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Optical Coherence Tomography
C H A P T E R
10 Optical Coherence Tomography Jorge Ruiz-Medrano⁎, Luis Arias⁎, Jose M. Ruiz-Moreno†,‡ ⁎
Ophthalmology Unit, Bellvitge University Hospital, Barcelona, Spain †Ophthalmology Unit, Puerta de Hierro Majadahonda University Hospital, Madrid, Spain ‡VISSUM Corporation, Madrid, Spain
INTRODUCTION The introduction of the optic coherence tomography (OCT) and its continuous development represents a clear breakthrough in choroidal imaging.1, 2 Initially, time domain OCT (TD-OCT) made it possible to study the posterior segment in vivo, but poor penetration below the retinal pigment epithelium (RPE) and its relatively low resolution did not allow for proper choroidal imaging. Spectral Domain OCT (SD-OCT) came along several years later, but, in spite of its obvious advantages over TD OCT, signal roll-off with depth and signal attenuation by pigmented tissues or media opacities still precluded choroidal imaging in most eyes. Then, Spaide et al. introduced enhanced depth imaging OCT (EDI-OCT), which provides consistent choroidal visualization in most eyes and allows quantitative and reproducible thickness measurements.3–6 The most recent innovative technology available for OCT imaging is high penetration, longer wavelength swept-source OCT (SS-OCT).7–9 The choroid, its thickness, profile, and vascular distribution have become a hot research topic, with numerous papers being published on this matter.10–16 This research has made evident that the choroid can show certain alterations in several diseases, including central serous chorioretinopathy (CSCR).17–20
CHOROID The main characteristic of the choroid of CSCR patients is an increased thickness in comparison to healthy population according to age and axial length, in both the affected and the contralateral eye,18, 19, 21 and CSCR is listed among the diseases included in the pachychoroid spectrum.22 Furthermore, Daruich et al. state that the choroid seems to be thicker in the affected eye in cases affecting one eye only when compared to the healthy eye.21 As our research showed, the subfoveal choroid of healthy, emmetropic populations was 301.89 ± 80.53 μm thick
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(95% confidence interval: 292.34–311.43), while mean horizontal macular choroidal thickness (MCT) was 258.69 ± 64.59 μm (95% confidence interval: 251.04–266.35).14 And although recent studies proposed 395 μm as a threshold in order to talk about thickened choroid, there is no established definition.21, 23 Ambiya et al. showed that baseline choroidal thickness had a statistically significant association with the need for treatment (odds ratio (OR), 0.989; CI 0.979– 0.999; P = .048) and concluded in their paper that subfoveal CT ≤ 356 μm usually is related to chronic cases and is more likely to require treatment.24 A reduction of choroidal thickness can be expected after the resolution of an acute episode.21 Although the choroid seems to be diffusely enlarged in CSC patients, they also tend to show focal thickening of large vessels. They tend to be located in the same spot as hypercyanescent areas on indocyanine green angiography (ICG), which speaks in favor of an increased permeability. Enlarged vessels in Haller’s layer might show a reduced Sattler’s and choriocapillary above them and also might be in relation with retinal pigment epithelium (RPE) detachments (Table 1). Agrawal et al. found in their research that the choroidal vascularity index (CVI) is increased in patients with CSCR in comparison to healthy age-matched controls. That means vascular component is increased when compared with the stroma in acute CSC. Increased CVI was noted in the fellow eye of the subjects with acute CSC in comparison with agematched healthy subjects. This index did not change after laser treatment.25, 26 Hyperreflective spots and thickened hyperreflective vessel walls also have been described, mostly in chronic CSC cases (Fig. 1). Patients with chronic forms of CSC show the presence of hyperreflective spots in 83.3% of the cases and hyperreflective choroidal vessel walls in 75%, whereas patients with an acute course had the same alterations in 33% and 6.7% of cases,
TABLE 1 Key Optical Coherence Tomography in Central Serous Chorioretinopathy Choroid
Increased thickness (case and fellow eye) Focal vessel thickening Increased Haller’s layer thickness Reduced Sattler’s and choriocapillaris Thickened vessel walls (chronic) Hyperreflective spots in stroma (chronic) Choroidal neovascularization (chronic)
Retinal pigment epithelium
Pigment epithelium detachments Loss of third outer retinal band (RPE phagosomes, acute) Excrescences Local epitheliopathy Diffuse epitheliopathy
Neurosensory retina
Neurosensory detachment Elongation of photoreceptor outer segments Loss of second outer retinal band (photoreceptor’s ellipsoid) Disappearance of outer segments + thinning of ONL (chronic) Hyperreflective spots (chronic) Intraretinal cysts (chronic) GCC reduction (acute and chronic)
GCC, ganglion cell complex; ONL, outer nuclear layer; RPE, retinal pigment epithelium.
