Development of a supercontinuum laser source interferometer with sub-micron resolution to understand tear film structure and function in dry eye disease

开发具有亚微米分辨率的超连续谱激光源干涉仪，以了解干眼病的泪膜结构和功能

• 批准号: 10284120
• 负责人: Yuqiang Bai
• 金额: $ 25.87万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10284120
• 关键词: Address; Affect; Agreement; Area; Automobile Driving; Back; Biological; Blindness; Blinking; Caliber; Clinical; Complex; Cornea; Custom; Databases; Deposition; Desiccation; Detection; Development; Diagnosis; Discipline; Disease; Disease Management; Dry Eye Syndromes; Economic Burden; Eye; Fiber; Film; Glass; Goals; Halogens; Health; Human; Image; In Vitro; Infection; Inflammation; Institutional Review Boards; Interferometry; Investigation; Lasers; Lead; Light; Lipids; Liquid substance; Maps; Measures; Methods; Mind; Modeling; Monitor; Nature; Noise; Optical Coherence Tomography; Optics; Osmolar Concentration; Pain; Participant; Pattern; Phase; Prevalence; Property; Publishing; Quality of life; Recurrence; Research; Resolution; Role; Scanning; Signal Transduction; Societies; Source; Spatial Distribution; Spottings; Structure; Surface; Symptoms; System; Techniques; Testing; Thermography; Thick; Thinness; Time; Tungsten; United States; Vision; Visual; Work; accurate diagnosis; base; design; disease diagnosis; evaporation; eye dryness; health care economics; high resolution imaging; human subject; imaging system; improved; innovation; lens; mathematical model; nanometer; novel; ocular surface; submicron; ultra high resolution

Project Summary In humans, the precorneal tear film (PCTF) is a thin layer (~3-5 µm) of a complex biological fluid coating the ocular surface, that serves to nourish and protect the ocular surface and provide a smooth refractive optical surface for vision. In dry eye disease, the PCTF becomes thinner, and destabilizes (evaporates) rapidly leading to hyperosmolarity, inflammation, and ocular surface desiccation. More than 30 million people in the United States are impacted by dry eye disease and the economic burden to society is estimated to be over $50 billion. Dry eye disease continues to be a challenge to diagnose, monitor, and treat because as many dry eye tests are conducted inconsistently, lack sufficient reliability or accuracy, and do not correlate with symptoms of the disease. Clinical measures of tear film dynamics (thinning and breakup) are subjective in nature and generally lack validity and repeatability. Therefore, novel, non-invasive optical measures that are highly reliable and accurate are needed to better diagnose the disease, in addition to monitor the impact of treatments. In prior work, we published a mathematical model to systematically analyze the light reflected back from the cornea surface. With this model, the thickness of the PCTF is insensitive to the noise arising from the cornea or light source. The model was validated using a fiber-based interferometry system. The main drawback of that interferometry system is that it is spatially limited to a single point at the apex of the cornea (~30 µm). Although our other previous studies revealed that the distribution of PCTF varied over the ocular surface, and the characterization of these attributes in a large fieldview will provide critical information to diagnose and monitor dry eye disease, the current system was limited to a single point due to the poor focusing property of the thermal light source. A supercontinuum (SC) light source can upgrade the current system to a point-scanning system. Furthermore, the proposed SC interferometer will enable a wide field view of the PCTF by a customized objective lens. The lens will be developed based on our previous investigation, with a focal field specifically designed for imaging over the cornea surface. This innovative interferometer will achieve unprecedented thickness sensitivity (~0.33 µm) of the tear film across the human cornea. Aim 1 is to construct a supercontinuum light source interferometer with a high resolution (~0.33 µm), and a wide field-of-view. In Aim 2, test and validate the new system by examining in vitro agreement and variance with flat thickness standards and curved glass model eyes. Aim 3 will apply the new system to characterize the PCTF of human subjects with and without dry eye disease. The long-term impact of this research will improve our understanding of the mechanisms driving tear film dynamics to better understand mechanisms of disease or to development novel treatments that address mechanisms of tear film instability.

项目摘要 在人类中，珍贵的泪膜（PCTF）是复杂的生物流体涂层的薄层（〜3-5 µm） 眼表，可滋养和保护眼表并提供光滑的折射光学 视力的表面。在干眼症中，PCTF变得更薄，并迅速前进（蒸发） 到高渗透性，感染和眼表面欲望。曼联有超过3000万人 各州受到干眼症的影响，据估计，社会的经济燃烧将超过500亿美元。 干眼症仍然是诊断，监测和治疗的挑战，因为许多干眼测试是 进行不一致的行为，缺乏足够的可靠性或准确性，并且与 疾病。泪膜动力学（变薄和分裂）的临床测量本质上是主观的，通常是 没有有效性和可重复性。因此，高度可靠且 除了监测治疗的影响外，还需要精确诊断疾病。 在先前的工作中，我们发布了一个数学模型，以系统地分析反射的光 角膜表面。使用该模型，PCTF的厚度对角膜或角膜引起的噪声不敏感 光源。使用基于光纤的干扰系统验证了该模型。那的主要缺点 干涉测量系统在空间上限于角膜顶点处的单点（〜30 µm）。虽然 我们以前的其他研究表明，PCTF的分布在眼表面各不相同，并且 在大型实地视图中的这些属性的表征将为诊断和监视提供关键信息 干眼症，由于热的聚焦特性较差，目前的系统仅限于单点 光源。 SuperContinuum（SC）光源可以将当前系统升级到点扫描系统。 此外，拟议的SC干涉仪将通过定制目标使PCTF的宽大视野视图 镜片。镜头将根据我们先前的调查开发，该焦点专门为焦点场设计 在角膜表面成像。这种创新的干涉仪将达到前所未有的厚度灵敏度 （〜0.33 µm）的撕裂膜遍布人角膜。 AIM 1是构建超脑光源 具有高分辨率（〜0.33 µm）的干涉仪和广泛的视野。在AIM 2中，测试和验证新的 通过检查体外一致性和与平坦厚度标准品和弯曲玻璃模型眼睛的差异来进行系统。 AIM 3将应用新系统来表征有或没有干眼症的人类受试者的PCTF。 这项研究的长期影响将提高我们对驱动撕裂膜的机制的理解 动力学以更好地了解疾病的机制或开发针对解决的新型治疗方法 撕裂膜不稳定性的机制。