Abstract
Choroidal imaging is a fast developing field of research. This chapter highlights the use of new technology in this field including; spectral domain optical coherence tomography (SD-OCT), enhanced-depth imaging OCT (EDI-OCT), swept-source OCT (SS-OCT), OCT angiography, wide field OCT/ICGA, and en-face imaging. It is hoped that as these techniques become ingrained in clinical practice, there will be an improved understanding of the choroid and the development of choroid-specific biomarkers that will improve understanding in this field.
Keywords
Choroid, SS-OCTA, Wide-field imaging, Choroidal imaging, Spectral domain optical coherence tomography angiography, Swept source optical coherence tomography angiography, Wide-field imaging, Fluorescein angiography, Indocyanine green angiography
Seventy percent of the total blood flow to the eye travels through the vascular network that is the choroid. Its primary function is to provide nutrients to the outer retinal structures, as well as the foveal avascular zone. However, there is evidence to suggest that the choroid has other roles including; thermoregulation in ocular tissues, modulation of intraocular pressure via vasomotor control of blood flow, and drainage of aqueous humor via the uveoscleral pathway.
Anatomy of the Choroid
The outer retina is dependent on the nutrients provided to it by the choroidal vasculature that consists of Bruch’s membrane, the choriocapillaris layer (CC), Sattler’s layer which contains medium diameter vessels, Haller’s layer that contains large diameter vessels, the suprachoroidal potential space, and finally the choroidal–scleral interface.
Anatomy of the Choroid
The outer retina is dependent on the nutrients provided to it by the choroidal vasculature that consists of Bruch’s membrane, the choriocapillaris layer (CC), Sattler’s layer which contains medium diameter vessels, Haller’s layer that contains large diameter vessels, the suprachoroidal potential space, and finally the choroidal–scleral interface.
Diseases that Affect the Choroid
Dilation of the choroidal vessels may lead to an increased choroidal thickness as seen in central serous chorioretinpathy (CSCR), and this may be associated with an increase in the choroidal hydrostatic pressure and vascular permeability. The reverse of this situation is choroid thinning, when there is a reduction in the nourishment to the retina as in old age and in age-related macular degeneration (AMD).
The high blood flow in the choroid also predisposes it to the embolic spread of metastatic tumors and infectious diseases including cytomegalovirus and toxoplamosis. The choroid is also the site of a number of inflammatory disorders involving the posterior segment of the eye including Vogt–Koyanaghi–Harada disease, birdshot chorioretinopathy, and choroidal granulomas in sarcoidosis or tuberculosis.
Current Techniques
Dye-Based Angiography
Traditional imaging modalities, including fluorescein angiography (FA), indocyanine-green angiography (ICGA), and ultrasonography, offer only an incomplete view of the in-vivo structure of the choroid and offer only poor quantitative data for research due to the poor resolution and repeatability inherent in the technology. Clinically, FA and ICGA are still considered the gold standard for imaging the choroidal vasculature. These imaging modalities are dynamic and allow direct visualization of the filling of large choroidal vessels and eventual leakage and/or pooling of dye. Of the two modalities, ICGA is superior for visualizing the choroidal vasculature as it has a longer wavelength of fluorescence than FA, this helps to enhance the visualization of structures beneath blood, exudates or retinal pigment epithelium (RPE) detachments in greater detail. ICGA has also been shown to reveal more detail in choroidal neovascularization (CNV) and has a greater sensitivity at detecting choroidal polyps than FA.
However, in both these techniques the microvascular architecture and feeder vessels of the choroid are often obscured in conditions such as neovascular AMD (nAMD) by hyperfluorescence in the late phase of dye transit, which can limit precise assessment of CC and the choroid. In addition, these modalities are invasive involving the use of intravenous contrast that can result in systemic side effects and rarely anaphylaxis.
Laser Doppler Flowmetry
Laser doppler flowmetry is a technique that is primarily used in research to allow the noninvasive measurement of choroidal blood flow by measuring the speed and number of the erythrocytes moving in a sampling volume. This in-vivo technique has provided evidence that decreased flow in the choroidal vasculature may be linked to various diseases including diabetic retinopathy, AMD, and retinitis pigmentosa.
