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Other Imaging Modalities in CSC
C H A P T E R
14 Other Imaging Modalities in CSC Alexei N. Kulikov, Dmitrii S. Maltsev Department of Ophthalmology, Military Medical Academy, St Petersburg, Russia
IR-REFLECTANCE Color fundus photography has become one of the basic imaging modalities for the documentation of the posterior eye segment because of its relative simplicity and because the image produced is the closest to the natural eye fundus in appearance. Compared to indirect ophthalmoscopy, however, color fundus photography does not provide any additional information about retinal pathology. Moreover, some subtle changes of the retina or retinal pigment epithelium might be missed in low-resolution pictures. In addition, the visible light used in color fundus photography is associated with a substantial number of chromatic aberrations and low penetration in ocular media with decreased transparency, and causes the pupil constriction that restricts evaluation of the eye fundus. Nevertheless, color fundus photography is of high clinical importance because it serves as a reference point for other imaging modalities. Monochromatic imaging, particularly if performed with scanning laser ophthalmoscope (SLO), has higher contrast, better resolution, and smaller depth of focus than color fundus photography. The confocal principle of the SLO ensures that light scattered from layers other than the point of illumination will be blocked. Use of an infrared laser source (790 nm) in SLO excludes pupil constriction and allows eye fundus examination to be performed, even in patients with mild cataract or vitreal hemorrhage. However, the absorption, reflection, and scattering of infrared illumination by intraocular tissues is significantly different compared to the visible spectrum. The main chromophores of the eye fundus that interact with infrared light are melanin, hemoglobin, fibrine, and lipids. The clusters of melanin reflect a substantial proportion of IR light, therefore, pigmentary changes demonstrate hyperreflectivity (Fig. 1). In contrast, atrophic or attenuated areas of RPE such as PED have a hyporeflective appearance. At the same time, a thin layer of melanin (normal RPE in low pigmented or myopic eyes) is relatively penetrable for intense IR wavelength. Lipids are highly reflective and lipid exudation, although rarely found in CSC patients, might indicate a chronic exudation associated with secondary neovascularization (Fig. 2). Furthermore, any macular pathology characterized by sub-RPE deposition of abnormal material can result in scattering or deeper penetration of IR light and consequently in decreased reflectance of a particular RPE region. Mild alterations of RPE without decrease of the RPE Central Serous Chorioretinopathy https://doi.org/10.1016/B978-0-12-816800-4.00013-9
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FIG. 1 Multimodal imaging of the right eye in a patient with resolved acute CSC and persistent PED. (А) IRreflectance demonstrates a sharply demarcated round hyporeflective area (arrowhead) with hyperreflective flecks. (B) Dark field-SLO demonstrates an area of RPE atrophy and pigment clumps (arrowhead). (C) Cross-sectional OCT scan shows PED (arrowhead) with hyperreflective clusters and hyperpermeability on the top of the PED.
FIG. 2 Multimodal imaging of the left eye in a patient with chronic CSC complicated by choroidal neovascularization. (А) IR-reflectance demonstrates accumulation of hard exudates (arrowhead). The black line corresponds to horizontal OCT scan. The white line corresponds to vertical OCT scan. (B) Horizontal cross-sectional OCT scan shows RPE irregularity, hard exudates in the outer retina, and subretinal hyperreflective material. (C) Vertical cross- sectional OCT scan shows RPE irregularity, subretinal hyperreflective material, and intraretinal cystic fluid.
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FIG. 3 Multimodal imaging of the right eye in a patient with resolved acute CSC. (А) IR-reflectance demonstrates a hyperreflective area (arrowhead) corresponding to the former leakage site. The white line corresponds to the OCT scan. (B) Cross-sectional OCT scan shows minute REP attenuation (arrowhead) responsible for IR hyperreflectivity.
thickness, however, might be associated with isolated changes in the reflection profile and might appear as hyperreflective signals (Fig. 3) or as a combination of hyperreflective and hyporeflective signals. This becomes clear in the visualization of small RPE bumps and drusen. Small and medium drusen are more likely to appear hyperreflective; large drusen (drusenoid PED) are typically hyporeflective because the density of pigmentation decreases above large drusen (Fig. 4). Fibrin has little effect on the transmission of IR light in ocular media. A substantial accumulation of subretinal fibrin, however, could appear on IR-reflectance image as smooth and hyporeflective retinal regions (Fig. 5). Macular pigment has no effect on IR light, therefore the IR-reflectance image of the central retina does not distinguish the macular and foveal regions except for the foveal indentation, which can be revealed because of changes in the IR light reflection. In young patients, fovea and the parafoveal region can be distinguished with a pin-hole aperture because of increased reflectivity of the inner limiting membrane. Although numerous findings can be revealed with IR-reflectance and its modifications, the place of the IR-reflectance in the detection of macular disease, particularly CSC, appears to be underestimated and requires detailed evaluation. The image obtained with SLO depends on the size of the confocal aperture in two ways: with a wide aperture, the amount of the light increases and, therefore, the fundus of heavily
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FIG. 4 Multimodal imaging of the left eye in a patient with dry AMD. (А) IR-reflectance demonstrates a hyporeflective area (arrowheads) corresponding to a group of drusenoid PEDs and soft drusen, hyperreflective numerous small hyporeflective spots corresponding to reticular drusen (arrow). (B) RM-SLO demonstrates marked elevations (arrowheads) corresponding to a group of drusenoid PEDs and soft drusen as well as numerous small bumps corresponding to reticular pseudodrusen (arrow). (C) DF-SLO demonstrates bright areas (arrowheads) corresponding to large drusenoid PEDs and accumulation of pigment clumps at the border of PEDs (asterisk). (D) Cross-sectional OCT scan through drusenoid PEDs (represented by the black line on IR-reflectance image). (E) Cross-sectional OCT scan through drusen and pigment clumps (asterisk) (represented by the dashed line on IR-reflectance image). (F) Crosssectional OCT scan through reticular pseudodrusen (represented by the white line on IR-reflectance image).
pigmented eyes with small pupil or opacification of the eye media can be evaluated; and the intensity of light scattering also increases and consequently the contrast of the eye fundus image decreases. The higher amount of illumination, however, allows for better penetration through the RPE, and large choroidal vessels become visible (Fig. 6). This approach allows fast evaluation of the choroidal vasculature and classification of choroidal vasculature pattern in several main groups (Fig. 7) suggested by Savastano MS and coauthors using en face OCT.1 NSD causes a significant scattering of IR light. This depends on the height of the detachment because the larger the distance between the detached retina and the RPE, the greater the divergence of the laser beam scattered by the detached retina. Therefore, in the RI-reflectance image, the height of NSD can be evaluated indirectly by the degree of darkness in the NSD area. The eccentricity of the NSD also affects its appearance because the incidence angle of illumination increases, as consequently does the scattering of the light on the NSD borders. Therefore, central NSD typically appears to be not clearly demarcated. Additional
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FIG. 5 Multimodal imaging of both eyes in a patient with acute CSC. (A) IR-reflectance of the right eye demonstrates neurosensory detachment with an accumulation of subretinal fibrin (arrowheads). (B) IR-reflectance of the left eye demonstrates subretinal fibrin accumulation (arrow) within small neurosensory detachment. (C) Cross-sectional OCT scan through the neurosensory detachment in the right eye (corresponds to the white line) demonstrates subretinal fibrin accumulation (arrowhead). (D) Cross-sectional OCT scan through the small neurosensory detachment in the left eye (corresponds to the white line) demonstrates subretinal fibrin accumulation (arrow).
