Monday, May 6, 2024
5/6/2024
DESCRIPTION (provided by applicant): As a result of discoveries made during the first project period, we propose a paradigm change for clinical assessment of the Optic Nerve Head (ONH), peripapillary retinal nerve fiber layer (RNFL) and macula based on acquisition and regionalization of Spectral Domain Optical Coherence Tomography (SDOCT) ONH, RNFL and macula datasets relative to the axis between the center of Bruch's Membrane Opening (BMO) and the fovea (the FoBMO axis). The 4 Specific Aims of this renewal proposal will use SDOCT FoBMO ONH, RNFL and macula imaging (SDOCT phenotyping) to test hypotheses regarding the pattern and timing of age- related and glaucomatous structural change in monkeys (Aims 1 and 2) so as to improve their clinical detection in humans (Aims 3 and 4). Aim 1 will SDOCT phenotype 150 healthy monkey eyes of 86 monkeys (ages 1-36 years) to determine the effect of age and a range of ocular and other demographic variables on global and FoBMO 30¿ sectoral SDOCT ONH, RNFL and macula anatomy. Aim 2 will SDOCT phenotype 80 monkey experimental glaucoma (EG) eyes within the longitudinal, post-laser SDOCT data sets from both eyes of 80 EG animals to generate the first longitudinal phenotyping of monkey EG. Aim 3 will apply Aim 1 and 2 techniques to improve human glaucoma detection through SDOCT phenotyping both eyes of 434 healthy and 457 ocular hypertensive human participants within cross-sectional SDOCT data sets. Aim 4 will apply Aim 2 techniques to improve human glaucoma structural progression detection within the longitudinal SDOCT datasets from both eyes of 227 participants in the Portland Progression Project (P3 Study). The methodology of SDOCT phenotyping includes FoBMO-based SDOCT acquisition, automated segmentation, manual correction, manual delineation, FoBMO regionalization, and quantification of cross-sectional and longitudinal Heidelberg Spectralis 870 standard and enhanced depth imaging data sets. Delineation of deep ONH, peripapillary scleral and scleral canal anatomy will be employed to characterize ONH tilt, torsion and the neural canal minimum and its area. Novel detection of the temporal raphe in the macula will be employed to improve the prediction of ONH rim tissue distribution in normal eyes and structure/structure correlations in glaucomatous damage. Expected outcomes include: 1) construction of an SDOCT FoBMO phenotyping strategy for the ONH, RNFL and macula tissues that improves the clinical detection of glaucomatous damage and its progression; 2) confirmation that SDOCT ONH onset and progression in glaucoma predicts the timing and location of subsequent RNFL and macula thickness loss; 3) the abandonment of clinician cup/disc ratio as the gold standard for clinical disc examination and its replacement with SDOCT anatomy and geometry as the gold standard for clinical ONH examination; 4) establishment of SDOCT FoBMO phenotyping as a shared standard for all ocular disease leading to its rapid translation to Genome Wide Association Study phenotyping and all subspecialties of ophthalmology and neurology that image the ONH, RNFL and macula tissues.
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