In vivo volumetric imaging of human retinal circulation with phase-variance optical coherence tomography

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 mm^2 and 1.5x1.5 mm^2 with fundus FA for a normal human subject. Additionally, a volumetric view of retinal capillaries and a stitched image acquired with ten 3x3 mm^2 pvOCT sub-volumes are presented. Visualization of retinal vasculature with pvOCT has potential for diagnosis of retinal vascular diseases

Imaging of the Lamina Cribrosa using Swept-Source Optical Coherence Tomography.

The lamina cribrosa (LC) is the presumed site of axonal injury in glaucoma. Its deformation has been suggested to contribute to optic neuropathy by impeding axoplasmic flow within the optic nerve fibers, leading to apoptosis of retinal ganglion cells. To visualize the LC in vivo, optical coherence tomography (OCT) has been applied. Spectral domain (SD)-OCT, used in conjunction with recently introduced enhanced depth imaging (EDI)-OCT, has improved visualization of deeper ocular layers, but in many individuals it is still limited by inadequate resolution, poor image contrast and insufficient depth penetrance. The posterior laminar surface especially is not viewed clearly using these methods. New generation high-penetration (HP)-OCTs, also known as swept-source (SS)-OCT, are capable to evaluate the choroid in vivo to a remarkable level of detail. SS-OCTs use a longer wavelength (1,050 nm instead of 840 nm) compared to the conventional techniques. We review current knowledge of the LC, findings from trials that use SD-OCT and EDI-OCT, and our experience with a prototype SS-OCT to visualize the LC in its entirety. Key Points What is known? •     The LC is the presumed site of axonal injury in glaucoma •     Compared to spectral domain-OCT, enhanced depth imaging-OCT improves imaging of the LC •     Even so, currently used SD-OCT techniques are restricted by poor wavelength penetrance of the deeper ocular layers What our findings add? •    SS-OCT may be a superior imaging modality for deep ocular structures •    Prior studies used SS-OCT to evaluate choroidal thickness in both healthy and 'normal tension glaucoma' eyes •    SS-OCT enables good evaluation of three-dimension (3D) lamina cribrosa morphology. How to cite this article: Nuyen B, Mansouri K, Weinreb RN. Imaging of the Lamina Cribrosa using Swept-Source Optical Coherence Tomography. J Current Glau Prac 2012;6(3): 113-119

The Relationship of the Clinical Disc Margin and Bruch's Membrane Opening in Normal and Glaucoma Subjects.

PurposeWe tested the hypotheses that the mismatch between the clinical disc margin (CDM) and Bruch's membrane opening (BMO) is a function of BMO area (BMOA) and is affected by the presence of glaucoma.MethodsA total of 45 normal eyes (45 subjects) and 53 glaucomatous eyes (53 patients) were enrolled and underwent radial optic nerve head (ONH) imaging with spectral domain optical coherence tomography. The inner tip of the Bruch's membrane (BM) and the clinical disc margin were marked on radial scans and optic disc photographs, and were coregistered with custom software. The main outcome measure was the difference between the clinical disc area (CDA) and BMOA, or CDA-BMOA mismatch, as a function of BMOA and diagnosis. Multivariate regression analyses were used to explore the influence of glaucoma and BMOA on the mismatch.ResultsGlobal CDA was larger than BMOA in both groups but the difference was statistically significant only in the normal group (1.98 ± 0.37 vs. 1.85 ± 0.45 mm2, P = 0.02 in the normal group; 1.96 ± 0.38 vs. 1.89 ± 0.56 mm2, P = 0.08 in the glaucoma group). The sectoral CDA-BMOA mismatch was smaller in superotemporal (P = 0.04) and superonasal (P = 0.05) sectors in the glaucoma group. The normalized CDA-BMOA difference decreased with increasing BMOA in both groups (P < 0.001). Presence or severity of glaucoma did not affect the CDA-BMOA difference (P > 0.14).ConclusionsClinical disc area was larger than BMOA in normal and glaucoma eyes but reached statistical significance only in the former group. The CDA-BMOA mismatch diminished with increasing BMOA but was not affected by presence of glaucoma. These findings have important clinical implications regarding clinical evaluation of the ONH

Visible Optical Coherence Tomography based Multimodal Imaging for Quantification of Retinal Lipofuscin