FIG. 6 IR-reflectance imaging of choroidal vasculature in a healthy eye. (A) IR-reflectance image obtained with an aperture of 1.5 mm. (B) IR-reflectance image obtained with an aperture of 3 mm. (C) IR-reflectance image obtained with an aperture of 4 mm. (D) IR-reflectance image obtained with an aperture of 7 mm. Note that differentiation of choroidal vasculature (arrowheads) as temporal herringbone enhancing with the enlargement of the aperture diameter.
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FIG. 7 Representative examples of IR-reflectance imaging of three different patterns of choroidal vasculature in eyes with CSC. (A) Laterally diagonal. (B) Branched from below. (C) Temporal herringbone.
FIG. 8 IR-reflectance imaging of neurosensory detachments in both eyes in a patient with acute CSC. (A) IR-reflectance image demonstrates mild hyporeflectivity within the paracentral neurosensory detachment. (B) IR-reflectance image demonstrates moderate hyporeflectivity within the central neurosensory detachment with thick photoreceptors outer segments layer. (C) Cross-sectional OCT scan (corresponding to the white line) revealed a shallow neurosensory detachment in the right eye. (D) Cross-sectional OCT scan (corresponding to the white line) revealed a relatively high neurosensory detachment with a thick photoreceptors’ outer segments layer in the left eye. Both the height of neurosensory detachment and presence of thick photoreceptors outer segments layer contribute to hyporeflectivity of the neurosensory detachment.
orphological changes also are able to affect the reflectivity of the IR light at the NSD area, m including, for example, thickening of photoreceptors outer segments layer (Fig. 8). In CSC patients, large choroidal vessels often can be visualized in proximity to or beneath the area responsible for the leakage (Fig. 9). These vessels can be visualized clearly with a wide aperture, which provides intense illumination of the eye fundus, and are highly likely related to choroidal hyperperfusion. PEDs, which can be found in a majority of CSC cases, appear as hyporeflective, sharply demarcated areas compared to neighboring RPE (Fig. 10). Large PED can be easily identified
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FIG. 9 Multimodal imaging of the left eye in a patient with acute nonresolving CSC. (A) IR-reflectance demonstrates a group of large choroidal vessels (arrow) crossing the center of the macula. Note that one of the large vessels lies just beneath the leakage point (arrowhead). (B) DF-SLO image demonstrates similarity to IR-reflectance. The group of large choroidal vessels (arrow) organized in the branched from below pattern and the large vessels lies just beneath the leakage site (arrowhead) appears as dark zones. (C) Fluorescent angiography demonstrates a leakage site (asterisk). (D) RM-SLO shows neuroepithelium detachment (black arrowheads).
independently regardless of whether it overlaps with NSD or with attached neuroepithelium above the EPD. Although there is a specific modification of infrared SLO that is better suited for the evaluation PED, NSD and their interrelationship (retro mode-SLO), conventional IR-reflectance also allows dynamic observation of morphological changes in CSC. With IR-reflectance NSD borders, however, could be poorly defined. In contrast to peaked round PEDs in acute CSC, flat, irregular PEDs typically do not demonstrate clear borders and are generally poorly distinguished (Fig. 11). In general, visualization of NSD and PED with IR-reflectance takes an intermediate position between color photography, which poorly differentiates these changes, and RM-SLO which clearly visualizes both on the sagittal plane. Areas of RPE atrophy, for example, within the areas of long-standing NSD, appear as relatively large, nonuniformly hyporeflective areas with irregular shape and hyperreflective flecks (melanin clumps) at the borders (Fig. 12). Relatively mild RPE attenuation can be found in CSC patients in association with the leakage site. Although the area of RPE changes is significantly wider than the leakage point in cases of acute CSC, it is typically limited by an area of 1.0–1.5 optic disc diameters. On an IR-reflectance image, it can be identified as a slightly hyporeflective area corresponding to
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FIG. 10 Follow-up examination of the left eye in a patient with acute CSC. (A) IR-reflectance image demonstrates an ill-defined neurosensory detachment (black arrowheads) and pigment epithelium detachment (white arrowhead). (B) IR-reflectance image at 2 weeks after presentation revealed the progression of neurosensory detachment (black arrowheads) and persistence pigment epithelium detachment (white arrowhead). (C) Cross-sectional OCT scan shows a neurosensory detachment and a pigment epithelium detachment (white arrowhead). (D) Cross-sectional OCT scan at 2 weeks after presentation showed the progression of neurosensory detachment and persistence of the pigment epithelium detachment (white arrowhead). (E) RM-SLO image demonstrates a clearly demarcated neurosensory detachment (black arrowheads) and pigment epithelium detachment (white arrowhead). (F) RM-SLO image at 2 weeks after presentation demonstrates the expansion of neurosensory detachment (black arrowheads) and a stable pigment epithelium detachment (white arrowhead).
the hypoautoflurescence signal on fundus autofluorescence. The closest correlation, however, can be found between areas of RPE attenuation on IR-reflectance and translucent area on DF-SLO. The latter indicates local loss of pigmentation of the eye fundus and most probably represents washout of melanin from RPE. The area of RPE washout increases with the duration of the CSC episode and, when noticed at presentation, might be a measure of the duration of the case (Fig. 13). Moreover, we suppose that the preservation of RPE on DFSLO (and IR-reflectance) could reflect the remaining potential of a particular leakage site to self-resolution because it is understood that RPE plays a crucial role in the healing of the leakage point/site.
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FIG. 11 IR-reflectance and OCT of the right eye in a patient with acute CSC. (A) IR-reflectance demonstrates a neurosensory detachment and an ill-defined pigment epithelium detachment (white arrowhead). (B) Cross-sectional OCT scan shows a neurosensory detachment and a flat pigment epithelium detachment (white arrowhead).
FIG. 12 IR-reflectance and OCT of the right eye in a patient with resolved CSC and poor final visual acuity (BCVA 20/200). (A) IR-reflectance demonstrates a pigment epithelium detachment (arrowhead) and a hyporeflective area (arrows) corresponding to the RPE attenuation and outer retinal thinning on cross-sectional OCT scan. (B) Cross-sectional OCT scan revealed persistent pigment epithelium detachment (arrowhead), hypertransmission of the signal in the choroid because of partial RPE atrophy, disruption of the ellipsoid zone and thinning of outer retinal layers (arrows).
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FIG. 13 A representative example of detection of RPE attenuation at the leakage site in a patient with acute nonresolving CSC (duration of the episode reported of 8 months) using infrared technique. (A) IR-reflectance image demonstrates hyporeflective area around the leakage point. (B) DF-SLO image shows an area of RPE translucency associated with the leakage point. (C) Pseudo-SLO image superimposed on multispectral image demonstrates the position of the OCT cross-sectional scan. (D) Retinal thickness map demonstrates two NSDs. (E) OCT cross-sectional scan crossing the zone of RPE attenuation reveals NSD and PED corresponding to the leakage point.
