Corneal Ulcer, Eye Infections, Bacterial
Conditions
Keywords
Bacterial Infections, Eye Diseases, Bacterial Keratitis, Visual Acuity
Brief summary
The purpose of this study is to determine whether adding topical steroids improves the outcomes of bacterial corneal ulcers, especially visual acuity.
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.
Interventions
DRUGPlacebo
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
DRUGAntibiotics
moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
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
Sponsors
Aravind Eye Hospitals, India
Dartmouth-Hitchcock Medical Center
National Eye Institute (NEI)
Thomas M. Lietman
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| Ocular Perforations | At the time of perforation | — |
| 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. |
| Infiltrate/Scar Size, Correcting for Infiltrate/Scar Size at Enrollment | 3 months from enrollment | — |
| 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. |
| 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 |
| 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. |
| 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 |
| 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. |
Countries
India, United States
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 details
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%).
Participants by arm
| Arm | Count |
|---|---|
| Steroid 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 | 250 |
| Placebo 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 | 250 |
| Total | 500 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 3 |
| Overall Study | Lost to Follow-up | 19 | 18 |
| Overall Study | Patient did not visit in f/u window | 6 | 9 |
Baseline characteristics
| Characteristic | Steroid | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 4 Participants | 3 Participants | 7 Participants |
| Age, Categorical >=65 years | 56 Participants | 49 Participants | 105 Participants |
| Age, Categorical Between 18 and 65 years | 190 Participants | 198 Participants | 388 Participants |
| Age, Continuous | 52.0 years | 54.5 years | 53.0 years |
| Region of Enrollment India | 243 participants | 242 participants | 485 participants |
| Region of Enrollment United States | 7 participants | 8 participants | 15 participants |
| Sex: Female, Male Female | 124 Participants | 103 Participants | 227 Participants |
| Sex: Female, Male Male | 126 Participants | 147 Participants | 273 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 250 | 34 / 250 |
| serious Total, serious adverse events | 15 / 250 | 13 / 250 |
Outcome results
Primary
Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 3 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Steroid | Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 3 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate | 0.48 logMAR |
| Placebo | Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 3 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate | 0.49 logMAR |
p-value: 0.8295% CI: [-0.085, 0.068]Regression, Linear
Secondary
Best Hard Contact Lens Corrected Visual Acuity Measured in logMAR, Correcting for Best Spectacle Corrected Visual Acuity at Enrollment
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Steroid | Best Hard Contact Lens Corrected Visual Acuity Measured in logMAR, Correcting for Best Spectacle Corrected Visual Acuity at Enrollment | 0.42 logMAR |
| Placebo | Best Hard Contact Lens Corrected Visual Acuity Measured in logMAR, Correcting for Best Spectacle Corrected Visual Acuity at Enrollment | 0.41 logMAR |
p-value: 0.87395% CI: [-0.07, 0.08]Regression, Linear
Secondary
Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 12 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Steroid | Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 12 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate | 2.90 logMAR |
| Placebo | Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 12 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate | 2.87 logMAR |
p-value: 0.3995% CI: [-0.12, 0.05]Regression, Linear
Secondary
Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR Using MIC (Minimum Inhibitory Concentration) to Moxifloxacin as a Covariate
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
Population: The study population analyzed for this outcome includes only those study subjects for whom an MIC value was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Steroid | Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR Using MIC (Minimum Inhibitory Concentration) to Moxifloxacin as a Covariate | 0.50 logMAR | 95% Confidence Interval 0.58 |
| Placebo | Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR Using MIC (Minimum Inhibitory Concentration) to Moxifloxacin as a Covariate | 0.46 logMAR | 95% Confidence Interval 0.49 |
p-value: 0.7895% CI: [-0.09, 0.07]Regression, Linear
Secondary
Infiltrate/Scar Size, Correcting for Infiltrate/Scar Size at Enrollment
Time frame: 3 months from enrollment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Steroid | Infiltrate/Scar Size, Correcting for Infiltrate/Scar Size at Enrollment | 3.07 mm |
| Placebo | Infiltrate/Scar Size, Correcting for Infiltrate/Scar Size at Enrollment | 3.02 mm |
p-value: 0.495% CI: [-0.09, 0.15]Regression, Linear
Secondary
Ocular Perforations
Time frame: At the time of perforation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Steroid | Ocular Perforations | 7 participants |
