Worsening pain or vision
- Increasing redness or discharge
- New white spot or enlarging opacity
- Inability to keep up with drop regimen
Patient Counseling
- Discontinue all contact lens wear until cleared by ophthalmology [5]
- Do not share eye drops or towels
- Adherence to intensive drop schedule is critical — set alarms
- Expect gradual improvement over days to weeks; some corneal scarring may be permanent
- Bring contact lenses, case, and solution to ophthalmology visit for culture [3]
Expected Recovery
- Most small noncentral bacterial ulcers resolve with empiric therapy [3]
- Central ulcers may result in permanent visual impairment from scarring
- Fungal and Acanthamoeba keratitis have prolonged courses and worse prognosis [1][6]
References
1. Eye Infections. — Durand ML, Barshak MB, Sobrin L. The New England Journal of Medicine. 2023.
2. Corneal Collagen Cross-Linking for Bacterial Infectious Keratitis. — Davis SA, Bovelle R, Han G, Kwagyan J. The Cochrane Database of Systematic Reviews. 2020.
3. Bacterial Keratitis Preferred Practice Pattern®. — Rhee MK, Ahmad S, Amescua G, et al. Ophthalmology. 2024.
4. The Red Eye. — Leibowitz HM. The New England Journal of Medicine. 2000.
5. Wilderness Medical Society Clinical Practice Guidelines for Treatment of Eye Injuries and Illnesses in the Wilderness: 2024 Update. — Paterson R, Drake B, Tabin G, Cushing T. Wilderness & Environmental Medicine. 2024.
6. The Global Incidence and Diagnosis of Fungal Keratitis. — Brown L, Leck AK, Gichangi M, Burton MJ, Denning DW. The Lancet. Infectious Diseases. 2021.
7. FDA Drug Label. — Updated date: 2024-06-13. Food and Drug Administration.
8. Topical Antibiotics for Treating Bacterial Keratitis: A Network Meta-Analysis. — Song A, Yang Y, Henein C, et al. The Cochrane Database of Systematic Reviews. 2025.