Because of high penetration of IR light in neuroepithelium, IR-reflectance easily detects changes in the outer retina if they are not fully transparent for IR illumination, particularly, hyperreflective foci that have been found using OCT in outer retina in different conditions. Numerous studies demonstrated the appearance of hyperreflective foci in eyes with exudative maculopathies (retinal vein occlusion, CSC) and showed that this might indicate progression of neurodegeneration and predicts poor visual outcome.2, 3 Several studies suggest different explanations for intraretinal hyperreflective foci, such as early deposition of hard exudates, appearance of lipid-laden macrophages, degeneration of photoreceptor and abnormal retinal pigment epithelium cells. In CSC, intrarenal hyperreflective foci are noticeable on cross-sectional OCT scans in longstanding cases.4 However, en face imaging is able to provide better representation of their quantitative characteristics. The problem of using en face OCT to image hyperreflective foci
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is that the depth of the foci can vary within the neuroepithelium, which means that not all of them can be visualized within a thin slab. In CSC, the presence of hyperreflective foci in the photoreceptor layer and the increase of their number with outer retinal atrophy, suggests that hyperreflective foci result from the degeneration of the photoreceptors. The difference in the depth of the localization of the foci is at least partially dependent on the preservation of the photoreceptors’ outer segments layer. If the outer segments are absent, the foci appear closer to the outer retinal surface. Moreover, analysis of a group of CSC eyes (data not published) shows that hyperreflective foci tend to be distributed mostly within the part of the NSD where the PROS layer is thin. Therefore, the detached retina that neighbors normal neuroepithelium demonstrates only few or no hyperreflective foci (except in cases where leakage point is at the border of the NSD). Additionally, in acute nonresolving cases, hyperreflective foci often are present around the leakage point. It is reasonable to expect this, as the correlation between PROS thinning and leakage point has already been described.5 The advantage of IR-reflectance is its ability to identify intraretinal foci independently of their depth within the neuroepithelium. The smallest foci might be missed, however, because the resolution of the SLO is somewhat lower than that of OCT (Fig. 14). Precise focus of SLO on the detached neuroepithelium is needed for clear visualization of the foci. When applying precise focusing on the RPE, the contrast of the optic disc cup appears to be more distinct compared to color photography and so IR-reflectance might have the potential for application in glaucoma. In conclusion, the key characteristic of IR-reflectance is that the normal neuroepithelium is transparent in this mode. Therefore, IR-reflectance is suitable for the evaluation of RPE that demonstrates a wide range of abnormalities in CSC, these abnormalities being the common or even leading finding in CSC. In IR-reflectance, the appearance of the eye fundus results from reflection and scattering of IR light by melanin and is dependent on the diameter of the confocal aperture and the position of the focus.
MULTISPECTRAL IMAGING Because the light of different wavelengths penetrates the retina at different depths, the application of monochromatic modalities allows the demonstration of details at the various layers of the retina. The application of only a single wavelength unavoidably leads to loss of significant amount of diagnostic information, but a combination of several monochromatic modes that call for multispectral imaging can overcome this challenge. At the same time, using several distinct wavelengths might reduce the number of chromatic aberrations compared to full visible spectrum. When attempting to approximate the multispectral image to conventional color fundus photography, it can include two or three main channels of the RGB model: red + green or red + green + blue.
MONOCHROMATIC SLO Blue light (490 nm) is reflected by inner retinal layers: inner limiting membrane and nerve fibers layer. Because this wavelength interacts intensely with the inner retina, it is not suitable
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FIG. 14 Multimodal imaging of the left eye in a patient with nonresolved CSC. (A) IR-reflectance image f ocused on the RPE, and attached neuroepithelium demonstrates hyporeflectivity of the NSD area. RPE bumps and PED associated with leakage represented by hyperreflective flecks (white arrowhead) and hyporeflective spot (black arrowhead), respectively. (B) IR-reflectance image focused on the apex of NSD demonstrates numerous intraretinal hyperreflective foci. (C) En face OCT image at the level of RPE shares similar pattern with IR-reflectance image focused on the RPE and attached neuroepithelium and demonstrates RPE bumps and PED. (D) En face OCT image at the level of photoreceptors outer segments layer demonstrates numerous large intraretinal hyperreflective foci. (E) En face OCT image at the level of ellipsoid zone and outer nuclear layer demonstrates numerous small i ntraretinal hyperreflective foci. (F) Cross-sectional OCT scan through the center of the macula demonstrates RPE bump (white arrowhead) and PED (black arrowhead) and large hyperreflective foci at the level of the photoreceptors’ outer segments layer. (F) Cross-sectional OCT scan through the upper part of NSD demonstrates small hyperreflective foci at the level of the photoreceptors outer segments layer (arrows), RPE bump (white arrowhead), and PED (black arrowhead). (G) Cross-sectional OCT scan through the upper part of NSD demonstrates small hyperreflective foci at the level of the ellipsoid zone and outer nuclear layer.
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for evaluation of the outer retina. This option provides detailed information about vitreoretinal interface abnormalities. In the study of Feng HL and coauthors, inner retinal alterations were best visualized on blue reflectance but poorly defined with IR-reflectance, which is consistent with the inner location of these changes. A combination of infrared, as well as red wavelength with green and blue wavelength to generate a multicolor image, appears to decrease the clarity of inner retinal surface imaging. An additional option based on the blue wavelength is the evaluation of macular pigment density. Changes of RPE are not detectable in this mode and, although large NSD can be identified, generally this mode provides no additional information in CSC eyes. There are two main chromophores in the posterior eye segment for green wavelength (532 nm): melanin and blood. Therefore, alterations of retinal microvessels (telangiectases, microaneurisms, capillary nonperfusion), as well as retinal neovascularization and any intraocular hemorrhages, are perfectly visible with this wavelength. Because this wavelength is absorbed substantially by melanin, all pigmented structures are of high contrast in this mode. In real settings, melanin of RPE completely blocks deeper penetration of green light, thus choroid is nondifferentiating. Monochromatic SLO in red light (660 nm) provides the highest penetrability among other wavelengths of the visible spectrum and allows us to visualize the general pattern of the choroidal vasculature and choroidal mass lesions.
PSEUDOCOLOR SLO Several currently available SLO platforms that incorporate color monochromatic imaging options also provide pseudocolor imaging, including F-10 (NIDEK) and HRA (Heidelberg Engineering). In general, the main differences observed between the multicolor image and the color fundus photography is the improved demarcation of the optic disc, retinal vessels, and large choroidal vessels. In their study, Reznicek L and coauthors showed that en face SLO multicolor images are suitable not only to depict epiretinal membranes, but also to reveal a precise demarcation of epiretinal membrane borders (Fig. 15), which could be useful for pre- or postoperative examinations. Thus, the multispectral image can be a useful adjunct to the currently used OCT en face images.6 An interesting option supported by pseudocolor SLO is a compilation of the image from two channels, for example, green and red. Using this approach Tadayoni R et al. was the first to characterize the dark arcuate striae in eyes after inner limiting membrane peeling that represents dissociation of optic nerve fiber layer.7 The borders of the areas of geographic atrophy are more clearly demarcated with multicolor images than with color fundus photography. Reticular pseudodrusen also can be imaged more distinctly with multicolor imaging. The multicolor imaging might add some benefits in distinguishing hemorrhages across different retinal layers. In combination with OCT, multicolor imaging might improve detection rates of diabetic retinopathy, for example, if used as a screening approach. The borders of the NSD in CSC and the multiple areas of NSD are more sharply demarcated with multicolor imaging than with color fundus photography. Multicolor imaging in addition to IR and FAF imaging might be useful to detect subtle changes in the retinal structure that might not be clinically apparent after the resolution of the subretinal fluid from CSCR.8 II. IMAGING
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FIG. 15 Multispectral imaging of the right eye in a patient with epiretinal membrane. Blue light monochromatic and blue-green images provide the most precise delineation of epiretinal membrane. B: blue; G: green; R: red.
