NOVEL GLAUCOMA DIAGNOSTICS FOR STRUCTURE AND FUNCTION

该项目的长期目标是早期发现青光眼和青光眼进展。我们的假设是青光眼通过神经节细胞体及其轴突的损失导致神经纤维层（NFL）和黄斑变薄，并且变薄的早期阶段或变薄的进展在临床上无法检测到，但可以通过光学相干断层扫描（OCT）检测到。我们假设OCT NFL和黄斑评估比视神经头（ONH）评估对青光眼损伤及其进展更敏感，并且OCT的敏感性可以随着分辨率的增加而增加。高分辨率OCT可以提供更精确的NFL测量和测量黄斑神经节细胞层，甚至可以计数神经节细胞。我们假设多焦电生理技术（MFERG）可以客观地评估功能性青光眼。最后，我们建议使用1.3微米OCT测量前房角、虹膜和睫状体。OCT是我们开发的一项新技术，它允许对生物组织的微观结构进行无创、非接触、横断面断层成像。商用OCT单元提供约10微米的分辨率，而我们开发的一种新的高分辨率仪器的分辨率约为1-3微米。我们的具体目标是：1)使用临床OCT对正常和青光眼受试者的乳头周围NFL厚度和黄斑厚度进行横断面量化，并将结果与常规评估和定量ONH测量相关联。2)使用临床OCT对正常和青光眼受试者的乳头周围NFL和黄斑厚度进行纵向量化。继续使用原型OCT进行目前的纵向研究。3)研究超高分辨率OCT对正常和青光眼受试者的乳头周围NFL、黄斑NFL和黄斑神经节细胞层厚度进行量化。4)量化正常和青光眼受试者的MFERG反应；将这些反应与常规和OCT检查联系起来。5)展示前房、眼角、虹膜、睫状体在1.3微米波长下的OCT成像。6)观察激光诱导青光眼猴模型OCT和MFERG的纵向变化，并将其与组织学联系起来。该方案符合1999年NEI国家计划的目标和宗旨，即“制定改进措施，帮助青光眼的临床诊断；监测疾病进展…改进的诊断技术包括视觉功能、视神经和神经纤维层结构的测量……”国家计划进一步指出，“新的诊断和成像方法的发展为青光眼的早期诊断和确定青光眼损害的进展提供了更可靠和客观的方法……OCT是目前正在评估的另一种有前途的成像技术。”我们解决国家计划战略研究问题，“青光眼的视觉功能丧失与视神经和视网膜神经纤维层的结构变化之间的关系是什么？”[国家眼科顾问委员会1999]

The broad, long term objectives of this program are the early detection of glaucoma and glaucomatous progression. Our hypothesis is that glaucoma causes thinning of the nerve fiber layer (NFL) and macula, through losses of ganglion cell bodies and their axons, an that the earliest stages of thinning, or progression of thinning, are not detectable clinically, but are detectable by Optical Coherence Tomography (OCT). We hypothesize that OCT NFL and macular assessments are more sensitive to glaucomatous damage and its progression than optic nerve head (ONH) assessment, and that OCT's sensitivity can be increased with increased resolution. High resolution OCT can give more precise NFL measurements and measure the macular ganglion cell layer, perhaps even count ganglion cells. We hypothesize that objective functional glaucoma assessment can be done with multifocal electroretionography (MFERG), a new electrophysiologic technique. Finally, we propose that 1.3 micron OCT can be used for anterior chamber angle, iris and ciliary body measurements. OCT is a new technology that we have developed that permits the noninvasive, non-contact, cross-sectional tomographic imaging of microstructure in biological tissues. A commercial OCT unit provides approximately 10 micron resolution, while a new, high resolution instrument that we have developed approaches approximately 1-3 micron resolution. Our specific aims are 1) To quantify circumapapillary NFL thickness and macular thickness cross-sectionally in normal and glaucomatous subjects using clinical OCT, and to correlate findings with conventional evaluation and quantitative ONH measurements. 2) To quantify peripapillary NFL and macular thickness longitudinally in normal and glaucomatous subjects using clinical OCT. To continue current longitudinal studies using prototype OCT. 3) To investigate ultrahigh resolution OCT to quantify peripapillary NFL, macular NFL, and macular ganglion cell layer thickness in normal and glaucomatous subjects. 4) To quantify MFERG responses in normal and glaucomatous subjects; to correlate these responses to conventional and OCT examinations. 5) To demonstrate OCT imaging of the anterior chamber, angle, iris and ciliary body at 1.3 micron wavelength. 6) To demonstrate longitudinal changes in OCT and MFERG measurements in the laser induced glaucoma monkey model, and to correlate findings with histology. This program is in accordance with the goals and objectives of the 1999 NEI's National Plan, "[to] develop improved measures to aid in the clinical diagnosis of glaucoma; monitor progression of disease ...improved diagnostic techniques encompassing measures of visual function, optic nerve and nerve fiber layer structure..." The National Plan further states, "The development of new diagnostic and imaging methods provides more reliable and objective methods for early diagnosis of glaucoma and for determining progression of glaucomatous damage ...OCT is another promising imaging technique currently under evaluation." We address the National Plan Strategic Research Question, "What is the relationship between visual function loss and structural changes to the optic nerve and retinal nerve fiber layer in glaucoma?" [National Advisory Eye Council 1999]