Gitanjali B. Baveja

BASICS

DESCRIPTION

• Local epithelial defect with degradation or inflammation of underlying tissue

• Synonyms: Corneal infiltrate, infectious or noninfectious keratitis

EPIDEMIOLOGY

Incidence

Bacterial keratitis

• 30,000 cases annually in the United States

• 10–30 cases per 100,000 of contact lens wearers per year (United States)

Prevalence

• Varies greatly geographically

• Secondary variable is etiology

RISK FACTORS

• Contact lens use

• Compromised host factors: Ocular surface disease

• Inadequate eyelid closure or apposition

• Corneal hypoesthesia

• Systemic autoimmune diseases (less likely to be central)

GENERAL PREVENTION

• Contact lens hygiene

• Preventing compromise of epithelium

• Sufficient lubrication

• Surgical correction of eyelid abnormalities

• Control of acute inflammatory state in autoimmune diseases

PATHOPHYSIOLOGY

• Breakdown of epithelium

• Marked inflammatory response: Leukocyte infiltration (usually neutrophils)

• Degradation of extracellular matrix: Prolonged activation of plasmin, matrix metalloproteinase secretion

ETIOLOGY

• 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

DIAGNOSIS

HISTORY

• 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)

PHYSICAL EXAM

• 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

• Hypopyon

DIAGNOSTIC TESTS & INTERPRETATION

Lab

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

Imaging

Slit lamp photography can document size and density of infiltrate.

Diagnostic Procedures/Other

• 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)

DIFFERENTIAL DIAGNOSIS

• 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

• Acanthamoeba

• 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

TREATMENT

MEDICATION

First Line

• 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.

Second Line

• 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

ADDITIONAL TREATMENT

General Measures

• 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

Additional Therapies

• Systemic antibiotics for Neisseria

• Systemic antifungals for Acanthamoeba

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

• 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

ADDITIONAL READING

• 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.

CODES

ICD9

• 370.00 Corneal ulcer, unspecified

• 370.03 Central corneal ulcer