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      Longitudinal Structural and Microvascular Observation in RCS Rat Eyes Using Optical Coherence Tomography Angiography

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          Abstract

          Purpose

          To evaluate the change of retinal thickness and ocular microvasculature in a rat model of retinitis pigmentosa using swept source optical coherence tomography angiography (SS-OCTA)

          Methods

          Three-weeks-old Royal College of Surgeons (RCS) rats ( n = 8) and age-matched control rats ( n = 14) were imaged by a prototype SS-OCTA system. Follow-up measurements occurred every three weeks on six RCS rats until week 18, and cross-sectional measurements were conducted on control rats. Thicknesses of different retinal layers and the total retina were measured. The enface angiograms from superficial vascular plexiform (SVP) and deep capillary plexiform (DCP) were analyzed, and the image sharpness was also extracted from the choroidal angiograms. Immunohistochemical analysis was done in the RCS rats after week 18, as well as in three-week-old RCS rats and age-matched controls.

          Results

          In RCS rats, the thicknesses of the ganglion cell complex, the nuclear layer, the debris/photoreceptor layer and the total retina decreased over the weeks ( P < 0.001). The SVP metrics remained unchanged whereas the DCP metrics decreased significantly over the weeks ( P < 0.001). The immunohistochemical analysis confirmed our OCTA findings of capillary dropout in the DCP. The choroidal plexus appeared indistinct initially due to scattering of light at the intact retinal pigment epithelium (RPE) and became more visible after week nine probably due to RPE degeneration. Loss of choriocapillaris was visualized at week 18. In control rats, no vascular change was detected, but nuclear layers, photoreceptor layers and total retina showed slight thinning with age ( P < 0.001).

          Conclusions

          Photoreceptor degeneration in RCS rats was associated with the loss of capillaries in DCP, but not in SVP. The OCTA imaging allows for the characterization of structural and angiographic changes in rodent models.

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          Most cited references68

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          Retinitis pigmentosa.

          Hereditary degenerations of the human retina are genetically heterogeneous, with well over 100 genes implicated so far. This Seminar focuses on the subset of diseases called retinitis pigmentosa, in which patients typically lose night vision in adolescence, side vision in young adulthood, and central vision in later life because of progressive loss of rod and cone photoreceptor cells. Measures of retinal function, such as the electroretinogram, show that photoreceptor function is diminished generally many years before symptomic night blindness, visual-field scotomas, or decreased visual acuity arise. More than 45 genes for retinitis pigmentosa have been identified. These genes account for only about 60% of all patients; the remainder have defects in as yet unidentified genes. Findings of controlled trials indicate that nutritional interventions, including vitamin A palmitate and omega-3-rich fish, slow progression of disease in many patients. Imminent treatments for retinitis pigmentosa are greatly anticipated, especially for genetically defined subsets of patients, because of newly identified genes, growing knowledge of affected biochemical pathways, and development of animal models.
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            Optical coherence tomography angiography

            Optical coherence tomography (OCT) was one of the biggest advances in ophthalmic imaging. Building on that platform, OCT angiography (OCTA) provides depth resolved images of blood flow in the retina and choroid with levels of detail far exceeding that obtained with older forms of imaging. This new modality is challenging because of the need for new equipment and processing techniques, current limitations of imaging capability, and rapid advancements in both imaging and in our understanding of the imaging and applicable pathophysiology of the retina and choroid. These factors lead to a steep learning curve, even for those with a working understanding dye-based ocular angiography. All for a method of imaging that is a little more than 10 years old. This review begins with a historical account of the development of OCTA, and the methods used in OCTA, including signal processing, image generation, and display techniques. This forms the basis to understand what OCTA images show as well as how image artifacts arise. The anatomy and imaging of specific vascular layers of the eye are reviewed. The integration of OCTA in multimodal imaging in the evaluation of retinal vascular occlusive diseases, diabetic retinopathy, uveitis, inherited diseases, age-related macular degeneration, and disorders of the optic nerve is presented. OCTA is an exciting, disruptive technology. Its use is rapidly expanding in clinical practice as well as for research into the pathophysiology of diseases of the posterior pole.
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              Optical coherence tomography: imaging of the choroid and beyond.

              Seventy percent of the blood flow to the eye goes to the choroid, a structure that is vitally important to the function of the retina. The in vivo structure of the choroid in health and disease is incompletely visualized with traditional imaging modalities, including indocyanine green angiography, ultrasonography, and spectral domain optical coherence tomography (OCT). Use of new OCT modalities, including enhanced depth imaging OCT, image averaging, and swept-source OCT, have led to increased visualization of the choroidal anatomy. The correlation of these new anatomical findings with other imaging modalities results increases understanding of many eye diseases and recognises of new ones. The status of the choroid appears to be a crucial determinant in the pathogenesis of diseases such as age-related choroidal atrophy, myopic chorioretinal atrophy, central serous chorioretinopathy, chorioretinal inflammatory diseases, and tumors. Extension of these imaging techniques has provided insights into abnormalities of the sclera and optic nerve. Future developments will include blood flow information, 3D rendering of various ocular structures, and the ability to evaluate changes in 3D structural information over time (4D imaging). Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Invest Ophthalmol Vis Sci
                Invest. Ophthalmol. Vis. Sci
                iovs
                IOVS
                Investigative Ophthalmology & Visual Science
                The Association for Research in Vision and Ophthalmology
                0146-0404
                1552-5783
                24 June 2020
                June 2020
                : 61
                : 6
                : 54
                Affiliations
                [1 ]Singapore Eye Research Institute, Singapore National Eye Centre, Singapore
                [2 ]SERI-NTU Advanced Ocular Engineering (STANCE) Program, Nanyang Technological University, Singapore
                [3 ]Academic Clinical Program, Duke-NUS Medical School, Singapore
                [4 ]Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore
                [5 ]Department of Ophthalmology, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
                [6 ]Department of Clinical Pharmacology, Medical University of Vienna, Austria
                [7 ]Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria
                Author notes
                Correspondence: Leopold Schmetterer, 20 College Road, The Academia, Level 6, Discovery Tower, 69856, Singapore; leopold.schmetterer@ 123456seri.com.sg .
                Article
                IOVS-19-28260
                10.1167/iovs.61.6.54
                7415900
                32579681
                2c51255f-ae08-48dd-be56-1ec597f97721
                Copyright 2020 The Authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 13 February 2020
                : 17 August 2019
                Page count
                Pages: 10
                Categories
                Multidisciplinary Ophthalmic Imaging
                Multidisciplinary Ophthalmic Imaging

                optical coherence tomography angiography,vascular imaging,retinal imaging,choroidal imaging,retinal degeneration

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