An advanced version of Jones matrix optical coherence tomography (JMT) is demonstrated for Doppler and polarization sensitive imaging of the posterior eye. JMT is capable of providing localized flow tomography by Doppler detection and investigating the birefringence property of tissue through a three-dimensional (3-D) Jones matrix measurement. Owing to an incident polarization multiplexing scheme based on passive optical components, this system is stable, safe in a clinical environment, and cost effective. Since the properties of this version of JMT provide intrinsic compensation for system imperfection, the system is easy to calibrate. Compared with the previous version of JMT, this advanced JMT achieves a sufficiently long depth measurement range for clinical cases of posterior eye disease. Furthermore, a fine spectral shift compensation method based on the cross-correlation of calibration signals was devised for stabilizing the phase of OCT, which enables a high sensitivity Doppler OCT measurement. In addition, a new theory of JMT which integrates the Jones matrix measurement, Doppler measurement, and scattering measurement is presented. This theory enables a sensitivity-enhanced scattering OCT and high-sensitivity Doppler OCT. These new features enable the application of this system to clinical cases. A healthy subject and a geographic atrophy patient were measured in vivo, and simultaneous imaging of choroidal vasculature and birefringence structures are demonstrated.

Over the past several years, optical coherence tomography (OCT) has evolved into a powerful tool for the in vivo investigation of cross-sectional retinal anatomy and pathology.^1,2 OCT extracts depth-resolved information about the intensity of backscattered light from retinal layers using low coherence interferometry. The amount of light backscattered/reflected from the retinal layers can provide critical information regarding tissue properties and underlying changes. Furthermore, measuring changes in the angular (directional) scattering of retina layers might further enhance our ability to sense microscopic changes in cellular and subcellular morphology that might precede and/or follow disease progression. However, this information is not utilized in current clinical OCT systems. The reduction in light scattered by the retinal nerve fiber layer (RFNL) near the optic nerve head is reported to be an early indicator of axonal degeneration and a sensitive way to detect glaucomatous damage.^{3 – 5} The reflection from the RFNL is found to be highly directional, and the implications of the variability caused by the directional reflectance on clinical measurements are reported.⁶ The directional scattering properties exhibited by the Henle’s fiber layer (HFL) in human retina account for their oblique orientation with respect to the outer nuclear layer (ONL). Therefore, directional OCT (dOCT) imaging of human retina enables the delineation of HFL from the ONL and accurate measurement of macular photoreceptor nuclear layer thickness, which are important biomarkers for retinal degenerations.^7,8 The directional reflectance property shown by the photoreceptor bands, known as the optical Stiles–Crawford effect (SCE), provides the information on the structural integrity of the photoreceptors. An OCT-based assessment of the reflectivity of the photoreceptors layer is reported to study SCE in human retina.⁹

A high-penetration swept-source optical coherence tomography (HP-SS-OCT) system based on a 1-μm short cavity laser is developed. Doppler OCT processing is applied, along with a custom-made numerical phase stabilization algorithm; this process does not require additional calibration hardware. Thus, our phase stabilization method is simple and can be employed in a variety of SS-OCT systems. The bidirectional blood flow and vasculature in the deep choroid was successfully imaged via two Doppler modes that use different time intervals for Doppler processing. En face projection image of squared power of Doppler shift is compared to ICGA, and the utility of our method is verified.

Vision researchers often use small animals due to the availability of many transgenic strains that model human diseases or express biomarkers. Adaptive optics (AO) enables non-invasive single-cell imaging in a living animal but often results in high system complexity. Sensorless AO (SAO) can provide depth-resolved aberration correction with low system complexity. We present a multi-modal sensorless AO en face retina imaging system that includes optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy (SLO), and fluorescence detection. We present a compact lens-based imaging system design that allows for a 50-degree maximum field of view (FOV), which can be reduced to the region of interest to perform SAO with the modality of choice. The system performance was demonstrated on wild type mice (C57BL/6J), and transgenic mice with GFP labeled cells. SAO SLO was used for imaging microglia (Cx3cr1-GFP) over ~1 hour, where dynamics of the microglia branches were clearly observed. Our results also include volumetric cellular imaging of microglia throughout the inner retina.

Optical coherence tomography (OCT) has revolutionized modern ophthalmology, providing depth resolved images of the retinal layers in a system that is suited to a clinical environment. Although the axial resolution of OCT system, which is a function of the light source bandwidth, is sufficient to resolve retinal features at a micrometer scale, the lateral resolution is dependent on the delivery optics and is limited by ocular aberrations. Through the combination of wavefront sensorless adaptive optics and the use of dual deformable transmissive optical elements, we present a compact lens-based OCT system at an imaging wavelength of 1060 nm for high resolution retinal imaging. We utilized a commercially available variable focal length lens to correct for a wide range of defocus commonly found in patient’s eyes and a novel multi-actuator adaptive lens for aberration correction to achieve near diffraction limited imaging performance at the retina. With a parallel processing computational platform, high resolution cross-sectional and en face retinal image acquisition and display was performed in real time. In order to demonstrate the system functionality and clinical utility, we present images of the photoreceptor cone mosaic and other retinal layers acquired in vivo from research subjects.