Neovascular age-related macular degeneration (AMD), characterized by the presence of choroidal neovascularization (CNV), accounts for the majority of AMD related vision loss. Invasive dye-based fluorescein angiography (FA) remains the gold standard for CNV detection. Using high-speed OCT systems, we have developed novel OCT angiography (OCTA) technologies to image CNV as well as vascular plexuses associated with AMD. Our recent clinical studies have demonstrated that (1) 33-mm OCTA has a sensitivity for subfoveal CNV detection comparable to FA; (2) OCTA derived quantitative metrics provide novel insight into the CNV response to anti-VEGF treatment; and (3) routine screening OCTA can detect treatment nave non-exudative CNV that carries high risk for progression and is invisible with FA. Currently, OCTA is limited by low transverse resolution, small field of view, and various artifacts. The current proposal will overcome these limitations by improving both the hardware platform and software algorithms to develop advanced OCTA. Its role in AMD evaluation and management will be tested in three clinical studies. 1. Develop high-resolution wide-field OCTA. We will develop a swept-source OCT prototype that is 4 times faster than current commercial OCT systems. A wide collimated beam will be used to improve transverse optical resolution. The high-speed and high-resolution OCTA will be able to image capillary-level details in a wide field of view. 2. Develop volumetric analysis of CNV and plexus-specific analysis of retinal and choroidal circulations. We will improve our algorithm to remove projection artifacts in the outer retina that arise from moving blood cells in superficial retinal vessels. Next, we will develop automated software to measure CNV volume and to detect defects in the choriocapillaris and retinal deep capillary plexus (DCP). 3. Evaluate advanced OCTA for AMD in clinical studies. Three studies will test the clinical applications of OCTA. Study 1: A cross-sectional analysis will compare the accuracy of OCTA versus FA to distinguish CNV as the etiology of macular edema versus control eyes with macular edema from retinal vein occlusion or diabetic retinopathy. Study 2: A longitudinal analysis of neovascular AMD under a treat-and-extend anti- VEGF regimen will determine if OCTA can predict recurrent exudation or hemorrhage. Study 3: An OCTA longitudinal screening of eyes with intermediate AMD will determine if choriocapillaris and retinal DCP defects presage CNV development. Non-exudative CNV detected with OCTA will be followed monthly and novel CNV volumetric analysis used to determine if rapid growth is a risk for development of exudation. If successful, OCTA will improve our capability to diagnose all macular CNVs, provide useful information to help determine appropriate anti-VEGF dosing intervals, and aid with surveillance of eyes at risk for development of neovascular AMD. OCTA is nearing its potential to replace the need for invasive FA.

Public Health Relevance

Timely diagnosis and treatment of choroidal neovascularization (CNV) is imperative to prevent vision loss from neovascular age-related macular degeneration (AMD). We will develop advanced optical coherence tomography angiography (OCTA) to overcome the limitations of current OCTA and make fluorescein angiography, the existing invasive and occasionally risky gold standard, obsolete in most cases. OCTA is a safe and non-invasive diagnostic test that will aid in our understanding of neovascular AMD and will provide new information to help clinicians with diagnosis and management decisions. 2

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY024544-05
Application #
9595014
Study Section
Neuroscience and Ophthalmic Imaging Technologies Study Section (NOIT)
Program Officer
Greenwell, Thomas
Project Start
2014-09-01
Project End
2022-08-31
Budget Start
2018-09-30
Budget End
2019-08-31
Support Year
5
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
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
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
Liu, Zhiming; Chen, Haolin; Jia, Yali et al. (2018) A two-dimensional fingerprint nanoprobe based on black phosphorus for bio-SERS analysis and chemo-photothermal therapy. Nanoscale 10:18795-18804
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

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