Corticosteroids for bacterial keratitis: the Steroids for Corneal Ulcers Trial (SCUT)

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Srinivasan M, et al. "Corticosteroids for bacterial keratitis: the Steroids for Corneal Ulcers Trial (SCUT)". Archives of Ophthalmology. 2012. 130(2):143-150.
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Clinical Question

In patients with culture-confirmed bacterial corneal ulcers, does the addition of topical corticosteroids to antibiotic therapy improve visual outcomes at 3 months?

Bottom Line

Topical corticosteroids do not improve visual outcomes, however they do not increase the risk of complications.

Major Points

The efficacy of corticosteroids as an adjunctive therapy in the treatment of bacterial corneal ulcers was previously unclear: in limiting the immune response, it might both prolong the course of the disease thereby worsening visual outcomes, or it might reduce infection-associated corneal scarring thereby improving visual outcomes. This double-blinded clinical trial showed that corticosteroids do not improve BSCVA at 3-months, but they also do not cause more adverse effects.

Guidelines

Design

  • Multicenter, double-blind, placebo-controlled, randomized, controlled trial
  • N=500
    • Corticosteroid (prednisolone 1.0%) (n=250)
    • Placebo (NaCl 0.9% with opaque preservative) (n=250)
  • Setting: Aravind Eye Care System, Dartmouth-Hitchcock Medical Center, UCSF
  • Enrollment: September 2006 to February 2010
  • Follow-up: q3d until re-epithelialization, at 3 weeks, at 3 months
  • Primary outcome: BSCVA at 3 Months

Population

Inclusion Criteria

  • Culture-positive bacterial ulcer
  • Received 48h of topical moxifloxacin before randomization

Exclusion Criteria

  • Corneal perforation or impending perforation
  • Evidence of fungus on KOH preparation, Giemsa, or evidence of acanthamoeba
  • Evidence or history of herpetic keratitis
  • Use of topical cortosteroid or systemic prednisolone during the course of the present ulcer
  • Previous PKP
  • Vision less than 6/60 in the fellow eye

Baseline Characteristics

  • Median age: 53 years
  • Sex: 45% Female
  • Injurious Object:
    • 38% Vegetative matter or wood
    • 24% Metal or other
    • 7% Unknown
    • 2% Contact lens

Interventions

  • Treatment arm: prednisolone sodium phosphate 1%
  • Control arm: NaCl 0.9% with preservative,
  • Drop schedule (applies to both arms): 1 drop four times a day for 1 week, 1 drop twice a day for 1 week, one drop once a day for 1 week, then discontinue.
  • Patients in both the treatment and control arm:
    • Moxifloxicin: 1 drop every hour while awake for 48h, then 1 drop every two hours until re-epithelialization, then four times a day until 3 weeks.
  • Treating phyicians could change or discontinue any medication if medically necessary

Outcomes

Data are provdied as differences between corticosteroid and placebo with 95% confidence interval

Primary Outcome

BSCVA at 3 Months from enrollment
Exact data not given, however multiple linear regression shows a P Value of 0.82

Secondary Outcomes

BSCVA at 3 weeks from enrollment
Corticosteroid treated patients had a 0.024 better logMAR acuity
Mean difference 0.024; −0.092 to 0.044; P = .49
Infiltrate / scar size at 3 weeks and 3 months
3 Week mean difference: 0.05 mm; −0.09 to 0.15; P = .60
3 Month mean difference: 0.06 mm; −0.07 to 0.17; P = .40
Time to reepithelialization.
7.0 Days (placebo) vs 7.5 Days (corticosteroid); P = 0.25

Subgroup Analysis

Patients with baseline BSCVA of count fingers or worse who were treated with corticosteroids had 0.17 better logMAR acuity
Mean 0.17, 95% CI, −0.31 to −0.02; P = .03;
Patients with ulcers covering the central 4mm pupil who were treated with corticosteroids had 0.20 better logMAR acuity
Mean 0.20, 95% CI, −0.37 to −0.04; P = .02
Patients with deeper ulcers at baseline who were treated with corticosteroids had 0.15 better logMAR acuity.
Mean 0.15, 95% CI, −0.31 to 0.01; P = .07
Patients with Nocardia-positive ulcers treated with corticosteroids had a larger infiltrate or scar at 3 months.
Mean Difference 0.47mm, 95% CI, 0.06 to 0.88, P=0.02
Early vs Late Intervention
Patients who began corticosteroids within 3 days of starting antibiotics had better BSCVA at 3 months compared to those who started placebo earlier (P = 0.01).

Adverse Events

Corneal perforation, No difference
7 patients vs 8 patients, P = 0.99
No healing of epithelial defect by 3 weeks, more in corticosteroid arm
44 patients vs 27 patients; P=0.04
Elevated IOP >25mmHg, more in placebo arm
2 patients vs 10 patients; P = 0.04

Criticisms

  • Treating physicians could change or discontinue any medication
  • Different bacterial isolates were found at the site in India than the site in the United States
  • The corticosteroid group had significantly more central ulcers (P = 0.02)
  • Of the patients who were initially evaluated to be enrolled, more than 25% were considered ineligible because they were believed to have an impending corneal perforation
  • External validity: 97% of enrolled patients were in India, 3% in US
  • All patients were treated with moxifloxacin despite the organisms having different susceptibilities to this drug
  • The dosing of the corticosteroid was not varied; all patients had a standard dosage schedule.

Funding

  • National Eye Institute Grants U10EY015114, K23EY017897, EY02162
  • Research to Prevent Blindness
  • Alcon / Novartis AG provided moxifloxacin

Further Reading

Herretes S, Wang X, Reyes JM. Topical corticosteroids as adjunctive therapy for bacterial keratitis. Cochrane Database Syst Rev. 2014;10(10):CD005430. Published 2014 Oct 16. doi:10.1002/14651858.CD005430.pub3

Palioura S, Henry CR, Amescua G, Alfonso EC. Role of steroids in the treatment of bacterial keratitis. Clin Ophthalmol. 2016;10:179–186. Published 2016 Jan 27. doi:10.2147/OPTH.S80411

Ray KJ, Srinivasan M, Mascarenhas J, et al. Early addition of topical corticosteroids in the treatment of bacterial keratitis. JAMA Ophthalmol. 2014;132(6):737–741. doi:10.1001/jamaophthalmol.2014.292

Srinivasan M, Mascarenhas J, Rajaraman R, et al. The steroids for corneal ulcers trial (SCUT): secondary 12-month clinical outcomes of a randomized controlled trial. Am J Ophthalmol. 2014;157(2):327–333.e3. doi:10.1016/j.ajo.2013.09.025

Tuli SS. Topical Corticosteroids in the Management of Bacterial Keratitis. Curr Ophthalmol Rep. 2013;1(4):10.1007/s40135-013-0026-0. doi:10.1007/s40135-013-0026-0