Improving Outcomes Assessment for Microbial Keratitis

改善微生物角膜炎的结果评估

• 批准号: 10449703
• 负责人: Nakul Shekhawat
• 金额: $ 22.43万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10449703
• 关键词: Affect; Anatomy; Anterior; Applied Research; Area; Biometry; Blindness; Categories; Characteristics; Cicatrix; Clinical; Clinical Microbiology; Clinical Research; Clinical Trials; Clinical assessments; Conduct Clinical Trials; Cornea; Corneal Diseases; Corneal Ulcer; Data; Densitometry; Disease; Educational workshop; Enrollment; Environment; Evidence based treatment; Evolution; Funding; Future; Goals; Heterogeneity; Immersion; India; Individual; Infection; K-Series Research Career Programs; Keratitis; Measurement; Measures; Mentors; Mentorship; Methodology; Modality; Modeling; Monitor; Multi-Institutional Clinical Trial; Multimodal Imaging; Natural History; Optical Coherence Tomography; Optics; Outcome; Outcome Assessment; Patients; Persons; Population; Prognosis; Prospective Studies; Prospective cohort study; Quality of life; Reproducibility; Research; Sample Size; Scientist; Severities; Statistical Models; Statistical Study; Stratification; Structure; Subgroup; Thinness; Time; Training; Treatment Efficacy; Universities; Vision; Visual; Visual Acuity; career development; clinical application; clinical care; clinical practice; clinical trial implementation; clinically relevant; cohort; comparative efficacy; comparison group; corneal scar; density; design; experience; follow-up; health care settings; imaging modality; improved; improved outcome; innovation; insight; microbial; new technology; novel; patient population; prospective; randomized trial; research study; slit lamp imaging; sugar; tomography; treatment response; ultrasound

ABSTRACT The overarching research goal of this K23 Mentored Career Development Award is to improve outcomes assessment for microbial keratitis (MK), or infectious corneal ulceration. MK affects 2 million people per year and causes significant harm to vision and quality of life. Meaningful measurement of MK for clinical and research purposes remains challenging. Traditional clinical assessments of MK severity and response to treatment are subjective and imprecise, making it difficult to compare efficacy of treatments in clinical research studies due to low reproducibility and increased sample size requirements. Prior MK clinical trials have used outcome metrics such as best spectacle-corrected visual acuity which are not disease-specific and may fail to capture key information about corneal damage caused by MK. These measurement limitations reduce the quality and impact of MK research. To date, most large-scale prospective randomized trials in MK have failed to demonstrate clinically meaningful or statistically significant differences in treatment response between groups. Single-center MK studies can also lack applicability to other healthcare settings due to differences in patient characteristics and microbial distributions across populations. Developing more objective, reproducible, clinically relevant, and generalizable outcome metrics and predictors for MK would enhance the clinical relevance and statistical power of future multicenter MK studies. New imaging modalities such as Scheimpflug tomography and anterior segment optical coherence tomography (ASOCT) can provide objective, precise, reproducible, and clinically relevant assessments of corneal structure, but these modalities have not been critically evaluated for MK clinical care or research using prospective studies. This application proposes to conduct a prospective cohort study of MK patients at Johns Hopkins. We will collect detailed clinical and microbiologic data and perform serial multimodal imaging using slit lamp photography, Scheimpflug tomography, and ASOCT over 6 months. Aim 1 will compare the reproducibility and concordance of ultrasound pachymetry, Scheimpflug tomography, and ASOCT for objective quantification of corneal thinning in MK. Aim 2 will evaluate Scheimpflug densitometry as a means of objectively quantifying longitudinal changes in corneal scar density in MK. Aim 3 will assess whether certain early anatomic or clinical features can improve prediction of subsequent visual outcomes in MK and whether these predictors are applicable across different MK populations and infection subgroups, indicating the suitability of these novel outcome metrics for use in collaborative multicenter clinical trials. This proposal will provide the candidate with the advanced training and research experience needed to become an expert in clinical trials methodology and an independently funded clinician-scientist in the field of cornea and external diseases. The candidate proposes a comprehensive training plan combining rigorous formal coursework, seminars, and workshops in the intellectually rich environment at Johns Hopkins University; world-class mentorship under Drs. Douglas Jabs, Thomas Lietman, Elizabeth Sugar, and Albert Jun; immersive experience with ongoing prospective multicenter clinical trials; and applied research experience. Specific training areas include: (1) advanced clinical trial methodology; (2) practical clinical trial implementation; (3) advanced biostatistics; (4) clinical and research expertise in microbial keratitis; and (5) career development as a clinician-scientist. Results from the candidate’s research will be used to develop a proposal for a R01 or UG1 funded clinical trial that will improve evidence-based treatment for cornea and external diseases.

