Detection of Glaucoma Progression with Macular OCT Imaging

描述(由申请人提供)：这是一个正式的申请职业发展奖(K23)的学术青光眼专家严重感兴趣的作用成像在青光眼使用光学相干断层扫描(OCT)。这将允许候选人建立一个临床研究计划，主要目标是通过使用光谱域OCT的黄斑成像来改善青光眼进展的检测。到拟议的研究完成时，候选人将拥有作为独立研究者继续研究的初步数据，并将收集一组晚期青光眼患者的纵向结构和功能数据，这将成为进一步改进黄斑OCT成像检测青光眼进展的平台。这些数据将帮助候选人为随后的R01提供初步结果，这将潜在地允许PI继续跟踪在K23奖励期间登记的患者。我拥有临床调查的理学硕士学位，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)。到获奖期结束时，我预计我将获得更多的经验、知识和导师，作为一名在青光眼领域取得成功的独立临床医生-科学家。我的长期目标是对青光眼患者进行纵向研究，在这些研究中，可以应用当前和即将进行的成像和功能测试，并研究它们对检测青光眼进展的有效性。我相信，我的导师们的综合技能和经验将为拟议的K奖带来成功的结果。我还设想自己将来会指导像我这样的候选人，这样我们的集体知识和智慧就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方面的个人研究计划；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方面的学分课程。这项建议的研究部分的主要目的是更好地描述黄斑SD-OCT成像在检测晚期青光眼青光眼进展中的作用。实现这一目标的具体目标如下：(1)比较各种全球和地区性黄斑措施检测青光眼的表现。我们将探讨影响各种黄斑预后指标表现的潜在因素。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信号强度和视网膜外部厚度等。我推测，视网膜外层(外核层到视网膜色素上皮-Bruchs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/内网状层)测量差异的最重要因素。(2)确定和比较通过第一个目标检测的候选黄斑测量在检测中晚期到重度青光眼中青光眼进展的有效性。中晚期至重度青光眼定义为视野平均偏差小于-6分贝或24-2视野累及中央10度。人们普遍认为，在晚期青光眼中测量视神经头或RNFL参数并不能为临床医生提供太多有用的信息。相比之下，中央黄斑神经节细胞是青光眼中最后死亡的细胞。晚期青光眼的黄斑成像指向这一区域，在那里仍有可能检测到变化。我假设黄斑OCT参数是有效的结构结果测量(生物标记物)，可以用来跟踪进展期青光眼的病程，并且这种测量与中心视野的变化显著相关。黄斑测量随时间的变化将首先与相应的视野变化(功能 进展)，随着时间的推移，中度到重度青光眼的眼睛。此外，还将探讨和比较预测青光眼进展的最佳候选黄斑测量方法的实用性。我推测进展性青光眼黄斑神经节细胞的进行性丢失和随后的视野进展之间可能存在一段滞后期，因此，在一个或多个黄斑预后指标中检测到恶化可以作为随后视野进展的替代指标。总而言之，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的作用提供坚实的基础。在青光眼后期及时发现进展可以通过早期积极的治疗显着减少视力残疾和失明，并有可能减轻青光眼给社会带来的经济负担。

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.