My objectives in seeking a K23 career development award are two-fold: 1) to use the infrastructure of the NEI-sponsored Steroid for Corneal Ulcers Trial (SCUT) to examine whether adding topical steroids improves clinical outcomes of subgroups of bacterial corneal ulcers;2) to develop my career as an independent investigator in ocular infection and inflammation by hands-on research experience, didactics and mentorship. There is ongoing controversy regarding the use of steroids in treating bacterial corneal ulcers. Additional data, including results in specific subgroups, are needed to help clinicians understand the risks vs benefits. Steroid for Corneal Ulcer Treatment (SCUT) is an NEI-funded, trial enrolling patients at the Proctor Foundation at UCSF, Arvind Eye Hospital in South India, and Dartmouth-Hitchcock Medical Center. The main objective of SCUT is to study the effect of topical steroids on bacterial corneal ulcers, as measured by outcomes including best corrected visual acuity and scar size at 3 months. The investigator proposes to perform ancillary studies comparing baseline characteristics and clinical outcome by organisms (Pseudomonas aeruginosa vs. all others) by genetic difference (Invasive via cytotoxic P. aeruginosa) and by antibiotic susceptibility.
Three specific aims will be addressed:
Aim 1 : to determine the effect of adjunctive topical steroid therapy on clinical outcomes in P. aeruginosa keratitis compared to bacterial keratitis due to the other organisms.
Aim 2 : To determine whether the invasive and cytotoxic subtypes of P. aeruginosa have different clinical signs at enrollment, or have a different response to treatment.
Aim 3 : To determine whether there is a correlation between antibiotic susceptibility and the clinical outcome in bacterial keratitis. The data and samples necessary for these aims are already being collected as part of the SCUT trial. As part of this research proposal, P.aeruginosa isolates will be subtyped for Aim 2 and the minimum inhibitory concentration of each bacterial isolate to the study antibiotic moxifloxacin will be determined for Aim 3. Regression models will be utilized to determine the impact of various factors, including treatment with steroids, bacterial isolate type, P.aeruginosa virulence factors, and minimum inhibitory concentration, on baseline characteristics and clinical outcomes in bacterial keratitis. Bacterial keratitis is a major cause of visual impairment worldwide, affecting both patients'quality of life and functional status. Our goal is to provide data to allow clinicians to risk-stratify patients with bacterial corneal ulcers in an evidence-based manner.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23EY017897-05
Application #
8018095
Study Section
Special Emphasis Panel (ZEY1-VSN (03))
Program Officer
Everett, Donald F
Project Start
2007-02-01
Project End
2012-07-31
Budget Start
2011-02-01
Budget End
2012-07-31
Support Year
5
Fiscal Year
2011
Total Cost
$239,496
Indirect Cost
Name
University of California San Francisco
Department
Ophthalmology
Type
Organized Research Units
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Sun, Catherine Q; Lalitha, Prajna; Prajna, N Venkatesh et al. (2014) Association between in vitro susceptibility to natamycin and voriconazole and clinical outcomes in fungal keratitis. Ophthalmology 121:1495-500.e1
Borkar, Durga S; Gonzales, John A; Tham, Vivien M et al. (2014) Association between atopy and herpetic eye disease: results from the pacific ocular inflammation study. JAMA Ophthalmol 132:326-31
Ray, Kathryn J; Srinivasan, Muthiah; Mascarenhas, Jeena et al. (2014) Early addition of topical corticosteroids in the treatment of bacterial keratitis. JAMA Ophthalmol 132:737-41
Lalitha, Prajna; Sun, Catherine Q; Prajna, N Venkatesh et al. (2014) In vitro susceptibility of filamentous fungal isolates from a corneal ulcer clinical trial. Am J Ophthalmol 157:318-26
Shakoor, Akbar; Esterberg, Elizabeth; Acharya, Nisha R (2014) Recurrence of uveitis after discontinuation of infliximab. Ocul Immunol Inflamm 22:96-101
Borkar, Durga S; Acharya, Nisha R; Leong, Chelsia et al. (2014) Cytotoxic clinical isolates of Pseudomonas aeruginosa identified during the Steroids for Corneal Ulcers Trial show elevated resistance to fluoroquinolones. BMC Ophthalmol 14:54
McClintic, Scott M; Prajna, Namperumalsamy V; Srinivasan, Muthiah et al. (2014) Visual outcomes in treated bacterial keratitis: four years of prospective follow-up. Invest Ophthalmol Vis Sci 55:2935-40
Srinivasan, Muthiah; Mascarenhas, Jeena; Rajaraman, Revathi et al. (2014) Visual recovery in treated bacterial keratitis. Ophthalmology 121:1310-1
Srinivasan, Muthiah; Mascarenhas, Jeena; Rajaraman, Revathi et al. (2014) The steroids for corneal ulcers trial (SCUT): secondary 12-month clinical outcomes of a randomized controlled trial. Am J Ophthalmol 157:327-333.e3
Prajna, N Venkatesh; Krishnan, Tiruvengada; Mascarenhas, Jeena et al. (2013) The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole. JAMA Ophthalmol 131:422-9

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