Dry eye affects six to seven million people in the United States alone. Meibomian gland disease is even more frequent, particularly in older patients. Clinically, patients may express a combination of two forms of dry eye, aqueous deficient and evaporative. Both mechanisms of development of dry eye share the common feature of instability of the tear film with rapid tear break-up time, suggesting there may be a shared structural abnormality of the tear film that is responsible for the instability. Disruption of the normal lipid-protein-aqueous structure of the tear film is probably this mechanical event. Understanding the normal lipid-protein-aqueous structure of the tear film is therefore critical to determine the etiology of the tear film instability due to dry eye disease and meibomian gland disease. Recent advances in spectroscopic technology make it feasible to measure simultaneously and, in individuals without pooling or serial collection, the pool of meibomian lipid on the lid margins, lipids in the meibomian glands, and the lacrimal lipids, many of which are bound to lipocalin or complexed with other proteins found in tears. We propose to use the latest spectroscopic innovations to determine the relationships among tear lipid structure, interactions, rate of tear evaporation, dry eye symptoms and tear film instability. Advances in clinical diagnosis make it possible to group patients into a number of categories related to production-deficient and evaporative forms of dry eye and monitor their tear film stability. Because of our expertise in spectroscopic techniques, knowledge of lipid structure, and access to human tear lipid samples in normal subjects and those with dry eye disease, coupled with our clinical expertise, we are in a uniquely favorable position to identify the nature of the disturbance of the lipid-protein-aqueous interaction of the tear film that could lead to improved therapy.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY017094-05
Application #
7796598
Study Section
Anterior Eye Disease Study Section (AED)
Program Officer
Shen, Grace L
Project Start
2006-04-01
Project End
2011-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
5
Fiscal Year
2010
Total Cost
$248,974
Indirect Cost
Name
University of Louisville
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292
Foulks, Gary N; Borchman, Douglas; Yappert, Marta et al. (2013) Topical azithromycin and oral doxycycline therapy of meibomian gland dysfunction: a comparative clinical and spectroscopic pilot study. Cornea 32:44-53
Faheem, Samad; Kim, Sung-Hye; Nguyen, Jonathan et al. (2012) Wax-tear and meibum protein, wax-ýý-carotene interactions inýývitro using infrared spectroscopy. Exp Eye Res 100:32-9
Borchman, Douglas; Foulks, Gary N; Yappert, Marta C et al. (2012) Differences in human meibum lipid composition with meibomian gland dysfunction using NMR and principal component analysis. Invest Ophthalmol Vis Sci 53:337-47
Borchman, Douglas; Foulks, Gary N; Yappert, Marta C et al. (2012) Changes in human meibum lipid composition with age using nuclear magnetic resonance spectroscopy. Invest Ophthalmol Vis Sci 53:475-82
Ashraf, Zara; Pasha, Uzma; Greenstone, Victoria et al. (2011) Quantification of human sebum on skin and human meibum on the eye lid margin using Sebutapeýý, spectroscopy and chemical analysis. Curr Eye Res 36:553-62
Shrestha, Rashmi K; Borchman, Douglas; Foulks, Gary N et al. (2011) Analysis of the composition of lipid in human meibum from normal infants, children, adolescents, adults, and adults with meibomian gland dysfunction using ¹H-NMR spectroscopy. Invest Ophthalmol Vis Sci 52:7350-8
Borchman, Douglas; Foulks, Gary N; Yappert, Marta C et al. (2011) Human meibum lipid conformation and thermodynamic changes with meibomian-gland dysfunction. Invest Ophthalmol Vis Sci 52:3805-17
Foulks, Gary N; Borchman, Douglas; Yappert, Marta et al. (2010) Topical azithromycin therapy for meibomian gland dysfunction: clinical response and lipid alterations. Cornea 29:781-8
Borchman, Douglas; Yappert, Marta C; Foulks, Gary N (2010) Changes in human meibum lipid with meibomian gland dysfunction using principal component analysis. Exp Eye Res 91:246-56
Borchman, Douglas; Foulks, Gary N; Yappert, Marta C et al. (2010) Physical changes in human meibum with age as measured by infrared spectroscopy. Ophthalmic Res 44:34-42

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