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Bacterial keratitis

Edited by: Jeremy Tan, MD  

Last updated: July 15th, 2022

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Summary of Evidence

Antibiotic choice

Analysis of 16 studies showed no difference in comparative effectiveness between fluoroquinolones and aminoglycoside-cephalosporin treatment options in the management of bacterial keratitis. In terms of safety profile, fluoroquinolones decreased the risk of ocular discomfort and chemical conjunctivitis while ciprofloxacin increased the risk of white corneal precipitate compared with aminoglycoside-cephalosporin. {McDonald EM, Ram FS, Patel DV, McGhee CN. Topical antibiotics for the management of bacterial keratitis: an evidence-based review of high quality randomised controlled trials. Br J Ophthalmol. 2014 Nov;98(11):1470-7.}

Adjunctive corticosteroids

Topical corticosteroids may be associated with improved long-term clinical outcomes (visual acuity) in bacterial corneal ulcers not caused by Nocardia species.(SCUT, 2014) {Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Lalitha P, O’Brien KS, Glidden DV, Ray KJ, Oldenburg CE, Zegans ME, Whitcher JP, McLeod SD, Porco TC, Lietman TM, Acharya NR; Steroids for Corneal Ulcers Trial Group. The steroids for corneal ulcers trial (SCUT): secondary 12-month clinical outcomes of a randomized controlled trial. Am J Ophthalmol. 2014 Feb;157(2):327-333.e3.}

 

A subgroup analysis of the Steroids for Corneal Ulcers Trial (SCUT) showed a possible benefit to visual acuity for adjunctive topical corticosteroids given earlier (after 2-3 days of topical antibiotics) vs later (after 4 or more days) in the course of bacterial corneal ulcers. {Ray KJ, Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Glidden DV, Oldenburg CE, Sun CQ, Zegans ME, McLeod SD, Acharya NR, Lietman TM. Early addition of topical corticosteroids in the treatment of bacterial keratitis. JAMA Ophthalmol. 2014 Jun;132(6):737-41.}

 

Adjunctive topical corticosteroids had no superiority to placebo in VA and scar size at 3 months, except in patients with baseline BCVA count fingers or worse or central ulcers.(SCUT, 2012) {Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Lalitha P, Glidden DV, Ray KJ, Hong KC, Oldenburg CE, Lee SM, Zegans ME, McLeod SD, Lietman TM, Acharya NR; Steroids for Corneal Ulcers Trial Group. Corticosteroids for bacterial keratitis: the Steroids for Corneal Ulcers Trial (SCUT). Arch Ophthalmol. 2012 Feb;130(2):143-50.}

 

 

Evidence

1. Risk factors

1.1 Contact lens wear

Review

2017 Kam et.al.

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2017
Review

The majority of infections in association with orthokeratology lens wear resulted in the formation of corneal scars and almost 10% of eyes needed surgical treatment. {Kam KW, Yung W, Li GKH, Chen LJ, Young AL. Infectious keratitis and orthokeratology lens use: a systematic review. Infection. 2017 Dec;45(6):727-735.}

  • Analysis of 29 articles involving 173 eyes of infectious keratitis in association with orthokeratology lens wear
  • Findings:
    • Mean age at presentation: 15.4 years
    • male-to-female ratio 1:1.7
    • positive microbiological cultures reported in 69.4% of cases
    • Pseudomonas aeruginosa and Acanthamoeba were the most common etiological agents
    • mean duration of hospitalization 7.7 days
    • LogMAR VA improved from 1.17 to 0.33 from presentation to final visit

Kam et.al.
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2. Treatment

2.1 Antibiotic choice

Review

2014 McDonald et.al.

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2014
Review

Analysis of 16 studies showed no difference in comparative effectiveness between fluoroquinolones and aminoglycoside-cephalosporin treatment options in the management of bacterial keratitis. In terms of safety profile, fluoroquinolones decreased the risk of ocular discomfort and chemical conjunctivitis while ciprofloxacin increased the risk of white corneal precipitate compared with aminoglycoside-cephalosporin. {McDonald EM, Ram FS, Patel DV, McGhee CN. Topical antibiotics for the management of bacterial keratitis: an evidence-based review of high quality randomised controlled trials. Br J Ophthalmol. 2014 Nov;98(11):1470-7.}

