Endothelium/Descemet's membrane Complex Optical Tomography

 描述(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，是为了恢复继发性角膜内皮功能衰竭而丧失的视力。超过25%的移植最终会失败，而导致内皮细胞排斥反应是唯一最重要的原因。保护内皮的关键是对细胞损伤进行早期和准确的诊断，以便在不可逆转的损伤发生之前及时启动治疗。目前的诊断技术在保护内皮细胞方面存在不足。我们的初步研究旨在解决这一关键需求，揭示了利用高清晰度光学相干断层扫描(HDOCT)揭示的在体角膜内皮/后弹力膜(EN/DM)特征诊断角膜移植排斥反应的巨大潜力。然而，他们也强调了阻碍建立这项新技术的技术限制。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物EN/DM，并在临床研究的背景下，验证TH开发的技术在早期和准确诊断移植排斥反应方面的应用。该项目由巴斯科姆·帕尔默眼科研究所(BPEI)医学博士、FRCS博士穆罕默德·阿布·舒沙领导。他是一位训练有素的角膜专家，在角膜成像和以患者为中心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，降低内皮细胞衰竭的风险，并在多中心临床试验中测试他的技术。这项建议的三个目标反映了他的目标，包括：(1)开发和验证自动化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、依赖于操作员的，并且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图像以包括中心旁和周边角膜移植物，以解决当前技术限制，即无法描述旁中心和周边EN/DM，尽管这些都是典型的排斥反应开始。(3)通过一项概念性临床研究，验证宽厚角膜移植EN/DM断层厚度图比中心性EN/DM厚度图更准确、更早地诊断角膜移植排斥反应的预测。除了研究活动，他还 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。他组建了一支杰出的导师团队(Victor Perez博士、Fabrice Manns博士和Sonia Yoo博士)，他们在专注于角膜移植排斥反应和生物医学角膜成像技术的基础、翻译和患者导向研究方面拥有丰富的经验。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合作伙伴关系，以加强他的建议以及短期和长期成功的可能性。

 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.