Elsevier

Survey of Ophthalmology

Volume 64, Issue 3, May–June 2019, Pages 312-333
Survey of Ophthalmology

Major review
Choroidal imaging biomarkers

https://doi.org/10.1016/j.survophthal.2018.11.002Get rights and content

Abstract

The choroid is the vascular coat of the eye, and its role has been studied in multiple chorioretinal disorders. Recent advancements in choroidal imaging techniques, including enhanced depth imaging optical coherence tomography, swept source optical coherence tomography, en face optical coherence tomography, and optical coherence tomography angiography have facilitated an in-depth analysis of the choroid. The gradual shift from manual to automated segmentation and binarization methods have led to precise and reproducible measurements of choroidal parameters. These qualitative and quantitative parameters, called choroidal imaging biomarkers, have evolved over the past decade from a simple linear subfoveal choroidal thickness to more complex 3D choroidal reconstruction, thus widening the spectrum encompassing multiple parameters. These biomarkers have provided a better understanding of the pathogenesis, are helpful in diagnostic dilemmas, and, in the future may also help to devise treatment options. The lack of normative data, absence of standardized parameters, and limitations of the imaging techniques, however, have led to ambiguity and difficulty in the interpretation of these variables. We attempt to address these lacunae in the literature and provide a basic understanding of the choroid in both health and disease using these choroidal 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

References (176)

  • H.J. Cho et al.

    Effects of choroidal vascular hyperpermeability on anti–vascular endothelial growth factor treatment for polypoidal choroidal vasculopathy

    Am J Ophthalmol

    (2013)
  • W. Choi et al.

    Ultrahigh-Speed, Swept-Source Optical Coherence Tomography Angiography in Nonexudative Age-Related Macular Degeneration with Geographic Atrophy

    Ophthalmology

    (2015)
  • S.E. Chung et al.

    Choroidal thickness in polypoidal choroidal vasculopathy and exudative age-related macular degeneration

    Ophthalmology

    (2011)
  • J.R. de Oliveira Dias et al.

    Natural History of Subclinical Neovascularization in Nonexudative Age-Related Macular Degeneration Using Swept-Source OCT Angiography

    Ophthalmology

    (2018)
  • D. Ferrara et al.

    En face enhanced-depth swept-source optical coherence tomography features of chronic central serous chorioretinopathy

    Ophthalmology

    (2014)
  • I. Flores-Moreno et al.

    The relationship between axial length and choroidal thickness in eyes with high myopia

    Am J Ophthalmol

    (2013)
  • T. Fujiwara et al.

    Enhanced depth imaging optical coherence tomography of the choroid in highly myopic eyes

    Am J Ophthalmol

    (2009)
  • Y. Jia et al.

    Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration

    Ophthalmology

    (2014)
  • P. Jirarattanasopa et al.

    Assessment of macular choroidal thickness by optical coherence tomography and angiographic changes in central serous chorioretinopathy

    Ophthalmology

    (2012)
  • L. Kuehlewein et al.

    Optical Coherence Tomography Angiography of Type 1 Neovascularization in Age-Related Macular Degeneration

    Am J Ophthalmol

    (2015)
  • A. Abbouda et al.

    Identifying characteristic features of the retinal and choroidal vasculature in choroideremia using optical coherence tomography angiography

    Eye

    (2018)
  • M. Adhi et al.

    Analysis of morphological features and vascular layers of choroid in diabetic retinopathy using spectral-domain optical coherence tomography

    JAMA Ophthalmol

    (2013)
  • M. Adhi et al.

    Analysis of the thickness and vascular layers of the choroid in eyes with geographic atrophy using spectral-domain optical coherence tomography

    Retina

    (2014)
  • A. Agarwal et al.

    Choroidal Structural Changes in Tubercular Multifocal Serpiginoid Choroiditis

    Ocul Immunol Inflamm

    (2018)
  • K. Aggarwal et al.

    The role of optical coherence tomography angiography in the diagnosis and management of acute vogt-koyanagi-harada disease

    Ocul Immunol Inflamm

    (2018)
  • R. Agrawal et al.

    Choroidal vascularity index in central serous chorioretinopathy

    Retina

    (2016)
  • R. Agrawal et al.

