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 for perimetry 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 ophthalmoscope (AOSLO) as well as custom use of spectral domain optical 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 affect conventional perimetry.
Specific Aim 1 will determine the role of ganglion cell dysfunction in between-subject differences in the amount of visual loss corresponding to clinically observed reflectance defects, and assess longitudinal changes.
Specific Aim 2 will utilize the synergy between structural and functional measures to develop perimetric algorithms that interact dynamically with information about RNFL structure.
Specific Aim 3 will develop methods that dramatically improve the ability to detect wedge defects that are poorly sampled by conventional perimetry.

Public Health Relevance

New clinical imaging methods reveal en face defects in the retinal nerve fiber layer, which identify regions of visual loss. The proposed research will employ state-of-the-art adaptive optics imaging and microperimetry systems to understand the pathophysiology of the en face defects seen clinically. By revealing the pathophysiology, this project has the potential to dramatically improve detection of glaucoma, a leading cause of blindness and visual impairment, and to provide improved methods for evaluating progression and assessing effectiveness of treatment.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Study Section
Diseases and Pathophysiology of the Visual System Study Section (DPVS)
Program Officer
Liberman, Ellen S
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Indiana University Bloomington
Schools of Optometry/Opht Tech
United States
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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
Gardiner, Stuart K; Swanson, William H; Demirel, Shaban (2016) The Effect of Limiting the Range of Perimetric Sensitivities on Pointwise Assessment of Visual Field Progression in Glaucoma. Invest Ophthalmol Vis Sci 57:288-94

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