Ultrasound
Ultrasound (US) uses sound waves to visualize the choroid and still plays an important role in the diagnosis of choroidal thickening and ocular tumors (i.e., melanomas). US technology provides a real-time, noninvasive safe imaging technique that offers improved visualization of structures that are obscured by opaque media such as in vitreous haze secondary to inflammation or hemorrhage. Nevertheless, new technologies are starting to supersede US due to it interoperator variability and the poor image resolution, which makes the detection of small changes in the choroid difficult.
Optical Coherence Technology
With increasing resolution, optical coherence technology (OCT) has become a core investigation in chorioretinal diseases. It has increased the visualization of the choroidal anatomy and has allowed quantitative assessment of the choroidal vasculature. This chapter highlights the use of this new technology, including the use of spectral domain optical coherence tomography (SD-OCT), enhanced-depth imaging OCT (EDI-OCT), swept-source OCT (SS-OCT), wide field OCT/ICGA, and en-face imaging.
Spectral Domain Optical Coherence Tomography
SD-OCT technology provides high-resolution and cross-sectional images in a noninvasive manner. The process involves the detection of light echoes using an interferometer with a high-speed spectrometer. When light is directed toward the retina, a small portion of this light is then reflected back to the spectrometer and analyzed, the rest is scattered. A technique called interferometry is used to ensure that this scattered light does not interfere with image acquisition. Despite this technology revolutionizing care and monitoring in patients with posterior segment disease, its utility for visualizing the choroid has been limited for a number of reasons including a reduction in sensitivity and resolution of the image with increasing distance from the zero-delay and increased light scattering at the retinal pigment epithelium.
EDI-OCT, first described by Spaide, aimed to overcome some of these issues and improve the quality of the images acquired using SD-OCT. The zero-delay line refers to the line of symmetry around which images are inverted on SD-OCT. Generally, structures closer to the zero-delay line will have the clearest images. Sensitivity roll-off refers to the decreased resolution and clarity of a structure that is farther from this point. When imaging the retina the zero-delay line is positioned at the posterior vitreous, this optimizes the visualization of the retinal structures but often only provides limited information on the choroid. In EDI-OCT, this line is set adjacent to the choroid, allowing improved image acquisition of the choroid. By displacing the instrument to image deeper layers an inverted image is acquired, anterior structures such as the retina and the vitreous are imaged lower on the screen. This has the effect of improving the visualization of the choroid, enhancing its illumination and increasing the clarity of the structures imaged. This technique has been refined and is now available in the software of many different OCT devices. These devices can now perform EDI-OCT automatically without requiring the user to invert the image ( Fig. 20.1 ).
Successful examination and measurement of choroidal thickness in normal and pathologic states is well reported using a number of commercial SD-OCT devices. Early studies into this technique involved manual measurements to be acquired; however, recent software updates have been released that may automate this process. The conclusions drawn from choroidal thickness are only useful if they encompass the entire choroid up to scleral interface. On the contrary, even with the EDI technique this is not always the case; studies using SD-OCT system report a clear visualization of the choroid–scleral interface in only 70–75% of healthy and diseased states. This is not ideal and can result in falsely low readings of choroidal thickness, which can affect the results and the conclusions drawn from these studies. This poor sensitivity is likely due to the short ~840 nm wavelength used in the SD-OCT devices that has poor penetration under the RPE. SS-OCT devices that use a longer wavelength ~1050 nm may therefore improve these techniques.
