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: 8866409
• 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 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8866409
• 关键词: Age; Area; Award; Biological Markers; Biometry; Blindness; Bruch' s basal membrane structure; Caring; Clinical Research; 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; clinical investigation; 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.

描述（由申请人提供）：本申请是向一位对光学相干断层扫描 (OCT) 成像在青光眼中的作用非常感兴趣的学术青光眼专家申请职业发展奖 (K23) 的正式申请。这将使候选人能够建立一个临床研究计划，其主要目标是通过频域 OCT 黄斑成像改进青光眼进展的检测。当拟议的研究完成时，候选人将获得作为独立研究者继续进行研究的初步数据，并将收集一组晚期青光眼患者的纵向结构和功能数据，这些数据将作为进一步改进黄斑 OCT 成像对青光眼进展检测的平台。这些数据将帮助候选者提供后续 R01 的初步结果，这可能使 PI 能够继续跟踪 K23 奖励期注册的患者。 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）。到奖励期结束时，我预计我将获得作为青光眼领域的独立临床医生科学家所需的额外经验、知识和指导。我的长期目标是对青光眼患者进行纵向研究，可以应用当前和即将进行的成像和功能测试，并研究它们在检测青光眼进展方面的效用。我相信，我的导师的综合技能和经验将为拟定的 K 奖带来成功的结果。我还设想自己将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传递给下一代有抱负的临床医生科学家。 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项目； 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。 该提案研究部分的主要目标是更好地描述黄斑 SD-OCT 成像在检测晚期青光眼中青光眼进展中的作用。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果测量性能的潜在因素。这些协变量包括年龄、种族、眼轴长度、视盘大小、中央角膜厚度、OCT 信号强度和外视网膜厚度等。我假设外层视网膜（外核层到视网膜色素上皮-布鲁赫膜复合体）的厚度可能是解释视网膜内层厚度（GCC 或神经节细胞/内丛状层）测量变异性的最重要因素。 (2) 确定和比较通过第一个目标检测到的候选黄斑测量值对于检测中度晚期至重度青光眼的青光眼进展的效用。 中度至重度青光眼将被定义为视野平均偏差低于-6 dB的眼睛或24-2视野中央10度受累的眼睛。人们普遍认为，晚期青光眼中视神经乳头或 RNFL 参数的测量并不能为临床医生提供太多有用的信息。相比之下，黄斑中央神经节细胞在青光眼中最后死亡。晚期青光眼的黄斑成像针对该区域，仍然可以检测到变化。我假设黄斑 OCT 参数是有效的结构结果测量（生物标志物），可用于追踪晚期青光眼的病程，并且此类测量与中央视野的变化显着相关。随着时间的推移，黄斑测量值的变化将首先与相应的视野变化（功能性视野）相关联。 随着时间的推移，患有中度晚期至重度青光眼的眼睛会出现进展）。还将探索和比较最佳候选黄斑测量方法在预测随后的青光眼进展方面的效用。我推测，晚期青光眼中黄斑神经节细胞的逐渐丧失与随后的视野进展之间可能存在一段滞后期，因此，检测到一项或多项黄斑结果指标的恶化可以用作后续视野进展的代表。 总的来说，这些研究将为更好地理解黄斑 OCT 成像并将其整合到青光眼患者的护理中提供坚实的基础。及时发现晚期青光眼进展可以通过早期积极治疗显着减少视力障碍和失明，并有可能减轻青光眼给社会带来的经济负担。