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FIG. 1 Hyperreflective spots in the choroidal stroma and thickened hyperreflective vessel walls on a chronic CSCR patient.
respectively.27 Daruich et al. describe the presence of more dilated choroidal vessels together with the presence of hyperreflective vessel walls, suggesting parietal structural changes in chronic cases.21 They found these changes to be present in 84% of CSC eyes versus 16% of unaffected eyes. They conclude that large vessel walls harbor a granular hyperreflectivity suggesting possible changes in vascular wall structure. Lehmann et al. relate the presence of hyperreflective spots to disease activity, because quiescent CSC patients in their study did not show any.28 In our cases, hyperreflective spots were clearly visible throughout the choroid, especially below areas of RPE damage. These RPE changes are more frequent in patients suffering from chronic forms of the disease, so the presence of hyperreflective spots should not be related to chronic forms only. It is true that other chronic pathologies with choroidal involvement and RPE damage (CSC, age-related macular degeneration, focal chorioretinal atrophy) seem to show window defects, showing a more reflective choroid, but not necessarily hyperreflective spots nor wall-thickening. En face OCT provides a different scope to analyze the choroidal vasculature. CSC patients show a diffuse crowding of deep choroidal layers, most frequently in temporal quadrants and usually involving the macula, while presenting with focal alterations in the majority of cases (Fig. 2).22 These focal enlargements usually match areas of hyperreflectivity on ICG, areas of thickened choroid or focally enlarged vessels.22 Savastano et al. described five different patterns of large choroidal vessel distribution in their research: temporal herringbone, branched from below, laterally diagonal, doubled arcuate, and reticular. Their results show that most frequent patterns in acute and chronic CSCR patients were reticular and laterally diagonal.29 They conclude that the presence of certain patterns probably depends on the patient’s anatomical factors, not being able to establish whether they might change with time in either healthy or affected eyes.
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FIG. 2 En face OCT showing a diffuse crowding of deep choroidal layers, with visibly enlarged vessels.
RETINAL PIGMENT EPITHELIUM Cuenca et al. affirm in a recent paper that the third hyperreflective band of the OCT study of the macula is made mainly of cones’ phagosomes, located in the upper part of the RPE; the fourth band corresponds to an accumulation of mitochondria in its bottom half.30 This research would explain the most prominent sign of acute CSC patients: the disappearance of this third band in the area of neurosensory retinal detachment (NRD), with a preservation of the fourth band (Figs. 3 and 4) on OCT images. The RPE would not be able to phagocyte the detached external segments of the photoreceptors, so there is no accumulation of phagosomes in the upper part of the RPE. Excrescences on the RPE are commonly found in these patients, and some authors have linked them to lesions and leak areas from the choroid to the subretinal space. These areas usually are located over dilated choroidal vessels (Figs. 5 and 6). This finding was described by a previous study, in which acute CSCR OCT findings were compared to fluorescein angiography (FA) results in 39 eyes from 36 patients. Two patterns of distinct OCT findings were described. In the first one, an optically empty vaulted area of different heights was observed under the neurosensory retina in 36 eyes, being related to fluorescein filled areas; in 35 of them, highly characteristic small bulges could be observed protruding from the RPE, angiographically related to leaking spots. The authors concluded that OCT could help the understanding of the mechanisms of the disease.31 More recent studies combining OCT and FA for the analysis of active CSCR cases identified RPE elevations or detachments of the retinal pigment epithelium (PED) in most32–34 or all of the cases.35 On the other hand, atrophic changes of the RPE usually are found in chronic II. IMAGING
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FIG. 3 Right eye of a patient showing an acute episode of CSCR. Swept source optical coherence tomography (SS-OCT) shows the presence of fluid over the retinal pigment epithelium, causing a neurosensory detachment. The nasal aspect of this detachment shows a preserved first hyperreflective band (external limiting membrane), with a disappearance of the second and third bands in the context of photoreceptor elongation.
