Detection of Glaucoma Progression with Macular OCT Imaging

利用黄斑 OCT 成像检测青光眼进展

• 批准号: 8353379
• 负责人: Kouros Nouri-Mahdavi
• 金额: $ 22.91万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8353379
• 关键词: Age; Area; Award; Biological Markers; Biometry; Blindness; Bruch' s basal membrane structure; Caring; Clinical Research; Clinical Trials; Complement; Complex; Computer Vision Systems; Cornea; Data; Detection; Diagnosis; Diagnostic Imaging; Disease; Early Diagnosis; Enrollment; Epidemiology; Ethical Issues; Evaluation; Eye; Foundations; Functional Imaging; Future; Glaucoma; Goals; Gold; Human; Image; Image Analysis; Individual; Inner Plexiform Layer; K-Series Research Career Programs; Knowledge; Lead; Legal Blindness; Length; Longitudinal Studies; Master of Science; Measurement; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Morbidity - disease rate; Nerve Fibers; Noise; Ophthalmologist; Optic Disk; Optical Coherence Tomography; Outcome; Outcome Measure; Patients; Performance; Process; Proxy; Quality of life; Race; Research; Research Personnel; Retinal; Role; Scientist; Signal Transduction; Societies; Solid; Specialist; Staging; Structure of retinal pigment epithelium; Testing; Thick; Time; Vision; Visual; Visual Fields; advanced disease; biomathematics; central visual field; disability; experience; follow-up; ganglion cell; image processing; improved; interest; macula; next generation; programs; retina outer nuclear layer; retinal nerve fiber layer; skills

DESCRIPTION (provided by applicant): This application is a formal request for a career development award (K23) for an academic glaucoma specialist with a serious interest in the role of imaging in glaucoma using optical coherence tomography (OCT). This will allow the candidate to establish a clinical research program with the main goal of improving detection of glaucoma progression through macular imaging with spectral-domain OCT. By the time the proposed research is accomplished, the candidate will have preliminary data for continuing his research as an independent investigator and will have collected longitudinal structural and functional data in a group of advanced glaucoma patients that will serve as a platform for further improving detection of glaucoma progression with macular OCT imaging. The data will help the candidate provide preliminary results for a subsequent R01 that would potentially allow the PI to continue follow-up of the patients enrolled in the K23 award period. I have a Master's of Science degree in Clinical Investigation under my belt and intend to deepen my skills in the field of imaging and biostatistics (to be used for enhancing and handling OCT images and for analyzing longitudinal data) by completing the proposed didactic program. By the end of the award period, I expect that I will have gained additional experience, knowledge, and mentorship required to prosper as an independent clinician-scientist in the field of glaucoma. My long-term goal is to carry out longitudinal studies of glaucoma patients where current and upcoming imaging and functional tests can be applied and their utility for detection of glaucoma progression can be investigated. I am confident that the combined skills and experience of my mentors will lead to a successful outcome for the proposed K award. I also envisage myself mentoring candidates like myself in future so that our collective knowledge and wisdom can be passed along to the next generation of aspiring clinician-scientists. My objectives during the award period are as follows: 1) To develop an individual research program in glaucoma diagnostic imaging; 2) to successfully complete credited coursework in biomathematics, advanced biostatistics, computer vision (image processing), epidemiology, and ethical issues in research. The main goal of the research component of this proposal is to better delineate the role of macular SD- OCT imaging for detection of glaucoma progression in advanced glaucoma. The specific aims through which this goal will be accomplished are as follows: (1) To compare the performance of various global and regional macular measures to detect glaucoma. The potential factors influencing the performance of various macular outcome measures will be explored. Such covariates include age, race, axial length, disc size, central corneal thickness, OCT signal strength, and outer retinal thickness among others. I hypothesize that the thickness of the outer retina (outer nuclear layer to retinal pigment epithelium-Bruch's membrane complex) may be the most important factor explaining the measurement variability of the inner retinal layer thickness (GCC or ganglion cell/inner plexiform layers). (2) To determine and compare the utility of the candidate macular measures, detected through the first aim, for detection of glaucoma progression in moderately advanced to severe glaucoma. Moderately advanced to severe glaucoma will be defined as eyes with visual field mean deviation worse than -6 dB or eyes with involvement of the central 10 degrees on the 24-2 visual field. It is widely accepted that measurement of the optic nerve head or RNFL parameters in advanced glaucoma does not provide clinicians with much useful information. In contrast, the central macular ganglion cells are the last to die in glaucoma. Macular imaging in advanced glaucoma is directed towards this area where detection of change may still be possible. I hypothesize that macular OCT parameters are valid structural outcome measures (biomarkers) that can be used to follow the course of the disease in advanced glaucoma and that such measures are significantly correlated with changes in the central visual field. Changes in the macular measures over time will be first correlated with the corresponding visual field change (functional progression) over time in eyes with moderately advanced to severe glaucoma. The utility of the best candidate macular measures for predicting subsequent glaucoma progression will also be explored and compared. I hypothesize that there may be a lag period between progressive loss of macular ganglion cells and subsequent visual field progression in advanced glaucoma, and therefore, detection of worsening in one or more macular outcome measures can be used as a proxy for subsequent visual field progression. Collectively, these studies will provide a solid foundation for better understanding and integration of macular OCT imaging in the care of glaucoma patients. Timely detection of glaucoma progression in the later stages can significantly reduce visual disability and blindness through earlier aggressive treatment and will potentially reduce glaucoma's financial burden to society. PUBLIC HEALTH RELEVANCE: Detection of glaucoma progression remains a challenging task in eyes demonstrating significant damage. Even small amounts of progression in advanced glaucoma can have important consequences with regard to patient's visual function and quality of life. The results of the proposed study will potentially lead to more effective and earlier detection of glaucoma progression and will allow ophthalmologists to step up treatment in a timely manner. This will in turn result in less visual morbidity and reduced blindness from glaucoma, which is projected to cause more than 10 million cases of legal blindness around the world in 2020.

