Our group has demonstrated that optical coherence tomography angiography (OCTA) can address many of the disadvantages of fluorescein angiography (FA) in diabetic retinopathy (DR). OCTA uses the intrinsic contrast of blood cell motion and therefore does not require dye injection, making it entirely non-invasive and suitable for routine examination. OCTA is three-dimensional and can detect retinal neovascularization by the presence of flow in the normally avascular vitreous space, and can detect capillary dropout in the retinal and choroidal circulations separately. The OCTA technology used by previous studies is limited by the small fields of view (2.4-6 mm) and the projection artifacts in the deeper layers, which are caused by flowing blood cells in the more superficial vessels. The current proposal will overcome the previous limitations by improving both the hardware platform and software algorithms to obtain wide-field (WF) and projection-resolved (PR) OCTA. 1. Develop wide-field (WF) OCT system for imaging peripheral retinal circulation. We have developed a 200-kHz swept-source optical coherence tomography (SS-OCT) system. This system is ready for use in clinical studies. We propose to further increase system speed and develop automatic registration and montage algorithms to create ultrawide-field OCTA. 2. Improve the projection-resolved (PR) OCTA algorithm for imaging of retinal and choroidal plexuses. We have preliminarily demonstrated that separation of three retinal plexuses improved the detection of early vascular changes in DR. We will refine this algorithm and apply it to the WF-OCTA on the high-speed SS-OCT systems. 3. Quantify neovascularization and nonperfusion areas using WF- and PR-OCTA in DR. We will further optimize the automated quantification of all relevant DR endpoints, including nonperfusion of all vascular layers, neovascularization, cyst volume, and retinal thickness maps on both commercial and custom OCT systems proposed in this study. 4. Evaluate advanced OCTA for DR in clinical studies. The clinical studies with DR and control subjects are as follows: (1) cross-sectional study to determine if WF- and PR-OCTA can detect nonperfusion and other microvasculopathies with better sensitivity than conventional OCTA and if they can detect these changes even in diabetics without photographic signs of DR; (2) long-term prospective observational study to determine if quantitative WF- and PR-OCTA parameters can predict the risk of DR progression; and (3) short-term study in patients undergoing treatment for diabetic macular edema or neovascularization to validate WF- and PR-OCTA measurements of nonperfusion and neovascularization in comparison with ultrawide-field FA.

Public Health Relevance

Optical coherence tomography angiography (OCTA) is a new dye-less and injection-free technology that can provide fast and economical three-dimensional imaging of retinal blood vessels. It is ideal for routine use in diabetic patients to monitor for worsening of retinopathy by detecting and measuring damage to blood vessels and new blood vessel growth. The proposed project will increase the field of view by 10-fold over existing commercial technology and improve the ability to visualize and measure damage to blood vessels in deeper layers of the retina, not possible with current technology.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY027833-03
Application #
9690151
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Greenwell, Thomas
Project Start
2017-05-01
Project End
2021-04-30
Budget Start
2019-05-01
Budget End
2020-04-30
Support Year
3
Fiscal Year
2019
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
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Pechauer, Alex D; Hwang, Thomas S; Hagag, Ahmed M et al. (2018) Assessing total retinal blood flow in diabetic retinopathy using multiplane en face Doppler optical coherence tomography. Br J Ophthalmol 102:126-130
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
McClintic, Scott M; Gao, Simon; Wang, Jie et al. (2018) Quantitative Evaluation of Choroidal Neovascularization under Pro Re Nata Anti-Vascular Endothelial Growth Factor Therapy with OCT Angiography. Ophthalmol Retina 2:931-941
Wang, Zhuo; Camino, Acner; Hagag, Ahmed M et al. (2018) Automated detection of preserved photoreceptor on optical coherence tomography in choroideremia based on machine learning. J Biophotonics 11:e201700313
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
Lu, Yansha; Simonett, Joseph M; Wang, Jie et al. (2018) Evaluation of Automatically Quantified Foveal Avascular Zone Metrics for Diagnosis of Diabetic Retinopathy Using Optical Coherence Tomography Angiography. Invest Ophthalmol Vis Sci 59:2212-2221
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
Patel, Rachel; Wang, Jie; Campbell, J Peter et al. (2018) Classification of Choroidal Neovascularization Using Projection-Resolved Optical Coherence Tomographic Angiography. Invest Ophthalmol Vis Sci 59:4285-4291
Simonett, Joseph M; Huang, David; Jia, Yali (2017) Quantitative optical coherence tomography angiography of the peripapillary circulation in glaucoma. Ann Eye Sci 2:

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