The recent introduction of optical coherence tomography angiography (OCTA) has remarkably expanded our knowledge of the choroid through in vivo investigation of the anatomical and pathological ...features of this important vascular layer. New insights elucidating the morphological features of the choroid, in both physiological and pathological conditions, indicate that this vascular structure plays a crucial role in many chorioretinal disorders. In this article, a review of the salient histological and anatomical features of the choroid, essential for the proper interpretation of in vivo imaging, is followed by a discussion of the fundamental principles of OCTA and the application of this advanced imaging modality to study and understand the choroid. The current limitations of OCTA and potential advancements that may improve the widespread adoption of this tool are also discussed. A detailed review of the OCTA features of the choroid in the healthy eye is followed by relevant findings in major chorioretinal diseases, including age-related macular degeneration, central serous chorioretinopathy, uveitis, and inherited retinal disorders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Conventionally rendered optical coherence tomography (OCT) images of the posterior segment contain shadows which influence the visualization of deep structures such as the choroid. The purpose of ...this study was to determine whether OCT shadow compensation (SC) alters the appearance of the choroid and the apparent choroidal vascularity index (CVI), an OCT-derived estimated ratio of luminal to total choroidal volume. All scans were shadow compensated using a previously published algorithm, binarized using a novel validated algorithm and extracted binarized choroid to estimate CVI. On 27 raw swept-source OCT volume-scans of healthy subjects, the effect of SC on CVI was established both qualitatively and quantitatively. In shadow compensated scans, the choroid was visualized with greater brightness than the neurosensory retina and the masking of deep tissues by retinal blood vessels was greatly reduced. Among study subjects, significant mean difference in CVI of -0.13 was observed between raw and shadow compensated scans. Conventionally acquired OCT underestimates both choroidal reflectivity and calculated CVI. Quantitative analysis based on subjective grading demonstrated that SC increased the contrast between stromal and luminal regions and are in agreement with true tissue regions. This study is warranted to determine the effects of SC on CVI in diseased eyes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Pachychoroid disease Cheung, Chui Ming Gemmy; Lee, Won Ki; Koizumi, Hideki ...
Eye,
01/2019, Volume:
33, Issue:
1
Journal Article
Peer reviewed
Open access
Pachychoroid is a relatively novel concept describing a phenotype characterized by attenuation of the choriocapillaris overlying dilated choroidal veins, and associated with progressive retinal ...pigment epithelium dysfunction and neovascularization. The emphasis in defining pachychoroid-related disorders has shifted away from simply an abnormally thick choroid (pachychoroid) toward a detailed morphological definition of a pathologic state (pachychoroid disease) with functional implications, which will be discussed in this review. Several clinical manifestations have been described to reside within the pachychoroid disease spectrum, including central serous chorioretinopathy, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization, focal choroidal excavation, peripapillary pachychoroid syndrome. These conditions all exhibit the characteristic choroidal alterations and are believed to represent different manifestations of a common pathogenic process. This review is based on both the current literature and the clinical experience of our individual authors, with an emphasis on the clinical and imaging features, management considerations, as well as current understanding of pathogenesis of these disorders within the context of the recent findings related to pachychoroid disease.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Basal laminar deposit (BLamD) is a consistent finding in age-related macular degeneration (AMD). We quantified BLamD thickness, appearance, and topography in eyes of aged donors with and without AMD ...and evaluated its relationship to other components of the retinal pigment epithelium-basal lamina/Bruch's membrane (RPE-BL-BrM) complex.
Donor eyes (n = 132) were classified as normal (n = 54), early to intermediate AMD (n = 24), geographic atrophy (GA; n = 13), and neovascular AMD (NV; n = 41). In high-resolution histology, we assessed RPE, BLamD, and BrM thicknesses and phenotypes at 3309 predefined locations in the central (foveal and perifovea) and superior (perifoveal) sections. Pre-mortem optical coherence tomography (OCT) imaging of a 90-year-old woman was compared to postmortem histopathology.
