This Phase-II proposal seeks to elucidate the structure-function relationships between visual field threshold sensitivity and the structural features of the retinal layers, the optic nerve head, and the connecting nerve fiber bundles in glaucoma. This proposal extends our successful Phase-I research that established structure- structure relationships among retinal quantitative indices. In this Phase II, further advancements of spectral domain optical coherence tomography (SD OCT) image analysis will yield new damage metrics expected to correspond much better with visual field threshold sensitivity. The project is driven by an important clinical problem - the poor reliability and reproducibility of th visual field as a measure of irreversible damage to the retinal ganglion cells and their axons in glaucoma. Our long-term vision remains to determine/predict glaucoma visual function from objective structure measurements by OCT. Once achieved, this new approach will provide an objective and reproducible measure, complementing subjective functional assessment of glaucoma damage, decrease the need for frequent visual field testing resulting from long-term fluctuation of visual response, and improve glaucoma treatment based on reliable progression markers. Specifically, we will develop predictive models of increasing complexity yielding a patient- specific predictive model of glaucomatous damage. The overriding hypothesis motivating the proposed research is that novel quantitative metrics of the entire retinal ganglion cell-axonal complex morphology utilizing the nerve fiber bundle trajectories allow reliable prediction of visual function. We have identified the following specific aims:
Aim 1 : Establish a baseline for the focal structural-functional correlation in the retina covered by the Humphrey 24-2 perimetry test (24 degree radius visual field) by comparing 24-2 thresholds with their corresponding structural indices derived from registered multi-field SD-OCT scans in glaucoma and normal subjects. Derive a baseline predictive model of function from structural properties of the inner retinal layers, comprised of retinal ganglion cell and nerve fiber layers.
Aim 2 : Demonstrate that incorporating structural parameters along SD-OCT atlas-based retinal ganglion cell- axonal complex (RGC-AC) trajectories improves the performance of the predictive structure-function model.
Aim 3 : Evaluate whether prediction of 24-2 thresholds is improved by deriving individual-based RGC-AC trajectories instead of from an RGC-AC atlas. The proposed work will be performed using 7-field per eye 3D SD-OCT images accompanied by 24-2 visual field test data on the same day from 100 patients with glaucoma and 40 age-matched normal subjects.

Public Health Relevance

Three dimensional spectral OCT imaging provides a wealth of information about the morphology and tissue characteristics of retinal layers. We propose to study structural and functional relationships of the retina layers using multi-field 3-D OCT imaging. This study has potentially important consequences for glaucoma and other retinal disease diagnosis and treatment.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
4R01EY018853-07
Application #
8974836
Study Section
Neuroscience and Ophthalmic Imaging Technologies Study Section (NOIT)
Program Officer
Liberman, Ellen S
Project Start
2008-04-01
Project End
2017-11-30
Budget Start
2015-12-01
Budget End
2017-11-30
Support Year
7
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Iowa
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52246
Abramoff, Michael D; Fort, Patrice E; Han, Ian C et al. (2018) Approach for a Clinically Useful Comprehensive Classification of Vascular and Neural Aspects of Diabetic Retinal Disease. Invest Ophthalmol Vis Sci 59:519-527
Lynch, Stephanie K; Abràmoff, Michael D (2017) Diabetic retinopathy is a neurodegenerative disorder. Vision Res 139:101-107
Klein, Barbara E K; Johnson, Chris A; Meuer, Stacy M et al. (2017) Nerve Fiber Layer Thickness and Characteristics Associated with Glaucoma in Community Living Older Adults: Prelude to a Screening Trial? Ophthalmic Epidemiol 24:104-110
Guo, Zhihui; Kwon, Young H; Lee, Kyungmoo et al. (2017) Optical Coherence Tomography Analysis Based Prediction of Humphrey 24-2 Visual Field Thresholds in Patients With Glaucoma. Invest Ophthalmol Vis Sci 58:3975-3985
Miri, Mohammad Saleh; Robles, Victor A; Abràmoff, Michael D et al. (2017) Incorporation of gradient vector flow field in a multimodal graph-theoretic approach for segmenting the internal limiting membrane from glaucomatous optic nerve head-centered SD-OCT volumes. Comput Med Imaging Graph 55:87-94
Miri, Mohammad Saleh; Abràmoff, Michael D; Kwon, Young H et al. (2017) A machine-learning graph-based approach for 3D segmentation of Bruch's membrane opening from glaucomatous SD-OCT volumes. Med Image Anal 39:206-217
Philip, Ana-Maria; Gerendas, Bianca S; Zhang, Li et al. (2016) Choroidal thickness maps from spectral domain and swept source optical coherence tomography: algorithmic versus ground truth annotation. Br J Ophthalmol 100:1372-6
Kupersmith, Mark J; Garvin, Mona K; Wang, Jui-Kai et al. (2016) Retinal Ganglion Cell Layer Thinning Within One Month of Presentation for Non-Arteritic Anterior Ischemic Optic Neuropathy. Invest Ophthalmol Vis Sci 57:3588-93
Zarei, Kasra; Scheetz, Todd E; Christopher, Mark et al. (2016) Automated Axon Counting in Rodent Optic Nerve Sections with AxonJ. Sci Rep 6:26559
Sonka, Milan; Abràmoff, Michael D (2016) Quantitative analysis of retinal OCT. Med Image Anal 33:165-169

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