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Results of the SCUT trial show that adjunctive topical corticosteroid therapy in eyes with bacterial corneal ulcers is safe, might be particularly useful in eyes with severe ulcers or Pseudomonas infection, is more beneficial when started earlier than later, and should be avoided when Nocardia is the causative pathogen.
The prospective, randomized, placebo-controlled Steroids for Corneal Ulcer Trial (SCUT) was conducted to address the controversy over the role of topical corticosteroids in the management of bacterial corneal ulcers. The study’s main results showed that adding a topical corticosteroid to antibiotic treatment did not improve spectacle-corrected visual acuity (BSCVA) at 3 months nor lead to an increase in overall adverse events, said Thomas M. Lietman, MD.
“Based on these findings, ophthalmologists can feel comfortable using a topical corticosteroid in an eye with a culture-proven bacterial corneal ulcer whereas those who choose not to use a corticosteroid can also defend their decision,” said Dr. Lietman, director, Francis I. Proctor Foundation for Research in Ophthalmology, University of California, San Francisco (UCSF).
“However, findings from some analyses of secondary outcomes pointed to situations where corticosteroids might be preferred or avoided and suggested that when a corticosteroid is used, it is better to start the treatment earlier than later,” he said. Patients who were randomly assigned to treatment in SCUT were carefully selected, meaning they all had a culture-proven bacterial infection without evidence of fungal, Acanthamoeba, or herpetic keratitis, he noted.
Sponsored by the National Eye Institute, SCUT enrolled patients at three centers-Aravind Eye Care System in India, Dartmouth Medical School, Lebanon, New Hampshire, and UCSF, although the greatest number of participants were entered in India.
All patients were started on topical moxifloxacin, and after at least 48 hours, those with a culture-proven bacterial infection began adjunctive treatment with topical prednisolone phosphate, 1% or placebo with tapering of the dose over 3 weeks.
A total of 500 patients were randomly assigned to treatment. The most common isolates were Streptococcus pneumoniae (~50%), Pseudomonas aeruginosa (~25%), and Nocardia spp (~10%), although the latter organism was predominantly isolated in India and is rarely seen as a cause of keratitis in the United States, Dr. Lietman observed.
The primary endpoint analysis of BSCVA at 3 months showed no significant difference between treatment groups. The safety review found no significant differences in rates of most adverse events with two exceptions. The proportion of eyes without healing of the epithelial defect by day 21 was higher in the corticosteroid group compared with the controls, 17.6% versus 10.8%.
“This difference was also seen in the pilot trial, and so it seems to be a true finding that epithelial healing takes longer with corticosteroid use,” he said. “Final scar size and frequency of perforation were also not different between arms.”
The other difference was in the rate of IOP spikes (>25 mm Hg and <35 mm Hg), but these events occurred significantly less often in the corticosteroid-treated eyes than among the controls.
“It may be that decreasing the inflammation with corticosteroid treatment has a protective effect on IOP,” he said. Secondary outcome analyses included comparisons of corticosteroid versus no corticosteroid treatment in subgroups of eyes. The results of one analysis showed that eyes with P. aeruginosa infection had better BSCVA at 3 months when treated with the corticosteroid.
“Although the difference between groups was not statistically significant, the benefit favoring corticosteroid treatment was actually greatest in eyes with Pseudomonas infection than with any other pathogen,” he said. “Prior to SCUT, we would not have used a corticosteroid in an eye with a central Pseudomonas ulcer. It was encouraging to see, therefore, that eyes with Pseudomonas did not do worse when treated with a corticosteroid.”
Among eyes with a Nocardia corneal ulcer, however, BSCVA at 3 months was significantly worse in the corticosteroid group. The difference compared with controls was about 1 line, and an analysis of BSCVA outcomes at 1 year showed a significant difference favoring corticosteroid treatment when eyes with Nocardia were excluded.
“The message here is do not use corticosteroids to treat a corneal ulcer caused by Nocardia. In fact, the data suggests that perhaps Nocardia ulcers should have been excluded from SCUT,” he said. Other secondary outcome analyses compared BSCVA outcomes of the corticosteroid and placebo treatment groups in eyes with baseline BSCVA <20/400 or central ulcers.
For these subgroups with the “worst” ulcers, mean BSCVA at 3 months was significantly better in the corticosteroid group compared with controls.
Another secondary outcome analysis examined whether the timing of corticosteroid initiation affected functional outcomes. Its results showed a 1.1-line greater improvement in BSCVA among eyes that received corticosteroid treatment within 2 to 3 days versus in those where there was a longer delay, and the benefit of earlier treatment was statistically significant.
“This finding was somewhat surprising because it was previously thought that it was better to try to eliminate the bacteria before adding the corticosteroid,” he said.
Thomas M. Lietman, MDE: firstname.lastname@example.org
This article was adapted from Dr. Lietman’s presentation during Cornea Subspecialty Day at the 2017 meeting of the American Academy of Ophthalmology. Dr. Lietman has no relevant financial interests to disclose.