- Keratitis = inflammation of cornea.
- Approximately 50% of cases are infectious (of which ~80% are bacterial).
- Epithelium of cornea and conjunctiva continuous- same agents can cause both keratitis and conjunctivitis.
- Signs/symptoms: pain, +/- decreased vision, tearing, photophobia, blepharospasm, loss of transparency, ulcerated epithelium, stromal inflammation, keratolysis (loss of substance) and corneal scar/tear.
- Exam: topical anesthetic, slit lamp [inflammation +/- hypopyon (WBC in anterior chamber), hyphema, synechiae, glaucoma].
- Ddx: may include non-infectious considerations e.g., rheumatoid arthritis, SLE, Behçets, PAN, ankylosing spondylitis, Reiter’s, inflammatory bowel disease.
- With advanced infection: endophthalmitis may develop as complication.
- Infectious keratitis can lead to blindness; IMMEDIATE ophthalmology consult is mandatory and hospitalization strongly recommended in moderate to severe cases to monitor for corneal perforation.
- Obtain ophthalmology consultation.
- Corneal scrapings (multiple samples for Gram, Giemsa, AFB, GMS stains and cultures)
- Gram stain: diagnostic accuracy is 75% if 1 organism, only ~35% if >1 organism.
- Acanthamoeba (and other free-living ameoba): plate scraping on E. coli lawn, PCR (if available).
- Corneal biopsy (in nonsuppurative cases).
- If no diagnosis, then consider therapeutic keratoplasty for diagnosis/treatment.
- Routes of administration: solutions, subconjunctival, continuous lavage, hydrophilic contact lenses.
- All the following choices are ophthalmic solutions except where specifically noted.
- While awaiting culture data, and if suspect bacterial cause, start broad spectrum coverage and narrow spectrum later only when certain of offending process and culture data available.
- Gram-positives: cephalosporin (cefazolin) or topical vancomycin (if resistance suspected, MRSA).
- Gram-negatives (topicals): aminoglycosides [gentamicin (0.3%-1.5%), amikacin, tobramycin], ciprofloxacin 0.3%, norfloxacin 0.3% or ofloxacin 0.3%.
- Antifungals: amphotericin B 1.5mg/ml, fluconazole solution, chlorhexidine gluconate 0.2%, natamycin (broad-spectrum). Oral antifungals often necessary depending on infection.
- Acanthamoeba: polyhexamethylene biguanide (0.02%) or chlorhexidine gluconate (0.02%) PLUS propamidine isethionate (0.1%) or hexamidine (0.1%) +/- surgery.
- Use two compounds from above list as hourly drops x 48h, then decrease to q2h due to corneal toxicities.
- Length of treatment: 3 weeks, then taper.
- Topical voriconazole (1%) described as second line agent if unresponsive.
- Onchocerciasis: oral ivermectin.
- Herpes: debridement + trifluridine or acyclovir ophth solution X 10 d + corticosteroids for stromal keratitis.
- Consider acyclovir 400mg po twice-daily X 1 yr to prevent recurrence.
- Foscarnet IV used for cases of suspected or proven acyclovir-resistant HSV.
- Duration of therapy depends on disease, frequent slit lamp exams necessary. Early on, frequent (q 30min) applications necessary.
- Hospitalization for moderate to severe disease strongly recommended.
Selected Drug Comments
Topical formulation should cover most Gram-positive causes.
Topical formulation should cover most Gram-negative causes. Not often favored by ophthamologists due to increased local reactions to drug.
Topical formulation; covers most Gram-negative causes.
Commonly employed topical ophthalmic covering many Gram negative, Gram positive (except MRSA) and atypical agents.
- Interpretation of MIC resistance patterns should take into account the VERY HIGH concentrations of drug that can be achieved using topical ophthalmic applications.
- Contact lens associated keratitis: in addition to Pseudomonas, consider Acanthamoeba in this setting, especially if "sterile" standard cultures.
- FDA/CDC warning about fungal (Fusarium) keratitis in soft contact lens wearers; associated w/ a specific contact lens solution.
Pathogen Specific Therapy
1st Line Agent
2nd Line Agent
Basis for recommendation
- Thomas PA, Geraldine P: Infectious keratitis. Curr Opin Infect Dis 20:129, 2007 [PMID:17496570]
Comment: The authors of this recent comprehensive paper review the latest evidence for treating infectious keratitis.
- Suwan-Apichon O et al: Topical corticosteroids as adjunctive therapy for bacterial keratitis. Cochrane Database Syst Rev [PMID:17943856]
Comment: This comprehensive analysis revealed that there were no good quality randomized trials to guide recommendations for the use of adjunctive topical corticosteroids in bacterial keratitis.
- Chang DC et al: Multistate outbreak of Fusarium keratitis associated with use of a contact lens solution. JAMA 296:953, 2006 [PMID:16926355]
Comment: 164 cases were significantly more likely than controls to report using a specific contact lens solution, ReNu with MoistureLoc (69% vs 15%; OR13.3). Fusarium was not recovered from the factory, warehouse, solution filtrate, or unopened solution bottles; production of implicated lots was not clustered in time.
- Freitas D et al: An outbreak of Mycobacterium chelonae infection after LASIK. Ophthalmology 110:276, 2003 [PMID:12578767]
Comment: 10 pts developed M. chelonae keratitis after LASIK surgery. Patients were treated with topical clarithromycin (1%), tobramycin (1.4%), and ofloxacin (0.3%). Oral clarithromycin (500 mg twice a day) was prescribed for those patients who did not respond clinically to topical treatment. Flap removal was necessary in seven eyes.