In non-atrophic areas of AMD eyes, the RPE-BLamD is thick (normal = 13.7 µm, early-intermediate = 16.8 µm, GA = 17.4 µm, NV = 18.7 µm), because the BLamD is thick (normal = 0.3 µm, early-intermediate = 5.5 µm, GA = 4.1 µm, NV = 5.3 µm). RPE layer thickness is similar across these stages. Disease-associated variants of BLamD (thick, late, basal mounds) cluster subfoveally. A thick BLamD is visible on OCT as a hyporeflective split in the RPE-BL-BrM complex. BrM is thin (3.5 µm) in NV (normal = 4.2 µm, early to intermediate = 4.4 µm, and GA = 4.2 µm).
The RPE-BL-BrM complex is thick in AMD, driven by the accumulation and expansion of BLamD rather than expansion of either three-layer BrM, RPE-BL, or RPE. BLamD is clinically appreciable by OCT in some patients as a non-neovascular "split RPE-BL-BrM complex" or "double-layer sign." BLamD may contribute toward the formation and progression of high-risk drusen yet also exhibit protective properties.
To describe the use of optical coherence tomography angiography (OCT-A) for evaluating the spectrum of polypoidal vascular diseases.
Retrospective observational case series of seven patients with ...polypoidal choroidal vasculopathy (three cases) or polypoidal choroidal neovascularization (four cases). Optical coherence tomography angiography information was acquired using two different OCT-A devices (the Optovue RTVue XR Avanti SD-OCT and the Spectralis OCT angiography). Flow signals within branching vascular networks, type 1 neovascularization and polyps were evaluated. Comparisons were made between en face and cross-sectional OCT-A images. Vascular information from OCT-A was also compared with indocyanine green angiography.
En face images from OCT-A provided anatomical information about branching vascular networks that were comparable to indocyanine green angiography. Polyps were poorly resolved on en face OCT-A images but were clearly defined on cross-sectional OCT-A images. Cross-sectional OCT-A revealed flow signals within focal regions of the polyps with a significant portion of the polyp lumen being devoid of flow signal. Flow signals from cross-sectional OCT-A images also showed that branching vascular networks, type 1 neovascularization, and polyps were confined to the anatomic compartment between the retinal pigment epithelium and Bruch's membrane. It was not possible to detect leakage on en face or cross-sectional OCT-A.
The combination of en face and cross-sectional OCT-A images provides anatomical information about polypoidal structures that is comparable to indocyanine green angiography. OCT-A may be a useful modality for the management of polypoidal diseases. However, the limitations of OCT-A identified in this study suggest that it is not a replacement for indocyanine green angiography.
To correlate clinical manifestations with choroidal morphology in pachychoroid disorders, including central serous chorioretinopathy, pachychoroid pigment epitheliopathy, pachychoroid ...neovasculopathy, and polypoidal choroidal vasculopathy, using en face swept-source optical coherence tomography (OCT).
Patients with pachychoroid spectrum diagnoses were identified nonconsecutively through a review of charts and multimodal imaging. Each eye was categorized as uncomplicated pachychoroid, pachychoroid pigment epitheliopathy, central serous chorioretinopathy, pachychoroid neovasculopathy, or polypoidal choroidal vasculopathy. All patients included in this series then underwent bilateral swept-source OCT.
Sixty-six eyes of 33 patients were included. Numbers assigned to diagnostic categories were 8 uncomplicated pachychoroid, 13 pachychoroid pigment epitheliopathy, 27 central serous chorioretinopathy, 15 pachychoroid neovasculopathy, and 3 polypoidal choroidal vasculopathy. One eye was classified as normal. Swept-source OCT choroidal thickness maps confirmed increased thickness under the areas of pachychoroid pigment epitheliopathy, central serous chorioretinopathy, type 1 NV (pachychoroid neovasculopathy), or polyps (polypoidal choroidal vasculopathy). En face swept-source OCT showed dilated outer choroidal vessels in all eyes. In several eyes with a chronic disease, focal choriocapillaris atrophy with inward displacement of deep choroidal vessels was noted.