McDonald et.al.
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Review

2012 Hanet et.al.

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2012
Review

Analysis of 13 studies showed fluoroquinolones as empiric initial treatment was at least as effective as combined fortified antibiotics for the treatment of bacterial keratitis. {Hanet MS, Jamart J, Chaves AP. Fluoroquinolones or fortified antibiotics for treating bacterial keratitis: systematic review and meta-analysis of comparative studies. Can J Ophthalmol. 2012 Dec;47(6):493-9.}

Hanet et.al.
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Clinical Trial

1995 Hanet et.al.

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1995
Clinical Trial

The efficacy (time to healing) of ofloxacin was equivalent to fortified cefazolin and tobramycin in the treatment of bacterial keratitis, with reduced frequency of ocular toxic effects in the former (248 patients). {O’Brien TP, Maguire MG, Fink NE, Alfonso E, McDonnell P. Efficacy of ofloxacin vs cefazolin and tobramycin in the therapy for bacterial keratitis. Report from the Bacterial Keratitis Study Research Group. Arch Ophthalmol. 1995 Oct;113(10):1257-65.}

Hanet et.al.
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2.2 Adjunctive topical corticosteroids

Review

2014 Herretes et.al. (Cochrane)

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2014
Review

Analysis of 4 RCTs concluded: “inadequate evidence as to the effectiveness and safety of adjunctive topical corticosteroids compared with no topical corticosteroids in improving visual acuity, infiltrate/scar size, or adverse events among participants with bacterial keratitis. Current evidence does not support a strong effect of corticosteroid, but may be due to insufficient power to detect a treatment effect.” {Herretes S, Wang X, Reyes JM. Topical corticosteroids as adjunctive therapy for bacterial keratitis. Cochrane Database Syst Rev. 2014 Oct 16;10(10):CD005430.}

  • Analysis of 4 RCTs with total number of 611 patients (612 eyes). All trials compared treatment of bacterial keratitis with/without topical corticosteroids with follow-up period of 2 months to 1 year.

Herretes et.al. (Cochrane)
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Clinical Trial

2014 Ray et.al. (SCUT)

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2014
Clinical Trial

A subgroup analysis of the Steroids for Corneal Ulcers Trial (SCUT) showed a possible benefit to visual acuity for adjunctive topical corticosteroids given earlier (after 2-3 days of topical antibiotics) vs later (after 4 or more days) in the course of bacterial corneal ulcers. {Ray KJ, Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Glidden DV, Oldenburg CE, Sun CQ, Zegans ME, McLeod SD, Acharya NR, Lietman TM. Early addition of topical corticosteroids in the treatment of bacterial keratitis. JAMA Ophthalmol. 2014 Jun;132(6):737-41.}

  • Subgroup analysis of SCUT trial assessing timing of administration of adjunctive corticosteroids
    • Earlier administration (vs placebo): after 2-3 days of topical antibiotics
    • Later administration (vs placebo): after 4 or more days of topical antibiotics
  • Findings:
    • Patients in the earlier corticosteroid treatment group had approximately 1-line better visual acuity at 3 months than in the placebo group.
    • Patients in the earlier corticosteroid treatment group had approximately 1-line better visual acuity at 3 months than in the placebo group.
    • Patients with non-Nocardia keratitis or no topical antibiotic use before SCUT enrollment showed significant improvement in BCVA if corticosteroids were administered earlier rather than later.

