Development of a supercontinuum laser source interferometer with sub-micron resolution to understand tear film structure and function in dry eye disease

项目总结

Project Summary In humans, the precorneal tear film (PCTF) is a thin layer (~3-5 µm) of a complex biological fluid coating the ocular surface, that serves to nourish and protect the ocular surface and provide a smooth refractive optical surface for vision. In dry eye disease, the PCTF becomes thinner, and destabilizes (evaporates) rapidly leading to hyperosmolarity, inflammation, and ocular surface desiccation. More than 30 million people in the United States are impacted by dry eye disease and the economic burden to society is estimated to be over $50 billion. Dry eye disease continues to be a challenge to diagnose, monitor, and treat because as many dry eye tests are conducted inconsistently, lack sufficient reliability or accuracy, and do not correlate with symptoms of the disease. Clinical measures of tear film dynamics (thinning and breakup) are subjective in nature and generally lack validity and repeatability. Therefore, novel, non-invasive optical measures that are highly reliable and accurate are needed to better diagnose the disease, in addition to monitor the impact of treatments. In prior work, we published a mathematical model to systematically analyze the light reflected back from the cornea surface. With this model, the thickness of the PCTF is insensitive to the noise arising from the cornea or light source. The model was validated using a fiber-based interferometry system. The main drawback of that interferometry system is that it is spatially limited to a single point at the apex of the cornea (~30 µm). Although our other previous studies revealed that the distribution of PCTF varied over the ocular surface, and the characterization of these attributes in a large fieldview will provide critical information to diagnose and monitor dry eye disease, the current system was limited to a single point due to the poor focusing property of the thermal light source. A supercontinuum (SC) light source can upgrade the current system to a point-scanning system. Furthermore, the proposed SC interferometer will enable a wide field view of the PCTF by a customized objective lens. The lens will be developed based on our previous investigation, with a focal field specifically designed for imaging over the cornea surface. This innovative interferometer will achieve unprecedented thickness sensitivity (~0.33 µm) of the tear film across the human cornea. Aim 1 is to construct a supercontinuum light source interferometer with a high resolution (~0.33 µm), and a wide field-of-view. In Aim 2, test and validate the new system by examining in vitro agreement and variance with flat thickness standards and curved glass model eyes. Aim 3 will apply the new system to characterize the PCTF of human subjects with and without dry eye disease. The long-term impact of this research will improve our understanding of the mechanisms driving tear film dynamics to better understand mechanisms of disease or to development novel treatments that address mechanisms of tear film instability.