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Accurate and reproducible OCT angiography (OCTA) measurements are highly dependent on the overall phase stability of the sample. Raster-scanning OCT systems are vulnerable to eye motion, which makes phase correlation impossible if the retinal displacement is too large. Numerical methods exist to correct components of phase shifts due to the axial movement, but that due to lateral movement bigger, then imaging spot are not generally correctable. Real-time eye tracking provides a method to reduce the phase shifts caused by lateral eye movement. Here we report the advancements on monitoring ocular metrics during OCTA acquisition and its effects on image quality.

Objective optical assessment of photoreceptor function may permit earlier diagnosis of retinal disease than current methods such as perimetry, electrophysiology, and clinical imaging. Recent work with adaptive optics (AO) flood imaging, conventional OCT and phase-sensitive full-field OCT have revealed apparent changes in photoreceptor outer segment (OS) length in response to visible stimuli. In this work, we describe an AO-OCT system designed to measure these stimulus-evoked OS length changes. The OCT subsystem consisted of a Fourier-domain mode-locked laser that acquires A-scans at 1.64MHz and an AO subsystem providing diffraction-limited imaging with a closed-loop correction rate of 20Hz. To our knowledge this is the highest-speed AO-OCT system developed to date. Visible stimuli were delivered using a LED-based Maxwellian view channel incorporated into the system. In a dark-adapted healthy subject, 1-deg square volumetric images were acquired at a rate of 32Hz. Images were acquired for 10s, with a 10ms bleaching stimulus flash with variable intensity. Strip-based registration was used to track individual cones in the volume series, and time series of the resulting depth-resolved complex signal were analyzed. Stimulus-evoked changes in the morphology of OS and RPE were observed in the M-scan amplitude. In the M-scan phase, the difference between the IS/OS and COST was shown to increase in response to the stimulus flash, and the magnitude of the phase change depended upon flash intensity. These results suggest that cone OS elongates in response to visible stimuli, and that the length change scales with stimulus intensity.

We demonstrate OCT angiography (OCTA) and Doppler OCT imaging of the choroid in the eyes of two healthy volunteers and in a geographic atrophy case. We show that visualization of specific choroidal layers requires selection of appropriate OCTA methods. We investigate how imaging speed, B-scan averaging and scanning density influence visualization of various choroidal vessels. We introduce spatial power spectrum analysis of OCT en face angiographic projections as a method of quantitative analysis of choroicapillaris morphology. We explore the possibility of Doppler OCT imaging to provide information about directionality of blood flow in choroidal vessels. To achieve these goals, we have developed OCT systems utilizing an FDML laser operating at 1.7 MHz sweep rate, at 1060 nm center wavelength, and with 7.5 μm axial imaging resolution. A correlation mapping OCA method was implemented for visualization of the vessels. Joint Spectral and Time domain OCT (STdOCT) technique was used for Doppler OCT imaging.

We tested and compared the capability of multiple optical coherence tomography (OCT) angiography methods: phase variance, amplitude decorrelation and speckle variance, with application of the split spectrum technique, to image the choroiretinal complex of the human eye. To test the possibility of OCT imaging stability improvement we utilized a real-time tracking scanning laser ophthalmoscopy (TSLO) system combined with a swept source OCT setup. In addition, we implemented a post- processing volume averaging method for improved angiographic image quality and reduction of motion artifacts. The OCT system operated at the central wavelength of 1040nm to enable sufficient depth penetration into the choroid. Imaging was performed in the eyes of healthy volunteers and patients diagnosed with age-related macular degeneration.

We summarize the performance of an AO-OCT system with reference arm phase shifting for complex conjugate artifactfree imaging of in vivo retinal structures. As a complex conjugate artifact removal (CCR) method we used a previously reported technique requiring constant phase shifts between consecutive A-scans. In our system these shifts were generated by continuous beam path-length changes from offsetting the pivot point of the scanning mirror placed in the system reference arm. In order to reconstruct the complex spectral fringe pattern we used Fourier transformation along the transverse axis and a filtering algorithm. The suppression ratio of mirror complex artifact images was assessed based on acquired in vivo CCR AO-OCT images. Finally, potential problems and limitations connected with this acquisition scheme and data processing algorithms are discussed.

