Clinical Trial: Steroids for Corneal Ulcers Trial

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Steroids for Corneal Ulcers Trial

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 Summary:

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 corneal 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 were randomized to receive antibiotic plus steroid or antibiotic plus placebo. They were followed closely until re-epithelialization and then rechecked at three weeks, three months and 12 months post enrollment. A subset of patients were 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.

The pilot study was conducted from January 2005 to August 2005 at Aravind Eye Hospital to assess the feasibility and s
Sponsor: Thomas M. Lietman

Current Primary Outcome: Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR at 3 Months, Using Best Spectacle-corrected Enrollment Visual Acuity as a Co-variate [ Time Frame: 3 months from enrollment ]

Original Primary Outcome: Best spectacle-corrected visual acuity at three months after resolution of ulcer

Current Secondary Outcome:

• Infiltrate/Scar Size, Correcting for Infiltrate/Scar Size at Enrollment [ Time Frame: 3 months from enrollment ]
• Best Hard Contact Lens Corrected Visual Acuity Measured in logMAR, Correcting for Best Spectacle Corrected Visual Acuity at Enrollment [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
• Best Spectacle-corrected Visual Acuity (BSCVA) in logMAR Using MIC (Minimum Inhibitory Concentration) to Moxifloxacin as a Covariate [ Time Frame: 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.
• Subgroup Analysis Predicting 3 Month Best Spectacle-corrected Visual Acuity (BSCVA) by Causative Organism [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

Original Secondary Outcome: Best hard contact lens-corrected visual acuity 3 months after the resolution of ulcer, time to resolution, sub-group analysis to determine if the success of steroid use is dependent on the organism, size of scar post-treatment.

Information By: University of California, San Francisco

Dates:
Date Received: May 5, 2006
Date Started: September 2006
Date Completion:
Last Updated: December 12, 2013
Last Verified: December 2013