FIG. 4 SS-OCT of left eye of a patient with acute CSCR. Both aspects of the neurosensory detachment show an abrupt disappearance of the third hyperreflective band.
FIG. 5 SS-OCT of left eye of a patient with acute CSCR showing an evident elongation of photoreceptor with shedding over the retinal pigment epithelium. II. IMAGING
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FIG. 6 Vertical B-scan of an acute case of CSCR showing a choroidal excavation with shed material over the retinal pigment epithelium.
FIG. 7 Male patient with acute CSCR. OCT B-scan shows a dome-shaped retinal pigment epithelium detachment in the context of subretinal fluid close to an enlarged choroidal vessel.
cases, which will show on OCT as well. Long-standing cases labeled as “diffuse retinal pigment epitheliopathy” show extensive areas of RPE atrophy that are not necessarily related to the presence of subretinal fluid.21 PED are, in fact, one of the most characteristic findings in CSCR patients, appearing in 53%–100% of affected eyes, according to different series.33, 36, 37 It is more typical of chronic forms of the disease, and its appearance is not always related to a NRD, although they also are found in acute cases (Fig. 7). Daruich et al. state that PED usually are located over really dilated choroidal vessels (Fig. 7) or thickened choroid. Indocyanine green angiography studies have shown them to match areas of increased permeability, concluding that PED are a consequence of an altered choroidal flow.38 Different forms of PED have been described. In chronic forms, there are two predominant types: dome-shaped or regular and irregular or wavy flat.21 Both can coexist in the
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same eye (Fig. 8). Several mechanisms have been proposed to explain their existence, including mechanical stress resulting from increased intrachoroidal pressure caused by dilated choroidal vessels, reduced RPE adhesion, alteration of RPE ionic regulations, and atrophy caused by choriocapillaris hypoperfusion.21 Dome-shaped PEDs show a regular protrusion with no signs of RPE hyperplasia, a hyporreflective, homogeneous content, and a hyperreflective border.36, 37 In contrast, flat irregular PEDs (FIPED) show a hyperreflective content (Fig. 7). The double-layer sign was described when this hyperreflective content was seen over a thin hyperreflective band that is thought to be an intact Bruch’s membrane (Fig. 9).39 The key difference between simple acute CSCR and chronic cases is based on the extension of the RPE involvement. In addition, RPE tears, atrophy, and hypertrophic areas can be found. Some authors use the term diffuse or local epitheliopathy in different stages of the disease.40 The chronic course of the disease leads to a generalized atrophy with time with irregular PEDs. Ruling out choroidal neovascularization (CNV) is a challenge in these cases, as will be discussed later. The presence of drusen has not been described in CSCR patients, which supports theories about different mechanisms causing CSCR and age-related macular degeneration.
FIG. 8 Horizontal OCT B-scan of a patient with acute CSCR. A flat irregular pigment epithelium detachment can be seen inside a neurosensory detachment, with a regular, dome-shaped pigment epithelium detachment outside it.
FIG. 9 Chronic CSCR case with a flat, irregular PED with hyperreflective content and the double layer sign near an enlarged choroidal vessel.
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OCT study of chronic cases will be key to establish the presence of CNV in chronic cases. CNV appears in 2%–9% of chronic cases.38, 41 Some series have found no incidence, however, while more recent studies talk about a 30% prevalence in chronic cases with FIPEDs using OCT angiography.42 Alterations caused to the RPE and Bruch’s membrane are a possible mechanism causing the appearance of CNV in CSCR, as happens in highly myopic patients. CNV are usually type 2 in CSCR patients (Figs. 8 and 9).43 They must be differentiated from type 1 CNV, which is usually a complication of laser photocoagulation.44 In our experience, both types of CNV respond well to anti-VEGF treatment (Figs. 10–12).
FIG. 10 SS-OCT of the right eye of a male patient with type 2 CNV diagnosed during the follow-up of a chronic CSCR.
FIG. 11 OCT angiography study of the patient of Fig. 8, showing a clear neovascular complex (type 2).
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FIG. 12 The fluid disappears after one intravitreal injection of anti-VEGF.