| Placebo | Ocular Perforations | 8 participants |
p-value: >0.99Fisher Exact
Secondary
Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Steroid | Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth | >0-33% | 0.35 logMAR | Standard Deviation 0.5 |
| Steroid | Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth | >33%-67% | 0.52 logMAR | Standard Deviation 0.57 |
| Steroid | Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth | >67%-100% | 0.80 logMAR | Standard Deviation 0.61 |
| Placebo | Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth | >0-33% | 0.26 logMAR | Standard Deviation 0.4 |
| Placebo | Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth | >33%-67% | 0.47 logMAR | Standard Deviation 0.54 |
| Placebo | Subgroup Analysis of Best Spectacle-corrected Visual Acuity (BSCVA) by Categories of Infiltrate Depth | >67%-100% | 0.86 logMAR | Standard Deviation 0.67 |
Comparison: \>0-33%p-value: 0.3195% CI: [-0.05, 0.17]Regression, Linear
Comparison: \>33%-67%p-value: 0.9495% CI: [-0.13, 0.14]Regression, Linear
Comparison: \>67%-100%p-value: 0.0795% CI: [-0.31, 0.01]Regression, Linear
Secondary
Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Steroid | Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism | Nocardia spp | 0.54 logMAR | Standard Deviation 0.67 |
| Steroid | Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism | Streptococcus pneumoniae | 0.49 logMAR | Standard Deviation 0.56 |
| Steroid | Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism | Moraxella spp | 0.46 logMAR | Standard Deviation 0.61 |
| Steroid | Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism | Pseudomonas aeruginosa | 0.53 logMAR | Standard Deviation 0.54 |
| Placebo | Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism | Pseudomonas aeruginosa | 0.45 logMAR | Standard Deviation 0.56 |
| Placebo | Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism | Nocardia spp | 0.36 logMAR | Standard Deviation 0.64 |
| Placebo | Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism | Moraxella spp | 0.26 logMAR | Standard Deviation 0.65 |
| Placebo | Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism | Streptococcus pneumoniae | 0.52 logMAR | Standard Deviation 0.53 |
Comparison: Nocardia sppp-value: 0.395% CI: [-0.011, 0.35]Regression, Linear
Comparison: Streptococcus pneumoniaep-value: 0.8695% CI: [-0.12, 0.1]Regression, Linear
Comparison: Moraxella sppp-value: 0.6595% CI: [-0.34, 0.55]Regression, Linear
Comparison: Pseudomonas aeruginosap-value: 0.6795% CI: [-0.2, 0.13]Regression, Linear
Secondary
Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Steroid | Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group | <20/40 | 0.06 logMAR | Standard Deviation 0.3 |
| Steroid | Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group | 20/40 to 20/800 | 0.36 logMAR | Standard Deviation 0.43 |
| Steroid | Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group | Counting fingers (CF) or worse | 1.00 logMAR | Standard Deviation 0.55 |
| Placebo | Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group | <20/40 | -0.02 logMAR | Standard Deviation 0.12 |
| Placebo | Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group | 20/40 to 20/800 | 0.38 logMAR | Standard Deviation 0.38 |
| Placebo | Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Visual Acuity Group | Counting fingers (CF) or worse | 1.15 logMAR | Standard Deviation 0.61 |
Comparison: \<20/40p-value: 0.3395% CI: [-0.08, 0.25]Regression, Linear
Comparison: 20/40 to 20/800p-value: 0.8595% CI: [-0.09, 0.11]Regression, Linear
Comparison: CF or worsep-value: 0.0395% CI: [-0.31, -0.02]Regression, Linear
Secondary
Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Steroid | Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size | 0-1.90 mm | 0.18 logMAR | Standard Deviation 0.37 |
| Steroid | Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size | 1.91-2.70 mm | 0.39 logMAR | Standard Deviation 0.51 |
| Steroid | Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size | 2.71-4.06 mm | 0.53 logMAR | Standard Deviation 0.6 |
| Steroid | Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size | 4.07-8.90 mm | 0.85 logMAR | Standard Deviation 0.57 |
| Placebo | Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size | 4.07-8.90 mm | 0.96 logMAR | Standard Deviation 0.67 |
| Placebo | Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size | 0-1.90 mm | 0.19 logMAR | Standard Deviation 0.33 |
| Placebo | Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size | 2.71-4.06 mm | 0.53 logMAR | Standard Deviation 0.53 |
| Placebo | Subgroup Analysis Predicting Best Spectacle-corrected Visual Acuity (BSCVA) as Stratified by Categories of Infiltrate/Scar Size | 1.91-2.70 mm | 0.29 logMAR | Standard Deviation 0.44 |
Comparison: 0-1.90 mmp-value: 0.5395% CI: [-0.1, 0.2]Regression, Linear
Comparison: 1.91-2.70 mmp-value: 0.9595% CI: [-0.15, 0.16]Regression, Linear
Comparison: 2.71-4.06 mmp-value: 0.795% CI: [-0.12, 0.18]Regression, Linear
Comparison: 4.07-8.90 mmp-value: 0.0795% CI: [-0.31, 0.01]Regression, Linear
Secondary
Time to Resolution of Epithelial Defect
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Steroid | Time to Resolution of Epithelial Defect | 9.77 days | Standard Deviation 7.54 |
| Placebo | Time to Resolution of Epithelial Defect | 9.43 days | Standard Deviation 7.1 |
p-value: 0.4495% CI: [0.76, 1.12]Regression, Cox