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Optical Coherence Tomography Angiography: an Overview of The Review Optical coherence tomography angiography: an overview of the technology and an assessment of applications for clinical research Andrew Koustenis Jr,1 Alon Harris,1 Josh Gross,1 Ingrida Januleviciene,2 Aaditya Shah,1 Brent Siesky1 1Department of ABSTRACT it is now widely accepted that vascular factors play Ophthalmology, Indiana In recent years, ophthalmology has experienced a role in the risk of development and progression University School of Medicine, fi 2–6 Indianapolis, Indiana, USA signi cant developments with respect to imaging of the disease. Currently, other imaging modal- 2Eye Clinic of Lithuanian modalities. Optical coherence tomography angiography is ities are used to illustrate retinal capillary beds, University of Health Sciences, one such technology that seeks to improve diagnostics such as confocal scanning laser Doppler flowmetry Kaunas, Lithuania for retinal diseases. Using standard structural ocular (Heidelberg retinal flowmetry (HRF), Heidelberg coherence tomography hardware, optical coherence Engineering, Heidelberg, Germany), which mea- Correspondence to Professor Alon Harris, tomography angiography demonstrates the ability to sures the amount of a vascular tissue and blood Glaucoma Research and non-invasively visualise the vasculature in the retina and flow within the peripapillary retinal capillary Diagnostic Center, Eugene and the choroid with high resolution, allowing greater insight beds.7 In addition, fluorescein angiography (FA) is Marilyn Glick Eye Institute, into retinal vascular pathologies. In addition, retinal and used to visualise the superficial retinal vascular beds Indiana University School of fl fl Medicine, Indianapolis, choroidal vessel density and blood ow can be and extravasation of vascular uid secondary to IN 46202, USA; quantified, offering potential to assist in the diagnosis of retinal pathology. Other forms of OCT exist, such [email protected] a variety of retinal diseases. To date, numerous retinal as Doppler OCT, which assesses the retinal branch diseases, such as open-angle glaucoma, have been vessels for blood velocity and volumetric flow rate.8 Received 21 July 2016 found to possess a vascular component. Specifically, These imaging techniques, however, have found Revised 7 September 2016 fi Accepted 17 September 2016 ischaemia of the optic nerve head and lamina cribrosa limitation in their ability to con rm pathological Published Online First has been theorised as a causative factor in ganglion cell vascular mechanisms in the ONH and lamina cri- 4 October 2016 death; however, confirmation of this mechanism has brosa that could be involved in the development been prohibited by the limitations of currently existing and progression of OAG. OCT angiography imaging modalities. Optical coherence tomography (OCT-A) is a retinal vascular imaging technology angiography provides clear imaging of these regions and that uses a novel algorithm to generate high- the possibility to elucidate further understanding of resolution images and quantify vessel density and vascular factors that contribute to glaucoma blood flow of the retina and choroid. Vessel density development and progression. Furthermore, this imaging changes in OAG, which account for significant modality may provide insight to neural pathologies with blindness globally,9 have been demonstrated with vascular components such as Alzheimer’s disease. OCT-A. In this review, the authors discuss the Herein, the authors discuss the theory of operation for OCT-A technology and current OAG findings. In optical coherence tomography angiography and the addition, the authors offer speculation on further current findings from pilot studies with a focus on open- applications of OCT-A to investigate retinal vascu- angle glaucoma. In addition, speculation is offered for lar abnormalities associated with neurodegenerative future applications of the technology to study other diseases such as Alzheimer’s disease (AD). diseases with microvascular contributions. TECHNOLOGY OVERVIEW: FUNCTION, ADVANTAGES AND DISADVANTAGES INTRODUCTION OCT-A uses laser light to produce a clear image of Evaluation of retinal pathology in vivo has made the retinal and choroidal microvasculature. An great improvements as the advancement of imaging overview schematic of the system’s operation is modalities has allowed for the quantification of depicted in figure 1. various tissues. Optical coherence tomography The device incorporates an infrared laser that (OCT) was developed in the early 1990s and has shines on the posterior retina and is reflected by been used both in research and in clinical practice the tissue. The reflected light is detected by the to image retinal structures such as the retinal nerve instrument and, once converted from an analogue fibre layer (RNFL), macula and optic nerve head to digital signal, is processed by the system’s com- (ONH). Specifically, retinal structural deficits asso- puter.10 During a scan of an individual’s retina, ciated with the development and progression of individual scans of layers of the retina are collected, open-angle glaucoma (OAG) have been identified. which are known as A-scans. A-scans are compiled For example, Hoh et al1 found that in patients into a B-scan, which is used to analyse both cross- with OAG, OCT showed RNFL and macula thin- sectional structural information and blood flow fl To cite: Koustenis A , ning with disease progression. However, one limita- information. The data collected from the re ected Harris A, Gross J, et al. Br J tion of OCT is that it does not provide information light are usually used to assess structural aspects of Ophthalmol 2017;101:16– pertaining to retinal blood flow. As the aetiology of the ONH, such as RNFL and macula thickness. 