Visualization of flat NSD in different wavelengths results in a somewhat different appearance (Fig. 16). While IR and red light allow depiction of the flattest NSDs precisely, green and blue light can define only relatively high detachments. This appears understandable if we look at the line from blue to red monochromatic images where the area of the NSD increases with penetrability of the particular wavelength in the neuroepithelium. This indicates, however, that the multispectral (RGB) image would demonstrate color gradient from the apex to the periphery of NSD (Fig. 17). Different combinations of color channels result in different multicolor images, but their diagnostic value should be investigated further.
HYPERSPECTRAL IMAGING Color fundus photography uses visible light, which includes an infinite set of wavelengths from about 390 to 700 nm. Recent achievements in imaging technologies, however, allow modifying both the range and number of different wavelengths used in imaging that is applied in multispectral of hyperspectral modes. Outside of medicine, multispectral and hyperspectral imaging (HSI) are used in many other disciplines such as pharmaceutical research and production, agriculture, food quality control, biochemistry, and biomedicine. The main difference between multispectral and HSI is the number of separate wavelengths used in
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FIG. 16 Multispectral imaging of the right eye in a patient with acute CSC. Among IR-reflectance and infrared-green images allow for the most precise delineation of NSD. B: blue; G: green; IR: infrared; R: red.
the imaging. While multispectral imaging uses several to several tens of wavelengths, this number in HSI can be as high as 10,000. Many of the imaging spectrometers cover the entire wavelength region from 0.4 to 14 μm with a possible step of 0.1 nm. The main benefit of multispectral imaging or HSI of living tissues is explained by the fact that some tissues, including neural, are relatively transparent to light in the near-infrared range.9 Therefore, deep penetration provides more information about the anatomy of the tissues under evaluation. It is worth noting that short wavelengths (ultraviolet) are not used in HSI or multispectral imaging for medical purposes. Moreover, ultraviolet light is hardly used in HSI in ophthalmology because the cornea and ocular media containing water are not transparent for this wavelength. HSI obtains significant amount of data, but interpretation requires precise understanding about how the tissues under evaluation interact with particular wavelengths. In general, HSI is a mode that operates within a broad range of visible and near-infrared wavelengths that is used to illuminate the object and a sensor with a tunable optical filter to capture images in different wavelength separately. Acquisition modes for HSI include linear scanning, spectral scanning, and snapshot modes. The latter uses a white light source with
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FIG. 17 Multispectral (pseodocolor) imaging of the right eye in a patient with acute CSC. (A) Red (660 nm) monochromatic image is similar to that of infrared-reflectance. (B) Green (532 nm) monochromatic image. (C) Blue (490 nm) monochromatic image. (D) Multispectral (pseudocolor) image merged from three monochromatic images.
or without filter wheel, laser, and at least one charge-coupled device.9 One of potential advantages of this mode in real circumstances is that it captures the spectra for all ranges in one exposure of the flash, allowing exclusion of the misalignment of different images because of eye movements. Each particular zone within eye imaged fundus represented by a pixel of the resultant image and characterized by a specific interference pattern that includes spectral information about this particular region. In the prototype, described by Zamora G and coauthors, each resultant HSI represents a set of spectrograms obtained within a line on the eye fundus. Therefore, the image contains information about the position of a point measured, wavelength range, and reflectivity of the point at each band within this range. For example, in an HSI image, large retinal vessels produce spectral signatures at approximately 580 nm, the absorption wavelength of hemoglobin. The optic nerve head tissue demonstrated the most prominent spectral reflectance in the range of 640–650 nm.10 The most promising application for HSI is blood oximetry because two states of hemoglobin are the major absorbing substances in living tissues in the visible and NIR spectrum. In diabetic retinopathy, HSI reveals the different spectral properties of oxygenated and deoxygenated hemoglobin so retinal oxygen saturation can be mapped and evaluated.11 It would be interesting to apply HSI to the study of the pathophysiology of CSC and all pachychoroid spectrum, particularly the distribution of oxygenation of the choroid and oxygenation characteristics of pathological sites (leakage site or areas of pachychoroid pigment e pitheliopathy).
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Unfortunately, this area has not been investigated until now. The substantial problem of this approach in CSC is that transparency of RPE and choroid the for short wavelength part of the spectrum of HSI is limited, therefore oxygenation can be measured mostly in red and IR spectrum where extinction coefficients for oxygenated and deoxygenated hemoglobin are quite close. Another problem with this technique is the time-consumption of image processing because the data obtained in each wavelength should be merged with all others. In conclusion, the continuous progress in retinal imaging over the past decades has given us a deeper understanding of the pathophysiology of the whole spectrum of retinal pathology. CSC is just the most noticeable example of these revolutionary changes because this condition demonstrates a wide range of retinal and choroidal abnormalities and partially overlaps many other retinal diseases. Beyond the most widely used methods such as optical coherence tomography or fluorescein angiography, however, a number of methods are able to provide some extra data to current knowledge. Infrared-based scanning laser ophthalmoscopy in its different modifications is one of the clearest examples of how these methods can augment basic examination.
References 1. Savastano MC, Rispoli M, Savastano A, Lumbroso B. En face optical coherence tomography for visualization of the choroid. Ophthal Surg Lasers Imaging Retina. 2015;46(5):561–565. 2. Nishijima K, Murakami T, Hirashima T, et al. Hyperreflective foci in outer retina predictive of photoreceptor damage and poor vision after vitrectomy for diabetic macular edema. Retina. 2014;34(4):732–740. 3. Ogino K, Murakami T, Tsujikawa A, et al. Characteristics of optical coherence tomographic hyperreflective foci in retinal vein occlusion. Retina. 2012;32(1):77–85. 4. Lee H, Lee J, Chung H, Kim HC. Baseline spectral domain optical coherence tomographic hyperreflective foci as a predictor of visual outcome and recurrence for central serous chorioretinopathy. Retina. 2016;36(7):1372–1380. 5. Maltsev DS, Kulikov AN, Chhablani J. Topography-guided identification of leakage point in central serous chorioretinopathy: a base for fluorescein angiography-free focal laser photocoagulation. Br J Ophthalmol. 2018;4:. [Epub ahead of print]. 6. Reznicek L, Dabov S, Kayat B, et al. Scanning laser “en face” retinal imaging of epiretinal membranes. Saudi J Ophthalmol. 2014;28:134–138. 7. Tadayoni R, Paques M, Massin P, et al. Dissociated optic nerve fiber layer appearance of the fundus after idiopathic epiretinal membrane removal. Ophthalmology. 2001;108:2279–2283. 8. Tan AC, Fleckenstein M, Schmitz-Valckenberg S, Holz FG. Clinical application of multicolor imaging technology. Ophthalmologica. 2016;236(1):8–18. 9. Giannoni L, Lange F, Tachtsidis I. Hyperspectral imaging solutions for brain tissue metabolic and hemodynamic monitoring: past, current and future developments. J Opt. 2018;20(4):044009. 10. Zamora G, et al. Hyperspectral imaging analysis for ophthalmic applications. In: Ophthalmic Technologies XIV. vol. 5314. International Society for Optics and Photonics; 2004:138–150. 11. Cole ED, Novais EA, Louzada RN, Waheed NK. Contemporary retinal imaging techniques in diabetic retinopathy: a review. Clin Experiment Ophthalmol. 2016;44(4):289–299.
