NOVEL GLAUCOMA DIAGNOSTICS FOR STRUCTURE AND FUNCTION

该计划的广泛、长期目标是及早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丢失导致神经纤维层(NFL)和黄斑变薄，临床上无法检测到变薄的早期阶段，但光学相干断层扫描(OCT)可以检测到变薄的早期阶段。我们假设OCT NFL和黄斑评估比视神经头(ONH)评估对青光眼的损害及其进展更敏感，并且OCT的灵敏度可以随着分辨率的提高而提高。高分辨率OCT可以提供更精确的NFL测量，并测量黄斑神经节细胞层，甚至可能计算神经节细胞。我们假设，客观的功能性青光眼评估可以用一种新的电生理技术--多焦视网膜电图(MFERG)来完成。最后，我们建议1.3微米OCT可用于前房角、虹膜和睫状体的测量。OCT是我们开发的一种新技术，它允许对生物组织中的微结构进行非侵入性、非接触式、横断面层析成像。商用OCT装置提供大约10微米的分辨率，而我们开发的一种新的高分辨率仪器接近1-3微米的分辨率。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毛细血管周围NFL厚度和黄斑厚度进行横断面定量，并将结果与常规评估和定量ONH测量结果相关联。2)应用临床OCT对正常人和青光眼患者的黄斑厚度和乳头周围NFL进行纵向定量。使用Prototype OCT继续当前的纵向研究。3)探讨超高分辨率OCT对正常人和青光眼患者乳头周围神经纤维层、黄斑区神经纤维层和黄斑神经节细胞层厚度的定量研究。4)量化正常人和青光眼患者的MFERG反应；将这些反应与常规检查和OCT检查相关联。5)显示1.3微米波长的前房、房角、虹膜和睫状体的OCT图像。6)观察激光诱导的猴青光眼模型OCT和MFERG的纵向变化，并与组织学结果进行对照。这项计划符合1999年NEI国家计划的目标和目的，“[为了]制定改进的措施，以帮助青光眼的临床诊断；监测疾病的进展……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。”我们解决了国家计划战略研究问题，“青光眼患者视功能丧失与视神经和视网膜神经纤维层结构改变之间有什么关系？”[1999年国家眼科咨询委员会]

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]