Primary open-angle glaucoma (POAG) is an ocular disease characterized by progressive optic nerve damage, visual field loss and in many cases, elevation of intraocular pressure (IOP). Therapeutically lowering IOP confers protection against progression of POAG, and is the only known treatment for POAG. But simply lowering IOP is not always enough, and glaucomatous progression and blindness are not uncommon in patients receiving IOP-lowering treatment for glaucoma. IOP is known to fluctuate over time, and large fluctuations of IOP in treated glaucomatous eyes have recently been associated with progression despite mean IOP levels that appear to be therapeutically adequate. Thus, IOP variability is an important parameter to assess. The current model for IOP variability is single-day diurnal IOP variability. Our knowledge of diurnal IOP behavior is based on many single-day 24-hour (or less) diurnal IOP assessments in normal and glaucomatous eyes. Based on these one-day-in-time measurements, it is assumed that this IOP rhythm is symmetric between fellow eyes of individuals and remains a constant rhythm from day to day. This proposal challenges that dogma. Based upon our own preliminary studies and a very few studies which suggest that diurnal IOP rhythms change in patients over time, we hypothesize that IOP variabilityis a chaotic event over time in both normal and glaucomatous eyes, and that knowing the diurnal IOP rhythm of a given eye on a given day does not permit prediction of the diurnal rhythm on any other day. Disproving the existence of a regular and sustained diurnal IOP rhythm would force a paradigm shift toward more long-term indices of IOP variability. By collecting diurnal IOP measurements at baseline and 1 day, 1week, 1 month, six months, and one year later, we can achieve our specific aims to characterize the short- (days), intermediate- (weeks to months), and long-term (year) diurnal variability of intraocular pressure in normal and glaucomatous eyes. We hypothesize that repeated diumal measurements of intraocular pressure in normal and glaucomatous eyes will demonstrate significant variability in the diurnal IOP rhythms between patients, between fellow eyes, and within patients and eyes over time.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Small Research Grants (R03)
Project #
5R03EY015682-03
Application #
7355548
Study Section
Special Emphasis Panel (ZEY1-VSN (01))
Program Officer
Agarwal, Neeraj
Project Start
2006-02-02
Project End
2010-01-31
Budget Start
2008-02-01
Budget End
2010-01-31
Support Year
3
Fiscal Year
2008
Total Cost
$119,899
Indirect Cost
Name
West Virginia University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
191510239
City
Morgantown
State
WV
Country
United States
Zip Code
26506
Bailey, Jessica N Cooke; Gharahkhani, Puya; Kang, Jae H et al. (2018) Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets. Invest Ophthalmol Vis Sci 59:629-636
Khawaja, Anthony P; Cooke Bailey, Jessica N; Wareham, Nicholas J et al. (2018) Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma. Nat Genet 50:778-782
Realini, Tony; Gurka, Matthew J; Weinreb, Robert N (2017) Reproducibility of Central Corneal Thickness Measurements in Healthy and Glaucomatous Eyes. J Glaucoma 26:787-791
Pasquale, Louis R (2016) Vascular and autonomic dysregulation in primary open-angle glaucoma. Curr Opin Ophthalmol 27:94-101
Li, Zheng; Allingham, R Rand; Nakano, Masakazu et al. (2015) A common variant near TGFBR3 is associated with primary open angle glaucoma. Hum Mol Genet 24:3880-92
Liu, Yutao; Garrett, Melanie E; Yaspan, Brian L et al. (2014) DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma. Invest Ophthalmol Vis Sci 55:8251-8
Bailey, Jessica N Cooke; Yaspan, Brian L; Pasquale, Louis R et al. (2014) Hypothesis-independent pathway analysis implicates GABA and acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma. Hum Genet 133:1319-30
Ozel, A Bilge; Moroi, Sayoko E; Reed, David M et al. (2014) Genome-wide association study and meta-analysis of intraocular pressure. Hum Genet 133:41-57
Kang, J H; Loomis, S J; Yaspan, B L et al. (2014) Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma. Eye (Lond) 28:662-71
Springelkamp, Henriët; Höhn, René; Mishra, Aniket et al. (2014) Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. Nat Commun 5:4883

Showing the most recent 10 out of 20 publications