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14 Other Imaging Modalities in CSC Alexei N. Kulikov, Dmitrii S. Maltsev Department of Ophthalmology, Military Medical Academy, St Petersburg, Russia
IR-REFLECTANCE Color fundus photography has become one of the basic imaging modalities for the documentation of the posterior eye segment because of its relative simplicity and because the image produced is the closest to the natural eye fundus in appearance. Compared to indirect ophthalmoscopy, however, color fundus photography does not provide any additional information about retinal pathology. Moreover, some subtle changes of the retina or retinal pigment epithelium might be missed in low-resolution pictures. In addition, the visible light used in color fundus photography is associated with a substantial number of chromatic aberrations and low penetration in ocular media with decreased transparency, and causes the pupil constriction that restricts evaluation of the eye fundus. Nevertheless, color fundus photography is of high clinical importance because it serves as a reference point for other imaging modalities. Monochromatic imaging, particularly if performed with scanning laser ophthalmoscope (SLO), has higher contrast, better resolution, and smaller depth of focus than color fundus photography. The confocal principle of the SLO ensures that light scattered from layers other than the point of illumination will be blocked. Use of an infrared laser source (790 nm) in SLO excludes pupil constriction and allows eye fundus examination to be performed, even in patients with mild cataract or vitreal hemorrhage. However, the absorption, reflection, and scattering of infrared illumination by intraocular tissues is significantly different compared to the visible spectrum. The main chromophores of the eye fundus that interact with infrared light are melanin, hemoglobin, fibrine, and lipids. The clusters of melanin reflect a substantial proportion of IR light, therefore, pigmentary changes demonstrate hyperreflectivity (Fig. 1). In contrast, atrophic or attenuated areas of RPE such as PED have a hyporeflective appearance. At the same time, a thin layer of melanin (normal RPE in low pigmented or myopic eyes) is relatively penetrable for intense IR wavelength. Lipids are highly reflective and lipid exudation, although rarely found in CSC patients, might indicate a chronic exudation associated with secondary neovascularization (Fig. 2). Furthermore, any macular pathology characterized by sub-RPE deposition of abnormal material can result in scattering or deeper penetration of IR light and consequently in decreased reflectance of a particular RPE region. Mild alterations of RPE without decrease of the RPE Central Serous Chorioretinopathy https://doi.org/10.1016/B978-0-12-816800-4.00013-9
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FIG. 1 Multimodal imaging of the right eye in a patient with resolved acute CSC and persistent PED. (А) IRreflectance demonstrates a sharply demarcated round hyporeflective area (arrowhead) with hyperreflective flecks. (B) Dark field-SLO demonstrates an area of RPE atrophy and pigment clumps (arrowhead). (C) Cross-sectional OCT scan shows PED (arrowhead) with hyperreflective clusters and hyperpermeability on the top of the PED.
FIG. 2 Multimodal imaging of the left eye in a patient with chronic CSC complicated by choroidal neovascularization. (А) IR-reflectance demonstrates accumulation of hard exudates (arrowhead). The black line corresponds to horizontal OCT scan. The white line corresponds to vertical OCT scan. (B) Horizontal cross-sectional OCT scan shows RPE irregularity, hard exudates in the outer retina, and subretinal hyperreflective material. (C) Vertical cross- sectional OCT scan shows RPE irregularity, subretinal hyperreflective material, and intraretinal cystic fluid.
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FIG. 3 Multimodal imaging of the right eye in a patient with resolved acute CSC. (А) IR-reflectance demonstrates a hyperreflective area (arrowhead) corresponding to the former leakage site. The white line corresponds to the OCT scan. (B) Cross-sectional OCT scan shows minute REP attenuation (arrowhead) responsible for IR hyperreflectivity.
thickness, however, might be associated with isolated changes in the reflection profile and might appear as hyperreflective signals (Fig. 3) or as a combination of hyperreflective and hyporeflective signals. This becomes clear in the visualization of small RPE bumps and drusen. Small and medium drusen are more likely to appear hyperreflective; large drusen (drusenoid PED) are typically hyporeflective because the density of pigmentation decreases above large drusen (Fig. 4). Fibrin has little effect on the transmission of IR light in ocular media. A substantial accumulation of subretinal fibrin, however, could appear on IR-reflectance image as smooth and hyporeflective retinal regions (Fig. 5). Macular pigment has no effect on IR light, therefore the IR-reflectance image of the central retina does not distinguish the macular and foveal regions except for the foveal indentation, which can be revealed because of changes in the IR light reflection. In young patients, fovea and the parafoveal region can be distinguished with a pin-hole aperture because of increased reflectivity of the inner limiting membrane. Although numerous findings can be revealed with IR-reflectance and its modifications, the place of the IR-reflectance in the detection of macular disease, particularly CSC, appears to be underestimated and requires detailed evaluation. The image obtained with SLO depends on the size of the confocal aperture in two ways: with a wide aperture, the amount of the light increases and, therefore, the fundus of heavily
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FIG. 4 Multimodal imaging of the left eye in a patient with dry AMD. (А) IR-reflectance demonstrates a hyporeflective area (arrowheads) corresponding to a group of drusenoid PEDs and soft drusen, hyperreflective numerous small hyporeflective spots corresponding to reticular drusen (arrow). (B) RM-SLO demonstrates marked elevations (arrowheads) corresponding to a group of drusenoid PEDs and soft drusen as well as numerous small bumps corresponding to reticular pseudodrusen (arrow). (C) DF-SLO demonstrates bright areas (arrowheads) corresponding to large drusenoid PEDs and accumulation of pigment clumps at the border of PEDs (asterisk). (D) Cross-sectional OCT scan through drusenoid PEDs (represented by the black line on IR-reflectance image). (E) Cross-sectional OCT scan through drusen and pigment clumps (asterisk) (represented by the dashed line on IR-reflectance image). (F) Crosssectional OCT scan through reticular pseudodrusen (represented by the white line on IR-reflectance image).
pigmented eyes with small pupil or opacification of the eye media can be evaluated; and the intensity of light scattering also increases and consequently the contrast of the eye fundus image decreases. The higher amount of illumination, however, allows for better penetration through the RPE, and large choroidal vessels become visible (Fig. 6). This approach allows fast evaluation of the choroidal vasculature and classification of choroidal vasculature pattern in several main groups (Fig. 7) suggested by Savastano MS and coauthors using en face OCT.1 NSD causes a significant scattering of IR light. This depends on the height of the detachment because the larger the distance between the detached retina and the RPE, the greater the divergence of the laser beam scattered by the detached retina. Therefore, in the RI-reflectance image, the height of NSD can be evaluated indirectly by the degree of darkness in the NSD area. The eccentricity of the NSD also affects its appearance because the incidence angle of illumination increases, as consequently does the scattering of the light on the NSD borders. Therefore, central NSD typically appears to be not clearly demarcated. Additional
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FIG. 5 Multimodal imaging of both eyes in a patient with acute CSC. (A) IR-reflectance of the right eye demonstrates neurosensory detachment with an accumulation of subretinal fibrin (arrowheads). (B) IR-reflectance of the left eye demonstrates subretinal fibrin accumulation (arrow) within small neurosensory detachment. (C) Cross-sectional OCT scan through the neurosensory detachment in the right eye (corresponds to the white line) demonstrates subretinal fibrin accumulation (arrowhead). (D) Cross-sectional OCT scan through the small neurosensory detachment in the left eye (corresponds to the white line) demonstrates subretinal fibrin accumulation (arrow).
