Enhancing the Visualization of the Peripheral Retina with Wide Field-of-View Optical Coherence Tomography

The goal of my Ph.D. thesis is to enhance the visualization of the peripheral retina using wide-field optical coherence tomography (OCT) in a clinical setting.

OCT has gain widespread adoption in clinical ophthalmology due to its ability to visualize the diseases of the macula and central retina in three-dimensions, however, clinical OCT has a limited field-of-view of 300. There has been increasing interest to obtain high-resolution images outside of this narrow field-of-view, because three-dimensional imaging of the peripheral retina may prove to be important in the early detection of neurodegenerative diseases, such as Alzheimer's and dementia, and the monitoring of known ocular diseases, such as diabetic retinopathy, retinal vein occlusions, and choroid masses.

Before attempting to build a wide-field OCT system, we need to better understand the peripheral optics of the human eye. Shack-Hartmann wavefront sensors are commonly used tools for measuring the optical imperfections of the eye, but their acquisition speed is limited by their underlying camera hardware. The first aim of my thesis research is to create a fast method of ocular wavefront sensing such that we can measure the wavefront aberrations at numerous points across a wide visual field. In order to address aim one, we will develop a sparse Zernike reconstruction technique (SPARZER) that will enable Shack-Hartmann wavefront sensors to use as little as 1/10th of the data that would normally be required for an accurate wavefront reading. If less data needs to be acquired, then we can increase the speed at which wavefronts can be recorded.

For my second aim, we will create a sophisticated optical model that reproduces the measured aberrations of the human eye. If we know how the average eye's optics distort light, then we can engineer ophthalmic imaging systems that preemptively cancel inherent ocular aberrations. This invention will help the retinal imaging community to design systems that are capable of acquiring high resolution images across a wide visual field. The proposed model eye is also of interest to the field of vision science as it aids in the study of how anatomy affects visual performance in the peripheral retina.

Using the optical model from aim two, we will design and reduce to practice a clinical OCT system that is capable of imaging a large (800) field-of-view with enhanced visualization of the peripheral retina. A key aspect of this third and final aim is to make the imaging system compatible with standard clinical practices. To this end, we will incorporate sensorless adaptive optics in order to correct the inter- and intra- patient variability in ophthalmic aberrations. Sensorless adaptive optics will improve both the brightness (signal) and clarity (resolution) of features in the peripheral retina without affecting the size of the imaging system.

The proposed work should not only be a noteworthy contribution to the ophthalmic and engineering communities, but it should strengthen our existing collaborations with the Duke Eye Center by advancing their capability to diagnose pathologies of the peripheral retinal.

Neural Network Evidence for the Coupling of Presaccadic Visual Remapping to Predictive Eye Position Updating.

As we look around a scene, we perceive it as continuous and stable even though each saccadic eye movement changes the visual input to the retinas. How the brain achieves this perceptual stabilization is unknown, but a major hypothesis is that it relies on presaccadic remapping, a process in which neurons shift their visual sensitivity to a new location in the scene just before each saccade. This hypothesis is difficult to test in vivo because complete, selective inactivation of remapping is currently intractable. We tested it in silico with a hierarchical, sheet-based neural network model of the visual and oculomotor system. The model generated saccadic commands to move a video camera abruptly. Visual input from the camera and internal copies of the saccadic movement commands, or corollary discharge, converged at a map-level simulation of the frontal eye field (FEF), a primate brain area known to receive such inputs. FEF output was combined with eye position signals to yield a suitable coordinate frame for guiding arm movements of a robot. Our operational definition of perceptual stability was "useful stability," quantified as continuously accurate pointing to a visual object despite camera saccades. During training, the emergence of useful stability was correlated tightly with the emergence of presaccadic remapping in the FEF. Remapping depended on corollary discharge but its timing was synchronized to the updating of eye position. When coupled to predictive eye position signals, remapping served to stabilize the target representation for continuously accurate pointing. Graded inactivations of pathways in the model replicated, and helped to interpret, previous in vivo experiments. The results support the hypothesis that visual stability requires presaccadic remapping, provide explanations for the function and timing of remapping, and offer testable hypotheses for in vivo studies. We conclude that remapping allows for seamless coordinate frame transformations and quick actions despite visual afferent lags. With visual remapping in place for behavior, it may be exploited for perceptual continuity.

Circuits for Presaccadic Visual Remapping.

Saccadic eye movements rapidly displace the image of the world that is projected onto the retinas. In anticipation of each saccade, many neurons in the visual system shift their receptive fields. This presaccadic change in visual sensitivity, known as remapping, was first documented in the parietal cortex and has been studied in many other brain regions. Remapping requires information about upcoming saccades via corollary discharge. Analyses of neurons in a corollary discharge pathway that targets the frontal eye field (FEF) suggest that remapping may be assembled in the FEF's local microcircuitry. Complementary data from reversible inactivation, neural recording, and modeling studies provide evidence that remapping contributes to transsaccadic continuity of action and perception. Multiple forms of remapping have been reported in the FEF and other brain areas, however, and questions remain about reasons for these differences. In this review of recent progress, we identify three hypotheses that may help to guide further investigations into the structure and function of circuits for remapping.