SCUT: Steroids for Corneal Ulcers Trial

• Sponsor: Thomas M. Lietman (Other)
• Overall Status: Completed
• CT.gov ID: NCT00324168
• Collaborator: Aravind Eye Hospitals, India (Other), Dartmouth-Hitchcock Medical Center (Other), National Eye Institute (NEI) (NIH)
• Enrollment: 500
• Locations: 5
• Arms: 2
• Duration (Months): 75
• Patients Per Site: 100
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether adding topical steroids improves the outcomes of bacterial corneal ulcers, especially visual acuity.

Condition or Disease	Intervention/Treatment	Phase
Corneal Ulcer; Eye Infections, Bacterial	Drug: Antibiotics; Drug: Topical corticosteroid; Drug: Placebo	Phase 4

Detailed Description

Antimicrobial treatment of a bacterial corneal ulcer is generally effective in eradicating infection. However, "successful" treatment is not always associated with a good visual outcome. The scarring that accompanies the resolution of infection leaves many eyes blind. Some cornea specialists advocate the use of topical corticosteroids along with antibiotics in an effort to reduce immune-mediated tissue damage and scarring. Others fear using steroids to reduce the cornea's immune response will prolong or even exacerbate infection. Ophthalmologists have been divided on this issue for more than 30 years, and both approaches are acceptable according to the American Academy of Ophthalmology's Preferred Practice Patterns. Evidence from animal and human reports is mixed. A single randomized trial saw a non-significant benefit to steroids but was drastically underpowered (20 patients per study arm).

The study is a randomized, double-masked, placebo-controlled trial to determine whether adding topical steroids improves the outcomes of bacterial corneal ulcers. Five hundred bacterial corneal ulcers presenting to the Aravind Eye Hospitals, the University of California, San Francisco (UCSF) Proctor Foundation, and the Dartmouth-Hitchcock Medical Center will be randomized to receive antibiotic plus steroid or antibiotic plus placebo. Participants will be followed closely until re-epithelialization and then rechecked at three weeks, three months and 12 months post enrollment. A subset of patients will be contacted for a follow-up visit four years post enrollment. The primary outcome is best spectacle-corrected visual acuity three months after enrollment, using best spectacle-corrected enrollment visual acuity as a co-variate.

A pilot study was conducted from January 2005 to August 2005 at Aravind Eye Hospital to assess the feasibility and safety and to estimate the sample size of a larger main trial. Forty-two patients with culture-proven bacterial keratitis were enrolled. They were treated and followed up as in the main trial, up to three months from enrollment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 500 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Steroids for Corneal Ulcers Trial
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1	Drug: Antibiotics; moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization; Other Names: Vigamox ; Drug: Topical corticosteroid; prednisolone phosphate 1% with preservative four times a day for 1 week, then twice a day for 1 week, and finally once a day for 1 week
Placebo Comparator: 2	Drug: Antibiotics; moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization; Other Names: Vigamox ; Drug: Placebo; 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, then twice a day for 1 week, and finally once a day for 1 week

Outcome Measures

Primary Outcome Measures

1. Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 3 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate [3 months from enrollment]

   LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.

Secondary Outcome Measures

1. Infiltrate/Scar Size, Correcting for Infiltrate/Scar Size at Enrollment [3 months from enrollment]

2. Best Hard Contact Lens Corrected Visual Acuity Measured in logMAR, Correcting for Best Spectacle Corrected Visual Acuity at Enrollment [3 months from enrollment]

   LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.

3. Time to Resolution of Epithelial Defect [From enrollment up to 21 days]

   This outcome measured time from enrollment to resolution of the epithelial defect in days for up to 21 days. For three weeks patients were examined every 3 days for size of epithelial defect until the defect was gone.

4. Ocular Perforations [At the time of perforation]

5. Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 12 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate [12 months from enrollment]

   LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.

6. Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR Using MIC (Minimum Inhibitory Concentration) to Moxifloxacin as a Covariate [3 months after enrollment]

   Best spectacle-corrected visual acuity (BSCVA) for this outcome is measured in logMAR (logarithm of the Minimum Angle of Resolution) in which smaller values indicate better visual acuity. Minimum inhibitory concentration (MIC) to moxifloxacin was measured by E test and a log2-transformation of MIC was used in all analyses. In this analysis we add MIC to the model examining BSCVA at 3 months.

7. Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism [3 months after enrollment]

   BSCVA measured in logMAR will be estimated by causative organism (either Nocardia spp, Streptococcus pneumoniae, Moraxella spp, or Pseudomonas aeruginosa). BSCVA will be examined for each causative organism by mean and standard deviation as well as in a regression model.

8. Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group [3 months from enrollment]

   Best spectacle-corrected visual acuity (BSCVA) for this subgroup analysis was measured in logMAR and then categorized by equivalent Snellen fractions

9. Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth [3 months from enrollment]

   BSCVA measured in logMAR will be examined by categories infiltrate depth (categorized by depth percentage) by mean and standard deviation as well as in a regression model.

10. Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size [3 months from enrollment]

    Best-spectacle visual acuity (BSCVA) at 3 months from enrollment is stratified by categories of infiltrate/scar size and examined by treatment arm

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

At Presentation:

• Presence of a corneal ulcer at presentation

At Enrollment:

• Presence of bacteria on blood or chocolate agar culture

• Antibiotic given for > 48 hours

• The patient must be able to verbalize a basic understanding of the study after it is explained to the patient, as determined by physician examiner. This understanding must include a commitment to return for f/u visits.

• Appropriate consent

Exclusion Criteria

At Presentation:

• Overlying epithelial defect < 0.75 mm at its greatest width at presentation

• Corneal perforation or impending perforation

• Evidence of fungus on KOH, Giemsa at time of presentation

• Evidence of acanthamoeba by stain

• Evidence of herpetic keratitis by history or exam

• Corneal scar not easily distinguishable from current ulcer

• 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 prednisolone during the course of the present ulcer

• Age less than 16 years (before 16th birthday)

• Bilateral ulcers

• Previous penetrating keratoplasty

• Pregnancy (by history or urine test)

• Immediate steroid use necessary due to surgery or other condition

At Enrollment:

• Evidence of fungus on culture at time of enrollment

• Absence of bacteria on blood or chocolate agar culture

• Best spectacle-corrected vision worse than 6/60 in the fellow eye

• Corneal perforation or descemetocele

• Known allergy to study medications (steroid or preservative)

• No light perception in the affected eye

• Not willing to come to follow-up visits

• Not willing to participate

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Proctor Foundation, UCSF	San Francisco	California	United States	94143
2	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
3	Aravind Eye Hospital	Coimbatore	Tamil Nadu	India
4	Aravind Eye Hospital	Madurai	Tamil Nadu	India	625 020
5	Aravind Eye Hospital	Tirunelveli	Tamil Nadu	India

Sponsors and Collaborators

• Thomas M. Lietman
• Aravind Eye Hospitals, India
• Dartmouth-Hitchcock Medical Center
• National Eye Institute (NEI)

Investigators

• Principal Investigator: M. Srinivasan, M.S., O.D., Aravind Eye Hospital
• Principal Investigator: Mike Zegans, M.D., Dartmouth-Hitchcock Medical Center
• Principal Investigator: Nisha Acharya, M.D., M.S., Proctor Foundation, UCSF
• Study Director: Thomas M Lietman, M.D., Proctor Foundation, UCSF

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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. The steroids for corneal ulcers trial: study design and baseline characteristics. Arch Ophthalmol. 2012 Feb;130(2):151-7. doi: 10.1001/archophthalmol.2011.303. Epub 2011 Oct 10.

• Responsible Party: Thomas M. Lietman, Prinicpal Investigator, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00324168
• Other Study ID Numbers: H9332-21899-05; U10EY015114-01
• First Posted: May 10, 2006
• Last Update Posted: Aug 1, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Thomas M. Lietman, Prinicpal Investigator, University of California, San Francisco: Bacterial Infections; Eye Diseases; Bacterial Keratitis; Visual Acuity
• Additional relevant MeSH terms: Bacterial Infections; Corneal Ulcer; Eye Infections; Eye Infections, Bacterial; Ulcer; Anti-Bacterial Agents

Study Results

Participant Flow

Recruitment Details	Between September 1, 2006 and February 22, 2010, 1,769 patients were screened for the trial and 500 patients were enrolled.
Pre-assignment Detail	Common reasons for ineligibility include impending perforation (n=316, 25%), history of a corneal scar in the affected eye (n=123, 10%) and vision worse than 6/60 in the fellow eye (n=119, 9%).

