Dry eye is a common condition, but its etiology remains unclear. The symptoms of dry eye include ocular irritation and blurry vision. However, there are often few clinical signs of tissue damage to explain the symptoms. In recent years, improper wetting of the ocular surface, also known as tear instability or breakup, has been recognized as a core mechanism of dry eye. However, little is known about this phenomenon. Thus, it is the aim of this thesis to increase the understanding of the mechanism of tear breakup and its impact on dry eye symptoms.

The specific aim of Part 1 was to employ image analysis techniques to elucidate the possible mechanisms involved in tear breakup and their significance in dry eye. Areas of breakup were quantified by customized MATLAB programs to determine their spatial localization, temporal development, and repeatability by location. The rate of growth of areas of breakup was higher in dry eye and was more likely to be located over the central cornea.

The specific aim of Part 2 was to test the hypothesis that tear breakup results in transient high hyperosmolar conditions in the local area, which stimulates underlying corneal nerves and stresses the epithelium, and further leads to burning and stinging sensations and ocular inflammation. Psychophysical studies established a human threshold of 450mOsm/Kg for corneal detection of burning and stinging due to hyperosmolarity with an almost linear increase in discomfort above that level. Cell biology experiments showed that the pro-inflammatory signaling pathway (MAPK) was activated by transient hyperosmotic shock of 600mOsm/Kg in corneal epithelial cells. Taking together, these results suggest that the hyperosmolarity within areas of tear breakup may reach as high as 600mOsm/Kg.

The specific aim of Part 3 was to explore the optical and psychophysical impacts of tear breakup on vision in contact lens wearers. A Shack-Hartmann aberrometer was customized to simultaneously measure objective optical quality (wavefront), subjective visual performance (contrast sensitivity), and surface tear quality (retro-illumination). The results indicated that contrast sensitivity loss was highly correlated with changes in metrics of dioptric and catoptric optical quality during tear film breakup.