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

点击翻译按钮获取中文摘要

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.