Swept-Source Optical Coherence Tomography
SS-OCT uses a frequency swept-source light emitted at different frequencies to increase the scan acquisition speed. The commercially available and prototype SS-OCT systems have an axial scan rate that ranges from 100,000 to 400,000 A-scans per second, which is five to ten times that of the SD-OCT systems. This enables faster acquisition of B-scans and has the added benefit of increasing the field of view to 12×12 mm. Compared to SD-OCT, SS-OCT offers two distinct advantages for visualizing the choroid: First, the longer, ~1050 nm center wavelength used in SS-OCT systems is less attenuated by the RPE; second, SS-OCT does not use spectrometer-based detection and is less susceptible to sensitivity roll-off. Together, these two characteristics make SS-OCT less susceptible to low signal in regions below the RPE and have allowed greater visualization of the choroid. With the advent of the SS-OCT, it is now possible to gain in-vivo high-resolution choroidal images that clearly delineate the vascular layers that are known to exist from histological data ( Fig. 20.2 ). For these reasons, SS-OCT appears superior to the SD-OCT for measuring choroidal thickness as the choroidal–scleral interface is more easily delineated. When choroidal thickness measurements are obtained on both devices, there is a significant increase in the choroidal thickness recorded on the SS-OCT device. It is likely that this is due to the significantly improved visualization of the choroidal–scleral interface with the SS-OCT devices.
OCTA and the Choriocapillaris
The CC is the capillary network of the choroid that provides nutrients and removes waste products from the outer retinal structures. Histopathological studies have highlighted that poor choroidal perfusion may be a risk factor in many retinal diseases including nAMD, diabetic retinopathy, and the formation of drusen in dry AMD. Improved imaging of the choroidal vasculature will allow the early detection of choroidal vascular insufficiency, which may act as an early marker for several retinal diseases.
Optical coherence tomography angiography (OCTA) is a noninvasive technology that generates depth-resolved images of the vasculature by acquiring repeated B-scans from the same retinal and choroidal locations. Compared with stationary areas of the retina and choroid, the movement of erythrocytes within a vessel generates a decorrelation signal. An OCTA image is generated by displaying this OCTA signal as a grayscale image. High-density raster scanning of a two-dimensional area generates a volumetric rendering of blood flow allowing direct visualization of normal and abnormal retinal and choroidal blood vessels.
There are only a few studies to date that have attempted to visualize the CC using SD-OCTA. In 2012, Kurokawa et al . used adaptive optics (AOs) and long wavelength SD-OCTA at 91,000 A-scans per second to image the retinal and choroidal vasculature in healthy subjects. This was then replicated in patients with AMD in 2013 using phase variance SD-OCTA. Despite these successes, the shorter wavelength of light used in the SD-OCT machines has limited its clinical utility for imaging the CC as the signal has poor penetration through the RPE layer.
Swept-Source OCTA
Recently a SS-OCTA prototype has been developed at the Massachusetts Institute of Technology (MIT, Cambridge, MA) that uses a high speed vertical cavity surface emitting laser as the light source and operates at a ~1050-nm wavelength achieving a speed of 400,000 A-scans per second. Using this technology, the microvasculature of the CC, as well as tightly packed networks of feeding arterioles and draining venules can be visualized. Panoramic ultrawide field (UWF) stitched OCT angiograms of the CC spanning ~32 mm on the retina indicate that the vascular pattern of the CC changes depending on its fundus location. It is densely packed at the central fovea, becoming more diffuse and lobular as it moves toward the periphery. These OCTA findings are consistent with the ex-vivo postmortem studies.
The ability of the SS-OCTA technology to visualize the choriocapillaris has been compared to SD-OCTA technology by Lane and Moult et al . (2016). The RTVue Avanti with prototype AngioVue software for OCTA (Optovue, Inc., Fremont, CA) was compared with the prototype ultra-high speed ~1050-nm SS-OCT. The study compared the two technologies in their ability to visualize the CC under drusen. The SS-OCTA prototype was more robust in its imaging and provided fewer areas of signal loss under the drusen compared to the SD-OCTA device, this study also confirmed that there was increased CC dropout under drusen, which had previously been described in ex-vivo studies ( Fig. 20.3 ).
This technology has also been used to visualize CNV lesions that lie both superior and inferior to the RPE. Recent work by Novais et al . has indicated that SS-OCTA offers improved visualization of the CNV lesions when compared to commercial SD-OCT, the size of the CNV was also noted to be significantly larger when using the SS-OCTA technology ( Fig. 20.4 ). In particular, Sub-RPE CNV lesions are better visualized using SS-OCTA technology as it is left prone to signal roll off than the SD-OCTA devices.
