Major reviewChoroidal imaging biomarkers
Introduction
The choroid is the most vascularized structure of the eye and contributes to the majority of ocular blood supply, including outer retina.98 It thereby directly caters to the metabolic demand of the photoreceptor layer, and abnormalities of the choroid are implicated in various chorioretinal pathologies such as neovascular age-related macular degeneration (nAMD), central serous chorioretinopathy (CSCR), polypoidal choroidal vasculopathy (PCV), Vogt–Koyanagi–Harada disease (VKH), and diabetic retinopathy (DR).8, 28, 43, 171
The choroid is structurally divided into five layers, which from inner to outer aspect are Bruch membrane, layer of choriocapillaris (CC), Sattler and Haller layers, and the suprachoroidal lamina. The choroidal tissue has diverse functions apart from vascular supply which include absorption of light and thermoregulation.120
The inaccessibility of the choroidal structures to direct clinical examination makes the clinician rely on noninvasive imaging techniques for its evaluation. High-resolution in vivo cross-sectional imaging of the choroid is difficult owing to scattering at the level of retinal pigment epithelium (RPE) which prevents direct visualization.150 Multiple advancements in imaging techniques and instrumentation such as enhanced depth imaging (EDI) and swept-source optical coherence tomography (SS-OCT) have led to a better understanding of the choroidal disorders.42, 150 EDI in spectral domain (SD-OCT) was first introduced by Spaide et al150 by shifting the zero-delay line toward the choroid, thereby leading to improved image resolution and better delineation of choroidal details. This, along with image averaging, eye tracking, high-speed scan acquisition rate, and low speckle noise, has further made high-resolution choroidal imaging possible.42, 150
Our group introduced combined depth imaging that merges conventional SD-OCT images and EDI images with no loss of resolution at the vitreoretinal or choroidal level.18, 19 Introduction of long-wavelength SS-OCT added another dimension to choroidal imaging. This technique uses swept laser light source, and the interference spectrum is measured by using photodetectors, unlike the spectrophotometer used in SD-OCT. This leads to easier and faster scan acquisition with greater detail, thereby making detailed choroidal volume (CV) assessment possible.42, 131 Scanning protocols can vary from single-line scan (which can provide quantitative details including choroidal thickness [CT], vessel thickness, and vascularity index [CVI] in a 2D plane to a combination of multiple high-density line scans that facilitate creation of a 3D structure of the choroid to provide CV and en face OCT images in both SD-OCT and SS-OCT settings.93, 138 OCT angiography (OCTA) compares the difference in signal from repeated B-scans at specific cross sections and, by using motion contrast, generates a map of retinal and choroidal vasculature.25, 47
These major advance including cross-sectional, en face OCT, and OCTA–have led to a better understanding of choroidal details. They have led to introduction of multiple qualitative and quantitative parameters and indices that are objectively defined and reproducible with minimal interobserver and intraobserver variations, similar to the standardized parameters available in retinal imaging.
Section snippets
Choroidal biomarkers
“A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic or pathologic processes or pharmacological response to a therapeutic intervention.”65 In this context, choroidal biomarkers may be defined as the indices that are used to quantify objectively variables related to choroidal morphology or vascularity. These biomarkers can help to prognosticate and predict the course of illness in certain instances; however, reliably identifying the
Choroidal thickness
CT is the most studied choroidal biomarker and has been measured at the subfoveal level in most studies.36, 73, 107, 150 Conventionally, CT is measured from the posterior edge of RPE to CSI by identifying the RPE hyperreflectivity on OCT.68 CT depends on various physiological and pathological factors and varies with age, ethnicity, gender, refraction, axial length, or time (diurnal variation).36, 73, 96, 107, 158 On the other hand, various chorioretinal pathologies such as CSCR,84, 92 PCV,43, 83
En face OCT analysis of the choroid
En face OCT provides transverse confocal scanning with coronal or en face view and a topographic analysis of the choroid compared with the cross-sectional OCT scans.130 As data for en face are derived from axial scans, high-speed acquisition using SS-OCT compared with SD-OCT provides better topographical details.57 Motaghiannezam and coworkers114 used wide-angle en face imaging with 1060-nm SS-OCT to identify the choroidal vessels, their size, and distribution. High axial resolution of 5.9 μ
OCTA of the choroid
OCTA provides an en face–based in vivo view of the choroidal vasculature. This technique involves performing repeated OCT B-scans at the same spots and identification of motion contrast to provide information on blood flow characteristics.64, 101 The technology has evolved over the past decade with the introduction of multiple innovations based on either doppler shift69 or decorrelation (phase-based139 or intensity-based methods82). The addition of split-spectrum amplitude-decorrelation
Conclusion
Understanding about the choroid has tremendously improved after the introduction of OCT devices with enhanced penetration. Quantitative evaluation of CT and CV which shows large physiological variation is already available in few of the commercial devices. Further research on quantification of choroidal parameters including choroidal vascularity, vascular layer thickness, en face image analysis, 3D reconstruction, and OCTA will increase our understanding about the chorioretinal disorders. The
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