Interferometric Studies of the Fluid Dynamics of the Tear Film

描述(申请人提供)：这项研究计划的长期目标是分析眨眼间隙泪膜变薄所涉及的泪液动力学和特性，以及由此导致的眉板腺功能障碍(MGD)和其他干眼情况下的眼表损害。我们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。泪液变薄可能是由于泪液蒸发，也可能是由于泪液沿角膜表面的“切向流”发散。蒸发变薄会导致局部渗透压升高，从而导致高渗透压应激对眼表的损害。发散的切向血流可通过在不增加渗透压的情况下产生裂解(干斑)而导致眼表损伤。在这项研究中，将研究蒸发和发散切向流的相对贡献，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，因此也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量。蒸发速率和泪液稀释率将在低湿度和高湿度以及低和高气流速度的条件下进行测量。荧光“猝灭”现象(高浓度荧光素的荧光效率降低)也将被用来研究蒸发的影响。如果泪膜变薄是由于蒸发而不是切向流动，单位面积的荧光素应该保持不变，低浓度的荧光素荧光变化不大；但对于高浓度，随着泪膜变薄和浓度的增加，猝灭会导致荧光显著下降。利用这些原理，荧光测量将被用来研究蒸发如何影响泪液稀释率和荧光素分解时间。蒸发受到泪膜脂层中水分扩散的限制。为了研究泪液稀释率和脂肪厚度之间的关系，我们将使用我们实验室独有的脂肪厚度方法同时测量它们。此外，将获得脂层的高分辨率图像，以提供关于脂层的空间变异性及其对泪膜变薄的贡献的信息。还将研究荧光(分解)图像与同时脂类干扰图像的关系。一个有效的脂类蒸发屏障被认为需要足够的磷脂在极性脂类和水层之间形成良好的界面，因此将收集眉毛类脂样本来分析磷脂浓度。在这些研究中，MGD患者将在泪液稀释率、脂质厚度及其空间变异性以及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确定导致MGD眼表损伤的泪膜和外部因素的特征。公共卫生意义：干眼症是一种常见的视觉障碍，人们对此知之甚少。本项目将研究沿角膜表面的蒸发和泪液流动在导致这种综合征的眼表损伤中的作用。此外，还将研究干眼可能缺乏的脂层的特征。

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.