Endothelium/Descemet's membrane Complex Optical Tomography

内皮/后弹力层复合光学断层扫描

• 批准号: 9014307
• 负责人: Mohamed Fadel Abou Shousha
• 金额: $ 22.83万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9014307
• 关键词: Address; Advisory Committees; Affect; Algorithms; Basement membrane; Biophysics; Cell physiology; Characteristics; Clinic; Clinical Research; Complex; Cornea; Corneal Endothelium; Data; Dependency; Descemet' s membrane; Deterioration; Development; Development Plans; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic Sensitivity; Diagnostic Specificity; Dimensions; Disease; Doctor of Medicine; Doctor of Philosophy; Early Diagnosis; Endothelial Cells; Endothelium; Evolution; Eye; Failure; Fuchs' Endothelial Dystrophy; Functional disorder; Future; Goals; Graft Rejection; Hydration status; Image; Imaging technology; Injury; Institutes; Keratoplasty; Knowledge; Manuals; Maps; Measures; Membrane; Mentorship; Multi-Institutional Clinical Trial; Natural regeneration; Optical Coherence Tomography; Optical Tomography; Organ Transplantation; Pathology; Patients; Peripheral; Pilot Projects; Principal Investigator; Procedures; Quality of life; Research; Research Activity; Risk; Scanning; Scientist; Secondary to; Sensitivity and Specificity; Solid; Specialist; Staging; Stress; Structure; Swelling; Techniques; Technology; Testing; Thick; Time; Training; Transplantation; United States; Validation; Variant; Vision; Vision research; accurate diagnosis; base; career; career development; cell injury; endothelial dysfunction; experience; falls; functional loss; functional status; image processing; immunological status; improved; in vivo; instrumentation; novel; novel therapeutics; patient oriented research; prevent; programs; prospective; public health relevance; skills; success; technology/technique; tomography; tool

 DESCRIPTION (provided by applicant): More than 50% of corneal transplants, the most common form of solid organ transplantation, are performed to restore vision lost secondary to corneal endothelial failure. More than 25% of those transplants will eventually fail and endothelial cell rejection leading to failure is the single most important cause. The key to protec the endothelium is the early and accurate diagnosis of cell injury to promptly initiate treatment before irreversible damage occurs. Current diagnostic techniques fall short in protecting endothelial cells. Our pilot studies, aimed at addressing this critical need, revealed great potential of using in vivo corneal endothelium/Descemet's membrane (En/DM) characteristics, disclosed using high definition optical coherence tomography (HDOCT), in diagnosing corneal graft rejection. Yet, they also highlighted technology limitations hindering establishing this nove technique. This proposed research activity will focus on advancing HDOCT technology to better describe corneal grafts En/DM and validating, in the setting of a clinical study, the utility of th developed technology to early and accurately diagnose graft rejection. This project is led by Mohamed Abou Shousha, M.D., FRCS, Ph.D., of the Bascom Palmer Eye Institute (BPEI). He is a highly trained cornea specialist with broad experience in corneal imaging and patient oriented research. His career goals include developing the knowledge and skills to become an independent clinician-scientist while establishing diagnostic techniques to better diagnose corneal endothelial injury to decrease risk of endothelial failure and test his techniques in multi center clinical trials. The three aims of this proposal reflect his goals and include: (1) development and validation of automated En/DM tomographic thickness maps, to address technology limitations that only allow manual En/DM segmentation, which is time consuming, operator dependent and ignores tomography as an important dimension of En/DM structure. (2) Development and validation of instrumentations to extend En/DM images to include the paracentral and peripheral corneal graft, to address current technology limitation, which is the inability to describe the paracentral and peripheral En/DM despite that those are where rejection typically starts. (3) Verify the prediction that wide corneal graft En/DM tomographic thickness maps can diagnose corneal graft rejection more accurately and at an earlier stage than central En/DM thickness through a proof of concept clinical study. In addition to the research activity, he has a highly structured career development plan to further his research skills and develop the solid base for a successful career as an independent clinician- scientist. He has assembled an outstanding mentorship team (Drs. Victor Perez, Fabrice Manns, and Sonia Yoo) with extensive experience in basic, translational and patient oriented research focused on corneal grafts rejection and biomedical corneal imaging technology. He has also developed a strong scientific advisory committee and partnerships with collaborators at the BPEI's McKnight Vision Research Center and Ophthalmic Biophysics Center to strengthen his proposal and the likelihood of both short-term and long-term success.

 描述（由申请人提供）：超过50%的角膜移植（最常见的实体器官移植形式）用于恢复继发于角膜内皮衰竭的视力丧失。超过25%的移植最终会失败，导致失败的内皮细胞排斥是最重要的原因。保护内皮的关键是早期准确地诊断细胞损伤，以便在发生不可逆转的损伤之前及时启动治疗。目前的诊断技术在保护内皮细胞方面存在不足。我们的试点研究，旨在解决这一关键需求，揭示了巨大的潜力，在体内使用角膜内皮/后弹力层（En/DM）的特点，使用高清晰度光学相干断层扫描（HDOCT），在诊断角膜移植排斥反应。然而，他们也强调了阻碍建立这种新技术的技术限制。这项拟议的研究活动将侧重于推进HDOCT技术，以更好地描述角膜移植En/DM，并在临床研究的背景下验证所开发的技术在早期和准确诊断移植排斥反应方面的实用性。该项目由Mohamed Abou Shousha博士领导，FRCS，博士，巴斯科姆帕尔默眼科研究所（BPEI）的研究员。他是一位训练有素的角膜专家，在角膜成像和以患者为导向的研究方面拥有丰富的经验。他的职业目标包括发展知识和技能，成为一名独立的临床科学家，同时建立诊断技术，以更好地诊断角膜内皮损伤，降低内皮衰竭的风险，并在多中心临床试验中测试他的技术。该提案的三个目标反映了他的目标，包括：（1）开发和验证自动En/DM断层扫描厚度图，以解决仅允许手动En/DM分割的技术限制，这是耗时的，依赖于操作员，忽略了断层扫描作为En/DM结构的重要维度。(2)开发和验证仪器，以扩展En/DM图像，包括中央旁和外周角膜移植物，以解决当前技术限制，即无法描述中央旁和外周En/DM，尽管这些通常是排斥反应开始的地方。(3)通过一项概念验证临床研究，验证宽角膜移植片En/DM断层扫描厚度图可以比中央En/DM厚度图更准确地诊断角膜移植片排斥反应，并在更早的阶段进行诊断。除了研究活动，他 有一个高度结构化的职业发展计划，以进一步提高他的研究技能，并为作为一名独立的临床医生-科学家的成功职业生涯奠定坚实的基础。他组建了一个优秀的导师团队（维克托佩雷斯博士，Fabrice Manns和Sonia Yoo），在基础，转化和以患者为导向的研究方面拥有丰富的经验，专注于角膜移植排斥和生物医学角膜成像技术。他还建立了一个强大的科学咨询委员会，并与BPEI的McKnight视力研究中心和眼科生物物理中心的合作者建立了伙伴关系，以加强他的建议以及短期和长期成功的可能性。