FIG. 6 IR-reflectance imaging of choroidal vasculature in a healthy eye. (A) IR-reflectance image obtained with an aperture of 1.5 mm. (B) IR-reflectance image obtained with an aperture of 3 mm. (C) IR-reflectance image obtained with an aperture of 4 mm. (D) IR-reflectance image obtained with an aperture of 7 mm. Note that differentiation of choroidal vasculature (arrowheads) as temporal herringbone enhancing with the enlargement of the aperture diameter.
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FIG. 7 Representative examples of IR-reflectance imaging of three different patterns of choroidal vasculature in eyes with CSC. (A) Laterally diagonal. (B) Branched from below. (C) Temporal herringbone.
FIG. 8 IR-reflectance imaging of neurosensory detachments in both eyes in a patient with acute CSC. (A) IR-reflectance image demonstrates mild hyporeflectivity within the paracentral neurosensory detachment. (B) IR-reflectance image demonstrates moderate hyporeflectivity within the central neurosensory detachment with thick photoreceptors outer segments layer. (C) Cross-sectional OCT scan (corresponding to the white line) revealed a shallow neurosensory detachment in the right eye. (D) Cross-sectional OCT scan (corresponding to the white line) revealed a relatively high neurosensory detachment with a thick photoreceptors’ outer segments layer in the left eye. Both the height of neurosensory detachment and presence of thick photoreceptors outer segments layer contribute to hyporeflectivity of the neurosensory detachment.
orphological changes also are able to affect the reflectivity of the IR light at the NSD area, m including, for example, thickening of photoreceptors outer segments layer (Fig. 8). In CSC patients, large choroidal vessels often can be visualized in proximity to or beneath the area responsible for the leakage (Fig. 9). These vessels can be visualized clearly with a wide aperture, which provides intense illumination of the eye fundus, and are highly likely related to choroidal hyperperfusion. PEDs, which can be found in a majority of CSC cases, appear as hyporeflective, sharply demarcated areas compared to neighboring RPE (Fig. 10). Large PED can be easily identified
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FIG. 9 Multimodal imaging of the left eye in a patient with acute nonresolving CSC. (A) IR-reflectance demonstrates a group of large choroidal vessels (arrow) crossing the center of the macula. Note that one of the large vessels lies just beneath the leakage point (arrowhead). (B) DF-SLO image demonstrates similarity to IR-reflectance. The group of large choroidal vessels (arrow) organized in the branched from below pattern and the large vessels lies just beneath the leakage site (arrowhead) appears as dark zones. (C) Fluorescent angiography demonstrates a leakage site (asterisk). (D) RM-SLO shows neuroepithelium detachment (black arrowheads).
independently regardless of whether it overlaps with NSD or with attached neuroepithelium above the EPD. Although there is a specific modification of infrared SLO that is better suited for the evaluation PED, NSD and their interrelationship (retro mode-SLO), conventional IR-reflectance also allows dynamic observation of morphological changes in CSC. With IR-reflectance NSD borders, however, could be poorly defined. In contrast to peaked round PEDs in acute CSC, flat, irregular PEDs typically do not demonstrate clear borders and are generally poorly distinguished (Fig. 11). In general, visualization of NSD and PED with IR-reflectance takes an intermediate position between color photography, which poorly differentiates these changes, and RM-SLO which clearly visualizes both on the sagittal plane. Areas of RPE atrophy, for example, within the areas of long-standing NSD, appear as relatively large, nonuniformly hyporeflective areas with irregular shape and hyperreflective flecks (melanin clumps) at the borders (Fig. 12). Relatively mild RPE attenuation can be found in CSC patients in association with the leakage site. Although the area of RPE changes is significantly wider than the leakage point in cases of acute CSC, it is typically limited by an area of 1.0–1.5 optic disc diameters. On an IR-reflectance image, it can be identified as a slightly hyporeflective area corresponding to
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FIG. 10 Follow-up examination of the left eye in a patient with acute CSC. (A) IR-reflectance image demonstrates an ill-defined neurosensory detachment (black arrowheads) and pigment epithelium detachment (white arrowhead). (B) IR-reflectance image at 2 weeks after presentation revealed the progression of neurosensory detachment (black arrowheads) and persistence pigment epithelium detachment (white arrowhead). (C) Cross-sectional OCT scan shows a neurosensory detachment and a pigment epithelium detachment (white arrowhead). (D) Cross-sectional OCT scan at 2 weeks after presentation showed the progression of neurosensory detachment and persistence of the pigment epithelium detachment (white arrowhead). (E) RM-SLO image demonstrates a clearly demarcated neurosensory detachment (black arrowheads) and pigment epithelium detachment (white arrowhead). (F) RM-SLO image at 2 weeks after presentation demonstrates the expansion of neurosensory detachment (black arrowheads) and a stable pigment epithelium detachment (white arrowhead).
the hypoautoflurescence signal on fundus autofluorescence. The closest correlation, however, can be found between areas of RPE attenuation on IR-reflectance and translucent area on DF-SLO. The latter indicates local loss of pigmentation of the eye fundus and most probably represents washout of melanin from RPE. The area of RPE washout increases with the duration of the CSC episode and, when noticed at presentation, might be a measure of the duration of the case (Fig. 13). Moreover, we suppose that the preservation of RPE on DFSLO (and IR-reflectance) could reflect the remaining potential of a particular leakage site to self-resolution because it is understood that RPE plays a crucial role in the healing of the leakage point/site.
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FIG. 11 IR-reflectance and OCT of the right eye in a patient with acute CSC. (A) IR-reflectance demonstrates a neurosensory detachment and an ill-defined pigment epithelium detachment (white arrowhead). (B) Cross-sectional OCT scan shows a neurosensory detachment and a flat pigment epithelium detachment (white arrowhead).
FIG. 12 IR-reflectance and OCT of the right eye in a patient with resolved CSC and poor final visual acuity (BCVA 20/200). (A) IR-reflectance demonstrates a pigment epithelium detachment (arrowhead) and a hyporeflective area (arrows) corresponding to the RPE attenuation and outer retinal thinning on cross-sectional OCT scan. (B) Cross-sectional OCT scan revealed persistent pigment epithelium detachment (arrowhead), hypertransmission of the signal in the choroid because of partial RPE atrophy, disruption of the ellipsoid zone and thinning of outer retinal layers (arrows).
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FIG. 13 A representative example of detection of RPE attenuation at the leakage site in a patient with acute nonresolving CSC (duration of the episode reported of 8 months) using infrared technique. (A) IR-reflectance image demonstrates hyporeflective area around the leakage point. (B) DF-SLO image shows an area of RPE translucency associated with the leakage point. (C) Pseudo-SLO image superimposed on multispectral image demonstrates the position of the OCT cross-sectional scan. (D) Retinal thickness map demonstrates two NSDs. (E) OCT cross-sectional scan crossing the zone of RPE attenuation reveals NSD and PED corresponding to the leakage point.
