Improving Outcomes Assessment for Microbial Keratitis

改善微生物角膜炎的结果评估

• 批准号: 10630922
• 负责人: Nakul Shekhawat
• 金额: $ 22.47万
• 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/10630922
• 关键词: Affect; Anatomy; Anterior; Applied Research; Area; Biological; Biometry; Blindness; Categories; Characteristics; Cicatrix; Clinical; 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; Eyeglasses; Funding; Future; Goals; Heterogeneity; 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; 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; microbial based therapy; 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.

抽象的 这个K23指导职业发展奖的总体研究目标是改善成果 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重大伤害。 MK对临床和 研究目的仍然是挑战。传统对MK严重程度的临床评估和对 治疗是主观的和暗示的，因此很难比较临床研究的治疗效率 由于可重复性较低和样本量需求增加而导致的研究。先前使用的MK临床试验已使用 结果指标，例如最佳眼镜校正的视力，这些视力不是特定疾病的，可能无法 捕获有关MK造成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，MK中大多数大规模的前瞻性随机试验失败了 证明在临床上有意义或统计上有显着的治疗反应差异 组。单中心MK研究也可能缺乏针对其他医疗机构的适用性 人群之间的患者特征和微生物分布。发展更客观，可重复， MK的临床相关，可推广的结果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能力。新成像方式，例如scheimpflug 层析成像和前部光学连贯断层扫描（ASOCT）可以提供客观，精确， 可重现的角膜结构评估以及临床相关的评估，但这些方式尚未 使用前瞻性研究对MK临床护理或研究进行了批判性评估。此申请建议 对约翰·霍普金斯（Johns Hopkins）进行MK患者的前瞻性队列研究。我们将收集详细的临床和 微生物数据并使用缝隙摄影，Scheimpflug进行串行多模式成像 断层扫描，并在6个月内进行。 AIM 1将比较超声的可重复性和一致性 pachymetry，scheimpflug断层扫描和ASOCT，用于对MK中角膜变薄的客观定量。目标2 将评估scheimpflug光密度法作为客观量化角膜纵向变化的一种手段 MK中的疤痕密度。 AIM 3将评估某些早期解剖或临床特征是否可以改善预测 MK中随后的视觉结果以及这些预测因子是否适用于不同的MK 种群和感染亚组，表明这些新型结果指标适合用于 协作多中心临床试验。该建议将为候选人提供高级培训，并 研究经验需要成为临床试验方法的专家，并且是由独立资助的 角膜和外部疾病领域的临床科学家。候选人的提议是全面的 培训计划结合了严格的正式课程，智力丰富的正式课程和讲习班 约翰·霍普金斯大学的环境；博士的世界一流心态。道格拉斯·贾布斯（Douglas Jabs），托马斯·利特曼（Thomas Lietman）， 伊丽莎白·糖（Elizabeth Sugar）和阿尔伯特·朱（Albert Jun）；持续的潜在多中心临床试验的身临其境的经验；和 应用研究经验。特定培训领域包括：（1）高级临床试验方法； （2） 实践临床试验实施； （3）高级生物统计学； （4）微生物的临床和研究专业知识 角膜炎； （5）作为临床科学家的职业发展。候选人研究的结果将被使用 为R01或UG1基本临床试验制定建议，该试验将改善基于证据的治疗 角膜和外部疾病。