Interferometric Studies of the Fluid Dynamics of the Tear Film

描述（由申请人提供）：本研究项目的长期目标是分析眨眼之间泪膜变薄的泪液动力学和特征，以及睑板腺功能障碍（MGD）和其他干眼症导致的眼表损伤。我们的实验室开发了一种独特的方法来测量泪膜厚度和眨眼之间的泪液稀释率。泪液变薄可能是由蒸发引起的，也可能是泪液沿角膜表面发散的“切向流”引起的。蒸发变薄会引起局部渗透压升高，导致眼表高渗透压损伤。发散的切向流会在渗透压不增加的情况下产生破裂（干斑），从而引起眼表损伤。在这项研究中，蒸发和发散切向流的相对贡献将被研究，以评估高渗透压和干斑形成在眼表损伤中的作用。由于初步研究表明蒸发通常比发散切向流更重要，因此还将研究控制蒸发速率的外部因素。将建造一个“受控环境护目镜”来控制角膜上的湿度和空气流速。在低湿度和高湿度、低气流速度和高气流速度条件下测量蒸发速率和撕裂细化速率。荧光“猝灭”现象（在高浓度荧光素下荧光效率降低）也将用于研究蒸发的影响。如果泪膜变薄是由于蒸发而不是切向流动，则单位面积上荧光素的量应保持不变，并且在低浓度荧光素时，荧光素的变化应该很小；然而，对于高浓度，猝灭会导致荧光明显下降，因为泪膜变薄，浓度增加。利用这些原理，荧光测量将用于研究蒸发如何有助于撕裂稀释率和荧光素分解时间。蒸发受到水通过泪膜脂质层扩散的限制。为了研究撕裂变薄率和脂质厚度之间的关系，我们将使用我们实验室独有的脂质厚度方法同时测量它们。此外，将获得脂质层的高分辨率图像，以提供有关脂质层的空间变异性及其对泪膜变薄的贡献的信息。荧光（破裂）图像与同时发生的脂质干扰图像的关系也将被研究。有效的脂质蒸发屏障被认为需要足够的磷脂在极性脂质和水层之间形成良好的界面，因此将收集睑板脂质样品来分析磷脂浓度。在这些研究中，MGD患者将在撕裂变薄率、脂质厚度及其空间变异性和磷脂浓度方面与正常人进行比较。因此，这些研究的最终目的是帮助表征泪膜和导致MGD眼表损伤的外部因素。公共卫生相关性：干眼综合征是一种常见的视力障碍，对其了解甚少。本项目将探讨沿角膜表面蒸发和泪液流在引起该综合征的眼表损伤中的作用。此外，还将探讨干眼症中可能缺乏的脂质层的特征。

DESCRIPTION (provided by applicant): The long term goal of this research program is to analyze the tear dynamics and characteristics which are involved in tear film thinning between blinks, and the consequent ocular surface damage in meibomian gland dysfunction (MGD) and other dry eye conditions. Our laboratory has developed a unique method for measuring tear film thickness and tear thinning rate between blinks. Tear thinning could be caused either by evaporation or by divergent "tangential flow" of tears along the corneal surface. Evaporative thinning would cause an increase in local osmolarity, leading to ocular surface damage from hyperosmolar stress. Divergent tangential flow could cause ocular surface damage by generating breakup (dry spots) without increase in osmolarity. In this study, the relative contributions of evaporation and divergent tangential flow will be studied to evaluate the role of hyperosmolarity and dry spot formation in ocular surface damage. Because preliminary studies indicate that evaporation is generally more important than divergent tangential flow, external factors controlling evaporation rate will also be investigated. A "controlled environment goggle" will be constructed to control humidity and air flow rate over the cornea. Both evaporation rate and tear thinning rate will be measured in conditions of low and high humidity, and of low and high air flow speed. The phenomenon of fluorescence "quenching" (reduction of fluorescent efficiency at high concentrations of fluorescein) will also be used to study the effects of evaporation. If tear film thinning is due to evaporation rather than tangential flow, the amount of fluorescein per unit area should remain constant and there should be little change in fluorescence for low concentrations of fluorescein; for high concentrations, however, quenching will cause a marked fall in fluorescence as the tear film thins and concentration increases. Using these principles, fluorescence measurements will be used to study how evaporation contributes to tear thinning rate and to fluorescein breakup times. Evaporation is limited by diffusion of water through the lipid layer of the tear film. To study the relation between tear thinning rate and lipid thickness, they will be measured simultaneously, using a lipid thickness method unique to our laboratory. Additionally, high resolution images of the lipid layer will be obtained to give information about the spatial variability of the lipid layer, and its contribution to tear film thinning. The relation of fluorescent (breakup) images to simultaneous lipid interference images will also be studied. An effective lipid barrier to evaporation is thought to require enough phospholipid to form a good interface between polar lipids and the aqueous layer, so meibomian lipid samples will be collected to analyze phospholipid concentration. In these studies, patients with MGD will be compared to normals in terms of tear thinning rate, lipid thickness and its spatial variability, and phospholipid concentration. An ultimate aim of these studies is therefore to help characterize tear film and external factors which cause ocular surface damage in MGD. PUBLIC HEALTH RELEVANCE: Dry Eye Syndrome is a common visual disorder which is poorly understood. This project will investigate the role of both evaporation and tear flow along the corneal surface in causing the ocular surface damage in this syndrome. Additionally, the characteristics of the lipid layer which may be deficient in Dry Eye will be investigated.