We describe results of retinal imaging with a novel instrument that combines adaptive optics - Fourier-domain optical coherence tomography (AO-OCT) with an adaptive optics scanning laser ophthalmoscope (AO-SLO). One of the benefits of combining Fd-OCT with SLO includes automatic co-registration between the two imaging modalities and the potential for correcting lateral and transversal eye motion resulting in motion artifact-free volumetric retinal imaging. Additionally this allows for direct comparison between retinal structures that can be imaged with both modalities (e.g., photoreceptor mosaics or microvasculature maps). This dual imaging modality could provide insight into some retinal properties that could not be accessed by a single imaging system. Additionally, extension of OCT and SLO beyond structural imaging may open new avenues for diagnostics and testing in ophthalmology. In particular, non-invasive vasculature mapping with these modalities holds promise of replacing fluorescein angiography in vascular identification. Several new improvements of our system are described, including results of testing a novel 97-actuator deformable mirror and AO-SLO light intensity modulation. © 2010 SPIE.

We describe a novel instrument that combines adaptive optics - Fourier-domain optical coherence tomography (AO-OCT) with an adaptive optics scanning laser ophthalmoscope (AO-SLO). Both systems share a common AO sub-system and vertical scanner to permit simultaneous acquisition of retinal images from both OCT and SLO. One of the benefits of combining OCT with SLO includes automatic co-registration between the two imaging modalities and potential for correcting lateral and transversal eye motion resulting in motion artifact-free volumetric retinal imaging. Results of using this system for eye model imaging are presented. Feasibility for clinical application is briefly discussed as well as potential further improvements of the current system.

Imaging the structure and correlating it with the biochemical content of the retina holds promise for fundamental research and for clinical applications. Optical coherence tomography (OCT) is commonly used to image the 3D structure of the retina and while the added functionality of biochemical analysis afforded by Raman scattering could provide critical molecular signatures for clinicians and researchers, there are many technical challenges to combining these imaging modalities. We present an ex vivo OCT microscope combined with Raman spectroscopy capable of collecting morphological and molecular information about a sample simultaneously. The combined instrument will be used to investigate remaining technical challenges to combine these imaging modalities, such as the laser power levels needed to achieve a Raman signal above the noise level without damaging the sample.

Adaptive optics (AO) and optical coherence tomography (OCT) are powerful imaging modalities that, when combined, can provide high-resolution (3.5 μm isotropic), 3-D images of the retina. The AO-OCT system at UC Davis has demonstrated the utility of this technology for microscopic, volumetric, in vivo retinal imaging. The current system uses an AOptix bimorph deformable mirror (DM) for low-order, high-stroke correction and a 140-actuator Boston Micromachines DM for high-order correction. Developments to improve performance or functionality of the instrument are on-going. Based on previous work in system characterization we have focused on improved AO control. We present preliminary results and remaining challenges for a newly implemented Fourier transform reconstructor (FTR). The previously reported error budget analysis is also reviewed and updated, with consideration of how to improve both the amount of residual error and the robustness of the system. Careful characterization of the AO system will lead to improved performance and inform the design of future systems.

We describe and compare two volume visualization methods for Optical Coherence Tomography (OCT) retinal data sets. One of these methods is CPU-slicing, which is previously reported and used in our visualization engine. The other is GPU-ray casting. Several metrics including image quality, performance, hardware limitations and perception are used to grade the abilities of each method. We also discuss how to combine these methods to make a scalable volume visualization system that supports advanced lighting and dynamic volumetric shadowing techniques on a broad range of hardware. The feasibility of each visualization method for clinical application as well as potential further improvements are discussed.