Arm/Group Title	Steroid	Placebo
Arm/Group Description	Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, then twice a day for 1 week, and finally once a day for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, then twice a day for 1 week, and finally once a day for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Period Title: Overall Study
STARTED	250	250
COMPLETED	222	220
NOT COMPLETED	28	30

Baseline Characteristics

Arm/Group Title	Steroid	Placebo	Total
Arm/Group Description	Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Total of all reporting groups
Overall Participants	250	250	500
Age (Count of Participants)
<=18 years	4 1.6%	3 1.2%	7 1.4%
Between 18 and 65 years	190 76%	198 79.2%	388 77.6%
>=65 years	56 22.4%	49 19.6%	105 21%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	52.0	54.5	53.0
Sex: Female, Male (Count of Participants)
Female	124 49.6%	103 41.2%	227 45.4%
Male	126 50.4%	147 58.8%	273 54.6%
Region of Enrollment (participants) [Number]
United States	7 2.8%	8 3.2%	15 3%
India	243 97.2%	242 96.8%	485 97%

Outcome Measures

1. Primary Outcome

Title	Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 3 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate
Description	LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.
Time Frame	3 months from enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Steroid	Placebo
Arm/Group Description	Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Measure Participants	222	220
Mean (95% Confidence Interval) [logMAR]	0.48	0.49

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.82
	Comments
	Method	Regression, Linear
	Comments	Adjusted for enrollment BSCVA
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.009
	Confidence Interval	(2-Sided) 95%; -0.085 to 0.068
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Infiltrate/Scar Size, Correcting for Infiltrate/Scar Size at Enrollment
Time Frame	3 months from enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Steroid	Placebo
Arm/Group Description	Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Measure Participants	222	220
Mean (95% Confidence Interval) [mm]	3.07	3.02

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Best Hard Contact Lens Corrected Visual Acuity Measured in logMAR, Correcting for Best Spectacle Corrected Visual Acuity at Enrollment
Description	LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.
Time Frame	3 months from enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Steroid	Placebo
Arm/Group Description	Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Measure Participants	222	220
Mean (95% Confidence Interval) [logMAR]	0.42	0.41

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.873
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.07 to 0.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Time to Resolution of Epithelial Defect
Description	This outcome measured time from enrollment to resolution of the epithelial defect in days for up to 21 days. For three weeks patients were examined every 3 days for size of epithelial defect until the defect was gone.
Time Frame	From enrollment up to 21 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Steroid	Placebo
Arm/Group Description	Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Measure Participants	222	220
Mean (Standard Deviation) [days]	9.77 (7.54)	9.43 (7.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.76 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Ocular Perforations
Time Frame	At the time of perforation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Steroid	Placebo
Arm/Group Description	Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Measure Participants	222	220
Number [participants]	7 2.8%	8 3.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.99
	Comments
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 12 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate
Description	LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity.
Time Frame	12 months from enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Steroid	Placebo
Arm/Group Description	Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Measure Participants	222	220
Mean (95% Confidence Interval) [logMAR]	2.90	2.87

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.39
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR Using MIC (Minimum Inhibitory Concentration) to Moxifloxacin as a Covariate
Description	Best spectacle-corrected visual acuity (BSCVA) for this outcome is measured in logMAR (logarithm of the Minimum Angle of Resolution) in which smaller values indicate better visual acuity. Minimum inhibitory concentration (MIC) to moxifloxacin was measured by E test and a log2-transformation of MIC was used in all analyses. In this analysis we add MIC to the model examining BSCVA at 3 months.
Time Frame	3 months after enrollment

Outcome Measure Data

Analysis Population Description

The study population analyzed for this outcome includes only those study subjects for whom an MIC value was available.

