My primary research explores the mechanisms underlying the greater predilection to develop glaucomatous injury in individuals of African ancestry and investigates the morphometry of the optic nerve head as a biomarker to predict the development and progression of glaucomatous optic neuropathy. The overarching hypothesis is that variation in ONH morphometry and biomechanical properties are largely responsible for the increased in the susceptibility to IOP-related optic nerve injury associated with African ancestry. Related hypotheses are explored through patient-oriented research, including structural and functional evaluation of the optic nerve in the NEI-sponsored African Descent and Glaucoma Evaluation Study (ADAGES I and II) cohort (1), in-vivo studies imaging the lamina cribrosa, ADAGES IV (2), ex-vivo morphometric studies of the lamina cribrosa and posterior sclera utilizing post-mortem human donor tissues (3) and imaging-based health services research to improve care to underserved populations in the CDC-sponsored Eye Care Quality and Accessibility Improvement in the Community (EQUALITY) study.
1) ADAGES (I,II and III) is a NEI-funded multicenter cohort study designed to evaluation the structural and functional progression of the optic nerve in glaucoma in individuals of European (ED) and African descent (AD). The study began based on my K23 grant awarded in 2001 and is now in its 12th year. The other operational sites are the University of California, San Diego and Columbia University. This collaboration has resulted in 35 peer-reviewed manuscripts and 59 abstracts. This work has been previously funded through foundation and NIH support (Research to Prevent Blindness, Glaucoma Research Foundation, American Health Assistance Foundation, EyeSight Foundation of Alabama, NIH K23: EY 13959-01, NIH U10: EY 14267-01, NIH U10: EY 14267-02, NIH RO1: EY019869-01)
2) ADAGES IV: Using in-vivo imaging, we are evaluating structural biomarkers for glaucoma susceptibility within “deep” optic nerve structures visualized within SDOCT datasets. Our particular interest is in defining racial differences in the rate and mode of change in these structures over time to better understand potential differences in pathobiology and to better define progression of glaucomatous disease in this at-risk and underserved population. We have a developed particular focus on the deep optic nerve structures as they not only may serve as new disease biomarkers but also may have mechanistic involvement with the pathogenesis of axonal injury. (NIH R01: EY026574)
3) DONER (Digital Optic Nerve Episcopic Reconstruction) Library: We have developed a unique library of high-resolution 3D reconstructions from human donor eyes with associated clinical records. Donor ocular tissues were fixed at physiologic and elevated pressures to mimic in-vivo loading conditions in order to enable accurate morphometric and biomechanical analysis. This database currently contains over 190 reconstructed donor pairs. Each reconstruction was develop using an episcopic fluorescent technique that produces high-fidelity reconstructions of the load-bearing connective tissues of the optic nerve head to a resolution of 1.5 cubic micron voxel. We are utilizing these unique digital reconstructions to test the hypothesis that variations in three- dimensional (3D) laminar architecture are critical in determining individual susceptibility to glaucomatous injury. Specifically, that variations in laminar 3D architecture and biomechanical behavior are associated with well-described risk factors for glaucomatous disease such as increasing age and African ancestry. This work has been funded through the NEI and foundation support (NIH RO1: EY18926, NIH RO1: EY19333, NIH RO1: EY018923, Research to Prevent Blindness - Clinician Scientist Award, EyeSight Foundation Research Grant).