Because of high penetration of IR light in neuroepithelium, IR-reflectance easily detects changes in the outer retina if they are not fully transparent for IR illumination, particularly, hyperreflective foci that have been found using OCT in outer retina in different conditions. Numerous studies demonstrated the appearance of hyperreflective foci in eyes with exudative maculopathies (retinal vein occlusion, CSC) and showed that this might indicate progression of neurodegeneration and predicts poor visual outcome.2, 3 Several studies suggest different explanations for intraretinal hyperreflective foci, such as early deposition of hard exudates, appearance of lipid-laden macrophages, degeneration of photoreceptor and abnormal retinal pigment epithelium cells. In CSC, intrarenal hyperreflective foci are noticeable on cross-sectional OCT scans in longstanding cases.4 However, en face imaging is able to provide better representation of their quantitative characteristics. The problem of using en face OCT to image hyperreflective foci
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is that the depth of the foci can vary within the neuroepithelium, which means that not all of them can be visualized within a thin slab. In CSC, the presence of hyperreflective foci in the photoreceptor layer and the increase of their number with outer retinal atrophy, suggests that hyperreflective foci result from the degeneration of the photoreceptors. The difference in the depth of the localization of the foci is at least partially dependent on the preservation of the photoreceptors’ outer segments layer. If the outer segments are absent, the foci appear closer to the outer retinal surface. Moreover, analysis of a group of CSC eyes (data not published) shows that hyperreflective foci tend to be distributed mostly within the part of the NSD where the PROS layer is thin. Therefore, the detached retina that neighbors normal neuroepithelium demonstrates only few or no hyperreflective foci (except in cases where leakage point is at the border of the NSD). Additionally, in acute nonresolving cases, hyperreflective foci often are present around the leakage point. It is reasonable to expect this, as the correlation between PROS thinning and leakage point has already been described.5 The advantage of IR-reflectance is its ability to identify intraretinal foci independently of their depth within the neuroepithelium. The smallest foci might be missed, however, because the resolution of the SLO is somewhat lower than that of OCT (Fig. 14). Precise focus of SLO on the detached neuroepithelium is needed for clear visualization of the foci. When applying precise focusing on the RPE, the contrast of the optic disc cup appears to be more distinct compared to color photography and so IR-reflectance might have the potential for application in glaucoma. In conclusion, the key characteristic of IR-reflectance is that the normal neuroepithelium is transparent in this mode. Therefore, IR-reflectance is suitable for the evaluation of RPE that demonstrates a wide range of abnormalities in CSC, these abnormalities being the common or even leading finding in CSC. In IR-reflectance, the appearance of the eye fundus results from reflection and scattering of IR light by melanin and is dependent on the diameter of the confocal aperture and the position of the focus.
MULTISPECTRAL IMAGING Because the light of different wavelengths penetrates the retina at different depths, the application of monochromatic modalities allows the demonstration of details at the various layers of the retina. The application of only a single wavelength unavoidably leads to loss of significant amount of diagnostic information, but a combination of several monochromatic modes that call for multispectral imaging can overcome this challenge. At the same time, using several distinct wavelengths might reduce the number of chromatic aberrations compared to full visible spectrum. When attempting to approximate the multispectral image to conventional color fundus photography, it can include two or three main channels of the RGB model: red + green or red + green + blue.
MONOCHROMATIC SLO Blue light (490 nm) is reflected by inner retinal layers: inner limiting membrane and nerve fibers layer. Because this wavelength interacts intensely with the inner retina, it is not suitable
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FIG. 14 Multimodal imaging of the left eye in a patient with nonresolved CSC. (A) IR-reflectance image f ocused on the RPE, and attached neuroepithelium demonstrates hyporeflectivity of the NSD area. RPE bumps and PED associated with leakage represented by hyperreflective flecks (white arrowhead) and hyporeflective spot (black arrowhead), respectively. (B) IR-reflectance image focused on the apex of NSD demonstrates numerous intraretinal hyperreflective foci. (C) En face OCT image at the level of RPE shares similar pattern with IR-reflectance image focused on the RPE and attached neuroepithelium and demonstrates RPE bumps and PED. (D) En face OCT image at the level of photoreceptors outer segments layer demonstrates numerous large intraretinal hyperreflective foci. (E) En face OCT image at the level of ellipsoid zone and outer nuclear layer demonstrates numerous small i ntraretinal hyperreflective foci. (F) Cross-sectional OCT scan through the center of the macula demonstrates RPE bump (white arrowhead) and PED (black arrowhead) and large hyperreflective foci at the level of the photoreceptors’ outer segments layer. (F) Cross-sectional OCT scan through the upper part of NSD demonstrates small hyperreflective foci at the level of the photoreceptors outer segments layer (arrows), RPE bump (white arrowhead), and PED (black arrowhead). (G) Cross-sectional OCT scan through the upper part of NSD demonstrates small hyperreflective foci at the level of the ellipsoid zone and outer nuclear layer.
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for evaluation of the outer retina. This option provides detailed information about vitreoretinal interface abnormalities. In the study of Feng HL and coauthors, inner retinal alterations were best visualized on blue reflectance but poorly defined with IR-reflectance, which is consistent with the inner location of these changes. A combination of infrared, as well as red wavelength with green and blue wavelength to generate a multicolor image, appears to decrease the clarity of inner retinal surface imaging. An additional option based on the blue wavelength is the evaluation of macular pigment density. Changes of RPE are not detectable in this mode and, although large NSD can be identified, generally this mode provides no additional information in CSC eyes. There are two main chromophores in the posterior eye segment for green wavelength (532 nm): melanin and blood. Therefore, alterations of retinal microvessels (telangiectases, microaneurisms, capillary nonperfusion), as well as retinal neovascularization and any intraocular hemorrhages, are perfectly visible with this wavelength. Because this wavelength is absorbed substantially by melanin, all pigmented structures are of high contrast in this mode. In real settings, melanin of RPE completely blocks deeper penetration of green light, thus choroid is nondifferentiating. Monochromatic SLO in red light (660 nm) provides the highest penetrability among other wavelengths of the visible spectrum and allows us to visualize the general pattern of the choroidal vasculature and choroidal mass lesions.
PSEUDOCOLOR SLO Several currently available SLO platforms that incorporate color monochromatic imaging options also provide pseudocolor imaging, including F-10 (NIDEK) and HRA (Heidelberg Engineering). In general, the main differences observed between the multicolor image and the color fundus photography is the improved demarcation of the optic disc, retinal vessels, and large choroidal vessels. In their study, Reznicek L and coauthors showed that en face SLO multicolor images are suitable not only to depict epiretinal membranes, but also to reveal a precise demarcation of epiretinal membrane borders (Fig. 15), which could be useful for pre- or postoperative examinations. Thus, the multispectral image can be a useful adjunct to the currently used OCT en face images.6 An interesting option supported by pseudocolor SLO is a compilation of the image from two channels, for example, green and red. Using this approach Tadayoni R et al. was the first to characterize the dark arcuate striae in eyes after inner limiting membrane peeling that represents dissociation of optic nerve fiber layer.7 The borders of the areas of geographic atrophy are more clearly demarcated with multicolor images than with color fundus photography. Reticular pseudodrusen also can be imaged more distinctly with multicolor imaging. The multicolor imaging might add some benefits in distinguishing hemorrhages across different retinal layers. In combination with OCT, multicolor imaging might improve detection rates of diabetic retinopathy, for example, if used as a screening approach. The borders of the NSD in CSC and the multiple areas of NSD are more sharply demarcated with multicolor imaging than with color fundus photography. Multicolor imaging in addition to IR and FAF imaging might be useful to detect subtle changes in the retinal structure that might not be clinically apparent after the resolution of the subretinal fluid from CSCR.8 II. IMAGING
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FIG. 15 Multispectral imaging of the right eye in a patient with epiretinal membrane. Blue light monochromatic and blue-green images provide the most precise delineation of epiretinal membrane. B: blue; G: green; R: red.
