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Study Title and Description

Corticosteroids for bacterial corneal ulcers.



Key Questions Addressed
1 What are the effects of topical corticosteroids as adjunctive therapy for bacterial keratitis?
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Primary Publication Information
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TitleData
Title Corticosteroids for bacterial corneal ulcers.
Author Srinivasan M., Lalitha P., Mahalakshmi R., Prajna NV., Mascarenhas J., Chidambaram JD., Lee S., Hong KC., Zegans M., Glidden DV., McLeod S., Whitcher JP., Lietman TM., Acharya NR.
Country Aravind Eye Care System, Madurai, India.
Year 2009
Numbers Pubmed ID: 18829631

Secondary Publication Information
There are currently no secondary publications defined for this study.


Extraction Form: Topical corticosteroids as adjunctive therapy for bacterial keratitis 2014
Arms
Number Title Description Comments
1 Antibiotic-steroid Adjunctive topical corticosteroids, topical prednisolone phosphate 1% administered topically to the cornea 4 times a day for 1 week, followed by 2 times a day for 1 week, then once a day for 1 week, and then stopped.
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2 Antibiotic-only Adjunctive placebo, 0.9% sodium chloride, administered topically to the cornea 4 times a day for 1 week, followed by 2 times a day for 1 week, then once a day for 1 week and then stopped.
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Design Details
Question... Follow Up Answer Follow-up Answer
Page 198-202
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Study design RCT
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Number randomized Total: 42 participants: 22 in the placebo group and 20 in the steroid group
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Exclusions after randomization and reasons for exclusion none
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Number analyzed Total: 33 participants: 17 in the placebo group and 16 in the steroid group for analysis of best spectacle-corrected visual acuity at 3 months
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Unit of analysis 1 eye per individual
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Losses to follow-up and reasons for loss to follow-up at week 3, 5 participants in the placebo group and 1 participant in the steroid group discontinued intervention; at month 3, an additional 5 participants in the placebo group and 4 participants in the steroid group discontinued intervention; reasons for discontinuation were not specified
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How were missing data handled? excluded from analysis
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Reported power calculation yes: 42 participants (21 participants per arm) can provide 80% power to detect a 0.4 logMAR (4 Snellen lines) difference between the 2 study arms, assuming a SD of 0.4 in the 3-month BCVA
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Any issues with study design? none
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Country India
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Age (mean +/- SD) greater than 16 years: mean age was 44.1 years in the placebo group and 49.9 years in the steroid group
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Gender (male:female) 50:50 in the placebo group and 55:45 in the steroid group
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Inclusion criteria "presence of a corneal ulcer at presentation (defined by an epithelial defect and signs of stromal inflammation); cornea culture on blood or chocolate agar indicates the presence of bacteria; antibiotic given for more than 48 hours; the patient able to verbalise a basic understanding of the study after it was explained to the patient, as determined by a physician examiner (this understanding included a commitment to return for follow-up visits); appropriate consent"
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Exclusion criteria "overlying epithelial defect, 0.75 mm at its greatest width at presentation; impending perforation; evidence of fungus on KOH or Giemsa stain at time of presentation; evidence of acanthamoeba by stain; evidence of herpetic keratitis by history or exam; history of corneal scar in the affected eye; use of a topical steroid in the affected eye during the course of the present ulcer, including use after the symptoms of the ulcer started but before presentation; use of systemic steroids during the course of the present ulcer; age less than 16 years; bilateral ulcers; previous penetrating keratoplasty; pregnancy (by history or urine test); outside 200 km radius of Aravind Eye Hospital; evidence of fungus on culture at time of enrollment; best spectacle-corrected vision worse than 6/60 (20/200) in the fellow eye; corneal perforation or descemetocoele; known allergy to study medications (steroid or preservative); no light perception in the affected eye; not willing to participate or to return for follow-up visits"
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Equivalence of baseline characteristics yes
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Antibiotic-only group adjunctive placebo, 0.9% sodium chloride, administered topically to the cornea 4 times a day for 1 week, followed by 2 times a day for 1 week, then once a day for 1 week and then stopped
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Antibiotic-steroid group adjunctive topical corticosteroids, topical prednisolone phosphate 1% administered topically to the cornea 4 times a day for 1 week, followed by 2 times a day for 1 week, then once a day for 1 week and then stopped
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Note
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Length of follow-up Planned: 3 weeks and 3 months after enrollment; Actual: 3 weeks and 3 months after enrollment
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Primary outcome, as defined in the study best corrected visual acuity (BCVA) at 3 months, adjusting for enrolment BCVA and group
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Measurement of primary outcome in the study BCVA at 3 months in the study eye, using a linear regression model with 3-month logMAR BCVA as the outcome variable and treatment arm (placebo versus steroid) and enrolment logMAR BCVA as covariates
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Secondary outcomes and measurements, as defined in the study re-epithelialization time, infiltrate/scare size, and adverse events: BCVA at 3 weeks, adjusting for enrolment BCVA, and infiltrate/scar size at 3 weeks and 3 months, adjusting for enrolment infiltrate/scar size. For analysis, infiltrate/scar size was characterized by the geometric mean of the longest dimension and the longest perpendicular. The association between enrolment and 3-month BCVA was assessed using Pearson's correlation coefficient
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Adverse events reported yes
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Intervals at which outcome were assessed 3 weeks and 3 months after the enrollment
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Type of study published
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Study period 4 January 2005 to 20 August 2005
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Source of funding That Man May See and the South Asia Research Fund. The Department of Ophthalmology at UCSF is supported by a core grant from the National Eye Institute, EY02162. N Acharya is supported by a National Eye Institute K23EY017897 grant and a Research to Prevent Blindness Career Development Award. TM Lietman is supported by a National Eye Institute grant U10-EY015114 and a Research to Prevent Blindness award. M Zegans is supported by a K08 EY13977-01 NEI grant
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Declaration of interest "None declared. Alcon donated moxifloxacin for the study. The sponsors had no role in the design or conduct of the study, data analysis or manuscript preparation. None of the authors have any financial disclosures related to this manuscript."
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Reported subgroup analyses none
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Age, median (25th to 75th percentile)
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General therapy "treatment for all participants in the two groups included: administration of study drops (steroid or placebo) to the cornea four times a day for 1 week, followed by two times a day for 1 week, then once a day for 1 week and then stopped; all patients continued to receive topical moxifloxacin every 2 hours while awake until re-epithelialisation, and then four times a day until 3 weeks after enrolment; antibiotics were then discontinued unless the treating physician thought that longer treatment was warranted"
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Random sequence generation (selection bias):Authors' judgement Low risk
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Random sequence generation (selection bias):Support for judgement Randomization was done using "block randomisation in groups of ten generated by RAND command in Excel by TML; implementation including enrolment and assignment of participants by RM."
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Allocation concealment (selection bias):Authors' judgement Unclear risk
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Allocation concealment (selection bias):Support for judgement Did not describe explicitly; stated only that after a minimum of 48 hours of moxifloxacin treatment, patients were randomized (block randomization in groups of 10 generated by RAND command in Excel by TML; implementation including enrolment and assignment of participants by RM) to receive topical prednisolone phosphate 1% or placebo drops
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Masking of participants and personnel (performance bias):Authors' judgement Low risk
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Masking of participants and personnel (performance bias):Support for judgement "Double-masking of treatment assignment was achieved since the prednisolone phosphate solution could not be differentiated from the placebo. All study-site personnel and patients were masked to treatment assignment. Only the biostatisticians responsible for the randomisation coding and the study pharmacist were unmasked."
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Masking of outcome assessment (detection bias):Authors' judgement Low risk
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Masking of outcome assessment (detection bias):Support for judgement "Double-masking of treatment assignment was achieved since the prednisolone phosphate solution could not be differentiated from the placebo. All study-site personnel and patients were masked to treatment assignment. Only the biostatisticians responsible for the randomisation coding and the study pharmacist were unmasked."
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Incomplete outcome data (attrition bias):Authors' judgement High risk
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Incomplete outcome data (attrition bias):Support for judgement "Efficacy endpoints were analysed on an intent-to-treat basis for all randomised patients enrolled in the study. The primary analysis included patients with both enrolment and 3-month data. A sensitivity analysis was also performed in which 3-week values were carried forward to 3 months if the 3-month visit was missed." "Forty-two patients with culture-proven BK at Aravind Eye Hospital were enrolled: 22 in the placebo arm and 20 in the steroid arm. Thirty-three patients (79%) were followed-up at 3 months, and an additional three patients were followed-up at their 3-weeks but missed their 3-month visit."
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Selective reporting (reporting bias):Authors' judgement Low risk
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Selective reporting (reporting bias):Support for judgement We did not have access to the reported outcomes with the original study protocol. We assessed the selective outcome reporting by comparing the reported outcomes in the methods and results sections. Also, because this is the pilot trial for the SCUT trial, and the SCUT trial has a protocol, we compared these 2 studies and they have similarly reported all expected outcomes
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Other bias:Authors' judgement Low risk
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Other bias:Support for judgement No other bias identified
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Results & Comparisons


