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，角膜前泪膜（PCTF）充当眼表和角膜基质之间的界面。 眼内环境是眼表的重要组成部分，在维持眼表稳态中起着关键作用。干眼病 (DED)PCTF变得更薄，并迅速不稳定（蒸发），导致高渗， 炎症和眼表干燥。2020年，国家眼科研究所（NEI）发布了一项通知， 特别兴趣（NOSI）的前节倡议（ASI），“识别和开发新的 生物标记物和有效的方法来诊断干眼症。该通知强调，迫切需要 在症状发作之前诊断DED的生物标志物和方法。本提案的总体目标是 表征泪膜脂质层（TFLL）的微结构厚度变化及其与 DED的临床特征TFLL是PCTF的最外层，覆盖在水相上，并用作 屏障防止水分蒸发损失，并通过促进其水室的扩散来稳定水分 并降低表面张力。然而，TFLL延迟泪液蒸发和分泌的确切机制是不确定的。 促进PCTF的稳定性仍然知之甚少。例如，虽然大多数人会同意， 更厚的TFLL将更好地防止蒸发，从而防止DED，这种关系仍然存在 在文献中有争议;解决这一争议形成了这一建议的基础。根据NIH/NEI 在2021年获得的一项资助（R21 EY 033029）中，我们构建了一种新型激光源点扫描干涉仪， 以前所未有的分辨率对PCTF和TFLL相关结构的动力学进行体内评估， 灵敏度使用这个强大的系统，我们建议解决关键的，但以前未探索过，往往 TFLL与PCTF检查结果之间的相关性不一致。的中心假设 建议的研究是TFLL微观结构的厚度变化与临床相关， DED的特点我们将在同时进行的具体目标中检验这一假设：目标1：验证和量化 TFLL厚度与PCTF蒸发速率成反比关系。我们假设TFLL厚度 与PCTF蒸发成反比，TFLL的“薄”区域允许水的过度损失。 眼泪目标2：量化TFLL厚度变化对PCTF不稳定性的影响。我们假设陡峭的 在TFLL的“薄”和“厚”区域之间的界面处的应力梯度引起PCTF不稳定性。 总的来说，拟议的研究将引入两个新的参数来表征脂质层 微观结构，并将它们与PCTF蒸发和不稳定性相关联，这将通过 我们新的高分辨率干涉仪系统通过进一步的临床验证，这些参数将允许 DED的早期，非侵入性评估，并为新疗法的开发提供信息，以减缓或预防 发展DED。