Adaptive optics (AO) and optical coherence tomography (OCT) are powerful imaging modalities that, when combined, can provide high-resolution, 3-D images of the retina. The AO-OCT system at UC Davis has been under development for 2 years and has demonstrated the utility of this technology for microscopic, volumetric, in vivo retinal imaging. The current system uses a bimorph deformable mirror (DM) made by AOptix Technologies, Inc. for low-order, high-stroke correction and a 140-actuator mirco-electrical-mechanical-system (MEMS) DM made by Boston Micromachines Corporation for high-order correction. We present our on-going characterization of AO system performance. The AO-OCT system typically has residual wavefront error of 100 nm rms. The correctable error in the system is dominated by low-order error that we believe is introduced by aliasing in the control loop. Careful characterization of the AO system will lead to improved performance and inform the design of future systems.

Advances in Fourier-domain optical coherence tomography (Fd-OCT) permit visualization of three-dimensional morphology of in-vivo retinal structures in a way that promises to revolutionize clinical and experimental imaging of the retina. The relevance of these advances will be further increased by the recent introduction of several commercial Fd-OCT instruments that can be used in clinical practice. However, due to some inherent limitations of current Fd-OCT technology (e.g., lack of spectroscopic information, inability to measure fluorescent signals), it is important to co-register Fd-OCT data with images obtained by other clinical imaging modalities such as fundus cameras and fluorescence angiography to create a more complete interpretation and representation of structures imaged. The co-registration between different imaging platforms becomes even more important if small retinal changes are monitored for early detection and treatment. Despite advances in volume acquisition speed with FD-OCT, eye/head motion artifacts can be still seen on acquired data. Additionally high-sampling density, large field-of-view (FOV) Fd-OCT volumes may also be needed for comparison with conventional imaging. In standard Fd-OCT systems, higher sampling density and larger imaging FOV (with constant sampling densities) lead to longer acquisition time which further increases eye/head motion artifacts. To overcome those problems, we tested 3D stitching of multiple, smaller retinal volumes which can be acquired in a less time (reduction of motion artifacts) and/or when stitched create a larger FOV representation of the retina. Custom visualization software that makes possible manual co-registration and simultaneous visualization of volumetric Fd-OCT data sets is described. Volumetric visualizations of healthy retinas with corresponding fundus pictures are presented followed by examples of retinal volumes of high sampling density that are created from multiple "standard" Fd-OCT volumes.

We describe a compact MEMS-based adaptive optics (AO) optical coherence tomography (OCT) system with improved AO performance and ease of clinical use. A typical AO system consists of a Shack-Hartmann wavefront sensor and a deformable mirror that measures and corrects the ocular and system aberrations. Because of limitations on current deformable mirror technologies, the amount of real-time ocular-aberration compensation is restricted and small in previous AO-OCT instruments. In this instrument, we incorporate an optical apparatus to correct the spectacle aberrations of the patients such as myopia, hyperopia and astigmatism. This eliminates the tedious process of using trial lenses in clinical imaging. Different amount of spectacle aberration compensation was achieved by motorized stages and automated with the AO computer for ease of clinical use. In addition, the compact AO-OCT was optimized to have minimum system aberrations to reduce AO registration errors and improve AO performance.

Ultra-high isotropic resolution imaging of retinal structures was made possible with an adaptive optics system using dual deformable mirrors and a Fourier-domain optical coherence tomography (Fd-OCT) system with correction for longitudinal chromatic aberration. This system was used to image microscopic retinal structures of healthy as well as diseased retinas in vivo. The improved resolution and contrast enhanced visualization of morphological structures in the retina can be clearly seen. The benefits of this instrument are apparent from comparison of new images with those acquired using a previous generation AO-OCT instrument. Big change in the appearance of speckle field (reduction in speckle size) can be observed as well. Additionally, further improvements in volumetric data acquisition and image representation will be discussed. This includes creation of large Field of View (FOV) AO-OCT volume from multiple sub-volumes and its visualization. Also techniques and results of reducing speckle contrast by averaging multiple B-scans will be presented.

