Anatomical and functional imaging of the conventional outflow pathway

Project Summary: Glaucoma is the leading cause of irreversible blindness worldwide. Currently, the only effective treatment for glaucoma is intraocular pressure (IOP) reduction. Physiologically, IOP is regulated by the aqueous outflow from the anterior chamber of the eye, with the vast majority leaving through the conventional

outflow pathway. Despite the importance of the conventional outflow pathway, essential questions such as the relative contribution of the distal pathway to outflow resistance and the factors predisposing regions of the outflow pathway to be high and low flow remain unknown. Emerging imaging modalities such as optical coherence

tomography, mainly used for retinal imaging, can provide anatomical and functional information that will elucidate the physiological behavior of the outflow pathway in vivo. Recent evidence using aqueous angiography shows that flow patterns in the outflow pathway can be used to increase the effectiveness of minimally invasive

glaucoma surgery (MIGS). The PI is an MD/PhD trainee who proposes to utilize the ultrahigh (~1.3 microns in tissue) axial resolution of visible-light optical coherence tomography (vis-OCT) to noninvasively assess the physiology of the conventional outflow pathway in vivo. Using the information acquired for OCT, the goal is to

develop noninvasive methods to assess regional flow patterns and improve MIGS. Vis-OCT is capable of generating three-dimensional volumetric information consisting of both anatomical and functional data. Additionally, the shorter wavelengths of light used by vis-OCT increase its axial resolution and provides

increased sensitivity to slower blood flow and motion. Since increased resistance in any portion of the outflow pathway influences outflow, the high resolution of vis-OCT will be used to generate quantitative anatomical and functional measurements for all parts of the outflow pathway (trabecular meshwork, Schlemm’s canal, and distal

vasculature). Thus, it is hypothesized that anatomical and functional information generated from imaging the outflow pathway in rodents can serve as biomarkers for understanding the flow patterns within the outflow pattern. To investigate this hypothesis, the PI proposes two aims: Aim 1 utilizes vis-OCT for anatomical imaging,

measuring Schlemm canal volume and distal vasculature structure to make predictions to discover structural- function correlates related to regional outflow. Aim 2 focuses on the development of functional metrics, including the response of the pathway to pharmacological interventions and motion of the trabecular meshwork in

response to intraocular pressure changes, to predict regional outflow. The training environment is well suited for this investigation, with the mentors' labs being experts in designing OCT systems and the co-mentors lab being experts in imaging aqueous outflow. This research leverages a diverse group of mentors with expertise in

biophotonics, physiology, biomedical engineering, and clinical medicine. In addition to training the PI to become an independent researcher, the training plan shall also prepare the PI to become one of the physicians most knowledgeable in imaging and translating innovative technologies into clinical settings.