Glaucoma is a leading cause of blindness. Early diagnosis and close monitoring of glaucoma are important because the onset is insidious and the damage is irreversible. Advanced imaging modalities such as optical coherence tomography (OCT) have been used in the past 2 decades to improve the objective evaluation of glaucoma. OCT has higher axial spatial resolution than other posterior eye imaging modalities and can precisely measure neural structures. However, structural imaging alone has limited sensitivity for detecting early glaucoma and only moderate correlation with visual field (VF) loss. Using high-speed OCT systems, we have developed novel OCT angiography technologies to image vascular plexuses that supply the retinal nerve fibers and ganglion cells damaged by glaucoma. Our results showed that OCT angiographic parameters have better correlation with VF parameters. We have also found that measurement of focal and sectoral glaucoma damage using high-definition volumetric OCT angiographic and structural parameters improves diagnostic performance. The goal of the proposed project is to further improve the diagnosis and monitoring of glaucoma using ultrahigh-speed OCT and artificial intelligence machine learning techniques.
The specific aims are: 1. Develop quantitative wide-field OCT angiography. We will develop a swept-source OCT prototype that is 4 times faster than current commercial OCT systems. The higher speed will be used to fully sample the neural structures and associated capillary plexuses damaged by glaucoma. 2. Simulate VF by combining structural and angiographic OCT. Preliminary results showed that both structural and angiographic OCT parameters have high correlation with VF on a sector basis. It may be possible to accurately simulate VF results by combining these parameters using an artificial neural network. The simulated VF may be more precise and reliable than subjective VF testing. 3. Longitudinal clinical study in glaucoma diagnosis and monitoring. Our novel OCT structural and angiographic parameters have high accuracy in diagnosing glaucoma. Neural network analysis of structural and angiographic data from a larger clinical study could further improve diagnostic accuracy. Longitudinal follow-up will assess if simulated VF could monitor disease progression as well as actual VF. 4. Clinical study to assess the effects of glaucoma treatments. Preliminary results suggest that OCT angiography could detect the improvement in capillary density after glaucoma surgery and the effects of drugs. These intriguing effects will be tested in before-and-after comparison studies. If successful, we will have an OCT diagnostic system that in minutes provides objective information on the location and severity of glaucoma damage. This approach could replace time-consuming and unreliable VF testing. Measuring the improvement in retinal circulation could be a quicker way to detect the benefit of glaucoma therapies that work through neuroprotection or regeneration, compared to monitoring VF.

Public Health Relevance

Optical coherence tomography is a high-resolution imaging technology that can non-invasively measure both the eye structures and small blood vessels that are damaged by glaucoma, a leading cause of blindness. The proposed research will further improve this technology so that it can provide detailed measurement over wider areas inside the eye, detect earlier stages of glaucoma, evaluate the location and severity of glaucoma damage, monitor disease progression, and provide more timely assessment of the effectiveness of therapy. A goal of this project is to determine if this objective imaging technology can provide information that is equivalent to or better than subjective visual field testing, which though time-consuming and poorly reliable, is the current gold standard for long-term monitoring and management of glaucoma.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY023285-06
Application #
9564111
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Liberman, Ellen S
Project Start
2013-09-30
Project End
2021-05-31
Budget Start
2018-06-01
Budget End
2019-05-31
Support Year
6
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Zhu, Li; Zong, Yuan; Yu, Jian et al. (2018) Reduced Retinal Vessel Density in Primary Angle Closure Glaucoma: A Quantitative Study Using Optical Coherence Tomography Angiography. J Glaucoma 27:322-327
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Tan, Ou; Liu, Liang; Liu, Li et al. (2018) Nerve Fiber Flux Analysis Using Wide-Field Swept-Source Optical Coherence Tomography. Transl Vis Sci Technol 7:16
Hagag, Ahmed M; Pechauer, Alex D; Liu, Liang et al. (2018) OCT Angiography Changes in the 3 Parafoveal Retinal Plexuses in Response to Hyperoxia. Ophthalmol Retina 2:329-336
Shahidi, Mahnaz; Felder, Anthony E; Tan, Ou et al. (2018) Retinal Oxygen Delivery and Metabolism in Healthy and Sickle Cell Retinopathy Subjects. Invest Ophthalmol Vis Sci 59:1905-1909
Spain, Rebecca I; Liu, Liang; Zhang, Xinbo et al. (2018) Optical coherence tomography angiography enhances the detection of optic nerve damage in multiple sclerosis. Br J Ophthalmol 102:520-524
Camino, Acner; Zhang, Miao; Liu, Liang et al. (2018) Enhanced Quantification of Retinal Perfusion by Improved Discrimination of Blood Flow From Bulk Motion Signal in OCTA. Transl Vis Sci Technol 7:20
Patel, Rachel C; Wang, Jie; Hwang, Thomas S et al. (2018) Plexus-Specific Detection of Retinal Vascular Pathologic Conditions with Projection-Resolved OCT Angiography. Ophthalmol Retina 2:816-826
Wang, Xiaogang; Sun, Bin; Wang, Jie et al. (2018) Quantitative evaluation of retinal artery occlusion using optical coherence tomography angiography: A case report. Medicine (Baltimore) 97:e12652
Khuu, L-A; Tayyari, F; Sivak, J M et al. (2017) Aqueous humor endothelin-1 and total retinal blood flow in patients with non-proliferative diabetic retinopathy. Eye (Lond) 31:1443-1450

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