Correlating the microstructural thickness variations of the tear film lipid layer with clinical characteristics of dry eye with a novel optical method

用一种新颖的光学方法将泪膜脂质层的微观结构厚度变化与干眼的临床特征相关联

• 批准号: 10636304
• 负责人: Yuqiang Bai
• 金额: $ 9.38万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2023-10-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10636304
• 关键词: Address; Agreement; Air; Anterior; Area; Biological Markers; Characteristics; Clinical; Cornea; Desiccation; Development; Diagnosis; Disease; Dry Eye Syndromes; Environment; Exclusion; Eye; Film; Goals; Grant; Homeostasis; Human; Imaging Techniques; Inflammation; Lasers; Link; Lipids; Literature; Measurement; Measures; Methods; Microscopy; National Eye Institute; Optical Methods; Pattern; Phase; Play; Positioning Attribute; Predisposition; Research; Resolution; Role; Scanning; Severities; Source; Stress; Structure; Sum; Surface; Surface Tension; Symptoms; System; Techniques; Testing; Thick; Thinness; United States National Institutes of Health; Validation; Variant; Work; aqueous; diagnostic biomarker; evaporation; eye dryness; in vivo; interest; meter; novel; novel diagnostics; novel therapeutics; ocular surface; prevent; psychologic

Project Summary In the anterior eye, the precorneal tear film (PCTF) acts as the interface between the ocular surface and external environment and plays a critical role in maintaining ocular surface homeostasis. In dry eye disease (DED), the PCTF becomes thinner, and destabilizes (evaporates) rapidly leading to hyperosmolarity, inflammation, and ocular surface desiccation. In 2020, the National Eye Institute (NEI) released a Notice of Special Interest (NOSI) for the Anterior Segment Initiative (ASI), “Identification and Development of New Biomarkers and Effective Methods to Diagnose Dry Eye Disease.” The notice highlighted a critical need for biomarkers and methods to diagnose DED prior to the onset of symptoms. The overall goal of this proposal is to characterize microstructural thickness variations of the tear film lipid layer (TFLL) and their association with clinical characteristics of DED. TFLL, the outmost layer of PCTF, overlies the aqueous phase, and serves as the barrier against evaporative aqueous loss, and stabilize it by facilitating the spread of its aqueous compartment and reducing surface tension. However, the exact mechanism by which the TFLL retards tear evaporation and promotes PCTF stability remains poorly understood. For instance, while most would agree that a uniform and thicker TFLL would be more protective against evaporation, and therefore prevent DED, this relationship remains controversial in the literature; resolution of this controversy forms the basis of this proposal. Under a NIH/NEI grant in 2021(R21EY033029), we constructed a novel laser source point-scanning interferometer that enables the in vivo assessment of dynamics of PCTF and related structures of TFLL with unprecedented resolution and sensitivity. Using this powerful system, we propose to address critical yet previously unexplored and often inconsistent associations between TFLL and examination findings of PCTF. The central hypothesis of the proposed research is that thickness variations in the microstructure of TFLL are associated with clinical characteristics of DED. We will test this hypothesis in concurrent Specific Aims: Aim 1: Verify and quantify the inversely relationship between TFLL thickness and PCTF evaporation rate. We hypothesize that TFLL thickness is inversely proportional to PCTF evaporation, with “thin” regions of the TFLL allowing excessive loss of aqueous tears. Aim 2: Quantify the impact of TFLL thickness variations on PCTF instability. We hypothesize that steep stress gradients at the interface between “thin” and “thick” regions of the TFLL cause PCTF instability. Collectively, the proposed studies will introduce two new parameters to characterize the lipid layer microstructure and correlate them with PCTF evaporation and instability, which will be tested and validated with our novel high-resolution interferometric system. With further clinical validation, these parameters will allow for early, non-invasive assessment of DED and inform the development of new therapeutics to slow or prevent the development of DED.

项目摘要 在前眼中，先前的泪膜（PCTF）充当眼表和 外部环境和在维持眼表稳态中起着至关重要的作用。在干眼症中 （DED），PCTF变得更薄，不稳定（蒸发）迅速导致高渗透性， 炎症和眼表面干燥。 2020年，国家眼科研究所（NEI）发布了 前部倡议（ASI）的特殊兴趣（NOSI），“新的识别和发展 该通知突出了对干眼症的有效方法。 在症状发作之前，生物标志物和方法诊断为DED。该提议的总体目标是 表征泪膜脂质层（TFLL）的微观结构厚度变化及其与 DED的临床特征。 tfll是PCTF的最外层，覆盖了水相，并用作 防止蒸发水损失的障碍，并通过支撑其水舱的扩散来稳定它 并减少表面张力。但是，TFLL降低了撕裂蒸发的确切机制和 促进PCTF稳定性仍然很少了解。例如，虽然大多数人都同意， 更厚的TFLL将受到更大的保护，因此可以防止DED，这种关系仍然存在 文学中有争议；这一争议的解决构成了该提议的基础。在NIH/NEI下 赠款在2021年（R21EY033029），我们构建了一个新颖的激光源点扫描干涉仪，可实现 PCTF动力学和TFLL相关结构的体内评估，并以前所未有的分辨率和 灵敏度。使用这个强大的系统，我们建议解决关键但以前出乎意料的，并且经常 PCTF的TFLL与检查结果之间的关联不一致。中心假设 拟议的研究是，TFLL微观结构的厚度变化与临床有关 ded的特征。我们将以并发的特定目的来检验该假设：目标1：验证和量化 TFLL厚度与PCTF蒸发率之间的成反关系。我们假设TFLL厚度 与PCTF蒸发成反比，TFLL的“薄”区域允许过度损失水。 眼泪。目标2：量化TFLL厚度变化对PCTF不稳定性的影响。我们假设钢 TFLL的“薄”区域和“厚”区域之间的应力梯度会导致PCTF不稳定性。 总的来说，拟议的研究将引入两个新参数以表征脂质层 微观结构并将它们与PCTF蒸发和不稳定性相关联，将通过测试和验证 我们新颖的高分辨率干涉系统。通过进一步的临床验证，这些参数将允许 早期，对DED的非侵入性评估，并告知开发新的治疗剂，以减慢或防止 DED的发展。