Type 2 CNV also can occur in the context of pachychoroid neovasculopathy. These patients show type 1 CNV with similar findings to CSCR, with a thickened subfoveal choroid and hyperpermeability on ICG.45 Differential diagnosis between these and chronic CSCR is often complicated. AMD-related CNV patients with bad response to treatment and a thick choroid really could be cases of complicated chronic CSCR.
NEUROSENSORY RETINA Most of the changes induced by CSCR take place on the outer retina. Some authors state that retinal layers’ morphology remains unchanged in spite of the presence of subretinal fluid, with the exception of the elongation of photoreceptor outer segments.21 If the acute phase of the disease is analyzed in detail, however, the ELM is seen as unaltered while the second hyperreflective band (in a similar way as described before with the third band) disappears at the level of the neurosensory detachment (Figs. 3–6), finding an elongation of the photoreceptors instead. Without the proximity of the RPE, phagocytosis of the outer segments does not occur, and they grow toward the SRF cavity. According to Cuenca et al.,30 the second band is generated by the inner segments’ ellipsoids in agreement with Spaide and Curcio, who believe that the ellipsoids (compacted mitochondria), are responsible for the second hyperreflective band. That same paper suggests that the incomplete visualization of this band reflects a deterioration or disorganization of photoreceptor cells. The acute phase of CSCR causes a disorganization of photoreceptor cells with the described elongation of the outer segments, which would justify a shift in the location of mitochondria and, according to Wilson et al.,46 these changes in mitochondria morphologic features could modify the amount of light scattering and then modify the appearance of the OCT band, typical of this stage. The resolution of this neurosensory detachment allows for a reorganization of structures and the recuperation of complete integrity to the second and third outer retinal
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bands on OCT (Fig. 11). No alteration to any other retinal layer above the external limiting membrane is observed during the acute phase of this disease (Figs. 3–6). In addition to photoreceptor elongation in the area of SRF (Fig. 13),47 white-yellow opacities might be observed, producing an increased signal in FAF (Figs. 14 and 15).48 The persistence of this lengthening in time causes permanent subretinal deposits associated to a worse visual prognosis even after the disappearance of SRF.21 Long-lasting cases show a disappearance of outer segments, a disruption of the ellipsoid zone or the ELM and a thinning of the outer nuclear layer, which influence visual outcomes in a negative way.40, 49–51 Hyperreflective spots are seldom seen in the areas of elongated photoreceptors (Figs. 4–6), growing in number as the disease advances.52 These spots have been theorized to be macrophages and microglia
FIG. 13 Restoration after acute phase of CSCR of the four hyperreflective bands.
FIG. 14 White-yellow opacities in a chronic case of CSCR.
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FIG. 15 Increased autofluorescence shown by subretinal opacities on fundus autofluorescence.
FIG. 16 Vacuole sign. Hyporreflective space within hyperreflective subretinal fibrin, indicating disease activity.
activated by photoreceptor outer segments shedding.53 They also have been described within several retinal layers,36, 54 and some authors have related their presence to worse visual outcomes.55 Some cases might show a hyporeflective area within the fibrin which is probably a sign of disease activity called “vacuole sign” (Fig. 16).56 With regard to the inner retina, chronic cases have been found to suffer from fluctuating intraretinal cysts that are in relation with RPE misfunction.21 RPE defects can be accompanied by subretinal fibrin, seen as a hyperreflective fluid on OCT. Long-standing cases suffering from severe RPE damage might show a cystoid macular degeneration and visual acuity loss. Demirok et al. performed an OCT on 16 acute and 19 chronic CSCR cases, concluding that the ganglion cell complex was reduced significantly in both acute and chronic CSCR compared to healthy subjects.57
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WIDEFIELD OCT Although most OCT devices are focused on the macular area between the vascular arcades, widefield EDI-OCT provides information about the retina, RPE, and choroid beyond that point. Carrai et al. found in their research that there is a peripheral relative thinning of Sattler’s layer and choriocapillaris.58 They identified the outer choroidal layers as “hyporeflective lumina” in all eyes studied. They found a mean Haller’s layer thickness of 217.8 ± 41.4 μm. Ranging from 175.5 μm temporally to 235.5 μm superiorly. These studies could prove relevant for the study of CSCR and other pathologies.58