Results Data
Mean Difference 95% CI low 95% CI high P-Value Mean Difference 95% CI low 95% CI high P-Value Mean Difference 95% CI low 95% CI high P-Value
Outcome: Visual Acuity      Population: All Participants Between-Arm Comparisons
Time Point Measure Antibiotic-steroid Antibiotic-only Comparison Measure Antibiotic-only vs. Antibiotic-steroid


Baseline N/A

N Analyzed 20 22 -0.13
Mean 1.28 1.15 -0.48
SD 0.54 0.63 0.22
SE 0.48


3 weeks

N Analyzed 16 17 0.19
Mean 0.66 0.75 20.52
SD 0.68 0.75 0.15
SE 0.26


3 months

N Analyzed 16 17 0.09
Mean 0.71 0.59 20.41
SD 0.72 0.75 0.24
SE 0.60
Mean Difference 95% CI low 95% CI high P-Value Mean Difference 95% CI low 95% CI high P-Value
Outcome: Ulcer healing: size      Population: All Participants Between-Arm Comparisons
Time Point Measure Antibiotic-steroid Antibiotic-only Comparison Measure Antibiotic-steroid vs. Antibiotic-only


3 weeks

N Analyzed 16 17
Mean
SD
SE 0.23


3 months

N Analyzed 16 17
Mean
SD
SE 0.53
95% CI low 95% CI high Hazard Ratio (HR) P-value
Outcome: Ulcer healing: rate      Population: All Participants Between-Arm Comparisons
Time Point Measure Antibiotic-steroid Antibiotic-only Comparison Measure Antibiotic-only vs. Antibiotic-steroid


Not reported N/A

N Enrolled 20 22 0.23
Counts 8.6 days 6.3 days 0.94
SD 4.7 3.1 0.47
0.03

Adverse Events
Arm or Total Title Description Number of Events Comments
Antibiotic-steroid Ocular adverse events All occurred in the control group
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Antibiotic-only 4
Total 4