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Optical Coherence Tomography Angiography for the Anterior Segment Wen Di Lee1, Kavya Devarajan1, Jacqueline Chua1,2, Leopold Schmetterer1,2,3,4,5, Jodhbir S

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Optical Coherence Tomography Angiography for the Anterior Segment Wen Di Lee1, Kavya Devarajan1, Jacqueline Chua1,2, Leopold Schmetterer1,2,3,4,5, Jodhbir S Lee et al. Eye and Vision (2019) 6:4 https://doi.org/10.1186/s40662-019-0129-2 REVIEW Open Access Optical coherence tomography angiography for the anterior segment Wen Di Lee1, Kavya Devarajan1, Jacqueline Chua1,2, Leopold Schmetterer1,2,3,4,5, Jodhbir S. Mehta1,2,5 and Marcus Ang1,2* Abstract Optical coherence tomography angiography (OCTA) is a rapid and non-invasive technique for imaging vasculature in the eye. As OCTA can produce high-resolution cross-sectional images and allow depth-resolved analysis for accurate localization of pathology of interest, it has become a promising method for anterior segment imaging. Furthermore, OCTA offers a more patient-friendly alternative to the conventional invasive dye-based fluorescent angiography. However, conventional OCTA systems are typically designed and optimized for the posterior segment of the eye, and thus using OCTA for anterior segment imaging can present several difficulties and limitations. In this review, we summarized the recent developments and clinical applications in anterior segment OCTA (AS-OCTA) imaging, such as for the cornea, iris, sclera and conjunctiva. We also compared commercially available OCTA systems, discussed the limitations of adapting current OCTA technology for the anterior segment imaging, and proposed possible future directions for AS-OCTA systems. AS-OCTA provides potential for future clinical applications such as diagnosis of corneal and iris pathologies, pre-operative surgical planning, assessment of new anti- angiogenic therapeutics or evaluation of limbal stem cell deficiency. With further development, OCTA for anterior segment imaging in the clinics may become common in the near future. Keywords: Optical coherence tomography angiography, Vascularisation, Cornea, Iris, Anterior segment Background OCT angiography (OCTA) is an emerging technology Optical coherence tomography (OCT) imaging is a well- for imaging ocular vasculature [1]. It works on the con- established technology that enables non-invasive and cept of low coherence interferometry and analysis of signal rapid in vivo imaging of the eye [1]. Since it was first decorrelation between consecutive scans, by comparing introduced, OCT imaging has become an integral part of phase speckle contrast, changes in intensity or variation of clinical assessment. By applying low-coherence light and the full OCT signal [3, 5, 6]. OCTA is currently used clin- measuring the echo time delay of light backscattered ically for vascular imaging of the retina, choroid and optic from tissue structures, OCT can provide high-resolution nerve [7–9]. Commercially available systems are designed three-dimensional structural images, which are useful for to visualize retinal microvessels and have been useful in pre-operative diagnosis, intra-operative real-time imaging the assessment of pathologies in the posterior segment as well as post-operative evaluation of diseases [2]. Struc- of the eye, including retinal neovascularisation, retinal tural OCT systems produce poor delineation of blood artery and vein occlusion, and glaucoma [1, 10]. While vessels due to scattering of light [3]. However, with recent OCTA is now commonly utilized for the posterior seg- improvements in signal analysis, OCT systems are now ment, research on OCTA for the anterior segment is able to visualize vascular flow [4]. only in its infancy [11]. Anterior segment imaging of the vasculature is useful for a diverse number of clinical applications, ranging from diagnosis to monitoring treatment of corneal pathologies * Correspondence: [email protected] 1Singapore Eye Research Institute, Singapore National Eye Center, Singapore, [2, 6, 12]. Currently, assessment of anterior segment vas- Singapore culature is limited to slit-lamp photography (SLP) and 2Eye-ACP, Duke-NUS Graduate Medical School, Singapore, Singapore dye-based angiography. SLP is the most common method Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Lee et al. Eye and Vision (2019) 6:4 Page 2 of 9 to capture the anterior segment vasculature for clinical Lastly, OCTA has only a slight learning curve and can be and experimental applications [4]. However, SLP has lim- performed by trained technicians. This provides a more ited visualisation of vessels in the presence of corneal