We have combined Fourier-domain optical coherence tomography (FD-OCT) with a closed-loop adaptive optics (AO) system using a Hartmann-Shack wavefront sensor and a bimorph deformable mirror. The adaptive optics system measures and corrects the wavefront aberration of the human eye for improved lateral resolution (~4 μm) of retinal images, while maintaining the high axial resolution (~6 μm) of stand alone OCT. The AO-OCT instrument enables the three-dimensional (3D) visualization of different retinal structures in vivo with high 3D resolution (4×4×6 μm). Using this system, we have demonstrated the ability to image microscopic blood vessels and the cone photoreceptor mosaic.
We interfaced color Doppler Fourier domain optical coherence tomography (CD-FDOCT) with a commercial OCT system to perform in vivo studies of human retinal blood flow in real time. FDOCT does not need reference arm scanning and records one full depth and Doppler profile in parallel. The system operates with an equivalent A-scan rate of 25 kHz and allows real time imaging of the color encoded Doppler information together with the tissue morphology at a rate of 2–4 tomograms (40×512 pixel) per second. The recording time of a single tomogram (160×512 data points) is only 6,4ms. Despite the high detection speed we achieve a system sensitivity of 86dB using a beam power of 500µW at the cornea. The fundus camera allows simultaneous view for selection of the region of interest. We observe bi-directional blood flow and pulsatility of blood velocity in retinal vessels with a Doppler detection bandwidth of 12.5 kHz and a longitudinal velocity sensitivity in tissue of 200µm/s.
In vivo imaging of the human retina with a resolution that allows visualization of cellular structures has proven to be essential to broaden our knowledge about the physiology of this precious and very complex neural tissue that enables the first steps in vision. Many pathologic changes originate from functional and structural alterations on a cellular scale, long before any degradation in vision can be noted. Therefore, it is important to investigate these tissues with a sufficient level of detail in order to better understand associated disease development or the effects of therapeutic intervention. Optical retinal imaging modalities rely on the optical elements of the eye itself (mainly the cornea and lens) to produce retinal images and are therefore affected by the specific arrangement of these elements and possible imperfections in curvature. Thus, aberrations are introduced to the imaging light and image quality is degraded. To compensate for these aberrations, adaptive optics (AO), a technology initially developed in astronomy, has been utilized. However, the axial sectioning provided by retinal AO-based fundus cameras and scanning laser ophthalmoscope instruments is limited to tens of micrometers because of the rather small available numerical aperture of the eye. To overcome this limitation and thus achieve much higher axial sectioning in the order of 2-5µm, AO has been combined with optical coherence tomography (OCT) into AO-OCT. This enabled for the first time in vivo volumetric retinal imaging with high isotropic resolution. This article summarizes the technical aspects of AO-OCT and provides an overview on its various implementations and some of its clinical applications. In addition, latest developments in the field, such as computational AO-OCT and wavefront sensor less AO-OCT, are covered.
The visualization and assessment of retinal microvasculature are important in the study, diagnosis, monitoring, and guidance of treatment of ocular and systemic diseases. With the introduction of optical coherence tomography angiography (OCTA), it has become possible to visualize the retinal microvasculature volumetrically and without a contrast agent. Many lab-based and commercial clinical instruments, imaging protocols and data analysis methods and metrics, have been applied, often inconsistently, resulting in a confusing picture that represents a major barrier to progress in applying OCTA to reduce the burden of disease. Open data and software sharing, and cross-comparison and pooling of data from different studies are rare. These inabilities have impeded building the large databases of annotated OCTA images of healthy and diseased retinas that are necessary to study and define characteristics of specific conditions. This paper addresses the steps needed to standardize OCTA imaging of the human retina to address these limitations. Through review of the OCTA literature, we identify issues and inconsistencies and propose minimum standards for imaging protocols, data analysis methods, metrics, reporting of findings, and clinical practice and, where this is not possible, we identify areas that require further investigation. We hope that this paper will encourage the unification of imaging protocols in OCTA, promote transparency in the process of data collection, analysis, and reporting, and facilitate increasing the impact of OCTA on retinal healthcare delivery and life science investigations.
We present in vivo volumetric images of human retinal micro-circulation using Fourier-domain optical coherence tomography (Fd-OCT) with the phase-variance based motion contrast method. Currently fundus fluorescein angiography (FA) is the standard technique in clinical settings for visualizing blood circulation of the retina. High contrast imaging of retinal vasculature is achieved by injection of a fluorescein dye into the systemic circulation. We previously reported phase-variance optical coherence tomography (pvOCT) as an alternative and non-invasive technique to image human retinal capillaries. In contrast to FA, pvOCT allows not only noninvasive visualization of a two-dimensional retinal perfusion map but also volumetric morphology of retinal microvasculature with high sensitivity. In this paper we report high-speed acquisition at 125 kHz A-scans with pvOCT to reduce motion artifacts and increase the scanning area when compared with previous reports. Two scanning schemes with different sampling densities and scanning areas are evaluated to find optimal parameters for high acquisition speed in vivo imaging. In order to evaluate this technique, we compare pvOCT capillary imaging at 3x3 mm2 and 1.5x1.5 mm2 with fundus FA for a normal human subject. Additionally, a volumetric view of retinal capillaries and a stitched image acquired with ten 3x3 mm2 pvOCT sub-volumes are presented. Visualization of retinal vasculature with pvOCT has potential for diagnosis of retinal vascular diseases.