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      Comparison of Optical Coherence Tomography Angiography to Indocyanine Green Angiography and Slit Lamp Photography for Corneal Vascularization in an Animal Model

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          Abstract

          Corneal neovascularization (CoNV) could be treated by novel anti-angiogenic therapies, though reliable and objective imaging tools to evaluate corneal vasculature and treatment efficacy is still lacking. Optical coherence tomography angiography (OCTA) –currently designed as a retinal vascular imaging system— has been recently adapted for anterior-segment and showed good potential for successful imaging of CoNV. However, further development requires an animal model where parameters can be studied more carefully with histological comparison. Our study evaluated the OCTA in suture-induced CoNV in a rabbit model compared to indocyanine green angiography (ICGA) and slit-lamp photography (SLP). Overall vessel density measurements from OCTA showed good correlation with ICGA (0.957) and SLP (0.992). Vessels density by OCTA was higher than ICGA and SLP (mean = 20.77 ± 9.8%, 15.71 ± 6.28% and 17.55 ± 8.36%, respectively, P < 0.05). OCTA was able to depict CoNV similarly to SLP and ICGA, though it could better detect small vessels. Moreover, the depth and growth of vessels could be assessed using en-face and serial-scans. This study validated the OCTA in a rabbit model as a useful imaging tool for translational studies on CoNV. This may contribute to further studies on OCTA for anterior-segment including serial evaluation of emerging anti-angiogenic therapies.

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          Split-spectrum amplitude-decorrelation angiography with optical coherence tomography

          Amplitude decorrelation measurement is sensitive to transverse flow and immune to phase noise in comparison to Doppler and other phase-based approaches. However, the high axial resolution of OCT makes it very sensitive to the pulsatile bulk motion noise in the axial direction. To overcome this limitation, we developed split-spectrum amplitude-decorrelation angiography (SSADA) to improve the signal-to-noise ratio (SNR) of flow detection. The full OCT spectrum was split into several narrower bands. Inter-B-scan decorrelation was computed using the spectral bands separately and then averaged. The SSADA algorithm was tested on in vivo images of the human macula and optic nerve head. It significantly improved both SNR for flow detection and connectivity of microvascular network when compared to other amplitude-decorrelation algorithms.
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            Quantitative OCT angiography of optic nerve head blood flow

            Optic nerve head (ONH) blood flow may be associated with glaucoma development. A reliable method to quantify ONH blood flow could provide insight into the vascular component of glaucoma pathophysiology. Using ultrahigh-speed optical coherence tomography (OCT), we developed a new 3D angiography algorithm called split-spectrum amplitude-decorrelation angiography (SSADA) for imaging ONH microcirculation. In this study, a method to quantify SSADA results was developed and used to detect ONH perfusion changes in early glaucoma. En face maximum projection was used to obtain 2D disc angiograms, from which the average decorrelation values (flow index) and the percentage area occupied by vessels (vessel density) were computed from the optic disc and a selected region within it. Preperimetric glaucoma patients had significant reductions of ONH perfusion compared to normals. This pilot study indicates OCT angiography can detect the abnormalities of ONH perfusion and has the potential to reveal the ONH blood flow mechanism related to glaucoma.
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              Corneal neovascularization.

              Corneal neovascularization (NV) is a sight-threatening condition usually associated with inflammatory or infectious disorders of the ocular surface. It has been shown in the field of cancer angiogenesis research that a balance exists between angiogenic factors (such as fibroblast growth factor and vascular endothelial growth factor) and anti-angiogenic molecules (such as angiostatin, endostatin, or pigment epithelium derived factor) in the cornea. Several inflammatory, infectious, degenerative, and traumatic disorders are associated with corneal NV, in which the balance is tilted towards angiogenesis. The pathogenesis of corneal NV may be influenced by matrix metalloproteinases and other proteolytic enzymes. New medical and surgical treatments, including angiostatic steroids, nonsteroidal inflammatory agents, argon laser photocoagulation, and photodynamic therapy have been effective in animal models to inhibit corneal NV and transiently restore corneal "angiogenic privilege."
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                Author and article information

                Contributors
                marcus.ang@snec.com.sg
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                31 July 2018
                31 July 2018
                2018
                : 8
                : 11493
                Affiliations
                [1 ]ISNI 0000 0001 0706 4670, GRID grid.272555.2, Singapore Eye Research Institute, ; 169856 Singapore, Singapore
                [2 ]ISNI 0000 0004 0385 0924, GRID grid.428397.3, Eye-ACP, Duke-NUS Graduate Medical School, ; 169857 Singapore, Singapore
                [3 ]ISNI 0000 0001 2224 0361, GRID grid.59025.3b, Nanyang Technological University, ; 639798 Singapore, Singapore
                [4 ]ISNI 0000 0000 9259 8492, GRID grid.22937.3d, Department of Clinical Pharmacology, , Medical University of Vienna, ; 1090 Vienna, Austria
                [5 ]ISNI 0000 0000 9259 8492, GRID grid.22937.3d, Center for Medical Physics and Biomedical Engineering, , Medical University of Vienna, ; 1090 Vienna, Austria
                [6 ]ISNI 0000 0000 9960 1711, GRID grid.419272.b, Singapore National Eye Center, ; 168751 Singapore, Singapore
                Author information
                http://orcid.org/0000-0003-2220-4891
                Article
                29752
                10.1038/s41598-018-29752-5
                6068177
                30065317
                a62ecbc8-9d1c-446b-8f3b-33c70c43b108
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 October 2017
                : 26 June 2018
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