Corticosteroids for Bacterial Keratitis The Steroids for Corneal Ulcers Trial (SCUT)

Departments of Cornea and External Diseases, Aravind Eye Care System, Madurai, India.
Archives of ophthalmology (Impact Factor: 4.4). 02/2012; 130(2):143-50. DOI: 10.1001/archophthalmol.2011.315
Source: PubMed

ABSTRACT To determine whether there is a benefit in clinical outcomes with the use of topical corticosteroids as adjunctive therapy in the treatment of bacterial corneal ulcers.
Randomized, placebo-controlled, double-masked, multicenter clinical trial comparing prednisolone sodium phosphate, 1.0%, to placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and received topical moxifloxacin for at least 48 hours before randomization.
The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months from enrollment. Secondary outcomes included infiltrate/scar size, reepithelialization, and corneal perforation.
Between September 1, 2006, and February 22, 2010, 1769 patients were screened for the trial and 500 patients were enrolled. No significant difference was observed in the 3-month BSCVA (-0.009 logarithm of the minimum angle of resolution [logMAR]; 95% CI, -0.085 to 0.068; P = .82), infiltrate/scar size (P = .40), time to reepithelialization (P = .44), or corneal perforation (P > .99). A significant effect of corticosteroids was observed in subgroups of baseline BSCVA (P = .03) and ulcer location (P = .04). At 3 months, patients with vision of counting fingers or worse at baseline had 0.17 logMAR better visual acuity with corticosteroids (95% CI, -0.31 to -0.02; P = .03) compared with placebo, and patients with ulcers that were completely central at baseline had 0.20 logMAR better visual acuity with corticosteroids (-0.37 to -0.04; P = .02).
We found no overall difference in 3-month BSCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial corneal ulcers.
Adjunctive topical corticosteroid use does not improve 3-month vision in patients with bacterial corneal ulcers. Identifier: NCT00324168.

