Glaucoma is a leading cause of blindness and visual morbidity. Because the disease causes irreversible damage to neural tissue it is of upmost importance to identify glaucoma and its progression at the earliest possible stages. Through advancements in the use of optical coherence tomography (OCT) and other technologies, the long-term goal of this research project is to precisely and accurately detect ocular structural and functional changes associated with glaucoma and to identify eyes with glaucoma that are at risk for future disease progression. This is accomplished by consolidating our long-term data acquired from various generations of OCT technology over the last 19 years. By using innovative methods for image quality improvement along with signal morphing, it is now possible to reliably bridge data acquired by the different generations and manufacturers of OCT, creating the longest-term cohort of longitudinal OCT measurements of the retina and optic nerve head regions. Advanced retinal segmentation software will be applied enabling detailed discrimination of all retinal layers even in the presence of ocular co-morbidity coincident with glaucoma (a previous exclusion criteria), allowing maximal use of subject and patient data. Using this cohort, two methods will be uniquely applied for determining the long-term relationship between structure and function: Continuous-time hidden Markov model and Latent differential equation models. This would enhance understanding of the disease process and allow determination of the best methods to identify disease and its progression at various stages. We will utilize advanced innovative imaging technologies and methods to accurately and precisely detect evidence of early structural changes: Swept-source OCT, Adaptive-optics OCT and Polarization-sensitive OCT. These technologies will be used to image the retina, sclera and optic nerve head providing enhanced information of the lamina cribrosa and birefringence properties. Scans will be also acquired during and following provocative acute IOP elevation testing to asses the morphological and biomechanical responses as potential markers for current and future disease characterization. The outcomes of this research project will provide an innovative and enhanced evaluation of ocular structure and function in glaucoma that will expand our understanding of the disease pathophysiology, offer new diagnostic tools for early disease detection and disease progression and identify subjects at risk for rapid glaucoma progression.

Public Health Relevance

The focus of this research project is on the development and refinement of innovative analytical methods and cutting-edge technologies that will substantially improve detection of glaucoma as well as disease progression in order to prevent blindness.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY013178-15
Application #
8694395
Study Section
(DPVS)
Program Officer
Chin, Hemin R
Project Start
2000-08-01
Project End
2019-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
15
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Tran, Huong; Wallace, Jacob; Zhu, Ziyi et al. (2018) Seeing the Hidden Lamina: Effects of Exsanguination on the Optic Nerve Head. Invest Ophthalmol Vis Sci 59:2564-2575
Lavinsky, Fabio; Wu, Mengfei; Schuman, Joel S et al. (2018) Can Macula and Optic Nerve Head Parameters Detect Glaucoma Progression in Eyes with Advanced Circumpapillary Retinal Nerve Fiber Layer Damage? Ophthalmology 125:1907-1912
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
Voorhees, Andrew P; Jan, Ning-Jiun; Hua, Yi et al. (2018) Peripapillary sclera architecture revisited: A tangential fiber model and its biomechanical implications. Acta Biomater 79:113-122
Wang, Bo; Lucy, Katie A; Schuman, Joel S et al. (2018) Tortuous Pore Path Through the Glaucomatous Lamina Cribrosa. Sci Rep 8:7281
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
Rathi, Siddarth; Tsui, Edmund; Mehta, Nitish et al. (2017) The Current State of Teleophthalmology in the United States. Ophthalmology 124:1729-1734
Tieger, Marisa G; Hedges 3rd, Thomas R; Ho, Joseph et al. (2017) Ganglion Cell Complex Loss in Chiasmal Compression by Brain Tumors. J Neuroophthalmol 37:7-12
Tran, H; Grimm, J; Wang, B et al. (2017) Mapping in-vivo optic nerve head strains caused by intraocular and intracranial pressures. Proc SPIE Int Soc Opt Eng 10067:

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