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10 Optical Coherence Tomography Jorge Ruiz-Medrano⁎, Luis Arias⁎, Jose M. Ruiz-Moreno†,‡ ⁎
Ophthalmology Unit, Bellvitge University Hospital, Barcelona, Spain †Ophthalmology Unit, Puerta de Hierro Majadahonda University Hospital, Madrid, Spain ‡VISSUM Corporation, Madrid, Spain
INTRODUCTION The introduction of the optic coherence tomography (OCT) and its continuous development represents a clear breakthrough in choroidal imaging.1, 2 Initially, time domain OCT (TD-OCT) made it possible to study the posterior segment in vivo, but poor penetration below the retinal pigment epithelium (RPE) and its relatively low resolution did not allow for proper choroidal imaging. Spectral Domain OCT (SD-OCT) came along several years later, but, in spite of its obvious advantages over TD OCT, signal roll-off with depth and signal attenuation by pigmented tissues or media opacities still precluded choroidal imaging in most eyes. Then, Spaide et al. introduced enhanced depth imaging OCT (EDI-OCT), which provides consistent choroidal visualization in most eyes and allows quantitative and reproducible thickness measurements.3–6 The most recent innovative technology available for OCT imaging is high penetration, longer wavelength swept-source OCT (SS-OCT).7–9 The choroid, its thickness, profile, and vascular distribution have become a hot research topic, with numerous papers being published on this matter.10–16 This research has made evident that the choroid can show certain alterations in several diseases, including central serous chorioretinopathy (CSCR).17–20
CHOROID The main characteristic of the choroid of CSCR patients is an increased thickness in comparison to healthy population according to age and axial length, in both the affected and the contralateral eye,18, 19, 21 and CSCR is listed among the diseases included in the pachychoroid spectrum.22 Furthermore, Daruich et al. state that the choroid seems to be thicker in the affected eye in cases affecting one eye only when compared to the healthy eye.21 As our research showed, the subfoveal choroid of healthy, emmetropic populations was 301.89 ± 80.53 μm thick
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(95% confidence interval: 292.34–311.43), while mean horizontal macular choroidal thickness (MCT) was 258.69 ± 64.59 μm (95% confidence interval: 251.04–266.35).14 And although recent studies proposed 395 μm as a threshold in order to talk about thickened choroid, there is no established definition.21, 23 Ambiya et al. showed that baseline choroidal thickness had a statistically significant association with the need for treatment (odds ratio (OR), 0.989; CI 0.979– 0.999; P = .048) and concluded in their paper that subfoveal CT ≤ 356 μm usually is related to chronic cases and is more likely to require treatment.24 A reduction of choroidal thickness can be expected after the resolution of an acute episode.21 Although the choroid seems to be diffusely enlarged in CSC patients, they also tend to show focal thickening of large vessels. They tend to be located in the same spot as hypercyanescent areas on indocyanine green angiography (ICG), which speaks in favor of an increased permeability. Enlarged vessels in Haller’s layer might show a reduced Sattler’s and choriocapillary above them and also might be in relation with retinal pigment epithelium (RPE) detachments (Table 1). Agrawal et al. found in their research that the choroidal vascularity index (CVI) is increased in patients with CSCR in comparison to healthy age-matched controls. That means vascular component is increased when compared with the stroma in acute CSC. Increased CVI was noted in the fellow eye of the subjects with acute CSC in comparison with agematched healthy subjects. This index did not change after laser treatment.25, 26 Hyperreflective spots and thickened hyperreflective vessel walls also have been described, mostly in chronic CSC cases (Fig. 1). Patients with chronic forms of CSC show the presence of hyperreflective spots in 83.3% of the cases and hyperreflective choroidal vessel walls in 75%, whereas patients with an acute course had the same alterations in 33% and 6.7% of cases,
TABLE 1 Key Optical Coherence Tomography in Central Serous Chorioretinopathy Choroid
Increased thickness (case and fellow eye) Focal vessel thickening Increased Haller’s layer thickness Reduced Sattler’s and choriocapillaris Thickened vessel walls (chronic) Hyperreflective spots in stroma (chronic) Choroidal neovascularization (chronic)
Retinal pigment epithelium
Pigment epithelium detachments Loss of third outer retinal band (RPE phagosomes, acute) Excrescences Local epitheliopathy Diffuse epitheliopathy
Neurosensory retina
Neurosensory detachment Elongation of photoreceptor outer segments Loss of second outer retinal band (photoreceptor’s ellipsoid) Disappearance of outer segments + thinning of ONL (chronic) Hyperreflective spots (chronic) Intraretinal cysts (chronic) GCC reduction (acute and chronic)
GCC, ganglion cell complex; ONL, outer nuclear layer; RPE, retinal pigment epithelium.
