Pilot study emphasizes benefits of corneal ulcer treatment

Fort Lauderdale, FL-A pilot study of topical steroid therapy to treat bacterial corneal ulcers resulted in about a two-line improvement in visual acuity 3 weeks after the start of treatment and a one-line improvement by 3 months, neither of which reached statistical significance.

The use of steroids also resulted in a smaller scar/infiltrate size 3 weeks and 3 months after the start of therapy, but the decrease in the size of the scar did not reach statistical significance. Nisha Acharya, MD, reported the results at the annual meeting of the Association for Research in Vision and Ophthalmology.

"There is greater than a 90% success rate in eliminating bacterial keratitis," said Dr. Acharya, who is a clinical instructor at the F.I. Proctor Foundation of UCSF. "However, in developed countries, 25% of these patients end up with a visual acuity less than 20/200, and this number increases to 50% to 75% in developing countries."

"There is a need for a prospective trial to determine definitively if steroids should be used to treat bacterial corneal ulcers," Dr. Acharya said.

The pilot study, supported by the That Man May See Foundation, was a precursor to the main study, The Steroids for Corneal Ulcers Trial (SCUT), which will be funded by the National Institutes of Health. The objective of this multicenter, randomized controlled trial is to determine if a topical steroid can improve the visual outcome in patients with bacterial corneal ulcers.

The main trial will be conducted at the Proctor Foundation/University of California, San Francisco (UCSF); Dartmouth-Hitchcock Medical Center, Lebanon, NH; and the Aravind Eye Hospital in Madurai, India. Aravind Eye Hospital was the site of the pilot study because the incidence of bacterial corneal ulcers is 10 times greater than that in the United States. Muthiah Srinivasan, MBBS, is the lead investigator at Aravind Eye Hospital and Thomas Liet-man, MD, from UCSF is the principal investigator of the SCUT trial.

Dr. Acharya explained that 238 patients with a positive bacterial culture were assessed for their eligibility to enter the study from Jan. 4 to Aug. 20, 2005. Of these, 42 patients were enrolled. Cultures were taken to identify the bacterial organism and then 22 patients were randomly assigned to the placebo arm, which included placebo and antibiotics, and 20 to the steroid arm, which included topical prednisolone phosphate and antibiotics.

The inclusion criteria included an epithelial defect 1 mm or larger that was 1 mm or more from the limbus and a positive bacterial culture. Patients with a positive fungal culture were excluded.

Treatment protocol

When the patients first presented for treatment, moxifloxacin (Vigamox, Alcon Laboratories) was given every hour during waking hours for the first 48 hours followed by administration every 2 hours until re-epithelialization of the cornea occurred, and then four times daily until the steroid or placebo treatment was stopped. When the patients were enrolled, topical prednisolone phosphate or placebo was given four times daily for 1 week, twice daily for 1 week, and then once daily for 1 week. Both the physicians and patients were masked to the treatment.

The primary outcome was best spectacle-corrected visual acuity (BSCVA) 3 months after enrollment. The secondary outcomes included BSCVA at 3 weeks, infiltrate/scar size at 3 weeks and 3 months, and the time to re-epithelialization, Dr. Acharya explained.

Thirty-three patients (79%) completed the study.

"Steroid use was associated with an approximate two-line improvement in visual acuity 3 weeks after the start of steroid treatment (p = 0.34) and a one-line improvement by 3 months (p = 0.56), neither of which reached statistical significance," Dr. Acharya reported. "Given that the patients in the group that were randomly assigned to steroid treatment had slightly worse visual acuity than the placebo group, the net improvement in vision in the steroid group was greater than in the placebo group."