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      Vascular Changes and Neurodegeneration in the Early Stages of Diabetic Retinopathy: Which Comes First?

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          Abstract

          Introduction: Neurodegeneration is an early component of diabetic retinopathy (DR). It is unclear whether neurodegeneration is an independent factor or a consequence of damaged retinal vasculature. The aims of this study were to review the literature concerning neurodegeneration in diabetic patients without or with early DR, and to examine whether neurodegeneration precedes visible vasculopathy in the pathogenesis of DR. Methods: A systematic literature search was performed to identify studies which used optical coherence tomography (OCT) or multifocal electroretinography (mfERG) to detect neurodegeneration in patients with no or mild DR as compared to healthy controls. Outcome measures were mean retinal thickness (RT), mean retinal nerve fiber layer (RNFL) thickness and ganglion cell layer (GCL) thickness. Also, mfERG amplitude and implicit time were analyzed. Results: Eleven studies which used mfERG and/or OCT to detect neurodegeneration were included. Two OCT studies found significant thinning of RT, 2 found thinning of RNFL, whereas 1 found thickening of RT, RNFL and GCL in patients without DR. Two mfERG studies found a significant delay of implicit time in the same patient group. Retinal thinning and delay of implicit time were also detected in patients with mild DR. Conclusion: Retinal neurodegeneration is an early component of DR, which can precede visible vasculopathy.

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          Most cited references17

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          Characterization of outer retinal morphology with high-speed, ultrahigh-resolution optical coherence tomography.

          To visualize, quantitatively assess, and interpret outer retinal morphology by using high-speed, ultrahigh-resolution (UHR) OCT. Retinal imaging was performed in the ophthalmic clinic in a cross-section of 43 normal subjects with a 3.5-microm, axial-resolution, high-speed, UHR OCT prototype instrument, using a radial scan pattern (24 images, 1500 axial scans). Outer retinal layers were automatically segmented and measured. High-definition imaging was performed with a 2.8-microm axial-resolution, high-speed, UHR OCT research prototype instrument, to visualize the finer features in the outer retina. Quantitative maps of outer retinal layers showed clear differences between the cone-dominated fovea and the rod-dominated parafovea and perifovea, indicating that photoreceptor morphology can explain the appearance of the outer retina in high-speed, UHR OCT images. Finer, scattering bands were visualized in the outer retina using high-definition imaging and were interpreted by comparison to known anatomy. High-speed UHR OCT enables quantification of scattering layers in the outer retina. An interpretation of these features is presented and supported by quantitative measurements in normal subjects and comparison with known anatomy. The thick scattering region of the outer retina previously attributed to the retinal pigment epithelium (RPE) is shown to consist of distinct scattering bands corresponding to the photoreceptor outer segment tips, RPE, and Bruch's membrane. These results may advance understanding of the outer retinal appearance in OCT images. The normative measurements may also aid in future investigations of outer retinal changes in age-related macular degeneration and other diseases.
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            Retinal neurodegeneration: early pathology in diabetes

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              Detection of Early Diabetic Change with Optical Coherence Tomography in Type 2 Diabetes Mellitus Patients without Retinopathy

              Purpose: To detect early diabetic damage in type 2 diabetes mellitus patients with no diabetic retinopathy (NDR) using optical coherence tomography (OCT) and to evaluate OCT as a clinical test. Methods: Thirty-two patients with NDR (n = 32) were enrolled. We examined retinal and retinal nerve fiber layer (RNFL) thickness using OCT. Two healthy normal populations were also enrolled for the retinal thickness (n = 48) and RNFL thickness (n = 34). Both OCT measurements were obtained in four areas (temporal, superior, nasal and inferior). The receiver operator characteristic (ROC) curve was generated to evaluate the predictor variables. Results: Comparing the normal and NDR eyes, retinal thickness significantly increased (p = 0.03) and RNFL thickness significantly decreased (p = 0.02) in the superior areas. The area under the ROC curve was 0.65 for the superior retinal thickness and 0.63 for the superior RNFL thickness. Conclusions: Both OCT measurements can detect early retinal damage in NDR patients.
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                Author and article information

                Journal
                ORE
                Ophthalmic Res
                10.1159/issn.0030-3747
                Ophthalmic Research
                Ophthalmic Res
                S. Karger AG (Basel, Switzerland karger@ 123456karger.com http://www.karger.com )
                0030-3747
                1423-0259
                May 2016
                02 April 2016
                : 56
                : 1
                : 1-9
                Affiliations
                aResearch Unit of Ophthalmology, Institute of Clinical Research, University of Southern Denmark, and bDepartment of Ophthalmology, Odense University Hospital, Odense, Denmark
                Article
                ORE2016056001001 Ophthalmic Res 2016;56:1-9
                10.1159/000444498
                27035578
                3eadc05a-3347-409b-91b1-3418087d45bd
                © 2016 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 02 February 2016
                : 07 February 2016
                Page count
                Figures: 1, Tables: 7, References: 30, Pages: 9
                Categories
                Mini Review

                Medicine,General social science
                Diabetic retinopathy,Neurodegeneration,Multifocal electroretinography,Optical coherence tomography,Vasculopathy 

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