Assessing Ocular Hemodynamic Response to Surgical Intervention in Glaucoma PA-14-049: Mentored Patient-Oriented Research Career Development Award (Parent K23) Principal Investigator: O'Rese J. Knight, MD Institution: University of North Carolina at Chapel Hill (UNC) Candidate: O'Rese J. Knight, MD is a fellowship-trained glaucoma specialist who has been involved with patient-oriented research throughout his training and clinical career. He is currently an Assistant Professor in the UNC Department of Ophthalmology. He has specific interests in clinical outcomes research and is interested long-term in investigating emerging glaucoma medications and surgical techniques for clinical efficacy. The specific training objectives for the proposed career development award are: 1) gaining proficiency in clinical trial design, team leadership in research, and statistical analysis through coursework culminating in a Master's of Science in Clinical Research (MSCR), 2) completing the Responsible Conduct of Research training with the North Carolina Translational and Clinical Sciences Institute, and 3) conducting research focused on understanding the role of ocular hemodynamics in glaucoma pathogenesis, and evaluating whether OHD factors can be altered with medical and surgical interventions. His team of mentors and co-mentors include Donald Budenz, MD, MPH, Anthony Viera, MD, MPH, and Shawn Gomez, EngScD. Environment: The University of North Carolina is one of the nation's premier research institutions. It is a member of the Clinical and Translational Science Awards Consortium and has been since 2008. In FY2013, UNC ranked seventh among all universities nationwide in NIH funding. It provides an optimal environment for the proposed research. O'Rese will be completing his MSCR degree at the UNC Gillings' School of Global Public Health, which has been perennially recognized as the best public institution of public health. The Department of Ophthalmology is home to a number of extremely accomplished basic and clinical research scientists and boasts brand new facilities that are conducive to clinical research. Within the glaucoma division, there is an active and varied research portfolio which will provide O'Rese ample leadership experience in clinical research. The UNC research community is marked by its collegial nature, and this is demonstrated in the proposed research seamlessly spanning the Departments of Ophthalmology, Family Medicine, and Biomedical Engineering. O'Rese has taken the time to develop the necessary relationships with key stakeholders to accomplish the proposed research. UNC, in kind, has demonstrated its support of O'Rese's research career by providing the salary support that allowed him the time to complete the early work underpinning this current proposal. Research: Open angle glaucoma (OAG) is the third leading cause of blindness in the US, and is expected to affect 4.3 million Americans in 2032. Its pathogenesis is poorly understood and this has yielded treatment options that cannot optimally prevent glaucomatous vision loss. Elevated intraocular pressure (IOP) is widely seen as glaucoma's only modifiable risk factor, and thus all the current treatments are designed to reduce IOP. However, patients can continue to lose vision with appropriate IOP reduction. There are ocular hemodynamic (OHD) factors - ocular perfusion pressure (OPP), optic nerve blood flow (ONBF), and retinal oxygen saturation (RSO2) - which have been identified as contributory to glaucoma pathogenesis, but not adequately investigated as therapeutic targets. Thus the overarching goal of the proposed research is to assess whether OHD factors can enhance our ability to identify which patients are likely to slow or halt progressive visual field loss as a result of surgical intervention.
The specific aims are to gather preliminary data on the effect of cataract surgery, iStent implantation, and GDD implantation on: 1) circadian IOP trends, 2) (a) ONBF and (b) RSO2 trends, and 3) OPP trends in OAG. To accomplish this, 25 patients undergoing each procedure will complete OHD assessments before and after their respective surgeries. We hypothesize that there will be less circadian IOP variability and improved OPP, ONBF, and RSO2 after surgery. We expect that this research will yield a greater understanding of the hemodynamic mechanisms of glaucoma pathogenesis and provide insight into how to begin to integrate this understanding into clinical practice.
Glaucoma is the third leading cause of vision loss in the U.S., currently affecting 2.7 million Americans and accounting for nearly $3 billion/year in federal expenditures. Despite that burden, the current management options are not optimal; glaucoma patients often continue to lose vision even after their intraocular pressure has been adequately reduced. This study seeks to collect preliminary data on whether the ocular hemodynamic factors, which have been identified as contributory to glaucoma pathogenesis, can be established as new therapeutic targets.