Project Summary (no changes are expected to the Project Summary as a result of
this change of institutions)
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.
