Predicting and Improving Clinical Outcomes for Bacterial Keratitis

描述：我寻求K23职业发展奖项的目的有两个：1)使用nei赞助的角膜溃疡类固醇试验（SCUT）的基础设施来检查添加局部类固醇是否能改善细菌性角膜溃疡亚组的临床结果；2)通过实际的研究经验，教学和指导，发展我的职业生涯，成为一名独立的眼部感染和炎症研究者。关于使用类固醇治疗细菌性角膜溃疡一直存在争议。需要额外的数据，包括特定亚组的结果，以帮助临床医生了解风险与益处。类固醇治疗角膜溃疡（SCUT）是nei资助的一项试验，在UCSF的Proctor基金会、南印度的Arvind眼科医院和达特茅斯-希区柯克医疗中心招募患者。SCUT的主要目的是研究外用类固醇对细菌性角膜溃疡的影响，通过3个月时的最佳矫正视力和疤痕大小来衡量。研究者建议进行辅助研究，通过遗传差异（通过细胞毒性铜绿假单胞菌侵入）和抗生素敏感性来比较生物（铜绿假单胞菌与其他所有生物）的基线特征和临床结果。目的1：确定辅助局部类固醇治疗对铜绿假单胞菌角膜炎临床结果的影响，并与其他生物引起的细菌性角膜炎进行比较。目的2：确定P. aeruginosa的侵袭性和细胞毒性亚型在入组时是否有不同的临床症状，或者对治疗的反应是否不同。目的3：确定细菌性角膜炎的抗生素敏感性与临床结局之间是否存在相关性。作为SCUT试验的一部分，这些目标所需的数据和样本已经在收集中。作为本研究计划的一部分，铜绿假单胞菌分离株将在Aim 2中进行亚型分型，并在Aim 3中确定每种细菌分离株对研究抗生素莫西沙星的最低抑制浓度。回归模型将用于确定各种因素的影响，包括类固醇治疗、细菌分离物类型、铜绿假单胞菌毒力因素和最低抑制浓度，对细菌性角膜炎的基线特征和临床结果。细菌性角膜炎是世界范围内视力损害的主要原因，影响患者的生活质量和功能状态。我们的目标是提供数据，使临床医生能够以循证方式对细菌性角膜溃疡患者进行风险分层。

Description: 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.