Steroids for Corneal Ulcers Trial

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

Detailed Description
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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.

Official Title
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Steroids for Corneal Ulcers Trial

Conditions
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Corneal Ulcer, Eye Infections, Bacterial

Intervention / Treatment
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* Drug: Antibiotics
* Drug: Topical corticosteroid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: Antibiotics<br>* moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization<br>* Other names: Vigamox;Drug: Topical corticosteroid<br>* 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<br>|
| Placebo Comparator: 2<br> | Drug: Antibiotics<br>* moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization<br>* Other names: Vigamox;Drug: Placebo<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 3 months from enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infiltrate/Scar Size, Correcting for Infiltrate/Scar Size at Enrollment |  | 3 months from enrollment | 
| 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. | 3 months from enrollment | 
| 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. | From enrollment up to 21 days | 
| 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 | LogMAR (logarithm of the Minimum Angle of Resolution) is a measure of visual acuity in which the smaller values indicate better visual acuity. | 12 months from enrollment | 
| 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. | 3 months after enrollment | 
| 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. | 3 months after enrollment | 
| 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 | 3 months from enrollment | 
| 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. | 3 months from enrollment | 
| 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 | 3 months from enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bacterial Infections, Eye Diseases, Bacterial Keratitis, Visual Acuity