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FIG. 1 Hyperreflective spots in the choroidal stroma and thickened hyperreflective vessel walls on a chronic CSCR patient.
respectively.27 Daruich et al. describe the presence of more dilated choroidal vessels together with the presence of hyperreflective vessel walls, suggesting parietal structural changes in chronic cases.21 They found these changes to be present in 84% of CSC eyes versus 16% of unaffected eyes. They conclude that large vessel walls harbor a granular hyperreflectivity suggesting possible changes in vascular wall structure. Lehmann et al. relate the presence of hyperreflective spots to disease activity, because quiescent CSC patients in their study did not show any.28 In our cases, hyperreflective spots were clearly visible throughout the choroid, especially below areas of RPE damage. These RPE changes are more frequent in patients suffering from chronic forms of the disease, so the presence of hyperreflective spots should not be related to chronic forms only. It is true that other chronic pathologies with choroidal involvement and RPE damage (CSC, age-related macular degeneration, focal chorioretinal atrophy) seem to show window defects, showing a more reflective choroid, but not necessarily hyperreflective spots nor wall-thickening. En face OCT provides a different scope to analyze the choroidal vasculature. CSC patients show a diffuse crowding of deep choroidal layers, most frequently in temporal quadrants and usually involving the macula, while presenting with focal alterations in the majority of cases (Fig. 2).22 These focal enlargements usually match areas of hyperreflectivity on ICG, areas of thickened choroid or focally enlarged vessels.22 Savastano et al. described five different patterns of large choroidal vessel distribution in their research: temporal herringbone, branched from below, laterally diagonal, doubled arcuate, and reticular. Their results show that most frequent patterns in acute and chronic CSCR patients were reticular and laterally diagonal.29 They conclude that the presence of certain patterns probably depends on the patient’s anatomical factors, not being able to establish whether they might change with time in either healthy or affected eyes.
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FIG. 2 En face OCT showing a diffuse crowding of deep choroidal layers, with visibly enlarged vessels.
RETINAL PIGMENT EPITHELIUM Cuenca et al. affirm in a recent paper that the third hyperreflective band of the OCT study of the macula is made mainly of cones’ phagosomes, located in the upper part of the RPE; the fourth band corresponds to an accumulation of mitochondria in its bottom half.30 This research would explain the most prominent sign of acute CSC patients: the disappearance of this third band in the area of neurosensory retinal detachment (NRD), with a preservation of the fourth band (Figs. 3 and 4) on OCT images. The RPE would not be able to phagocyte the detached external segments of the photoreceptors, so there is no accumulation of phagosomes in the upper part of the RPE. Excrescences on the RPE are commonly found in these patients, and some authors have linked them to lesions and leak areas from the choroid to the subretinal space. These areas usually are located over dilated choroidal vessels (Figs. 5 and 6). This finding was described by a previous study, in which acute CSCR OCT findings were compared to fluorescein angiography (FA) results in 39 eyes from 36 patients. Two patterns of distinct OCT findings were described. In the first one, an optically empty vaulted area of different heights was observed under the neurosensory retina in 36 eyes, being related to fluorescein filled areas; in 35 of them, highly characteristic small bulges could be observed protruding from the RPE, angiographically related to leaking spots. The authors concluded that OCT could help the understanding of the mechanisms of the disease.31 More recent studies combining OCT and FA for the analysis of active CSCR cases identified RPE elevations or detachments of the retinal pigment epithelium (PED) in most32–34 or all of the cases.35 On the other hand, atrophic changes of the RPE usually are found in chronic II. IMAGING
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FIG. 3 Right eye of a patient showing an acute episode of CSCR. Swept source optical coherence tomography (SS-OCT) shows the presence of fluid over the retinal pigment epithelium, causing a neurosensory detachment. The nasal aspect of this detachment shows a preserved first hyperreflective band (external limiting membrane), with a disappearance of the second and third bands in the context of photoreceptor elongation.
