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 it has relatively good diagnostic accuracy and reproducibility in the measurement of neural structures damaged by glaucoma. However, the measurement of structure alone, with any imaging modality, has limited sensitivity for detecting early glaucoma and only moderate correlation with visual field (VF) loss. Using high-speed OCT systems, we have developed new methods to image and measure optic nerve head (ONH) and retinal blood flow. Preliminary results showed that VF loss was more highly correlated with retinal blood flow as measured by OCT than any neural structure measured by OCT or other imaging modality. Accordingly, the goal of the proposed project is to improve the diagnostic and prognostic evaluation of glaucoma by further developing novel functional OCT measurements using ultrahigh-speed (70-100 kHz) OCT technology.
The specific aims are: 1. Improve Doppler OCT measurement of retinal blood flow. Multi-circular scans of peripapillary retinal arteries and veins measure total retinal blood flow in 2 seconds. The use of faster OCT systems will allow automated measurement with improved reproducibility. 2. Develop quantitative OCT angiography of the ONH. Three dimensional (3D) OCT angiography has been made practical (3x3 mm scan in 3 seconds) by a novel split-spectrum amplitude-decorrelation algorithm. Preliminary results showed dramatic loss of ONH microcirculation in early glaucoma. Algorithmic improvement in angiography, segmentation, quantification, and automation are planned. 3. Measure nerve structure from the ONH to retinal ganglion cells. By registering several volumetric scans, we have demonstrated complete 3D characterization of the retinal fiber pathway from the ONH to the macula. Fully automated quantification of these structures will be developed. 4. Evaluate advanced OCT technologies in clinical studies. The utility of functional and structural OCT in glaucoma will be evaluated in a longitudinal observational study of 150 glaucoma and healthy subjects. The effect of IOP-lowering surgery on blood flow will be studied in 40 subjects. Retinal blood flow, ONH circulation, optic disc rim volume, peripapillary nerve fiber layer volume, and macular ganglion cell complex volume are all pieces of the same glaucoma puzzle. This project will develop novel imaging methods that allow us to look at the whole picture using one tool - ultrahigh-speed OCT.

Public Health Relevance

There is much evidence that optic nerve head and retinal blood flow are decreased in glaucoma, and vascular insufficiency may play a causative role in a subset of glaucoma patients. Because current technologies do not permit routine clinical measurement of ocular circulation, we will develop Doppler OCT to measure total retinal blood flow and OCT angiography to measure optic nerve head microcirculation, and demonstrate their utilities in a clinical study of glaucoma.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY023285-01
Application #
8479117
Study Section
Special Emphasis Panel (NOIT)
Program Officer
Agarwal, Neeraj
Project Start
2013-09-30
Project End
2017-08-31
Budget Start
2013-09-30
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$750,111
Indirect Cost
$255,662
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
Skalet, Alison H; Liu, Liang; Binder, Christina et al. (2018) Quantitative OCT Angiography Evaluation of Peripapillary Retinal Circulation after Plaque Brachytherapy. Ophthalmol Retina 2:244-250
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
Dongye, Changlei; Zhang, Miao; Hwang, Thomas S et al. (2017) Automated detection of dilated capillaries on optical coherence tomography angiography. Biomed Opt Express 8:1101-1109

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