Steroids for Corneal Ulcers Trial

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.

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