cost-effective method over invasive angiography, which is oedema, deposits or scars. Thus, image analysis often time consuming and requires a certified clinician to per- results in underestimation due to poor sensitivity to form the procedure [4, 12]. Nonetheless, it is also import- smaller vessels and interference from background iris ant to note the current limitations of OCTA. This vessels [4, 13]. Also, only two-dimensional informa- includes restricted field of view, lack of information on tion of the vasculature can be derived [13]. flow speed, projection and motion artefacts caused by Fluorescein angiography (FA) and indocyanine green scattering and lack of motion tracking system, inability to angiography (ICGA) are more reliable methods for evalu- differentiate afferent and efferent vessels and the need for ating normal and diseased vessels clinically [1, 4]. It has careful examination of artefacts that might be mistaken as been demonstrated that these techniques show better vessels, such as from hyper-reflective structures like cor- vessel delineation than SLP, especially for vessels beneath neal fibrosis [1, 3, 6]. corneal scars [1, 13]. In addition, leakage observed in FA The aim of this review is to summarize current develop- and ICGA can give information on vessel maturity while ments in adapting OCTA for anterior segment vasculature differentiating afferent and efferent vessels [1]. Further- imaging, including the cornea, iris, sclera and conjunctiva. more, since ICG is a large molecule that remains in vessels We also evaluate the different OCTA systems that are for long periods, ICG leakage is likely indicative of a available and discuss potential future directions and clin- pathological condition [8, 14]. However, these invasive ical applications of OCTA for anterior segment of the eye. techniques are rarely performed due to infrequent but severe adverse reactions associated with the dyes, includ- Review ing gastrointestinal side effects and anaphylactic shock, Anterior segment optical coherence tomography even for patients with no risk factors or history of allergies angiography technology [12, 13]. Patients who are pregnant or have impaired liver OCTA utilizes phase variations, differences in signal and kidney function are also not compatible with such amplitude or changes in full OCT signal in consecutive techniques [1, 8]. In addition, leakage may prevent B-scans to detect blood flow [4]. As current OCTA sys- visualization of deeper vessels, causing underestimation tems are designed for retinal imaging, adaptor lens is of the extent of vascularisation [8]. While current angiog- needed to image the anterior segment [2, 4, 8]. Current raphy methods allow qualitative assessment of the anterior systems use different algorithms to produce images, in- segment vasculature, objective and quantitative evaluation cluding full- or split-spectrum amplitude decorrelation is challenging. Furthermore, as anti-angiogenic therapeu- angiography (FSADA or SSADA, respectively), optical tics are developed, new non-invasive imaging techniques microangiography and ratio analysis [6]. In addition, that can quantitatively measure changes in anterior seg- these systems also differ in scanning speed, scan area, ment vasculature are needed [6]. As such, research in resolution and other internal software that allow for mo- OCTA for anterior segment imaging has been garnering tion correction, projection artefacts removal or automated attention and importance. segmentation, to name a few. A good image generally OCTA has many potential advantages over current an- requires a good balance between sampling density, field of terior segment imaging techniques. Firstly, OCTA can view and number of B-scans [3]. Oversampling will im- rapidly acquire images in a non-invasive and dye-free prove the quality of images but will increase the risk of way, thus avoiding dye-related side effects and offering a bulk motion artefacts. In addition, as lateral resolution more patient-friendly alternative to fluorescence angiog- depends on the spot size of the beam and oversampling raphy [6]. The absence of leakage also ensures that deeper ratio, a larger field of view will result in lower lateral reso- vessels are not obscured [3]. Secondly, OCTA can produce lution, implying that smaller vessels may not be detected high-resolution cross-sectional images, which can be for larger scan areas compared with smaller scan areas segmented into different layers, allowing visualization of [13]. Furthermore, each measurement takes about 3 to 6 s vessels at different depths [3]. Moreover, the en face mode and the area of the
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