Glaucoma is one of the leading causes of preventable blindness, and currently available treatments are not sufficient to halt progression in many patients. While much has been learned about the biology of glaucoma, development of new forms of treatment has been stymied by three barriers: high between-subject variability in ganglion cell number in normal eyes, high within-subject variability in patients with glaucoma, and the slow rate of progression of the disease. The proposed research integrates neural modeling and clinical research to develop improved methods for diagnosing glaucoma and for assessing progression towards blindness. The results are intended to improve measures for both clinical trials and ongoing patient care, while at the same time improving basic science understanding of the pathophysiology of glaucoma and providing guidance for biological studies of the disease process. Innovative uses of clinical devices will guide testing with custom systems, and statistical analyses will utilize the synergy between structural and functional measures of glaucomatous damage. High-resolution retinal imaging of retinal nerve fiber layer (RNFL) will be performed on patients with glaucoma using a custom advanced adaptive optics scanning laser ophthalmosope (AOSLO) as well as custom use of spectral domain ocular coherence tomography (SD-OCT). High-resolution perimetry will be performed in corresponding regions of the visual field, using custom stimuli that are resistant to optical artifacts that affet conventional perimetry. The results will be assessed with innovative statistical methods that utilize the synergy between perimetry and imaging measures.
Specific Aim 1 will apply these methods to people free of eye disease, building three-dimensional models of RNFL that capture both structure and thickness, with the goal of using structure to overcome the barrier of high between-subject variability in ganglion cell number in normal eyes.
Specific Aim 2 will focus on temporal retina, which has unique characteristics that make it possible to locate where retinal nerve fibers begin, starting with just a few axons. Temporal retina corresponds to nasal visual field, where visual field loss is common in early glaucoma, and the emphasis will be on detecting some of the earliest changes in a longitudinal study.
Specific Aim 3 will focus on the macula, which is of great importance because it provides high-resolution vision used for many activities of daily living. The macula also has unique characteristics that make it possible to image the starting locations of retinal nerve fibers, and is well-suited for high-resolution perimetry.
Specific Aim 4 will extend this approach to nasal retina, by examining patients with wedge RNFL defects that are narrow at the optic disc and then widen in a wedge of damaged RNFL. Whereas Specific Aims 2 & 3 address unique locations where RNFL fibers begin, Specific Aim 4 will address how to interpret RNFL defects across the rest of the retina.

Public Health Relevance

Glaucoma is a leading cause of blindness and visual impairment, and the proposed research will employ innovative methods of perimetry and imaging by applying biological knowledge to dramatically improve ability to assess progression of glaucomatous damage. The goal is to produce clinical methods that better identify the presence of glaucomatous damage and its progression. The potential public health benefit is substantial, given the large number of patients with glaucoma.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY024542-04
Application #
9316632
Study Section
Diseases and Pathophysiology of the Visual System Study Section (DPVS)
Program Officer
Liberman, Ellen S
Project Start
2014-08-01
Project End
2019-07-31
Budget Start
2017-08-01
Budget End
2019-07-31
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Indiana University Bloomington
Department
Type
Schools of Optometry/Opht Tech
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401
Alluwimi, Muhammed S; Swanson, William H; Malinovsky, Victor E et al. (2018) Customizing Perimetric Locations Based on En Face Images of Retinal Nerve Fiber Bundles With Glaucomatous Damage. Transl Vis Sci Technol 7:5
Alluwimi, Muhammed S; Swanson, William H; King, Brett J (2018) Identifying Glaucomatous Damage to the Macula. Optom Vis Sci 95:96-105
Ashimatey, Bright S; King, Brett J; Swanson, William H (2018) Retinal putative glial alterations: implication for glaucoma care. Ophthalmic Physiol Opt 38:56-65
Ramezani, Koosha; Marín-Franch, Iván; Hu, Rongrong et al. (2018) Prediction Accuracy of the Dynamic Structure-Function Model for Glaucoma Progression Using Contrast Sensitivity Perimetry and Confocal Scanning Laser Ophthalmoscopy. J Glaucoma 27:785-793
Alluwimi, Muhammed S; Swanson, William H; Malinovsky, Victor E et al. (2018) A basis for customising perimetric locations within the macula in glaucoma. Ophthalmic Physiol Opt 38:164-173
Ashimatey, Bright S; King, Brett J; Malinovsky, Victor E et al. (2018) Novel Technique for Quantifying Retinal Nerve Fiber Bundle Abnormality in the Temporal Raphe. Optom Vis Sci 95:309-317
Ashimatey, Bright S; King, Brett J; Burns, Stephen A et al. (2018) Evaluating glaucomatous abnormality in peripapillary optical coherence tomography enface visualisation of the retinal nerve fibre layer reflectance. Ophthalmic Physiol Opt 38:376-388
Swanson, William H; Dul, Mitchell W; Horner, Douglas G et al. (2017) Individual differences in the shape of the nasal visual field. Vision Res 141:23-29
Price, Derek A; Swanson, William H; Horner, Douglas G (2017) Using perimetric data to estimate ganglion cell loss for detecting progression of glaucoma: a comparison of models. Ophthalmic Physiol Opt 37:409-419
Ashimatey, Bright S; Swanson, William H (2016) Between-Subject Variability in Healthy Eyes as a Primary Source of Structural-Functional Discordance in Patients With Glaucoma. Invest Ophthalmol Vis Sci 57:502-7

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