FIG. 4 SS-OCT of left eye of a patient with acute CSCR. Both aspects of the neurosensory detachment show an abrupt disappearance of the third hyperreflective band.
FIG. 5 SS-OCT of left eye of a patient with acute CSCR showing an evident elongation of photoreceptor with shedding over the retinal pigment epithelium. II. IMAGING
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FIG. 6 Vertical B-scan of an acute case of CSCR showing a choroidal excavation with shed material over the retinal pigment epithelium.
FIG. 7 Male patient with acute CSCR. OCT B-scan shows a dome-shaped retinal pigment epithelium detachment in the context of subretinal fluid close to an enlarged choroidal vessel.
cases, which will show on OCT as well. Long-standing cases labeled as “diffuse retinal pigment epitheliopathy” show extensive areas of RPE atrophy that are not necessarily related to the presence of subretinal fluid.21 PED are, in fact, one of the most characteristic findings in CSCR patients, appearing in 53%–100% of affected eyes, according to different series.33, 36, 37 It is more typical of chronic forms of the disease, and its appearance is not always related to a NRD, although they also are found in acute cases (Fig. 7). Daruich et al. state that PED usually are located over really dilated choroidal vessels (Fig. 7) or thickened choroid. Indocyanine green angiography studies have shown them to match areas of increased permeability, concluding that PED are a consequence of an altered choroidal flow.38 Different forms of PED have been described. In chronic forms, there are two predominant types: dome-shaped or regular and irregular or wavy flat.21 Both can coexist in the
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same eye (Fig. 8). Several mechanisms have been proposed to explain their existence, including mechanical stress resulting from increased intrachoroidal pressure caused by dilated choroidal vessels, reduced RPE adhesion, alteration of RPE ionic regulations, and atrophy caused by choriocapillaris hypoperfusion.21 Dome-shaped PEDs show a regular protrusion with no signs of RPE hyperplasia, a hyporreflective, homogeneous content, and a hyperreflective border.36, 37 In contrast, flat irregular PEDs (FIPED) show a hyperreflective content (Fig. 7). The double-layer sign was described when this hyperreflective content was seen over a thin hyperreflective band that is thought to be an intact Bruch’s membrane (Fig. 9).39 The key difference between simple acute CSCR and chronic cases is based on the extension of the RPE involvement. In addition, RPE tears, atrophy, and hypertrophic areas can be found. Some authors use the term diffuse or local epitheliopathy in different stages of the disease.40 The chronic course of the disease leads to a generalized atrophy with time with irregular PEDs. Ruling out choroidal neovascularization (CNV) is a challenge in these cases, as will be discussed later. The presence of drusen has not been described in CSCR patients, which supports theories about different mechanisms causing CSCR and age-related macular degeneration.
FIG. 8 Horizontal OCT B-scan of a patient with acute CSCR. A flat irregular pigment epithelium detachment can be seen inside a neurosensory detachment, with a regular, dome-shaped pigment epithelium detachment outside it.
FIG. 9 Chronic CSCR case with a flat, irregular PED with hyperreflective content and the double layer sign near an enlarged choroidal vessel.
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OCT study of chronic cases will be key to establish the presence of CNV in chronic cases. CNV appears in 2%–9% of chronic cases.38, 41 Some series have found no incidence, however, while more recent studies talk about a 30% prevalence in chronic cases with FIPEDs using OCT angiography.42 Alterations caused to the RPE and Bruch’s membrane are a possible mechanism causing the appearance of CNV in CSCR, as happens in highly myopic patients. CNV are usually type 2 in CSCR patients (Figs. 8 and 9).43 They must be differentiated from type 1 CNV, which is usually a complication of laser photocoagulation.44 In our experience, both types of CNV respond well to anti-VEGF treatment (Figs. 10–12).
FIG. 10 SS-OCT of the right eye of a male patient with type 2 CNV diagnosed during the follow-up of a chronic CSCR.
FIG. 11 OCT angiography study of the patient of Fig. 8, showing a clear neovascular complex (type 2).
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FIG. 12 The fluid disappears after one intravitreal injection of anti-VEGF.