- Martins EN et al: Infectious keratitis: correlation between corneal and contact lens cultures. CLAO J 28:146, 2002 [PMID:12144234]
Comment: An overall concordance of 84.0% was found between cultures obtained from corneal scrapings and contact lenses, with a higher rate in fungal keratitis (100%) compared to amebic (80.0%) and bacterial (74.5%) keratitis in 113 Brazilian pts.
- Parmar P et al: Pneumococcal keratitis: a clinical profile. Clin Experiment Ophthalmol 31:44, 2003 [PMID:12580893]
Comment: A retrospective review of 58 patients with culture-proven pneumococcal keratitis which accounted for 33.3% of bacterial keratitis. Most cases presented with non-severe keratitis (77.5%), diplococci on Gram's stain were identified in 76% of cases. All patients received ciprofloxacin as first-line therapy. Eighty per cent responded well with complete healing of the ulcer. A second drug was required in 8.5%.
- Ohashi Y: Treatment of herpetic keratitis with acyclovir: benefits and problems. Ophthalmologica 211 Suppl 1:29, 1997 [PMID:9065935]
Comment: Benefits include: rapid resolution of epithelial keratitis, reduction of disturbances in ocular surface epithelia, & decreased incidence of necrotizing keratitis or subsequent corneal melting. On the other hand, persistent superficial punctate keratopathy, emergence of acyclovir resistance, and a gradual increase in progressive corneal endotheliitis are problematic.
- FlorCruz NV, Peczon IV, Evans JR: Medical interventions for fungal keratitis. Cochrane Database Syst Rev 2:, 2012 [PMID:22336802]
Comment: Authors note there is little robust data regarding the management of fungal keratitis. They suggest no data leads to a conclusion that one approach or combination approach offers superiority. Trials were small and variable. Products examined included: 1% topical itraconazole versus 1% topical itraconazole and oral itraconazole, different concentrations of silver sulphadiazine versus 1% miconazole, 1% silver sulphadiazine ointment versus 1% miconazole ointment, 2% econazole versus 5% natamycin, different concentrations of topical chlorhexidine gluconate versus 5% natamycin, 0.2% chlorhexidine gluconate versus 2.5% natamycin and voriconazole 1% versus natamycin 5%.
- Lalitha P et al: Antimicrobial susceptibility of Fusarium, Aspergillus, and other filamentous fungi isolated from keratitis. Arch Ophthalmol 125:789, 2007 [PMID:17562990]
Comment: Fungal ulcers are commonly treated empirically; this study from India suggests that there are multiple fungal causes of keratitis and that empiric antifungal treatment may lead to poor outcomes unless the organisms are identified and therapy is tailored appropriately.
- Oral acyclovir for herpes simplex virus eye disease: effect on prevention of epithelial keratitis and stromal keratitis. Herpetic Eye Disease Study Group. Arch Ophthalmol 118:1030, 2000 [PMID:10922194]
Comment: Long-term suppressive oral acyclovir therapy reduced the rate of recurrent HSV epithelial keratitis and stromal keratitis. Acyclovir benefit was greatest for patients who have experienced prior HSV stromal keratitis.
- Acyclovir for the prevention of recurrent herpes simplex virus eye disease. Herpetic Eye Disease Study Group. N Engl J Med 339:300, 1998 [PMID:9696640]
Comment: Randomized controlled study of 703 immunocompetent patients who had had ocular HSV within the last year to receive 400 mg po twice-daily of acyclovir or placebo. The authors found that 12 months of treatment with acyclovir reduced the rate of recurrent ocular & orofacial HSV disease & was most important in the setting of a history of HSV stromal keratitis.
- Parmar P et al: Comparison of topical gatifloxacin 0.3% and ciprofloxacin 0.3% for the treatment of bacterial keratitis. Am J Ophthalmol 141:282, 2006 [PMID:16458681]
Comment: RCT comparing ciprofloxacin (CIP) to gatifloxacin (GAT) in 208 pts with acute bacterial keratitis. A significantly higher proportion of ulcers in the GAT group exhibited complete healing compared with those in the CIP group (95.1% vs 80.9% P=.042).
- Chynn EW et al: Acanthamoeba keratitis. Contact lens and noncontact lens characteristics. Ophthalmology 102:1369, 1995 [PMID:9097775]
Comment: Retrospective study of 11 cases of Acanthamoeba keratitis showing that the time to diagnosis was much quicker in pts w/ history of contact lens use than in those without. Authors recommend that all patients with unresponsive microbial keratitis, even those without contact lens use, should be evaluated for Acanthamoeba.
- Alexandrakis G et al: Corneal biopsy in the management of progressive microbial keratitis. Am J Ophthalmol 129:571, 2000 [PMID:10844046]
Comment: Study of 33 consecutive patients who underwent a diagnostic corneal biopsy for progressive infectious keratitis despite intensive broad-spectrum topical antimicrobial therapy: Microbiologic evaluation of a diagnostic corneal biopsy contributed significantly to the diagnosis, treatment, and outcome of patients with progressive infectious keratitis.
- Visvesvara GS: Amebic meningoencephalitides and keratitis: challenges in diagnosis and treatment. Curr Opin Infect Dis 23:590, 2010 [PMID:20802332]
Comment: Author suggests for the treatment of Acanthamoeba keratitis one of two biguanides (polyhexamethylene biguanide (PHMB) and chlorhexidine PLUS one of two diamidines [propamidine isethionate (Brolene; Sanofi-Aventis, Paris, France) and hexamidine (Desomedine; Chauvin-Blache, Montpellier, France] Outcomes are improved with earlier recognition and combination therapy.
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