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.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Study Section
Anterior Eye Disease Study Section (AED)
Program Officer
Mckie, George Ann
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Ohio State University
Schools of Optometry/Ophthalmol
United States
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King-Smith, P Ewen; Kimball, Samuel H; Nichols, Jason J (2014) Tear film interferometry and corneal surface roughness. Invest Ophthalmol Vis Sci 55:2614-8
Braun, Richard J; Gewecke, Nicholas R; Begley, Carolyn G et al. (2014) A model for tear film thinning with osmolarity and fluorescein. Invest Ophthalmol Vis Sci 55:1133-42
King-Smith, P Ewen; Ramamoorthy, Padmapriya; Braun, Richard J et al. (2013) Tear film images and breakup analyzed using fluorescent quenching. Invest Ophthalmol Vis Sci 54:6003-11
King-Smith, P Ewen; Bailey, Melissa D; Braun, Richard J (2013) Four characteristics and a model of an effective tear film lipid layer (TFLL). Ocul Surf 11:236-45
King-Smith, P Ewen; Reuter, Kathleen S; Braun, Richard J et al. (2013) Tear film breakup and structure studied by simultaneous video recording of fluorescence and tear film lipid layer images. Invest Ophthalmol Vis Sci 54:4900-9
Nichols, Jason J; Bickle, Katherine M; Zink, Richard C et al. (2012) Safety and efficacy of topical azithromycin ophthalmic solution 1.0% in the treatment of contact lens-related dry eye. Eye Contact Lens 38:73-9
Schaumberg, Debra A; Nichols, Jason J; Papas, Eric B et al. (2011) The international workshop on meibomian gland dysfunction: report of the subcommittee on the epidemiology of, and associated risk factors for, MGD. Invest Ophthalmol Vis Sci 52:1994-2005
Dougherty, Bradley E; Nichols, Jason J; Nichols, Kelly K (2011) Rasch analysis of the Ocular Surface Disease Index (OSDI). Invest Ophthalmol Vis Sci 52:8630-5
Asbell, Penny A; Stapleton, Fiona J; Wickstrom, Kerstin et al. (2011) The international workshop on meibomian gland dysfunction: report of the clinical trials subcommittee. Invest Ophthalmol Vis Sci 52:2065-85
Geerling, Gerd; Tauber, Joseph; Baudouin, Christophe et al. (2011) The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment of meibomian gland dysfunction. Invest Ophthalmol Vis Sci 52:2050-64

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