Ray et.al. (SCUT)
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Clinical Trial

2014 Srinivasan et.al. (SCUT)

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2014
Clinical Trial

Topical corticosteroids may be associated with improved long-term clinical outcomes (visual acuity) in bacterial corneal ulcers not caused by Nocardia species. {Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Lalitha P, O’Brien KS, Glidden DV, Ray KJ, Oldenburg CE, Zegans ME, Whitcher JP, McLeod SD, Porco TC, Lietman TM, Acharya NR; Steroids for Corneal Ulcers Trial Group. The steroids for corneal ulcers trial (SCUT): secondary 12-month clinical outcomes of a randomized controlled trial. Am J Ophthalmol. 2014 Feb;157(2):327-333.e3.}

  • Randomized controlled trial of topical steroids vs placebo in culture-positive bacterial corneal ulcer (500 patients)
  • Findings:
    • 1 year
      • Corticosteroid use was associated with a mean 1-line VA improvement in non-Nocardia ulcers (no difference in VA in Nocardia ulcers).
      • Corticosteroid use was associated with larger mean scar size in Nocardia ulcers.

Srinivasan et.al. (SCUT)
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Clinical Trial

2012 Srinivasan et.al. (SCUT)

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2012
Clinical Trial

Adjunctive topical corticosteroids had no superiority to placebo in VA and scar size at 3 months, except in patients with baseline BCVA count fingers or worse or central ulcers. {Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Lalitha P, Glidden DV, Ray KJ, Hong KC, Oldenburg CE, Lee SM, Zegans ME, McLeod SD, Lietman TM, Acharya NR; Steroids for Corneal Ulcers Trial Group. Corticosteroids for bacterial keratitis: the Steroids for Corneal Ulcers Trial (SCUT). Arch Ophthalmol. 2012 Feb;130(2):143-50.}

  • Randomized controlled trial of topical steroids vs placebo in culture-positive bacterial corneal ulcer (500 patients)
  • Findings:
    • 3 months:
      • There was no difference in BCVA, infiltrate/scar size, time to re-epithelisation or corneal perforation.
      • A subgroup of patients with baseline BCVA of CF or worse or ulcers that were completely central had better VA with steroids than placebo.

Srinivasan et.al. (SCUT)
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3. Prognosis

Cohort study

2019 Prajna et.al.

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2019
Cohort study

Best-corrected vision (spectacle/contact lens) in the better eye was worse than 20/60 in 10 individuals (20.0%) in the bacterial ulcer group four years after treatment for keratitis. {Prajna NV, Srinivasan M, Mascarenhas J, Lalitha P, Rajaraman R, McClintic SM, O’Brien KS, Ray KJ, Acharya NR, Lietman TM, Keenan JD. Visual Impairment in Fungal Versus Bacterial Corneal Ulcers 4 Years After Successful Antimicrobial Treatment. Am J Ophthalmol. 2019 Aug;204:124-129.}

  • Prospective cohort study of 100 individuals with fungal or bacterial keratitis diagnosed 4 years prior
  • Findings:
    • Long-term visual outcomes were similar between fungal and bacterial ulcers, although fungal ulcers were more likely to produce severe visual impairment. (BCVA worse than 20/60 24% vs 20%)

Prajna et.al.
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Cohort study

2014 McClintic et.al.

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2014
Cohort study

Visual acuity may demonstrate improvement up to 12 months after diagnosis of bacterial keratitis, but not after that.

 

  • BCVA improved by 2.9 logMAR lines from enrollment to 3 weeks, 1.2 lines from 3 weeks to 3 months, and 0.8 lines from 3 to 12 months, but did not change significantly between 12 months and 4 years. {McClintic SM, Prajna NV, Srinivasan M, Mascarenhas J, Lalitha P, Rajaraman R, Oldenburg CE, O’Brien KS, Ray KJ, Acharya NR, Lietman TM, Keenan JD. Visual outcomes in treated bacterial keratitis: four years of prospective follow-up. Invest Ophthalmol Vis Sci. 2014 May 2;55(5):2935-40.}

McClintic et.al.
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References

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