Low-risk ulcer — empirical antibiotic therapy
A presumed bacterial abscess judged low-risk (no severity criterion) can be treated with broad-spectrum empiric antibiotic therapy, instilled hourly — most often a fluoroquinolone ± an aminoglycoside.
The so-called 4th-generation fluoroquinolones (moxifloxacin, gatifloxacin) have better in vitro activity against Gram-positives than ciprofloxacin or ofloxacin and are often used as monotherapy where available; their activity against Gram-negatives is comparable to that of the older fluoroquinolones. They are not marketed in France, where first-line empirical therapy relies on the older fluoroquinolones (ciprofloxacin, ofloxacin), usually combined with an aminoglycoside. Their role is debated: first-line for some, held in reserve as second-line by most experts to limit the emergence of resistance [5].
- Reassessment
- At 24-48 h: visual acuity, pain, infiltrate (size, depth), epithelial status, inflammation. Then progressive tapering of frequency. Total duration ~2 to 3 weeks.
- Reading the response
- The size of the infiltrate reflects the response to treatment; the size of the epithelial defect reflects drop toxicity.
During treatment of a bacterial abscess, an epithelial defect larger than the stromal infiltrate should raise concern for drop toxicity and prompt reducing the frequency of instillations, or even allowing a drug holiday.
No topical steroids for a bacterial abscess without a severity criterion.
Microbiological diagnosis & sampling technique
Patients with severity criteria — or worsening at 24-48 h despite treatment — must be re-examined for corneal scraping and sampling.
| Method | Target |
|---|---|
| Gram | Bacteria (G+ blue — "positive blue over you"; G− red) |
| Giemsa | Fungi |
| May-Grünwald-Giemsa (MGG) | Atypical bacteria (mycobacteria) |
| Calcofluor | Amoebae and fungi |
| Blood agar | Aerobic/anaerobic bacteria and fungi |
| Chocolate agar | Aerobic bacteria |
| Löwenstein-Jensen | Mycobacteria (slow culture) |
| Sabouraud | Fungi (slow culture, 5 days to 3 weeks) |
| Non-nutrient agar + E. coli | Amoebae (slow culture, 3-7 days) |
| PCR | Viruses (Herpes group), amoebae (highly sensitive), fungi (semi-nested) |
Confocal microscopy: aids the instant diagnosis of fungal and amoebic infections (sensitivity/specificity still debated, false positives/negatives; avoid if perforation is imminent). It visualizes the branching linear structures of filaments and, in amoebic involvement, the double-walled cysts and trophozoites (chain-like appearance carrying a poor prognosis); also useful for follow-up.
Others: corneal biopsy (chalazion trephine or 45° blade) in severe, deep forms or when cultures are negative; slit-lamp photographs to document the course; B-scan ultrasound if the posterior segment is not visible and endophthalmitis is suspected.
By an ophthalmologist, at the slit lamp or in the operating room under the microscope: single-dose anesthetic, sterile gloves, mechanical debridement of the abscess (dual purpose: reduce the infectious load and obtain a sample). If fungal infection is suspected, sample from the base of the abscess; if amoebic infection is suspected, wide epithelial debridement reduces the parasite load. First sample for direct examination, second for cultures; dedicated samples for PCR (HSV, VZV, amoebae).
NB: preferably sample before applying preserved drops or anti-infectives; in the contact lens wearer, also sample the lenses and case.
Targeted therapy, PACK-CXL & surgery
12.1 Bacterial infection with a severity criterion
After sampling, start hourly fortified antibiotic drops. For example, a "TGV" regimen:
| Antibiotic | Concentration | Spectrum |
|---|---|---|
| Ticarcillin / piperacillin | 4-6 mg/mL | G+ and G− |
| Gentamicin | 14 mg/mL | G− and G+ |
| Vancomycin | 25-50 mg/mL | G+ |
Adapt subsequently to the clinical response, iatrogenic toxicity, and susceptibility testing: for Gram-positive cocci, stop ticarcillin/gentamicin; for Gram-negative bacilli, stop vancomycin. Switching to commercial drops once susceptibility testing is available (fortified drops being toxic, costly, and poorly stable) or progressive tapering of the fortified drops are two schools of thought. Favorable course: shrinking of the infiltrated area, re-epithelialization, reduction of secretions and pain.