20. OAG has expanded to include multiple influences, However, in OCT-A, an additional algorithm is 16 Koustenis A , et al. Br J Ophthalmol 2017;101:16–20. doi:10.1136/bjophthalmol-2016-309389 Review signal-to-noise ratio (SNR). This is achieved via two methods: considering the number of B-scans (N) and the number of band- width segmentations (M). While the full scan is relatively short at about 3 s, saccadic movements of the eye can cause a low SNR. Therefore, averaging the decorrelation across the number of B-scans increases the SNR. In addition, the equation averages the decorrelation value across M number of bandwidth segmen- tations.10 This process is depicted in figure 2. In addition to having a high SNR, the SSADA algorithm has a high level of connectivity in the image. This means that the vas- culature shown in the image appears smooth and continuous.11 This is important for allowing the image to be interpreted clearly. Once the algorithm has processed the data, the output of the OCT-A algorithm is an image of the retinal and choroidal vascu- Figure 1 Overall schematic of the optical coherence tomography lature, which can be segmented into four zones: the superficial 10 angiography system. Adapted with permission. plexus, the deep plexus, the outer retina and the choroid.12 13 This includes the full depth of the optic disc.11 Therefore, the vasculature from the superficial retina to the lamina cribrosa can be seen,14 including into the pores of the lamina cribrosa. From applied to calculate blood flow. The algorithm discussed here is this image, qualitative assessments can be made for pathologies, – known as the split-spectrum amplitude decorrelation angiog- such as glaucoma and diabetic retinopathy.15 17 However, a raphy (SSADA) algorithm. This algorithm, which calculates the quantified assessment of blood flow can be obtained in the form 10 decorrelation in the reflected light, is shown in equation 1. of the flow index, as shown in equation 2, and the vessel density, which can be calculated as the per cent of an area con- NXÀ1 XM Dðx; zÞ¼ À 1 1 taining blood flow. 1 N À M 1 n¼ 1 m¼1 A DVdA Anðx; zÞ Anþ ðx; zÞ dA 1 M ¼ ; N ¼ A 2 2 ( 4 8) ½ð1=2ÞAnðx; zÞ þð1=2ÞAnþ1ðx; zÞ Equation 2: The flow index, an average of the decorrelation Equation 1: The SSADA algorithm calculates the decorrelation values for a given area, is useful in quantifying the in reflected light at consecutive points, allowing for the vascula- microvasculature.11 ture to be visualised.10 The resulting outputs of OCT-A offer improvements over that The SSADA algorithm considers the fluctuation in the ampli- of alternative imaging modalities. Compared with HRF, OCT-A tude (A) of the reflected light between the consecutive B-scans offers insight to vessel density, whereas HRF only provides at each spatial location within the collected data. The static insight into blood flow velocity and the amount of avascular tissue would have a low decorrelation value, meaning that the zone present in a field of view.7 Another common imaging amplitude of reflected light does not fluctuate between B-scans. modality is FA. FA is an invasive process, as it requires an inject- Therefore, blood flow is represented by a high decorrelation able dye. In addition, time must be allowed for the dye to circu- value, specifically over a threshold of D=0.125.10 A crucial late throughout the body before images can be taken. advantage of the SSADA algorithm is maximising the Furthermore, the dye can illicit an anaphylactic reaction in some Figure 2 Process of bandwidth segmentation, used by the split-spectrum amplitude decorrelation angiography algorithm to increase the signal-to-noise ratio. The bandwidth was segmented into four sections to maintain appropriate image resolution.10 Adapted with permission. Koustenis A , et al. Br J Ophthalmol 2017;101:16–20. doi:10.1136/bjophthalmol-2016-309389 17 Review patients.18 OCT-A eliminates these disadvantages, due to the short scan time and lack of a dye. In addition, the radial peripa- pillary capillaries (RPCs) that supply the RNFL can be seen with OCT-A, while not with FA.11 Furthermore, FA is limited in only providing a two-dimensional image, lacking depth information, while OCT-A allows for three-dimensional imaging.19 Finally, groups have shown OCT-A to have reasonable specificity and sensitivity when detecting pathologies such as choroidal neovas- cularisation CNV.20 While OCT-A has advantages over other imaging modalities, it is important to recognise limitations.
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