Ultrahigh axial resolution in adaptive optics - optical coherence tomography (AO-OCT) is fundamentally limited by the intrinsic chromatic aberrations of the human eye. Variation in refractive index of the ocular media with wavelength causes the spectral content of broadband light sources to focus at different depths in the retina for light entering the eye and at the imaging detector for light exiting. This effect has not been previously reported for ultrahigh-resolution OCT (without AO) likely because the effect is masked by the relatively long depth of focus dictated by the small pupils used in these systems. With AO, the pupil size is much larger and depth of focus substantially narrower. As such the chromatic aberrations of the eye can counteract the lateral resolution benefit of AO when used with broadband light sources. To more fully tap the potential of AO-OCT, compensation of the eye's chromatic and monochromatic aberrations must occur concurrently. One solution is to insert an achromatizing lens in front of the eye whose chromatic aberrations are equal but opposite in sign to that of the eye. In this paper we evaluate the efficacy of a novel design that uses a custom achromatizing lens placed near the fiber collimating optic. AO-OCT images are acquired on several subjects with and without the achromatizing lens and in combination with two light sources of different spectral width. The combination of the achromatizing lens and broadband light source yielded the sharpest images of the retina and the smallest speckle.

Two deformable mirrors (2DM) were used in an adaptive optics - optical coherence tomography (AO-OCT) system to image in vivo microscopic retinal structures of healthy and diseased retinas. As a result, multiple morphological structures not previously seen in vivo have been visualized. Among those presented are three-dimensional representations of the fovea and optic nerve head (ONH), revealing cellular structures and micro-vasculature. Drusen in macular degeneration and photoreceptor dystrophies are also presented. Different methods for displaying volumetric AO-OCT data to facilitate visualization of certain morphological details are compared.

Adaptive Optics (AO) have been increasingly combined with a variety of ophthalmic instruments over the last decade to provide cellular-level, in-vivo images of the eye. The use of MEMS deformable mirrors in these instruments has recently been demonstrated to reduce system size and cost while improving performance. However, currently available MEMS mirrors lack the required range of motion for correcting large ocular aberrations, such as defocus and astigmatism. In order to address this problem, we have developed an AO system architecture that uses two deformable mirrors, in a woofer / tweeter arrangement, with a bimorph mirror as the woofer and a MEMS mirror as the tweeter. This setup provides several advantages, including extended aberration correction range, due to the large stroke of the bimorph mirror, high order aberration correction using the MEMS mirror, and additionally, the ability to 'focus' through the retina. This AO system architecture is currently being used in four instruments, including an Optical Coherence Tomography (OCT) system and a retinal flood-illuminated imaging system at the UC Davis Medical Center, a Scanning Laser Ophthalmoscope (SLO) at the Doheny Eye Institute, and an OCT system at Indiana University. The design, operation and evaluation of this type of AO system architecture will be presented.

The ability to obtain true three-dimensional (3D) morphology of the retinal structures is essential for future clinical and experimental studies. It becomes especially critical if the measurements acquired with different instruments need to be compared, or precise volumetric data are needed for monitoring and treatment of retinal disease. On the other hand, it is well understood that optical coherence tomography (OCT) images are distorted by several factors. Only limited work has been performed to eliminate these problem s in ophthalmic retinal imaging, perhaps because they are less evident in the more common 2D representation mode of time-domain OCT. With recent progress in imaging speed of Fourier domain - OCT (Fd-OCT) techniques, however, 3D OCT imaging is more frequently being used, thereby exposing problems that have been ignored previously. In this paper we propose possible solutions to minimize and compensate for artifacts caused by subject eye and head motion, and distortions caused by the geometry of the scanning optics. The first is corrected by cross-correlation based B-scan registration techniques; the second is corrected by incorporating the geometry of the scanning beam into custom volume rendering software. Retinal volumes of optical nerve head (ONH) and foveal regions of healthy volunteer, with and without corrections, are presented. Finally, some common factors that may lead to increased distortions of the ophthalmic OCT imag e such as refractive error or position of the subject’s head are discussed. Keywords