Type 2 CNV also can occur in the context of pachychoroid neovasculopathy. These patients show type 1 CNV with similar findings to CSCR, with a thickened subfoveal choroid and hyperpermeability on ICG.45 Differential diagnosis between these and chronic CSCR is often complicated. AMD-related CNV patients with bad response to treatment and a thick choroid really could be cases of complicated chronic CSCR.
NEUROSENSORY RETINA Most of the changes induced by CSCR take place on the outer retina. Some authors state that retinal layers’ morphology remains unchanged in spite of the presence of subretinal fluid, with the exception of the elongation of photoreceptor outer segments.21 If the acute phase of the disease is analyzed in detail, however, the ELM is seen as unaltered while the second hyperreflective band (in a similar way as described before with the third band) disappears at the level of the neurosensory detachment (Figs. 3–6), finding an elongation of the photoreceptors instead. Without the proximity of the RPE, phagocytosis of the outer segments does not occur, and they grow toward the SRF cavity. According to Cuenca et al.,30 the second band is generated by the inner segments’ ellipsoids in agreement with Spaide and Curcio, who believe that the ellipsoids (compacted mitochondria), are responsible for the second hyperreflective band. That same paper suggests that the incomplete visualization of this band reflects a deterioration or disorganization of photoreceptor cells. The acute phase of CSCR causes a disorganization of photoreceptor cells with the described elongation of the outer segments, which would justify a shift in the location of mitochondria and, according to Wilson et al.,46 these changes in mitochondria morphologic features could modify the amount of light scattering and then modify the appearance of the OCT band, typical of this stage. The resolution of this neurosensory detachment allows for a reorganization of structures and the recuperation of complete integrity to the second and third outer retinal
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bands on OCT (Fig. 11). No alteration to any other retinal layer above the external limiting membrane is observed during the acute phase of this disease (Figs. 3–6). In addition to photoreceptor elongation in the area of SRF (Fig. 13),47 white-yellow opacities might be observed, producing an increased signal in FAF (Figs. 14 and 15).48 The persistence of this lengthening in time causes permanent subretinal deposits associated to a worse visual prognosis even after the disappearance of SRF.21 Long-lasting cases show a disappearance of outer segments, a disruption of the ellipsoid zone or the ELM and a thinning of the outer nuclear layer, which influence visual outcomes in a negative way.40, 49–51 Hyperreflective spots are seldom seen in the areas of elongated photoreceptors (Figs. 4–6), growing in number as the disease advances.52 These spots have been theorized to be macrophages and microglia
FIG. 13 Restoration after acute phase of CSCR of the four hyperreflective bands.
FIG. 14 White-yellow opacities in a chronic case of CSCR.
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FIG. 15 Increased autofluorescence shown by subretinal opacities on fundus autofluorescence.
FIG. 16 Vacuole sign. Hyporreflective space within hyperreflective subretinal fibrin, indicating disease activity.
activated by photoreceptor outer segments shedding.53 They also have been described within several retinal layers,36, 54 and some authors have related their presence to worse visual outcomes.55 Some cases might show a hyporeflective area within the fibrin which is probably a sign of disease activity called “vacuole sign” (Fig. 16).56 With regard to the inner retina, chronic cases have been found to suffer from fluctuating intraretinal cysts that are in relation with RPE misfunction.21 RPE defects can be accompanied by subretinal fibrin, seen as a hyperreflective fluid on OCT. Long-standing cases suffering from severe RPE damage might show a cystoid macular degeneration and visual acuity loss. Demirok et al. performed an OCT on 16 acute and 19 chronic CSCR cases, concluding that the ganglion cell complex was reduced significantly in both acute and chronic CSCR compared to healthy subjects.57
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WIDEFIELD OCT Although most OCT devices are focused on the macular area between the vascular arcades, widefield EDI-OCT provides information about the retina, RPE, and choroid beyond that point. Carrai et al. found in their research that there is a peripheral relative thinning of Sattler’s layer and choriocapillaris.58 They identified the outer choroidal layers as “hyporeflective lumina” in all eyes studied. They found a mean Haller’s layer thickness of 217.8 ± 41.4 μm. Ranging from 175.5 μm temporally to 235.5 μm superiorly. These studies could prove relevant for the study of CSCR and other pathologies.58
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