- Systemic antibiotics: endophthalmitis, panophthalmitis, perforation, scleritis, or to cover a "hot" keratoplasty.
- Intrastromal injection (e.g. cefuroxime, 30 G needle around the infiltrate, every 48-72 h): increases the stromal concentration while reducing surface toxicity.
Topical steroids remain controversial; if used (scar threatening the visual axis), it must be after significant improvement, likely for a non-bacterial etiology or co-infection, and after organism identification and susceptibility testing. Monitor for toxicity: white ciprofloxacin deposits at the base of the ulcer (delayed healing), aminoglycoside epithelial toxicity — allow drug holidays.
12.2 Fungal infection
Antifungals (other than natamycin under compassionate use) are not commercially available and are compounded in hospital.
| Class | Agents & key points |
|---|---|
| Polyenes | Amphotericin B 0.15-0.25% (yeasts ++, good penetration; adverse effects: superficial punctate keratitis, delayed healing, chemosis, yellow-green staining). Natamycin 5% (filaments + yeasts; first-line for filamentous/Fusarium — MUTT I; low toxicity, poor penetration). |
| Azoles (triazoles) | Itraconazole 1% (filaments); Voriconazole (filaments + yeasts/Candida; topical 1%, systemic, intrastromal 50 µg/0.1 mL, intracameral 100 µg); Fluconazole 0.3% (yeasts); ketoconazole, miconazole. |
| Echinocandins | Caspofungin (Aspergillus; topical 0.1 mg/mL, IV). |
| Pyrimidines | Flucytosine (5-fluorocytosine) 1% (yeasts). |
Hourly administration over 48 h with a loading dose (1 drop every 5 min for the first hour); systemic route discussed with infectious disease specialists; long duration (up to several months if deep stromal involvement); gentle debridement to remove necrotic tissue. Oral voriconazole provides no benefit (MUTT II) [10].
12.3 Amoebic infection
Goals: anti-amoebic, anti-inflammatory, and analgesic.
| Target | Agents |
|---|---|
| Trophozoites | Aromatic diamidines (propamidine/Brolène 0.1%, hexamidine/Désomédine); aminoglycosides (neomycin — neomycin + polymyxin B + bacitracin combination, tobramycin). |
| Cysts | Cationic biguanides (chlorhexidine 0.02%, PHMB 0.02%); imidazoles — rather amoebostatic (miconazole, ketoconazole, fluconazole, voriconazole). |
Most protocols combine diamidine-biguanide dual therapy (synergy). Mean duration ~2 months (epithelial involvement), several months if deep involvement; no consensus (risk of recurrence on discontinuation). The ODAK trial validated PHMB 0.08% monotherapy (~86% cure) [11]. Steroids (which promote encystment) should be avoided before 2 weeks of anti-amoebic treatment and reserved for specific indications (scleritis, uveitis). Analgesia: cycloplegic, amniotic membrane graft.
Intrastromal route (reference doses): voriconazole 50 µg/0.1 mL, amphotericin B 5 µg/0.1 mL, caspofungin, nystatin, miconazole, vancomycin 5 mg/0.1 mL, cefuroxime 25 µL/0.1 mL.
12.4 PACK-CXL
Photoactivated corneal cross-linking (PACK-CXL), as an adjunct to antibiotic therapy, may shorten healing time and reduce the need for surgery in bacterial and fungal keratitis; amoebae, particularly in cyst form, are by contrast resistant to it [13].
12.5 Surgery
- "Hot" corneal graft: for therapeutic failure despite well-conducted treatment, large perforation, or threatened scleral invasion.
- Amniotic membrane graft: for analgesic or tectonic purposes.