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 K23 指导职业发展奖的总体研究目标是改善成果 评估微生物性角膜炎（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 的有意义的测量对于临床和 研究目的仍然具有挑战性。 MK 严重程度和反应的传统临床评估 治疗具有主观性且不精确，因此很难在临床研究中比较治疗效果 由于重复性低和样本量要求增加而进行的研究。此前的 MK 临床试验已使用 结果指标，例如最佳眼镜矫正视力，不是特定于疾病的，可能无法 捕获有关 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 证明治疗反应之间具有临床意义或统计显着性差异 组。由于单中心 MK 研究的差异，单中心 MK 研究也可能缺乏对其他医疗保健环境的适用性。 患者特征和人群中的微生物分布。开发更客观、可重复、 MK 的临床相关且可推广的结果指标和预测因子将增强临床效果 未来多中心 MK 研究的相关性和统计能力。新的成像方式，例如 Scheimpflug 断层扫描和眼前节光学相干断层扫描（ASOCT）可以提供客观、精确、 可重复的、临床相关的角膜结构评估，但这些方法尚未得到证实 使用前瞻性研究对 MK 临床护理或研究进行严格评估。本申请建议 在约翰·霍普金斯大学对 MK 患者进行了一项前瞻性队列研究。我们将收集详细的临床和 微生物数据并使用裂隙灯摄影进行连续多模态成像，Scheimpflug 断层扫描和 ASOCT 超过 6 个月。目标 1 将比较超声的再现性和一致性 厚度测定法、Scheimpflug 断层扫描和 ASOCT 用于 MK 角膜变薄的客观量化。目标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 中的疤痕密度。目标 3 将评估某些早期解剖或临床特征是否可以改善预测 MK 中后续视觉结果的影响以及这些预测因子是否适用于不同的 MK 人群和感染亚组，表明这些新的结果指标适用于 协作多中心临床试验。该提案将为候选人提供高级培训和 成为临床试验方法学专家和独立资助的专家所需的研究经验 角膜和外部疾病领域的临床医生科学家。候选人提出了一项全面的 培训计划结合了严格的正式课程、研讨会和讲习班，为智力丰富的人提供培训 约翰霍普金斯大学的环境；博士的世界级指导。道格拉斯·贾布斯、托马斯·利特曼、 伊丽莎白·休格（Elizabeth Sugar）和艾伯特·君（Albert Jun）；正在进行的前瞻性多中心临床试验的沉浸式体验；和 应用研究经验。具体培训领域包括：（1）先进的临床试验方法； (2) 实际临床试验实施； (3)高级生物统计学； (4)微生物方面的临床和研究专业知识 角膜炎; (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使用 制定 R01 或 UG1 资助的临床试验提案，以改善以下疾病的循证治疗 角膜和外部疾病。