Although clinical manifestations of pachychoroid spectrum disorders vary considerably, these entities share morphologic findings in the choroid, including increased thickness and dilated outer choroidal vessels. En face swept-source OCT localizes these changes to disease foci and shows additional findings that may unify our understanding of disease pathogenesis.
Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) that leads to progressive and irreversible loss of visual function. Geographic atrophy is defined by the presence ...of sharply demarcated atrophic lesions of the outer retina, resulting from loss of photoreceptors, retinal pigment epithelium (RPE), and underlying choriocapillaris. These lesions typically appear first in the perifoveal macula, initially sparing the foveal center, and over time often expand and coalesce to include the fovea. Although the kinetics of GA progression are highly variable among individual patients, a growing body of evidence suggests that specific characteristics may be important in predicting disease progression and outcomes. This review synthesizes current understanding of GA progression in AMD and the factors known or postulated to be relevant to GA lesion enlargement, including both affected and fellow eye characteristics. In addition, the roles of genetic, environmental, and demographic factors in GA lesion enlargement are discussed. Overall, GA progression rates reported in the literature for total study populations range from 0.53 to 2.6 mm2/year (median, ∼1.78 mm2/year), assessed primarily by color fundus photography or fundus autofluorescence (FAF) imaging. Several factors that could inform an individual's disease prognosis have been replicated in multiple cohorts: baseline lesion size, lesion location, multifocality, FAF patterns, and fellow eye status. Because best-corrected visual acuity does not correspond directly to GA lesion enlargement due to possible foveal sparing, alternative assessments are being explored to capture the relationship between anatomic progression and visual function decline, including microperimetry, low-luminance visual acuity, reading speed assessments, and patient-reported outcomes. Understanding GA progression and its individual variability is critical in the design of clinical studies, in the interpretation and application of clinical trial results, and for counseling patients on how disease progression may affect their individual prognosis.
To systematically characterize histologic features of multiple chorioretinal layers in eyes with geographic atrophy, or complete retinal pigment epithelium (RPE) and outer retinal atrophy, secondary ...to age-related macular degeneration, including Henle fiber layer and outer nuclear layer; and to compare these changes to those in the underlying RPE-Bruch membrane-choriocapillaris complex and associated extracellular deposits.
Geographic atrophy was delimited by the external limiting membrane (ELM) descent towards Bruch membrane. In 13 eyes, histologic phenotypes and/or thicknesses of Henle fiber layer, outer nuclear layer, underlying supporting tissues, and extracellular deposits at four defined locations on the non-atrophic and atrophic sides of the ELM descent were assessed and compared across other tissue layers, with generalized estimating equations and logit models.
On the non-atrophic side of the ELM descent, distinct Henle fiber layer and outer nuclear layer became dyslaminated, cone photoreceptor inner segment myoids shortened, photoreceptor nuclei and mitochondria translocated inward, and RPE was dysmorphic. On the atrophic side of the ELM descent, all measures of photoreceptor health declined to zero. Henle fiber layer/outer nuclear layer thickness halved, and only Müller cells remained, in the absence of photoreceptors. Sub-RPE deposits remained, Bruch membrane thinned, and choriocapillaris density decreased.
The ELM descent sharply delimits an area of marked gliosis and near-total photoreceptor depletion clinically defined as Geographic atrophy (or outer retinal atrophy), indicating severe and potentially irreversible tissue damage. Degeneration of supporting tissues across this boundary is gradual, consistent with steady age-related change and suggesting that RPE and Müller cells subsequently respond to a threshold of stress. Novel clinical trial endpoints should be sought at age-related macular degeneration stages before intense gliosis and thick deposits impede therapeutic intervention.
To report 3 cases of pachychoroid neovasculopathy, a form of Type 1 (sub-retinal pigment epithelium) neovascularization, occurring over areas of increased choroidal thickness and dilated choroidal ...vessels.