Arm/Group Title	Steroid	Placebo
Arm/Group Description	Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Measure Participants	213	218
Mean (95% Confidence Interval) [logMAR]	0.50 (0.58)	0.46 (0.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.01
	Confidence Interval	() 95%; -0.09 to 0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.04
	Estimation Comments

8. Secondary Outcome

Title	Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism
Description	BSCVA measured in logMAR will be estimated by causative organism (either Nocardia spp, Streptococcus pneumoniae, Moraxella spp, or Pseudomonas aeruginosa). BSCVA will be examined for each causative organism by mean and standard deviation as well as in a regression model.
Time Frame	3 months after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Steroid	Placebo
Arm/Group Description	Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Measure Participants	222	220
Nocardia spp	0.54 (0.67)	0.36 (0.64)
Streptococcus pneumoniae	0.49 (0.56)	0.52 (0.53)
Moraxella spp	0.46 (0.61)	0.26 (0.65)
Pseudomonas aeruginosa	0.53 (0.54)	0.45 (0.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments	Nocardia spp
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; -.011 to 0.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments	Streptococcus pneumoniae
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.86
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.01
	Confidence Interval	() 95%; -0.12 to 0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments	Moraxella spp
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -0.34 to 0.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments	Pseudomonas aeruginosa
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.67
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group
Description	Best spectacle-corrected visual acuity (BSCVA) for this subgroup analysis was measured in logMAR and then categorized by equivalent Snellen fractions
Time Frame	3 months from enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Steroid	Placebo
Arm/Group Description	Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Measure Participants	222	220
<20/40	0.06 (0.30)	-0.02 (0.12)
20/40 to 20/800	0.36 (0.43)	0.38 (0.38)
Counting fingers (CF) or worse	1.00 (0.55)	1.15 (0.61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments	<20/40
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.08 to 0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments	20/40 to 20/800
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.85
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments	CF or worse
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.31 to -0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth
Description	BSCVA measured in logMAR will be examined by categories infiltrate depth (categorized by depth percentage) by mean and standard deviation as well as in a regression model.
Time Frame	3 months from enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Steroid	Placebo
Arm/Group Description	Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Measure Participants	222	220
>0-33%	0.35 (0.50)	0.26 (0.40)
>33%-67%	0.52 (0.57)	0.47 (0.54)
>67%-100%	0.80 (0.61)	0.86 (0.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments	>0-33%
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments	>33%-67%
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments	>67%-100%
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.31 to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size
Description	Best-spectacle visual acuity (BSCVA) at 3 months from enrollment is stratified by categories of infiltrate/scar size and examined by treatment arm
Time Frame	3 months from enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Steroid	Placebo
Arm/Group Description	Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization	Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
Measure Participants	222	220
0-1.90 mm	0.18 (0.37)	0.19 (0.33)
1.91-2.70 mm	0.39 (0.51)	0.29 (0.44)
2.71-4.06 mm	0.53 (0.60)	0.53 (0.53)
4.07-8.90 mm	0.85 (0.57)	0.96 (0.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments	0-1.90 mm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.10 to 0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments	1.91-2.70 mm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments	2.71-4.06 mm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Steroid, Placebo
	Comments	4.07-8.90 mm
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.31 to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	3 months from enrollment
Arm/Group Title	Steroid		Placebo
Arm/Group Description	Topical corticosteroid : prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization		Placebo : 0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week Antibiotics : moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
All Cause Mortality
	Steroid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Steroid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/250 (6%)		13/250 (5.2%)
Eye disorders
Corneal perforation	7/250 (2.8%)		8/250 (3.2%)
General disorders
Death	7/250 (2.8%)		5/250 (2%)
Infections and infestations
Systemic infection	1/250 (0.4%)		0/250 (0%)
Other (Not Including Serious) Adverse Events
	Steroid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/250 (17.6%)		34/250 (13.6%)
Eye disorders
Increase in hypopyon	4/250 (1.6%)		4/250 (1.6%)
Increase in infiltrate size >50%	9/250 (3.6%)		4/250 (1.6%)
No healing of epithelial defect by 21 days	44/250 (17.6%)		27/250 (10.8%)
Intraocular pressure (IOP) elevated >25mm Hg by <35 mm Hg	2/250 (0.8%)		10/250 (4%)
Progressive corneal thinning	0/250 (0%)		2/250 (0.8%)
General disorders
Other	9/250 (3.6%)		13/250 (5.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.