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.

项目概要 在前眼中，角膜前泪膜（PCTF）充当眼表面和眼球之间的界面。 外部环境在维持干眼病中的眼表稳态中起着至关重要的作用。 (DED)，PCTF 变薄，并迅速不稳定（蒸发），导致高渗透压， 2020 年，国家眼科研究所 (NEI) 发布了一份通知： 前段倡议 (ASI) 的特别兴趣 (NOSI)，“新的识别和开发” 该通知强调了诊断干眼病的生物标志物和有效方法。” 在症状出现之前诊断 DED 的生物标志物和方法 该提案的总体目标是 表征泪膜脂质层 (TFLL) 的微观结构厚度变化及其与 DED 的临床特征是 PCTF 的最外层，覆盖水相，并充当水相。 防止水分蒸发损失的屏障，并通过促进其水室的扩散来稳定它 然而，TFLL 延迟泪液蒸发的确切机制和 例如，对于促进 PCTF 稳定性仍知之甚少，尽管大多数人都同意统一和统一。 较厚的 TFLL 可以更好地防止蒸发，从而防止 DED，这种关系仍然存在 在文献中存在争议；这一争议的解决构成了该提案的基础。 2021年的资助（R21EY033029），我们构建了一种新型激光源点扫描干涉仪，使得 以前所未有的分辨率对 PCTF 和 TFLL 相关结构的动态进行体内评估 使用这个强大的系统，我们建议解决以前未探索过且经常发生的关键问题。 TFLL 与 PCTF 检查结果之间的不一致关联 的中心假设。 拟议的研究表明 TFLL 微观结构的厚度变化与临床相关 我们将在并发的具体目标中检验这一假设： 目标 1：验证并量化 TFLL 厚度与 PCTF 蒸发速率呈反比关系。 与 PCTF 蒸发成反比，TFLL 的“薄”区域允许水的过度损失 目标 2：量化 TFLL 厚度变化对 PCTF 不稳定性的影响。 TFLL“薄”和“厚”区域之间界面处的应力梯度导致 PCTF 不稳定。 总的来说，拟议的研究将引入两个新参数来表征脂质层 微观结构并将它们与 PCTF 蒸发和不稳定性相关联，这将通过以下方法进行测试和验证 我们的新型高分辨率干涉测量系统经过进一步的临床验证，这些参数将允许 对 DED 进行早期、非侵入性评估，并为新疗法的开发提供信息，以减缓或预防 DED DED 的发展。