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Available from: Jeena Mascarenhas, Mar 22, 2014
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    • "The Steroids for Corneal Ulcers Trial (SCUT), was a randomized controlled trial investigating the effects of adjunctive corticosteroid therapy to fluoroquinolone (moxifloxacin) treatment on the outcomes of bacterial keratitis [25,26]. Analysis of moxifloxacin resistance of bacterial keratitis isolates (including P, aeruginosa) from the SCUT study showed that increased resistance to this fluoroquinolone in vitro (i.e. "
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    ABSTRACT: To determine the relationship between type three secretion genotype and fluoroquinolone resistance for P. aeruginosa strains isolated from microbial keratitis during the Steroids for Corneal Ulcers Trial (SCUT) and for two laboratory strains, PA103 and PAO1. Confirmed P. aeruginosa isolates from the SCUT were divided into exoU(+) or exoU(-). The exoU(+) strains contained the gene encoding ExoU, a powerful phospholipase toxin delivered into host cells by the type three secretion system. Isolates were then assessed for susceptibility to fluoroquinolone, cephalosporin, and aminoglycoside antibiotics using disk diffusion assays. Etest was used to determine the MIC of moxifloxacin and other fluoroquinolones. Laboratory isolates in which the exoU gene was added or deleted were also tested. A significantly higher proportion of exoU(+) strains were resistant to ciprofloxacin (p = 0.001), gatifloxacin (p = 0.003), and ofloxacin (p = 0.002) compared to exoU(-) isolates. There was no significant difference between exoU(+) or exoU(-) negative isolates with respect to susceptibility to other antibiotics except gentamicin. Infections involving resistant exoU(+) strains trended towards worse clinical outcome. Deletion or acquisition of exoU in laboratory isolates did not affect fluoroquinolone susceptibility. Fluoroquinolone susceptibility of P. aeruginosa isolated from the SCUT is consistent with previous studies showing elevated resistance involving exoU encoding (cytotoxic) strains, and suggest worse clinical outcome from infections involving resistant isolates. Determination of exoU expression in clinical isolates of P. aeruginosa may be helpful in directing clinical management of patients with microbial keratitis.
    BMC Ophthalmology 04/2014; 14(1):54. DOI:10.1186/1471-2415-14-54 · 1.02 Impact Factor
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    • "Though corneal scarring is the third leading cause of blindness worldwide and affects over one million Americans every year [1], no effective therapy is yet available to treat corneal scarring. Steroids have been used, but their effectiveness remains controversial and they have significant side effects [2], [3]. Mitomycin C is commonly used in clinic to treat laser surgery-induced corneal scarring [4]–[6]. "
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    ABSTRACT: This study examined the effects of BMP7 gene transfer on corneal wound healing and fibrosis inhibition in vivo using a rabbit model. Corneal haze in rabbits was produced with the excimer laser performing -9 diopters photorefractive keratectomy. BMP7 gene was introduced into rabbit keratocytes by polyethylimine-conjugated gold nanoparticles (PEI2-GNPs) transfection solution single 5-minute topical application on the eye. Corneal haze and ocular health in live animals was gauged with stereo- and slit-lamp biomicroscopy. The levels of fibrosis [α-smooth muscle actin (αSMA), F-actin and fibronectin], immune reaction (CD11b and F4/80), keratocyte apoptosis (TUNEL), calcification (alizarin red, vonKossa and osteocalcin), and delivered-BMP7 gene expression in corneal tissues were quantified with immunofluorescence, western blotting and/or real-time PCR. Human corneal fibroblasts (HCF) and in vitro experiments were used to characterize the molecular mechanism mediating BMP7's anti-fibrosis effects. PEI2-GNPs showed substantial BMP7 gene delivery into rabbit keratocytes in vivo (2×10(4) gene copies/ug DNA). Localized BMP7 gene therapy showed a significant corneal haze decrease (1.68±0.31 compared to 3.2±0.43 in control corneas; p<0.05) in Fantes grading scale. Immunostaining and immunoblot analyses detected significantly reduced levels of αSMA (46±5% p<0.001) and fibronectin proteins (48±5% p<0.01). TUNEL, CD11b, and F4/80 assays revealed that BMP7 gene therapy is nonimmunogenic and nontoxic for the cornea. Furthermore, alizarin red, vonKossa and osteocalcin analyses revealed that localized PEI2-GNP-mediated BMP7 gene transfer in rabbit cornea does not cause calcification or osteoblast recruitment. Immunofluorescence of BMP7-transefected HCFs showed significantly increased pSmad-1/5/8 nuclear localization (>88%; p<0.0001), and immunoblotting of BMP7-transefected HCFs grown in the presence of TGFβ demonstrated significantly enhanced pSmad-1/5/8 (95%; p<0.001) and Smad6 (53%, p<0.001), and decreased αSMA (78%; p<0.001) protein levels. These results suggest that localized BMP7 gene delivery in rabbit cornea modulates wound healing and inhibits fibrosis in vivo by counter balancing TGFβ1-mediated profibrotic Smad signaling.
    PLoS ONE 06/2013; 8(6):e66434. DOI:10.1371/journal.pone.0066434 · 3.23 Impact Factor
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    ABSTRACT: To compare the clinical course and effect of adjunctive corticosteroid therapy in Pseudomonas aeruginosa with those of all other strains of bacterial keratitis. Subanalyses were performed on data collected in the Steroids for Corneal Ulcers Trial (SCUT), a large randomized controlled trial in which patients were treated with moxifloxacin and were randomly assigned to 1 of 2 adjunctive treatment arms: corticosteroid or placebo (4 times a day with subsequent reduction). Multivariate analysis was used to determine the effect of predictors, organism, and treatment on outcomes, 3-month best-spectacle-corrected visual acuity (BSCVA), and infiltrate/scar size. The incidence of adverse events over a 3-month follow-up period was compared using Fisher's exact test. SCUT enrolled 500 patients. One hundred ten patients had P. aeruginosa ulcers; 99 of 110 (90%) enrolled patients returned for follow-up at 3 months. Patients with P. aeruginosa ulcers had significantly worse visual acuities than patients with other bacterial ulcers (P = 0.001) but showed significantly more improvement in 3-month BSCVA than those with other bacterial ulcers, adjusting for baseline characteristics (-0.14 logMAR; 95% confidence interval, -0.23 to -0.04; P = 0.004). There was no significant difference in adverse events between P. aeruginosa and other bacterial ulcers. There were no significant differences in BSCVA (P = 0.69), infiltrate/scar size (P = 0.17), and incidence of adverse events between patients with P. aeruginosa ulcers treated with adjunctive corticosteroids and patients given placebo. Although P. aeruginosa corneal ulcers have a more severe presentation, they appear to respond better to treatment than other bacterial ulcers. The authors did not find a significant benefit with corticosteroid treatment, but they also did not find any increase in adverse events. ( number, NCT00324168.).
    Investigative ophthalmology & visual science 12/2011; 53(1):267-72. DOI:10.1167/iovs.11-7840 · 3.40 Impact Factor
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