描述（由申请人提供）：本申请是对使用光学相干断层扫描（OCT）成像在青光眼中的作用感兴趣的学术青光眼专家的职业发展奖（K23）的正式申请。这将允许候选人建立一个临床研究计划，其主要目标是通过光谱域OCT的黄斑成像来改善青光眼进展的检测。候选人将拥有作为独立研究者继续其研究的初步数据，并将收集一组晚期青光眼患者的纵向结构和功能数据，用于进一步改进使用黄斑OCT成像检测青光眼进展的平台。这些数据将帮助候选人提供后续R 01的初步结果，这可能使PI能够继续对K23奖励期入组的患者进行随访。 我拥有临床研究理学硕士学位，并打算通过完成拟议的教学计划来加深我在成像和生物统计学领域的技能（用于增强和处理OCT图像以及分析纵向数据）。在奖励期结束时，我希望我将获得额外的经验，知识和指导，以作为青光眼领域的独立临床科学家而繁荣。我的长期目标是对青光眼患者进行纵向研究，其中可以应用当前和即将到来的成像和功能测试，并可以研究其用于检测青光眼进展的效用。我相信，我的导师的技能和经验相结合，将导致一个成功的结果，拟议的K奖。我还设想自己在未来指导像我这样的候选人，以便我们的集体知识和智慧可以沿着下一代有抱负的临床科学家。 我在获奖期间的目标如下：1）开发青光眼诊断成像的个人研究计划; 2）成功完成生物数学，高级生物统计学，计算机视觉（图像处理），流行病学和研究中的伦理问题的学分课程。 本提案研究部分的主要目标是更好地描述黄斑SD-OCT成像在晚期青光眼中检测青光眼进展的作用。实现这一目标的具体目标如下：（1）比较各种全球和区域黄斑测量方法检测青光眼的性能。 将探讨影响各种黄斑结局指标性能的潜在因素。这些协变量包括年龄、种族、眼轴长度、椎间盘大小、中央角膜厚度、OCT信号强度和外视网膜厚度等。我推测外视网膜的厚度（外核层至视网膜色素上皮-布鲁赫膜复合体）可能是解释内视网膜层厚度（GCC或神经节细胞/内丛状层）测量变异性的最重要因素。 (2)确定并比较通过第一个目标检测的候选黄斑测量在检测中晚期至重度青光眼的青光眼进展中的效用。 中度晚期至重度青光眼将定义为视野平均偏差差于-6 dB的眼睛或24-2视野中央10度受累的眼睛。广泛认为晚期青光眼视神经乳头或RNFL参数的测量不能为临床医生提供很多有用的信息。相比之下，中央黄斑神经节细胞在青光眼中是最后死亡的。晚期青光眼的黄斑成像是针对这一领域的变化检测可能仍然是可能的。我假设黄斑OCT参数是有效的结构结果测量（生物标志物），可用于跟踪晚期青光眼的病程，并且这些测量与中央视野的变化显著相关。黄斑测量值随时间的变化将首先与相应的视野变化（功能性视野变化）相关联 进展）。最佳候选黄斑措施预测随后的青光眼进展的效用也将进行探讨和比较。我推测，在晚期青光眼中，黄斑神经节细胞的进行性丧失和随后的视野进展之间可能存在滞后期，因此，检测到一种或多种黄斑结局指标的恶化可用作随后视野进展的代表。 总的来说，这些研究将为更好地理解和整合黄斑OCT成像在青光眼患者护理中提供坚实的基础。在晚期及时检测青光眼进展可以通过早期积极治疗显着减少视力残疾和失明，并可能减少青光眼对社会的经济负担。 公共卫生相关性：青光眼进展的检测仍然是一项具有挑战性的任务，眼睛表现出显着的损害。即使是晚期青光眼的少量进展也会对患者的视觉功能和生活质量产生重要影响。拟议研究的结果可能会导致更有效和更早地检测青光眼进展，并使眼科医生能够及时加强治疗。这将反过来导致视力发病率降低，青光眼失明减少，预计到2020年，青光眼将在全世界造成超过1000万例法律的失明。