Steroids for Corneal Ulcers Trial (SCUT)

• Infiltrate/scar size, correcting for infiltrate/scar size at enrollment [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]
• Best hard contact lens corrected visual acuity, correcting for best spectacle corrected visual acuity at enrollment [ Time Frame: 3 months from enrollment ] [ Designated as safety issue: No ]
• Time to resolution of epithelial defect [ Time Frame: At the time of re-epithelialization ] [ Designated as safety issue: No ]
• Ocular perforations [ Time Frame: At the time of perforation ] [ Designated as safety issue: No ]
• Best spectacle-corrected logMAR visual acuity, using best spectacle-corrected enrollment visual acuity as a co-variate [ Time Frame: 12 months from enrollment ] [ Designated as safety issue: No ]
• The correlation between the best-corrected visual acuity and minimum inhibitory concentration to moxifloxacin [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]
• Analysis of outcomes will also be done by the following subgroups: causative organism, visual acuity group, duration of symptoms to enrollment, depth of ulcer, infiltrate scar size [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]

The purpose of this study is to determine whether adding topical steroids improves the outcomes of bacterial corneal ulcers, especially visual acuity.

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 UCSF Proctor Foundation, and the Dartmouth- Hitchcock Medical Center are being randomized to receive antibiotic plus steroid or antibiotic plus placebo. They are being followed closely until re- epithelialization and then rechecked at three weeks, three months and 12 months post enrollment. The primary outcome is best spectacle-corrected logMAR 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 safety and to estimate the sample size of a larger main trial. 42 patients with culture-proven bacterial keratitis were enrolled. They were treated and followed up as in the main trial, up to 3 months from enrollment.

• Corneal Ulcer
• Eye Infections, Bacterial

• Drug: Antibiotics
  moxifloxacin 0.5% every one hour for 48 hours while awake and then every 2 hours until re-epithelialization
  Other Name: Vigamox
• Drug: Topical corticosteroid
  prednisolone phosphate 1% with preservative four times a day for 1 week, BID for 1 week, QD for 1 week
• Drug: Placebo
  0.9% NaCl and preservative (same as in steroid) four times a day for 1 week, BID for 1 week, QD for 1 week

• Active Comparator: 1
  Interventions:

  • Drug: Antibiotics
  • Drug: Topical corticosteroid
• Placebo Comparator: 2
  Interventions:

  • Drug: Antibiotics
  • Drug: Placebo

• Oldenburg CE, Lalitha P, Srinivasan M, Manikandan P, Bharathi MJ, Rajaraman R, Ravindran M, Mascarenhas J, Nardone N, Ray KJ, Glidden DV, Acharya NR, Lietman TM. Moxifloxacin susceptibility mediates the relationship between causative organism and clinical outcome in bacterial keratitis. Invest Ophthalmol Vis Sci. 2013 Feb 28;54(2):1522-6. doi: 10.1167/iovs.12-11246.
• Ray KJ, Prajna L, Srinivasan M, Geetha M, Karpagam R, Glidden D, Oldenburg CE, Sun CQ, McLeod SD, Acharya NR, Lietman TM. Fluoroquinolone treatment and susceptibility of isolates from bacterial keratitis. JAMA Ophthalmol. 2013 Mar;131(3):310-3. doi: 10.1001/jamaophthalmol.2013.1718.
• Lalitha P, Srinivasan M, Rajaraman R, Ravindran M, Mascarenhas J, Priya JL, Sy A, Oldenburg CE, Ray KJ, Zegans ME, McLeod SD, Lietman TM, Acharya NR. Nocardia keratitis: clinical course and effect of corticosteroids. Am J Ophthalmol. 2012 Dec;154(6):934-939.e1. doi: 10.1016/j.ajo.2012.06.001. Epub 2012 Sep 5.
• Lalitha P, Srinivasan M, Manikandan P, Bharathi MJ, Rajaraman R, Ravindran M, Cevallos V, Oldenburg CE, Ray KJ, Toutain-Kidd CM, Glidden DV, Zegans ME, McLeod SD, Acharya NR, Lietman TM. Relationship of in vitro susceptibility to moxifloxacin and in vivo clinical outcome in bacterial keratitis. Clin Infect Dis. 2012 May;54(10):1381-7. Epub 2012 Mar 23.
• Dalmon C, Porco TC, Lietman TM, Prajna NV, Prajna L, Das MR, Kumar JA, Mascarenhas J, Margolis TP, Whitcher JP, Jeng BH, Keenan JD, Chan MF, McLeod SD, Acharya NR. The clinical differentiation of bacterial and fungal keratitis: a photographic survey. Invest Ophthalmol Vis Sci. 2012 Apr 2;53(4):1787-91. Print 2012.
• Sy A, Srinivasan M, Mascarenhas J, Lalitha P, Rajaraman R, Ravindran M, Oldenburg CE, Ray KJ, Glidden D, Zegans ME, McLeod SD, Lietman TM, Acharya NR. Pseudomonas aeruginosa keratitis: outcomes and response to corticosteroid treatment. Invest Ophthalmol Vis Sci. 2012 Jan 25;53(1):267-72. Print 2012 Jan.
• Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Lalitha P, Glidden DV, Ray KJ, Hong KC, Oldenburg CE, Lee SM, Zegans ME, McLeod SD, Lietman TM, Acharya NR; Steroids for Corneal Ulcers Trial Group. Corticosteroids for bacterial keratitis: the Steroids for Corneal Ulcers Trial (SCUT). Arch Ophthalmol. 2012 Feb;130(2):143-50. Epub 2011 Oct 10.
• Srinivasan M, Mascarenhas J, Rajaraman R, Ravindran M, Lalitha P, Glidden DV, Ray KJ, Hong KC, Oldenburg CE, Lee SM, Zegans ME, McLeod SD, Lietman TM, Acharya NR; Steroids for Corneal Ulcers Trial Group. The steroids for corneal ulcers trial: study design and baseline characteristics. Arch Ophthalmol. 2012 Feb;130(2):151-7. Epub 2011 Oct 10.
• Srinivasan M, Lalitha P, Mahalakshmi R, Prajna NV, Mascarenhas J, Chidambaram JD, Lee S, Hong KC, Zegans M, Glidden DV, McLeod S, Whitcher JP, Lietman TM, Acharya NR. Corticosteroids for bacterial corneal ulcers. Br J Ophthalmol. 2009 Feb;93(2):198-202. Epub 2008 Oct 1.

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 descemetocoele
• 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

• Aravind Eye Hospitals, India
• Dartmouth-Hitchcock Medical Center