Gitanjali B. Baveja
• Local epithelial defect with degradation or inflammation of underlying tissue
• Synonyms: Corneal infiltrate, infectious or noninfectious keratitis
• 30,000 cases annually in the United States
• 10–30 cases per 100,000 of contact lens wearers per year (United States)
• Varies greatly geographically
• Secondary variable is etiology
• Contact lens use
• Compromised host factors: Ocular surface disease
• Inadequate eyelid closure or apposition
• Corneal hypoesthesia
• Systemic autoimmune diseases (less likely to be central)
• Contact lens hygiene
• Preventing compromise of epithelium
• Sufficient lubrication
• Surgical correction of eyelid abnormalities
• Control of acute inflammatory state in autoimmune diseases
• Breakdown of epithelium
• Marked inflammatory response: Leukocyte infiltration (usually neutrophils)
• Degradation of extracellular matrix: Prolonged activation of plasmin, matrix metalloproteinase secretion
• Infectious: Bacterial, fungal, viral, acanthamoeba
• Noninfectious/sterile: Neurotrophic, autoimmune related, corneal exposure (inadequate eyelid closure)
COMMONLY ASSOCIATED CONDITIONS
• Infectious ulcer: Contact lens abuse/overwear, trauma
• Neurotrophic keratitis: VII nerve palsy, herpes simplex, herpes zoster
• Sterile ulcer: Rheumatoid arthritis, systemic lupus erythematosus, Wegener’s granulomatosis, Sjögren’s syndrome
• Exposure keratopathy: Thyroid orbitopathy
• Elicit comprehensive history of contact lens wear if applicable including extended vs daily wear, storage/disinfecting methods, swimming with lenses, exposure to any source of water, including tap water, lake, pond, etc.
• Recent trauma to the ocular surface including acid/alkali burn
• History of dry eyes
• Comprehensive review of systems (especially autoimmune diseases)
• Eyelid examination to determine adequate closure, apposition, trichiasis
• Conjunctival injection
• Tear film insufficiency
• Epithelial loss (fluorescein staining)
• Density and size of stromal infiltrate
• Thinning of stromal tissue
• Anterior chamber cell and flare
DIAGNOSTIC TESTS & INTERPRETATION
Initial lab tests
• Corneal cultures: Scrapings obtained from border of infiltrate and placed on specific culture media
• Can use Kimura spatula or moistened calcium alginate swab
• Blood agar: Aerobic bacteria (S. aureus, S. epidermidis, S. pneumoniae, P. aeruginosa), saprophytic fungi, Nocardia
• Chocolate agar: Aerobic and facultative bacteria (N. gonorrhea, H. influenzae, Bartonella)
• Thioglycollate broth: Aerobic, facultative, anaerobic bacteria
• Thayer–Martin agar: Neisseria
• Lowenstein–Jensen agar: Mycobacteria, Nocardia
• Nonnutrient agar with E. coli overlay: Acanthamoeba
Follow-up & special considerations
• Central ulcers should be cultured prior to starting topical antibiotics.
• Also culture if ulcer is nonresponsive to topical antibiotics
Slit lamp photography can document size and density of infiltrate.
• Special stains include gram stain (bacteria), Giemsa stain (Chlamydia, Acanthamoeba, Acid fast stain (Mycobacteria), Calcofluor white (Acanthamoeba)
• Corneal biopsy if unresponsive to treatment
• Confocal microscopy (Acanthamoeba)
• Gram positive: S. aureus, Coagulase Negative Staph, Streptococcus pneumoniae, Streptococcus viridians, Corynebacterium diphtheriae. Propionibacterium, Mycobacterium, Bacillus cereus
• Gram negative: Pseudomonas, Serratia, Proteus mirabilis, H. influenzae, Moraxella, Neisseria
• Fungal: Candida, Fusarium, Aspergillus, Curvularia, Mucor, Rhizopus
• Neurotrophic keratitis
• Herpes simplex keratitis
• Exposure keratopathy
• Autoimmune diseases (primarily peripheral corneal ulcer): Rheumatoid arthritis, Systemic Lupus Erythematosis (SLE), Wegener’s granulomatosis, collagen vascular diseases
• 4th-generation fluoroquinolone: 1 drop every 15 min for the 1st hour, then per hour around the clock
• 4th generation: Moxifloxacin, gatifloxacin, besifloxacin
• Others: Ciprofloxacin, levofloxacin 1.5%
• For severe or nonresponsive infiltrate: Fortified topical antibiotics can be prepared by the pharmacy.
• Fortified vancomycin 25–50 mg/mL combined with fortified tobramycin/gentamicin 9–14 mg/mL or combined with fortified ceftazidime 50 mg/mL
• Regimen can be modified according to culture results/susceptibility testing.
• If unresponsive and culture negative consider acanthamoeba, fungal keratitis, atypical organisms.
• Acanthamoeba: Topical ophthalmic Neosporin, PHMB, hexamidine, chlorhexidine
• Fungal keratitis: Topical natamycin 5%, amphotericin B, imidazoles (voriconazole, itraconazole, ketoconazole, clotrimazole, fluconazole)
• Nontuberous mycobacteria: Amikacin/clarithromycin 20–40 mg/mL
• Nocardia: Amikacin 20–40 mg/mL
• Cycloplegic agent helps with pain and prevents synechiae: Homatropine 5% b.i.d., isopto-hyoscine 0.25% t.i.d., atropine 1% q.i.d.
• Topical ointment or gel at bedtime: Ciloxan/erythromycin/bacitracin ointment, azithromycin (viscous drop)
Issues for Referral
Refer to cornea specialist if:
• Unable to culture
• Unresponsive to treatment (24–48 h)
• Progressive lesion
• Atypical infiltrate
• Systemic antibiotics for Neisseria
• Systemic antifungals for Acanthamoeba
• Daily follow-up until lesion is stabilized
• Criteria of stabilization: Healing of overlying epithelium, resolution of hypopyon, decrease in density of infiltrate, no further thinning of cornea, improvement in visual acuity, symptomatic improvement
• Baum J, Barza M. The evolution of antibiotic therapy for bacterial conjunctivitis and keratitis. Cornea 2000;19(5):659–672.
• Charukamnoetkanok P, Pineda R. Controversies in management of bacterial keratitis. Int Ophthalmol Clin 2005;45(4):199–210.
• Loh AR, Hong K, Lee S, Mannis M, Acharya NR. Practice patterns in the management of fungal corneal ulcers. Cornea 2009;28(8):856–859.
• Acharya NR, Srinivasan M, Mascarenhas J, et al. The steroid controversy in bacterial keratitis. Arch Ophthalmol 2009;127(9):1231.
• Kaye S, Tuft S, Neal T, et al. Bacterial susceptibility to topical antimicrobials and clinical outcome in bacterial keratitis. Invest Ophthal Visual Sci 2010;51(1):362–368.
• 370.00 Corneal ulcer, unspecified
• 370.03 Central corneal ulcer