Tear dynamics: Tear osmolarity and reflex features of the lacrimal functional unit

The focus of this thesis is tear dynamics and the regulation of tear secretion by the Lacrimal Functional Unit (LFU), a collection of functions that control tear secretion and maintain a healthy ocular surface. Tear secretion was assessed with the Schirmer test and tear osmolarity (tOsm), in standardised environmental conditions achieved using a controlled environment chamber (CEC). The experiments involved normal and dry eye disease (DED) subjects, including Sjögren Syndrome DED. A novel approach to sheathing the Schirmer strip was tested for the first time in a regulated range of relative humidities achieved in the CEC. This was designed to highlight an artefact of measurement, and free the test from its dependence on ambient conditions. A period of evaporative suppression, achieved innovatively by eye closure, was shown to drive tOsm down, in normal and DED subjects, to a basal level that fell within the range of plasma osmolarity. This basal tear osmolarity value could be used as a non-invasive measure of systemic dehydration, particularly of use in a care home setting and as a reference against which to gauge the severity of DED in an individual. Using the sheathed Schirmer strip the existence of ‗cross-connections‘ in humans was investigated for the first time using unilateral anaesthesia in an attempt to answer the question of whether afferent corneal inputs from one eye may have some influence on the lacrimal output of the fellow eye. Previously only studies involving animals had reported positive findings in this area. The relative contributions of each eye to the reflex tear response are relevant in unilateral trigeminal sensory loss cases since sensory input from the healthy eye could reinforce tear secretion of the affected fellow eye. Lastly, an experiment was designed to strengthen our understanding of the mechanism of the LFU in providing a compensatory response in desiccating conditions. This approach differed from previous studies as it included both normal and DED subjects and involved creating a sensory blockade using topical anaesthesia to increase the stress level experienced by the LFU.