摘要 这个K23指导职业发展奖的首要研究目标是提高成果 评估微生物角膜炎（MK）或感染性角膜溃疡。MK每年影响200万人 并对视力和生活质量造成严重损害。MK的有意义的测量用于临床和 研究目的仍然具有挑战性。MK严重程度的传统临床评估和对 治疗是主观的和不精确的，使得难以在临床研究中比较治疗的效果 由于重复性低和增加的样本量要求，研究中出现了一些问题。之前的MK临床试验使用了 结果指标，如最佳视力矫正视力，其不是疾病特异性的， 捕捉由MK引起的角膜损伤的关键信息。这些测量限制降低了 MK研究的质量和影响。迄今为止，大多数MK的大规模前瞻性随机试验都失败了 证明治疗应答之间存在具有临床意义或统计学意义的差异 组单中心MK研究也可能由于以下方面的差异而缺乏对其他医疗机构的适用性： 患者特征和人群中的微生物分布。开发更客观，可重复， MK的临床相关和可推广的结局指标和预测因子将增强临床 未来多中心MK研究的相关性和统计功效。新的成像模式，如Scheimpflug 断层扫描和眼前节光学相干断层扫描（ASOCT）可以提供客观的，精确的， 角膜结构的可重复性和临床相关评估，但这些模式尚未被 使用前瞻性研究对MK临床护理或研究进行批判性评价。本申请建议 在约翰霍普金斯医院对MK患者进行前瞻性队列研究。我们将收集详细的临床和 微生物学数据，并使用裂隙灯摄影进行系列多模态成像，Scheimpflug 断层扫描和ASOCT超过6个月。目的1将比较超声的可重复性和一致性 角膜厚度测量、Scheimpflug断层扫描和ASOCT，用于客观定量MK患者的角膜变薄。目的2 将评估Scheimpflug密度测定法作为客观量化角膜纵向变化的一种手段， MK瘢痕密度。目标3将评估是否某些早期解剖或临床特征可以提高预测 MK的后续视觉结果以及这些预测因素是否适用于不同的MK 人群和感染亚组，表明这些新的结局指标适用于 多中心协作临床试验。该提案将为候选人提供高级培训， 研究经验需要成为一个专家在临床试验方法和独立资助的 角膜和外部疾病领域的临床科学家。候选人提出了一个全面的 培训计划结合了严格的正式课程，研讨会和讲习班，在智力丰富的 约翰霍普金斯大学的环境;在道格拉斯贾布斯，托马斯利特曼， Elizabeth Sugar和Albert Jun;正在进行的前瞻性多中心临床试验的沉浸式体验;以及 应用研究经验。具体培训领域包括：（1）高级临床试验方法学;（2） 实际的临床试验实施;（3）先进的生物统计学;（4）微生物临床和研究专业知识 角膜炎;和（5）作为临床医生-科学家的职业发展。候选人的研究结果将被用于 为R 01或UG 1资助的临床试验制定一项提案，以改善循证治疗， 角膜和外部疾病。