NOVEL GLAUCOMA DIAGNOSTICS FOR STRUCTURE AND FUNCTION

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The broad, long term objectives of this program are the early detection of glaucoma and glaucomatous progression. Our hypothesis is that glaucoma causes thinning of the nerve fiber layer (NFL) and macula, through losses of ganglion cell bodies and their axons, an that the earliest stages of thinning, or progression of thinning, are not detectable clinically, but are detectable by Optical Coherence Tomography (OCT). We hypothesize that OCT NFL and macular assessments are more sensitive to glaucomatous damage and its progression than optic nerve head (ONH) assessment, and that OCT's sensitivity can be increased with increased resolution. High resolution OCT can give more precise NFL measurements and measure the macular ganglion cell layer, perhaps even count ganglion cells. We hypothesize that objective functional glaucoma assessment can be done with multifocal electroretionography (MFERG), a new electrophysiologic technique. Finally, we propose that 1.3 micron OCT can be used for anterior chamber angle, iris and ciliary body measurements. OCT is a new technology that we have developed that permits the noninvasive, non-contact, cross-sectional tomographic imaging of microstructure in biological tissues. A commercial OCT unit provides approximately 10 micron resolution, while a new, high resolution instrument that we have developed approaches approximately 1-3 micron resolution. Our specific aims are 1) To quantify circumapapillary NFL thickness and macular thickness cross-sectionally in normal and glaucomatous subjects using clinical OCT, and to correlate findings with conventional evaluation and quantitative ONH measurements. 2) To quantify peripapillary NFL and macular thickness longitudinally in normal and glaucomatous subjects using clinical OCT. To continue current longitudinal studies using prototype OCT. 3) To investigate ultrahigh resolution OCT to quantify peripapillary NFL, macular NFL, and macular ganglion cell layer thickness in normal and glaucomatous subjects. 4) To quantify MFERG responses in normal and glaucomatous subjects; to correlate these responses to conventional and OCT examinations. 5) To demonstrate OCT imaging of the anterior chamber, angle, iris and ciliary body at 1.3 micron wavelength. 6) To demonstrate longitudinal changes in OCT and MFERG measurements in the laser induced glaucoma monkey model, and to correlate findings with histology. This program is in accordance with the goals and objectives of the 1999 NEI's National Plan, "[to] develop improved measures to aid in the clinical diagnosis of glaucoma; monitor progression of disease ...improved diagnostic techniques encompassing measures of visual function, optic nerve and nerve fiber layer structure..." The National Plan further states, "The development of new diagnostic and imaging methods provides more reliable and objective methods for early diagnosis of glaucoma and for determining progression of glaucomatous damage ...OCT is another promising imaging technique currently under evaluation." We address the National Plan Strategic Research Question, "What is the relationship between visual function loss and structural changes to the optic nerve and retinal nerve fiber layer in glaucoma?" [National Advisory Eye Council 1999]