Adaptive Optics - Optical Coherence Tomography (AO-OCT) has demonstrated a promising improvement in lateral resolution for retinal imaging compared to standard OCT. Recent developments in Fourier-domain OCT technology allow AO-OCT instruments to acquire three-dimensional (3D) retinal structures with high speed and high "volumetric" resolution (in all three dimensions). One of the most important factors (besides acquisition speed) that will determine the true potential of this technique is its ability to achieve diffraction-limited lateral resolution (~3 μm) while operating in the ultrahigh axial resolution range (~3 μm) offered by OCT. Theoretical studies have shown that the eye's chromatic aberrations may drastically reduce volumetric resolution. This is a critical finding because for "standard" stand alone ultrahigh OCT, increasing the spectral bandwidth of the light source improves axial resolution without compromising lateral resolution. To study the effects of spectral bandwidth on AO-OCT systems for retinal imaging two different light sources offering 6 and 3 μm axial resolution were tested. This comparison was based on both AO correcting system performance as well as the quality of corresponding OCT images.

A design for a high-resolution scanning instrument is presented for in vivo imaging of the human eye at the cellular scale. This system combines adaptive optics technology with a scanning laser ophthalmoscope (SLO) to image structures with high lateral (~2 μm) resolution. In this system, the ocular wavefront aberrations that reduce the resolution of conventional SLOs are detected by a Hartmann-Shack wavefront sensor, and compensated with two deformable mirrors in a closed-loop for dynamic correction and feedback control. A laser beam is scanned across the retina and the reflected light is captured by a photodiode, yielding a two-dimensional image of the retina at any depth. The quantity of back-scattered light from the retina is small (0.001% of reflection) and requires the elimination of all parasite reflections. As an in vivo measurement, faint cellular reflections must be detected with a low-energy source, a supraluminescent laser diode, and with brief exposures to avoid artifacts from eye movements. The current design attempts to optimize trade-offs between improved wavefront measurement and compensation of the optical aberrations by fractioning the light coming to the wavefront sensor, better sensitivity by increasing the input light energy or the exposure time and the response speed of the system. This instrument design is expected to provide sufficient resolution for visualizing photoreceptors and ganglion cells, and therefore, may be useful in diagnosing and monitoring the progression of retinal pathologies such as glaucoma or aged-related macular degeneration.

We built a Fourier domain optical coherence tomography (FD-OCT) system using a line scan CCD camera that allows real time data display and acquisition. This instrument is able to produce 2D B-scans as well as 3D data sets with human subjects in vivo in clinical settings. In this paper we analyze the influence of varying exposure times of the CCD detector on image quality. Sensitivity values derived from theoretical predictions have been compared with measurements (obtained with mirrors and neutral density filters placed in both interferometer arms). The results of these experiments, discussion about differences between sensitivity values, potential sources of discrepancies, and recommendations for optimal exposure times will be described in this paper. A short discussion of observed artifacts as well as possible ways to remove them is presented. The influence of relative retinal position with respect to reference mirror position will also be described.

Adaptive optics (AO), a mature technology developed for astronomy to compensate for the effects of atmospheric turbulence, can also be used to correct the aberrations of the eye. The classic phoropter is used by ophthalmologists and optometrists to estimate and correct the lower-order aberrations of the eye, defocus and astigmatism, in order to derive a vision correction prescription for their patients. An adaptive optics phoropter measures and corrects the aberrations in the human eye using adaptive optics techniques, which are capable of dealing with both the standard low-order aberrations and higher-order aberrations, including coma and spherical aberration. High-order aberrations have been shown to degrade visual performance for clinical subjects in initial investigations. An adaptive optics phoropter has been designed and constructed based on a Shack-Hartmann sensor to measure the aberrations of the eye, and a liquid crystal spatial light modulator to compensate for them. This system should produce near diffraction-limited optical image quality at the retina, which will enable investigation of the psychophysical limits of human vision. This paper describes the characterization and operation of the AO phoropter with results from human subject testing.

I want to begin by thanking each of you for attending. This session is very, very exciting to me, and I know that it willbe exciting and rewarding to you as well. We will begin by acknowledging Dr. All an Rodrigues and Dr. Danny Rich. We are the progenitors of this session. I believe that it is incumbent upon us to prepare ourselves, our companies or organizations for tomorrow by staying abreast of the state of-the-art, changes in technology, science, and trends, in our ever-changing world.