Retinal degeneration is the leading cause of irreversible low vision and blindness in the world, that describes conditions characterized by progressive loss of photoreceptors. Retinal Pigment Epithelium (RPE) is located under photoreceptors’ outer segments and plays an important role in the maintenance of photoreceptors by completing the visual cycle and phagocytosis of shed photoreceptor outer segments. Lipofuscin, a byproduct of the visual cycle, is a nondegradable compound that accumulates in the RPE cells and eventually damages the RPE cells and inevitably causes photoreceptor degeneration. Lipofuscin is the major cause of fundus fluorescence that can be detected by Fundus Autofluorescent (FAF) imaging systems. Reliable and quantified FAF values are necessary for lipofuscin quantification which can be a significant tool in the diagnosis of retinal degenerative disease in early stages and provide a better opportunity for treatment before the loss of vision stage. However, FAF is attenuated by the ocular media prior to the RPE, including cornea, lens, vitreous body, retinal layers in front of the RPE, and the melanin granules within the RPE cells that migrate to the apical region upon light exposure. This attenuation varies among people and for an individual over time and cannot be measured directly, thus hurdles measurement of the true FAF values. Further, differences in acquisition systems such as illumination power and detector sensitivity, directly affect the measured FAF. This issue has been addressed by implementing a reference target in the FAF imaging system. Normalizing the FAF signal to that of the target eliminates the dependency on the acquisition parameters. However, the issue of pre-RPE and RPE melanin attenuation remains unresolved. Further, the fluorescence characteristics of the commercially available fluorescent reference are quite different than retinal lipofuscin that challenges the quantification of the absolute amount of lipofuscin in the RPE. In this dissertation, we propose a new multimodal imaging system based on visible-light optical coherence tomography (VIS-OCT) that provides a three-dimensional image. The technology simultaneously acquires VIS-OCT and FAF with a single broadband visible light source. Since both images are originated from the same group of photons and travel through the same ocular media at the same time, the attenuation factor is similar in both modalities. Therefore, by normalizing FAF by VIS-OCT of the RPE layer, the attenuation of the pre_RPE media can be eliminated. Further, we implemented two reference targets to quantify VIS-OCT and FAF and eliminate the dependency on acquisition parameters. These references were later substituted by a single customized reference that consists of the major lipofuscin fluorophore, called A2E. The quantitative imaging independent of system fluctuation, and attenuation of pre-RPE and RPE melanin was successfully tested on retinal simulating phantoms, in vivo on the animal retina, and human subjects. The in vivo quantification in small animals linearly correlates with A2E content measured by mass spectrometry. Quantitative imaging of human retinas is consistent with the linear accumulation of lipofuscin with age. The VIS-OCT-FAF has the potential for clinical diagnosis

Multidimensional en-face OCT imaging of the retina.

Fast T-scanning (transverse scanning, en-face) was used to build B-scan or C-scan optical coherence tomography (OCT) images of the retina. Several unique signature patterns of en-face (coronal) are reviewed in conjunction with associated confocal images of the fundus and B-scan OCT images. Benefits in combining T-scan OCT with confocal imaging to generate pairs of OCT and confocal images similar to those generated by scanning laser ophthalmoscopy (SLO) are discussed in comparison with the spectral OCT systems. The multichannel potential of the OCT/SLO system is demonstrated with the addition of a third hardware channel which acquires and generates indocyanine green (ICG) fluorescence images. The OCT, confocal SLO and ICG fluorescence images are simultaneously presented in a two or a three screen format. A fourth channel which displays a live mix of frames of the ICG sequence superimposed on the corresponding coronal OCT slices for immediate multidimensional comparison, is also included. OSA ISP software is employed to illustrate the synergy between the simultaneously provided perspectives. This synergy promotes interpretation of information by enhancing diagnostic comparisons and facilitates internal correction of movement artifacts within C-scan and B-scan OCT images using information provided by the SLO channel

Two-dimensional segmentation of the retinal vascular network from optical coherence tomography

The automatic segmentation of the retinal vascular network from ocular fundus images has been performed by several research groups. Although different approaches have been proposed for traditional imaging modalities, only a few have addressed this problem for optical coherence tomography (OCT). Furthermore, these approaches were focused on the optic nerve head region. Compared to color fundus photography and fluorescein angiography, two-dimensional ocular fundus reference images computed from three-dimensional OCT data present additional problems related to system lateral resolution, image contrast, and noise. Specifically, the combination of system lateral resolution and vessel diameter in the macular region renders the process particularly complex, which might partly explain the focus on the optic disc region. In this report, we describe a set of features computed from standard OCT data of the human macula that are used by a supervised-learning process (support vector machines) to automatically segment the vascular network. For a set of macular OCT scans of healthy subjects and diabetic patients, the proposed method achieves 98% accuracy, 99% specificity, and 83% sensitivity. This method was also tested on OCT data of the optic nerve head region achieving similar results

Two-dimensional segmentation of the retinal vascular network from optical coherence tomography

The automatic segmentation of the retinal vascular network from ocular fundus images has been performed by several research groups. Although different approaches have been proposed for traditional imaging modalities, only a few have addressed this problem for optical coherence tomography (OCT). Furthermore, these approaches were focused on the optic nerve head region. Compared to color fundus photography and fluorescein angiography, two-dimensional ocular fundus reference images computed from three-dimensional OCT data present additional problems related to system lateral resolution, image contrast, and noise. Specifically, the combination of system lateral resolution and vessel diameter in the macular region renders the process particularly complex, which might partly explain the focus on the optic disc region. In this report, we describe a set of features computed from standard OCT data of the human macula that are used by a supervised-learning process (support vector machines) to automatically segment the vascular network. For a set of macular OCT scans of healthy subjects and diabetic patients, the proposed method achieves 98% accuracy, 99% specificity, and 83% sensitivity. This method was also tested on OCT data of the optic nerve head region achieving similar results