A retrospective observational case series of three patients who underwent comprehensive ophthalmic examination and multimodal imaging with fundus photography, fundus autofluorescence, spectral domain optical coherence tomography, enhanced depth imaging optical coherence tomography, fluorescein angiography, and indocyanine green angiography.
In all 3 eyes of 3 patients, aged 55 years to 63 years, there was Type 1 neovascularization overlying a localized area of choroidal thickening and dilated choroidal vessels seen with enhanced depth imaging optical coherence tomography. With indocyanine green angiography, there were large choroidal veins and choroidal hyperpermeability seen beneath the area of the neovascular tissue in all three eyes. No eyes had evidence of submacular exudative detachment or autofluorescence changes to suggest antecedent acute or chronic central serous chorioretinopathy. No eyes had drusen or degenerative changes to suggest age-related macular degeneration or other degenerative diseases. In one patient, the fellow unaffected eye demonstrated retinal pigment epithelium abnormalities, best seen with fundus autofluorescence, overlying focal dilated choroidal vessels seen with enhanced depth imaging optical coherence tomography and associated choroidal hyperpermeability seen with indocyanine green angiography, consistent with the diagnosis of pachychoroid pigment epitheliopathy. All three eyes showed the appearance of polypoidal structures within the neovascular tissue.
Pachychoroid neovasculopathy falls within a spectrum of diseases associated with choroidal thickening that includes pachychoroid pigment epitheliopathy, central serous chorioretinopathy, and polypoidal choroidal vasculopathy and should be considered as a possible diagnosis in eyes with features of Type 1 neovascularization and choroidal thickening in the absence of characteristic age-related macular degeneration or degenerative changes. Pachychoroid neovasculopathy may occur as a focal abnormality within the macula, even in myopic eyes with normal subfoveal choroidal thickness. Pachychoroid neovasculopathy can ultimately progress to the development of polypoidal choroidal vasculopathy.
Drusenoid pigment epithelium detachment (DPED) is a known precursor to geographic atrophy in age-related macular degeneration (AMD). We sought histologic correlates for spectral-domain (SD) optical ...coherence tomography (OCT) signatures in DPED and determined the frequency and origin of these OCT signatures in a clinical cohort of DPED eyes.
Laboratory imaging and histologic comparison, and retrospective, observational cohort study.
Four donor eyes with histopathologic diagnosis of AMD (2 with nonneovascular DPED and 2 with neovascular pigment epithelium detachment PED) and 49 eyes of 33 clinic patients with nonneovascular DPED more than 2 mm in diameter.
Donor eyes underwent multimodal ex vivo imaging, including SD OCT, then processing for high-resolution histologic analysis. All clinic patients underwent SD OCT, near-infrared reflectance, and color photography.
Histologic correlates for SD OCT signatures in DPED, estimate of coverage by different retinal pigment epithelium (RPE) phenotypes in the DPED surface; frequency and origin of histologically verified SD OCT signatures in a clinical cohort of DPED eyes, and comparisons of histologic features between neovascular PED and DPED resulting from AMD.
Intraretinal and subretinal hyperreflective foci as seen on SD OCT correlated to RPE cells on histologic examination. Hypertransmission of light below the RPE-basal lamina band correlated with dissociated RPE. Subretinal hyperreflective material resulting from acquired vitelliform lesions corresponded to regions of apically expelled RPE organelles. In the clinical cohort, all histologically verified reflectivity signatures were visible and quantifiable. The appearance of intraretinal hyperreflective foci was preceded by thickening of the RPE-basal lamina band. Compared with PEDs associated with neovascular AMD, DPEDs had different crystallization patterns, no lipid-filled cells, and thinner basal laminar deposits.
Multiple RPE fates in AMD, including intraretinal cells that are highly prognostic for progression, can be followed and quantified reliably using eye-tracked serial SD OCT. This information may be particularly useful for obtaining an accurate timeline of incipient geographic atrophy in clinic populations and for quantifying anatomic end points and response to therapy in AMD clinical trials.
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