Glaucoma is one of the leading causes of treatable blindness in the world. However, the manner and rate of disease progression varies markedly between patients, and so predicting future progression and hence the prognosis for an individual is challenging. Much of the previous work in this field has concentrated on determining whether a patient with certain risk factors will develop glaucoma. There has been less attention paid to the likelihood that a patient will suffer significant loss of vision as a result of their glaucoma, or how soon vision loss may manifest. The overall goal of this project is to improve the ability to predict the future course of an individual's disease, and so enable the clinician to adapt their management strategy accordingly. Better knowledge of glaucomatous pathophysiology will also be gained, with meaningful implications for developing new methods of diagnosis and treatment strategies. The primary tool used in this project will be longitudinal data collected biannually from over 250 subjects with early or suspected glaucoma, and 50 normal subjects. For the majority of the glaucoma subjects, up to ten years of prior information is available and will also be used. The first part of the project aims to improve understanding of the structure-function relationship in glaucoma. Three non-competing hypotheses will be tested that seek to explain the weak observed correlation between functional change (to the patient's visual field) and structural change (to the optic nerve head and/or retinal nerve fiber layer). The first experiment will determine the true underlying correlation after taking into account the variability inherent in the testing procedures. The second experiment will compare changes to the optic nerve head surface topography against subsurface changes and changes to the retinal nerve fiber layer, to determine whether there is temporal dissociation caused by surface change not driven by a loss of neural tissue. The third experiment will use a sampling-limited test of retinal ganglion cell density, to determine whether there is temporal dissociation caused by dysfunctional retinal ganglion cells that are still present in the retina but have altered response characteristics. Results from these three experiments will provide new insights into the disease process, with possible implications for future development of testing and treatment strategies. The second part of the project aims to use this new information and advanced analysis techniques (including regression trees) to better predict the future rate of functional change on a per-eye basis. First, subsequent change will be predicted based on test results at one time point. Second, improved predictions will be made when a series of test results are available. The fundamental motivation for this project is to enable a clinician to prevent severe visual disability or blindness in an ocular hypertensive or glaucoma patient, by identifying a rapid progression rate or a high likelihood for rapid progression at the earliest stages of the disease.

Public Health Relevance

This project seeks to predict the future rate of vision loss in patients with glaucoma, both earlier and more accurately than is currently possible. If a patient is at risk of rapid disease progression, possibly resulting in eventual visual disability or blindness, this may warrant more frequent monitoring and/or more aggressive therapy. The project will also provide new information about glaucomatous pathophysiology, which can be used to direct future developments in diagnostic testing and treatment strategies.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY019674-04
Application #
8321571
Study Section
Special Emphasis Panel (ZEY1-VSN (01))
Program Officer
Everett, Donald F
Project Start
2009-09-30
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$363,528
Indirect Cost
$125,928
Name
Emanuel Hospital and Health Center
Department
Type
DUNS #
050973098
City
Portland
State
OR
Country
United States
Zip Code
97232
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Ren, Ruojin; Yang, Hongli; Gardiner, Stuart K et al. (2014) Anterior lamina cribrosa surface depth, age, and visual field sensitivity in the Portland Progression Project. Invest Ophthalmol Vis Sci 55:1531-9
Deng, Lisha; Demirel, Shaban; Gardiner, Stuart K (2014) Reducing variability in visual field assessment for glaucoma through filtering that combines structural and functional information. Invest Ophthalmol Vis Sci 55:4593-602
He, Lin; Ren, Ruojin; Yang, Hongli et al. (2014) Anatomic vs. acquired image frame discordance in spectral domain optical coherence tomography minimum rim measurements. PLoS One 9:e92225
Pathak, Manoj; Demirel, Shaban; Gardiner, Stuart K (2013) Nonlinear, multilevel mixed-effects approach for modeling longitudinal standard automated perimetry data in glaucoma. Invest Ophthalmol Vis Sci 54:5505-13
Gardiner, Stuart K; Johnson, Chris A; Demirel, Shaban (2011) Cup size predicts subsequent functional change in early glaucoma. Optom Vis Sci 88:1470-6
Gardiner, Stuart K; Demirel, Shaban; Johnson, Chris A et al. (2011) Assessment of linear-scale indices for perimetry in terms of progression in early glaucoma. Vision Res 51:1801-10
Gardiner, Stuart K; Demirel, Shaban; Johnson, Chris A (2011) Perimetric indices as predictors of future glaucomatous functional change. Optom Vis Sci 88:56-62