Glaucoma is a disease characterized by optic nerve damage (retinal ganglion cell loss), and is one of the leading causes of blindness. It is estimated that 2 million people in the United States have been diagnosed with glaucoma, 1 million others have undiagnosed glaucoma, and up to 6 million (including 4-8 percent of people over 40) are at risk of developing glaucoma. Our current understanding of early damage in glaucoma, however, remains limited. Histopathologic studies in humans and experimental primate glaucoma models suggest that there can be substantial loss of retinal ganglion cells before reliable changes in visual function can be measured. This project will investigate a new method of noninvasively monitoring retinal ganglion cell loss, and potential functional and structural predictors of this loss.
Our first aim determines the effect of glaucomatous retinal ganglion cell loss on cortical responses. Most new visual function tests for glaucoma have attempted to isolate and measure response properties of retinal ganglion cell subpopulations. We will use a noninvasive electrophysiology procedure, the multifocal Visual Evoked Potential (mfVEP), to measure cortical responses and the consequences of retinal ganglion cell loss on these responses. Because cortical responses are dependent on summed ganglion cell input, we propose that the mfVEP may be a more sensitive indicator of visual function loss, and may correlate more strongly with early structural optic nerve damage than other visual function measures. However, it is possible that retinal ganglion cell malfunction (sick cells) precedes the ganglion cell dropout (dead cells) investigated as part of our first aim.
Our second aim therefore examines a method of functionally distinguishing sick from dead ganglion cells. We hypothesize that sick ganglion cells will show normal flicker sensitivity at lower adaptation levels, but will show deficits when challenged with higher adaptation levels. We will test the hypothesis that flicker adaptation dysfunction will predict future visual field deficits produced by retinal ganglion cell loss. In addition to these functional predictors of ganglion cell loss, our third aim evaluates the importance of structural damage to the optic nerve head (using stereo optic disc photographs and measurements with Heidelberg Retinal Tomography images) for predicting the location of future visual function deficits indicative of ganglion cell loss. Together, these objectives will provide a better understanding of the underlying basis of early glaucomatous damage.
| Lloyd, Michael J; Mansberger, Steven L; Fortune, Brad A et al. (2013) Features of optic disc progression in patients with ocular hypertension and early glaucoma. J Glaucoma 22:343-8 |
| Gardiner, Stuart K; Johnson, Chris A; Demirel, Shaban (2012) The effect of test variability on the structure-function relationship in early glaucoma. Graefes Arch Clin Exp Ophthalmol 250:1851-61 |
| Twa, Michael D; Parthasarathy, Srinivasan; Johnson, Chris A et al. (2012) Morphometric analysis and classification of glaucomatous optic neuropathy using radial polynomials. J Glaucoma 21:302-12 |
| Gardiner, Stuart K; Johnson, Chris A; Demirel, Shaban (2012) Factors predicting the rate of functional progression in early and suspected glaucoma. Invest Ophthalmol Vis Sci 53:3598-604 |
| Gardiner, Stuart K; Demirel, Shaban; Johnson, Chris A (2011) Perimetric indices as predictors of future glaucomatous functional change. Optom Vis Sci 88:56-62 |
| Gardiner, Stuart K; Johnson, Chris A; Demirel, Shaban (2011) Cup size predicts subsequent functional change in early glaucoma. Optom Vis Sci 88:1470-6 |
| Gardiner, Stuart K; Demirel, Shaban; Johnson, Chris A et al. (2011) Assessment of linear-scale indices for perimetry in terms of progression in early glaucoma. Vision Res 51:1801-10 |
| Anderson, Andrew John; Johnson, Chris A; Werner, John S (2011) Measuring visual function in age-related macular degeneration with frequency-doubling (matrix) perimetry. Optom Vis Sci 88:806-15 |
| O'Leary, Neil; Crabb, David P; Mansberger, Steven L et al. (2010) Glaucomatous progression in series of stereoscopic photographs and Heidelberg retina tomograph images. Arch Ophthalmol 128:560-8 |
| Demirel, Shaban; Fortune, Brad; Fan, Juanjuan et al. (2009) Predicting progressive glaucomatous optic neuropathy using baseline standard automated perimetry data. Invest Ophthalmol Vis Sci 50:674-80 |
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