What is the treatment for corneal ulcers?

Treatment of Corneal Ulcer

Initiate immediate intensive broad-spectrum topical antibiotics after obtaining corneal scrapings for culture, using either fluoroquinolone monotherapy (moxifloxacin 0.5% or gatifloxacin 0.5%) or fortified antibiotic combinations (cefazolin plus tobramycin/gentamicin), with loading doses every 5-15 minutes followed by hourly around-the-clock application for severe cases. 1, 2, 3

Immediate Diagnostic Steps

Before starting any treatment, obtain corneal scrapings from the ulcer base and periphery using a sterile blade under slit-lamp visualization after applying proparacaine 0.5% anesthetic. 4, 2 This is mandatory when hypopyon is present or when there are ≥1+ cells in the anterior chamber, as these indicate severe infection. 2

• Inoculate samples directly onto blood agar, chocolate agar, and thioglycolate broth at the bedside 2
• Perform Gram stain and Giemsa stain for immediate pathogen identification 2
• Do not tap the hypopyon unless concurrent endophthalmitis from trauma or surgery is suspected, as it is typically sterile 4

Initial Antibiotic Regimen

For Moderate to Severe Ulcers or Central Location:

Fortified antibiotics are preferred for severe cases, known resistant organisms, or patients with recent fluoroquinolone use, hospitalization, advanced age, or recent ocular surgery due to increasing fluoroquinolone resistance. 2, 3

• Start cefazolin (fortified) plus tobramycin or gentamicin (fortified) with loading doses every 5-15 minutes, then hourly around the clock 5, 3
• Subconjunctival injections may be added but systemic antibiotics are rarely needed unless there is scleral extension or impending perforation 1, 3

For Less Severe Ulcers:

Fluoroquinolone monotherapy with moxifloxacin 0.5% or gatifloxacin 0.5% is as effective as fortified combinations for most bacterial keratitis. 2

Essential Adjunctive Measures

• Cycloplegics: Apply atropine 1% or homatropine 5% to reduce pain and prevent synechiae formation 4
• Antibiotic ointment at bedtime during the intensive phase 5
• Aggressive lubrication with preservative-free artificial tears 5

Monitoring and Treatment Modification

Initial Assessment (24-48 Hours):

Examine daily until clear improvement is documented. 4, 2 Signs of positive response include:

• Reduced pain and discharge (earliest signs) 5, 2
• Decreased eyelid edema and conjunctival injection 5
• Consolidation and sharper demarcation of infiltrate borders 5, 2
• Reduced stromal infiltrate density without progressive thinning 5, 2
• Initial re-epithelialization 5

Important caveat: Pseudomonas and gram-negative organisms may show increased inflammation in the first 24-48 hours despite appropriate therapy—this does not necessarily indicate treatment failure. 2

If No Improvement at 48-72 Hours:

• Modify therapy based on culture results and sensitivities 2
• Consider that medication toxicity can mimic treatment failure, causing persistent epithelial defects despite infection control 2
• Re-evaluate for fungal or atypical organisms if bacterial cultures are negative 4, 6

Tapering Strategy

Once clear improvement is established:

• Begin gradual tapering to avoid antibiotic toxicity 5
• Never reduce dosing below 3-4 times daily during active treatment, as lower frequencies are subtherapeutic and promote resistance 5
• Continue treatment for minimum 14-21 days even with clinical improvement to prevent relapse 4
• Abrupt cessation increases recurrence risk 5

Corticosteroid Therapy (Controversial but Evidence-Based)

Add topical corticosteroids only after 2-3 days of progressive improvement with antibiotics, after pathogen identification, and after ruling out fungal infection (especially Nocardia). 1

The 2024 American Academy of Ophthalmology guidelines, based on the Steroids for Corneal Ulcer Trial (SCUT), found:

• No overall benefit of routine corticosteroid use 1
• Potential benefit in Pseudomonas keratitis and severe cases (ulcers covering central 4-mm pupil or vision of counting fingers or worse) 1
• Poor outcomes with Nocardia keratitis—avoid corticosteroids entirely 1
• Better visual outcomes when started within 2-3 days of antibiotics rather than after 4+ days 1

If using corticosteroids:

• Start with prednisolone phosphate 1% or dexamethasone 0.1% twice daily 1
• Monitor IOP within 1-2 days of initiation 1
• Use minimum amount needed to control inflammation 1
• Discuss risks of cataract and glaucoma with patient 1

For fungal keratitis: Avoid corticosteroids initially, as outcomes are worse with higher perforation rates. 4

Special Considerations for Fungal Ulcers

If fungal infection is suspected or confirmed:

• Natamycin is first-line for filamentous fungi, but failure to improve after 7-10 days suggests resistance 6
• Consider fluconazole 400-800 mg daily orally for susceptible Candida species 4
• Aspergillus may require voriconazole or amphotericin B from the outset 4
• Use oral doxycycline or minocycline 100 mg twice daily to inhibit matrix metalloproteinases and reduce corneal melting 4

Surgical Intervention

Consider surgery when:

• Progressive stromal thinning despite maximal medical therapy 4
• Impending or frank corneal perforation 4, 7
• No response to medical treatment after 7-10 days 6, 7

Surgical options include:

• Tissue adhesive with bandage contact lens for small perforations with good surrounding tissue 4
• Amniotic membrane transplantation to stabilize the ocular surface 4, 8
• Therapeutic penetrating keratoplasty for large perforations or progressive disease 4, 7
• Conjunctival flaps for recalcitrant cases 7

Critical Pitfalls to Avoid

• Delaying corneal scraping leads to incorrect differentiation between bacterial and fungal keratitis 4
• Using preserved anesthetics or cycloplegics before cultures reduces culture yield 4
• Starting corticosteroids early can cause rapid progression of fungal keratitis 4
• Inadequate initial dosing frequency for severe ulcers—must start with loading doses then hourly application 5
• Prolonged full-dose therapy causes corneal epithelial toxicity 5
• Assuming all fungi respond to natamycin—Aspergillus often requires alternative agents 4

Follow-Up and Patient Education

• Severe cases require daily examination initially until stable or improving 1, 4
• Educate patients about risk of permanent visual loss and need for strict adherence 1
• For contact lens wearers: discuss risks of overnight wear (20 per 10,000 wearers/year vs. 1-2 per 10,000 for daily wear) and consider switching to daily disposable lenses 1
• Report adverse events related to contact lenses to FDA MedWatch 1