Visualization of flat NSD in different wavelengths results in a somewhat different appearance (Fig. 16). While IR and red light allow depiction of the flattest NSDs precisely, green and blue light can define only relatively high detachments. This appears understandable if we look at the line from blue to red monochromatic images where the area of the NSD increases with penetrability of the particular wavelength in the neuroepithelium. This indicates, however, that the multispectral (RGB) image would demonstrate color gradient from the apex to the periphery of NSD (Fig. 17). Different combinations of color channels result in different multicolor images, but their diagnostic value should be investigated further.
HYPERSPECTRAL IMAGING Color fundus photography uses visible light, which includes an infinite set of wavelengths from about 390 to 700 nm. Recent achievements in imaging technologies, however, allow modifying both the range and number of different wavelengths used in imaging that is applied in multispectral of hyperspectral modes. Outside of medicine, multispectral and hyperspectral imaging (HSI) are used in many other disciplines such as pharmaceutical research and production, agriculture, food quality control, biochemistry, and biomedicine. The main difference between multispectral and HSI is the number of separate wavelengths used in
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FIG. 16 Multispectral imaging of the right eye in a patient with acute CSC. Among IR-reflectance and infrared-green images allow for the most precise delineation of NSD. B: blue; G: green; IR: infrared; R: red.
the imaging. While multispectral imaging uses several to several tens of wavelengths, this number in HSI can be as high as 10,000. Many of the imaging spectrometers cover the entire wavelength region from 0.4 to 14 μm with a possible step of 0.1 nm. The main benefit of multispectral imaging or HSI of living tissues is explained by the fact that some tissues, including neural, are relatively transparent to light in the near-infrared range.9 Therefore, deep penetration provides more information about the anatomy of the tissues under evaluation. It is worth noting that short wavelengths (ultraviolet) are not used in HSI or multispectral imaging for medical purposes. Moreover, ultraviolet light is hardly used in HSI in ophthalmology because the cornea and ocular media containing water are not transparent for this wavelength. HSI obtains significant amount of data, but interpretation requires precise understanding about how the tissues under evaluation interact with particular wavelengths. In general, HSI is a mode that operates within a broad range of visible and near-infrared wavelengths that is used to illuminate the object and a sensor with a tunable optical filter to capture images in different wavelength separately. Acquisition modes for HSI include linear scanning, spectral scanning, and snapshot modes. The latter uses a white light source with
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FIG. 17 Multispectral (pseodocolor) imaging of the right eye in a patient with acute CSC. (A) Red (660 nm) monochromatic image is similar to that of infrared-reflectance. (B) Green (532 nm) monochromatic image. (C) Blue (490 nm) monochromatic image. (D) Multispectral (pseudocolor) image merged from three monochromatic images.
or without filter wheel, laser, and at least one charge-coupled device.9 One of potential advantages of this mode in real circumstances is that it captures the spectra for all ranges in one exposure of the flash, allowing exclusion of the misalignment of different images because of eye movements. Each particular zone within eye imaged fundus represented by a pixel of the resultant image and characterized by a specific interference pattern that includes spectral information about this particular region. In the prototype, described by Zamora G and coauthors, each resultant HSI represents a set of spectrograms obtained within a line on the eye fundus. Therefore, the image contains information about the position of a point measured, wavelength range, and reflectivity of the point at each band within this range. For example, in an HSI image, large retinal vessels produce spectral signatures at approximately 580 nm, the absorption wavelength of hemoglobin. The optic nerve head tissue demonstrated the most prominent spectral reflectance in the range of 640–650 nm.10 The most promising application for HSI is blood oximetry because two states of hemoglobin are the major absorbing substances in living tissues in the visible and NIR spectrum. In diabetic retinopathy, HSI reveals the different spectral properties of oxygenated and deoxygenated hemoglobin so retinal oxygen saturation can be mapped and evaluated.11 It would be interesting to apply HSI to the study of the pathophysiology of CSC and all pachychoroid spectrum, particularly the distribution of oxygenation of the choroid and oxygenation characteristics of pathological sites (leakage site or areas of pachychoroid pigment e pitheliopathy).
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Unfortunately, this area has not been investigated until now. The substantial problem of this approach in CSC is that transparency of RPE and choroid the for short wavelength part of the spectrum of HSI is limited, therefore oxygenation can be measured mostly in red and IR spectrum where extinction coefficients for oxygenated and deoxygenated hemoglobin are quite close. Another problem with this technique is the time-consumption of image processing because the data obtained in each wavelength should be merged with all others. In conclusion, the continuous progress in retinal imaging over the past decades has given us a deeper understanding of the pathophysiology of the whole spectrum of retinal pathology. CSC is just the most noticeable example of these revolutionary changes because this condition demonstrates a wide range of retinal and choroidal abnormalities and partially overlaps many other retinal diseases. Beyond the most widely used methods such as optical coherence tomography or fluorescein angiography, however, a number of methods are able to provide some extra data to current knowledge. Infrared-based scanning laser ophthalmoscopy in its different modifications is one of the clearest examples of how these methods can augment basic examination.
References 1. Savastano MC, Rispoli M, Savastano A, Lumbroso B. En face optical coherence tomography for visualization of the choroid. Ophthal Surg Lasers Imaging Retina. 2015;46(5):561–565. 2. Nishijima K, Murakami T, Hirashima T, et al. Hyperreflective foci in outer retina predictive of photoreceptor damage and poor vision after vitrectomy for diabetic macular edema. Retina. 2014;34(4):732–740. 3. Ogino K, Murakami T, Tsujikawa A, et al. Characteristics of optical coherence tomographic hyperreflective foci in retinal vein occlusion. Retina. 2012;32(1):77–85. 4. Lee H, Lee J, Chung H, Kim HC. Baseline spectral domain optical coherence tomographic hyperreflective foci as a predictor of visual outcome and recurrence for central serous chorioretinopathy. Retina. 2016;36(7):1372–1380. 5. Maltsev DS, Kulikov AN, Chhablani J. Topography-guided identification of leakage point in central serous chorioretinopathy: a base for fluorescein angiography-free focal laser photocoagulation. Br J Ophthalmol. 2018;4:. [Epub ahead of print]. 6. Reznicek L, Dabov S, Kayat B, et al. Scanning laser “en face” retinal imaging of epiretinal membranes. Saudi J Ophthalmol. 2014;28:134–138. 7. Tadayoni R, Paques M, Massin P, et al. Dissociated optic nerve fiber layer appearance of the fundus after idiopathic epiretinal membrane removal. Ophthalmology. 2001;108:2279–2283. 8. Tan AC, Fleckenstein M, Schmitz-Valckenberg S, Holz FG. Clinical application of multicolor imaging technology. Ophthalmologica. 2016;236(1):8–18. 9. Giannoni L, Lange F, Tachtsidis I. Hyperspectral imaging solutions for brain tissue metabolic and hemodynamic monitoring: past, current and future developments. J Opt. 2018;20(4):044009. 10. Zamora G, et al. Hyperspectral imaging analysis for ophthalmic applications. In: Ophthalmic Technologies XIV. vol. 5314. International Society for Optics and Photonics; 2004:138–150. 11. Cole ED, Novais EA, Louzada RN, Waheed NK. Contemporary retinal imaging techniques in diabetic retinopathy: a review. Clin Experiment Ophthalmol. 2016;44(4):289–299.
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