A new technique for monitoring blood flow will help investigate eye functions and retinal disease.Poor blood supply is one of the main causes of several retinal diseases. Vascular disorders and impaired circulation are observed in major eye diseases that cause blindness, including age-related macular degeneration (AMD) 1 and glaucoma. 2 A noninvasive, 3D imaging tool for major vascular systems of the eye might be helpful for understanding and diagnosing eye diseases. Circulation abnormalities are typically diagnosed using fluorescence angiography, in which injected fluorescent dye is detected. However, this technique is invasive, may have side effects, and cannot be used for patients who are allergic to the dye. In addition, axial resolution-in the light's direction of travel-is poor. This is significant when distinguishing between vascular systems in the retina and the choroid (a layer of blood-rich tissue behind the retina), or recording details of the fine and complex 3D network of choroidal vessels.Other existing eye-imaging techniques have similar problems. Ultrasound Doppler imaging can be used to visualize the crosssectional flow distribution in the eye. However, its limited acquisition speed prevents 3D in vivo imaging while its axial resolution is also insufficient. Scanning-laser Doppler flowmetry is noninvasive and can quantify the microvascular blood flow but it cannot distinguish between the choroidal and retinal vascular systems. We have developed 3D angiography for the eyeoptical coherence angiography (OCA)-based on optical coherence tomography (OCT). OCT is widely used in clinical ophthalmology to visualize the retina's 3D microstructure. 3 OCA uses high-speed Fourier-domain OCT for 3D in vivo imaging of the human eye. To enhance the choroid's contrast, we use light sources with a central wavelength of around 1µm. 4 Scattering OCA uses differences between the optical properties of blood and the surrounding tissue to increase the contrast in the eye vasculature, 5 while Doppler OCA uses phase-resolved Doppler analysis with OCT 6 to detect blood flow. 7 Figure 1. (a) Combination of 3D volume-rendered OCT and scattering OCA in vivo images of human macula. (b) Stereo view of the macula's choroidal vessels. (c) En face projection of choroidal vessels.We developed clinical prototypes of 1µm Fourier-domain OCT, which we used to scan the eyes of healthy human volunteers in vivo. The 3D data sets obtained were processed with scattering and/or Doppler OCA.Since rich pigments are present in choroidal tissue, the backscattered-light intensity from this tissue type is larger than that from blood. Unfortunately, it also causes OCT signal decay in the choroid. This attenuation must be considered in scattering OCA when attempting to obtain a clear 3D choroidal vascular image. The retinal pigment epithelium (RPE), a monocellular layer between retina and choroid, is segmented in OCT crosssectional images. We extracted choroidal images sliced at equal distances from the RPE and applied segmentation based on image s...

Retinal, choroidal and scleral imaging by using swept-source optical coherence tomography (SS-OCT) with a 1-microm band probe light, and high-contrast and three-dimensional (3D) imaging of the choroidal vasculature are presented. This SS-OCT has a measurement speed of 28,000 A-lines/s, a depth resolution of 10.4 microm in tissue, and a sensitivity of 99.3 dB. Owing to the high penetration of the 1-microm probe light and the high sensitivity of the system, the in vivo sclera of a healthy volunteer can be observed. A software-based algorithm of scattering optical coherence angiography (S-OCA) is developed for the high-contrast and 3D imaging of the choroidal vessels. The S-OCA is used to visualize the 3D choroidal vasculature of the in vivo human macula and the optic nerve head. Comparisons of S-OCA with several other angiography techniques including Doppler OCA, Doppler OCT, fluorescein angiography, and indocyanine green angiography are also presented.

Phase retardation imaging including local birefringence imaging of biological tissues is described by generalized Jones-matrix optical coherence tomography. The polarization properties of a local tissue can be obtained from two Jones matrices that are measured by backscattered lights from the front and back boundaries of the local tissue. The error in the phase retardation measurement due to background noise is analyzed theoretically, numerically, and experimentally. The minimum detectable phase retardation is estimated from numerical simulations. The theoretical analysis suggests that the measurements with two orthogonal input polarization states have the lowest retardation error. Local birefringence imaging is applied to the human anterior eye chamber and skin in vivo.

We present fiber-based polarization-sensitive swept-source optical coherence tomography (SS-OCT) based on continuous source polarization modulation. The light source is a frequency swept laser centered at 1.31 microm with a scanning rate of 20 kHz. The incident polarization is modulated by a resonant electro-optic modulator at 33.3 MHz, which is one-third of the data acquisition frequency. The zeroth- and first-order harmonic components of the OCT signals with respect to the polarization modulation frequency have the polarimetric information of the sample. By algebraic and matrix calculations of the signals, this system can measure the depth-resolved Jones matrices of the sample with a single wavelength scan. The phase fluctuations of the starting trigger of wavelength scan and the polarization modulation are cancelled by monitoring the OCT phase of a calibration mirror inserted into the sample arm. We demonstrate the potential of the system by the measurement of chicken breast muscle and the volumetric measurement of an in vivo human anterior eye segment. The phase retardation image shows an additional contrast in the fibrous tissue such as the collagen fiber in the trabecular meshwork and sclera.

Comprehensive angiography provides insight into the diagnosis of vascular-related diseases. However, complex microvascular networks of unstable in vivo organs such as the eye require micron-scale resolution in three dimensions and a high sampling rate to access a wide area as maintaining the high resolution. Here, we introduce dual-beam-scan Doppler optical coherence angiography (OCA) as a label-free comprehensive ophthalmic angiography that satisfies theses requirements. In addition to high resolution and high imaging speed, high sensitivity to motion for detecting tiny blood flow of microvessels is achieved by detecting two time-delayed signals with scanning of two probing beams separated on a sample. We present in vivo three-dimensional imaging of the microvasculature of the posterior part of the human eye. The demonstrated results show that this technique may be used for comprehensive ophthalmic angiography to evaluate the vasculature of the posterior human eye and to diagnose variety of vascular diseases.

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Phase retardation of in vivo human retinal nerve fiber layer (RNFL) is quantitatively measured by two methods--polarization-sensitive spectral-domain optical coherence tomography (PS-SD-OCT) and scanning laser polarimetry (SLP). An en face cumulative phase retardation map is calculated from the three-dimensional (3-D) phase retardation volume of healthy and glaucomatous eyes measured by PS-SD-OCT. It is shown that the phase retardation curves around the optic nerve head measured by PS-SD-OCT and SLP have similar values except near the retinal blood vessels. PS-SD-OCT can measure the cumulative phase retardation of RNFL as well as SLP, which will allow the evaluation of RNFL for glaucomatous eyes.

GDx and polarization-sensitive spectral-domain OCT are complementary in probing birefringence properties in exudative AMD. Polarimetry findings in exudative AMD emphasized different features and were related to the progression of the disease, potentially providing a noninvasive tool for microstructure in exudative AMD.