    Choroidal vascularity index as a measure of vascular status of the choroid: Measurements in healthy eyes from a population-based study

    Sci Rep

    (2016)
  • R. Agrawal et al.

    Choroidal vascularity index in Vogt-Koyanagi-Harada disease: an EDI-OCT derived tool for monitoring disease progression

    Transl Vis Sci Technol

    (2016)
  • R. Agrawal et al.

    Choroidal vascularity index (CVI)-a novel optical coherence tomography parameter for monitoring patients with panuveitis?

    PLoS One

    (2016)
  • R. Agrawal et al.

    Influence of scanning area on choroidal vascularity index measurement using optical coherence tomography

    Acta Ophthalmol

    (2017)
  • M. Al-Sheikh et al.

    Quantitative OCT angiography of the retinal microvasculature and the choriocapillaris in myopic eyes

    Invest Ophthalmol Vis Sci

    (2017)
  • D. Alonso-Caneiro et al.

    Automatic segmentation of choroidal thickness in optical coherence tomography

    Biomed Opt Express

    (2013)
  • R.A. Alshareef et al.

    Choroidal vascular analysis in myopic eyes: evidence of foveal medium vessel layer thinning

    Int J Retina Vitreous

    (2017)
  • F. Alten et al.

    Exploring choriocapillaris under reticular pseudodrusen using OCT-Angiography

    Graefes Arch Clin Exp Ophthalmol

    (2016)
  • R. Aoyagi et al.

    Subfoveal choroidal thickness in multiple evanescent white dot syndrome

    Clin Exp Optom

    (2012)
  • E. Balestrieri et al.

    Choroidal vessel characterization using en-face optical coherence tomography measurement

    (2014)
  • G. Barteselli et al.

    Combined depth imaging using optical coherence tomography as a novel imaging technique to visualize vitreoretinal choroidal structures

    Retina

    (2013)
  • G. Barteselli et al.

    Macular choroidal volume variations in highly myopic eyes with myopic traction maculopathy and choroidal neovascularization

    Retina

    (2014)
  • M. Battaglia Parodi et al.

    Vascular abnormalities in patients with Stargardt disease assessed with optical coherence tomography angiography

    Br J Ophthalmol

    (2017)
  • A. Boltz et al.

    Choroidal blood flow and progression of age-related macular degeneration in the fellow eye in patients with unilateral choroidal neovascularization

    Invest Ophthalmol Vis Sci

    (2010)
  • M.A. Bonini Filho et al.

    Association of Choroidal Neovascularization and Central Serous Chorioretinopathy With Optical Coherence Tomography Angiography

    JAMA Ophthalmol

    (2015)
  • E. Brewer et al.

    Analysis of the Vascular Layers and Morphology of the Choroid in Eyes with Diabetic Retinopathy using Spectral-Domain Optical Coherence Tomography

    Invest Ophthalmol Vis Sci

    (2013)
  • J. Chhablani et al.

    Repeatability and reproducibility of manual choroidal volume measurements using enhanced depth imaging optical coherence tomography

    Invest Ophthalmol Vis Sci

    (2012)
  • J. Chhablani et al.

    Choroidal thickness in macular telangiectasia type 2

    Retina

    (2014)
  • J. Chhablani et al.

    Choroidal thickness profile in inherited retinal diseases in Indian subjects

    Indian J Ophthalmol

    (2015)
  • J. Chhablani et al.

    Choroidal thickness profile in healthy Indian subjects

    Indian J Ophthalmol

    (2014)
  • J.K. Chhablani et al.

    Choroidal thickness profile in healthy Indian children

    Indian J Ophthalmol

    (2015)
  • Y.T. Chi et al.

    Optical Coherence Tomography Angiography for Assessment of the 3-Dimensional Structures of Polypoidal Choroidal Vasculopathy

    JAMA Ophthalmol

    (2017)
  • W. Choi et al.

    Choriocapillaris and choroidal microvasculature imaging with ultrahigh speed OCT angiography

    PLoS One

    (2013)
  • M.A. Choma et al.

    Sensitivity advantage of swept source and Fourier domain optical coherence tomography

    Opt Express

    (2003)
  • Cited by (94)

    View all citing articles on Scopus

    Funding: None.

    Financial Disclosure: No financial disclosures.

    View full text