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

项目摘要 在人类中，角膜前泪膜(PCTF)是一层薄(~3-5微米)的复杂生物流体，覆盖在 眼表，用于滋养和保护眼表，并提供平滑的屈光 为了视觉而浮出水面。在干眼症中，PCTF变薄，并迅速失去稳定(蒸发) 高渗透压、炎症和眼表干燥症。美国有3000多万人 各州受到干眼病的影响，给社会造成的经济负担估计超过500亿美元。 干眼病仍然是诊断、监测和治疗的一个挑战，因为许多干眼测试都是 行为不一致，缺乏足够的可靠性或准确性，与 疾病。泪膜动力学的临床测量(变薄和破裂)本质上是主观的，通常 缺乏效度和可重复性。因此，新的、非侵入性的光学测量具有高度可靠和 除了监测治疗的影响外，还需要准确的数据来更好地诊断疾病。 在之前的工作中，我们发布了一个数学模型来系统地分析从 角膜表面。在此模型中，PCTF的厚度对来自角膜或 光源。该模型使用基于光纤的干涉测量系统进行了验证。这样做的主要缺点是 干涉测量系统在空间上仅限于角膜顶端的一个点(~30微米)。虽然 我们以前的其他研究表明，PCTF在眼表面的分布是不同的，并且 在大型Fieldview中对这些属性进行表征将为诊断和监控提供关键信息 干眼症，由于热聚焦性能差，目前的系统仅限于单点 光源。超连续谱(SC)光源可以将当前系统升级为点扫描系统。 此外，拟议的SC干涉仪将能够通过定制的物镜获得PCTF的大视场 镜头。该透镜将在我们之前的研究基础上开发，并专门为 在角膜表面成像。这款创新的干涉仪将达到前所未有的厚度灵敏度 (约0.33微米)的泪膜穿过人的角膜。目标1是构建一个超连续谱光源 干涉仪具有高分辨率(~0.33微米)和大视场。在目标2中，测试并验证新的 系统通过与平板厚度标准和曲面玻璃模型眼的体外一致性和差异来检验。 目标3将应用新的系统来表征患有和不患有干眼病的受试者的PCTF。 这项研究的长期影响将提高我们对泪膜驱动机制的理解 动力学以更好地了解疾病的机制或开发新的治疗方法 泪膜不稳定的机制。

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.