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      Assessment of the retinal posterior pole in dominant optic atrophy by spectral-domain optical coherence tomography and microperimetry

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          Abstract

          Background

          To assess posterior pole (PP) retinal structure in patients with genetically confirmed autosomal dominant optic atrophy (ADOA) using new spectral domain optical coherence tomography (SD-OCT) segmentation technology. To analyze retinal PP thickness in relation to retinal sensitivity data from microperimetry (MP) in ADOA patients.

          Methods and findings

          This prospective cross-sectional study included 11 patients with ADOA and 11 age-matched healthy subjects. All participants underwent both a “Posterior Pole” and “peripapillary RNFL (pRNFL)” scanning protocol using SD-OCT. Functional mapping of the PP was also performed using MP. A customized program was implemented in order to achieve accurate superimposition of MP sensitivity map onto SD-OCT map. The thickness of the PP different retinal layers and pRNFL was obtained and measured for each eye. Mean retinal sensitivity values and fixation stability were obtained and compared between ADOA patients and healthy subjects. Correlation analysis was performed on a point-to-point basis to evaluate the association between mean thickness and retinal sensitivity of each retinal layer. Total retinal thickness (TRT), Retinal Nerve Fiber Layer (RNFL), Ganglion Cell Layer (GCL), Inner Plexiform Layer (IPL), Inner Nuclear Layer (INL) and Inner Retinal Layers (IRL) at the posterior pole as well as pRNFL were significantly thinner in ADOA patients ( P < 0.0001). On the contrary, the Outer Plexiform Layer (OPL) and the Outer Nuclear Layer (ONL) were significantly thicker in the ADOA group ( P < 0.001). No significant differences were found in Retinal Pigment Epithelium (RPE) and Outer Retinal Layers (ORL) thickness between ADOA and controls. The average PP retinal sensitivity was significantly reduced in ADOA patients compared with controls ( P < 0.001), as measured by microperimeter Nidek MP-1 (MP1). Fixation stability was significantly worse in the ADOA group ( P = 0.01). The most severe sensitivity defects in ADOA patients were found at the level of the papillo-macular bundle (PMB).

          Conclusions

          Inner retinal layers showed pathological changes in ADOA patients. In addition, the whole retinal PP (not only the PMB) was significantly altered in ADOA, both in terms of retinal thickness and sensitivity.

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          Most cited references36

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          Glaucoma diagnostic accuracy of ganglion cell-inner plexiform layer thickness: comparison with nerve fiber layer and optic nerve head.

          To determine the diagnostic performance of macular ganglion cell-inner plexiform layer (GCIPL) thickness measured with the Cirrus high-definition optical coherence tomography (HD-OCT) ganglion cell analysis (GCA) algorithm (Carl Zeiss Meditec, Dublin, CA) to discriminate normal eyes and eyes with early glaucoma and to compare it with that of peripapillary retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) measurements. Evaluation of diagnostic test or technology. Fifty-eight patients with early glaucoma and 99 age-matched normal subjects. Macular GCIPL and peripapillary RNFL thicknesses and ONH parameters were measured in each participant, and their diagnostic abilities were compared. Area under the curve (AUC) of the receiver operating characteristic. The GCIPL parameters with the best AUCs were the minimum (0.959), inferotemporal (0.956), average (0.935), superotemporal (0.919), and inferior sector (0.918). There were no significant differences between these AUCs and those of inferior quadrant (0.939), average (0.936), and superior quadrant RNFL (0.933); vertical cup-to-disc diameter ratio (0.962); cup-to-disc area ratio (0.933); and rim area (0.910), all P>0.05. The ability of macular GCIPL parameters to discriminate normal eyes and eyes with early glaucoma is high and comparable to that of the best peripapillary RNFL and ONH parameters. Proprietary or commercial disclosure may be found after the references. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
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            Reproducibility of nerve fiber layer thickness measurements using optical coherence tomography.

            Optical coherence tomography (OCT) is a new technology that uses near-infrared light in an interferometer to produce approximately 10-microns resolution cross-sectional images of the tissue of interest. The authors performed repeated quantitative assessment of nerve fiber layer thickness in individuals with normal and glaucomatous eyes, and they evaluated the reproducibility of these measurements. The authors studied 21 eyes of 21 subjects by OCT. Each subject underwent five repetitions of a series of scans on five separate occasions within a 1-month period. Each series consisted of three circular scans around the optic nerve head (diameters, 2.9, 3.4, and 4.5 mm). Each series was performed separately using internal (fixation with same eye being studied) and external (fixation with contralateral eye) fixation techniques. The eye studied and the sequence of testing were assigned randomly. Internal fixation (IF), in general, provides a slightly higher degree of reproducibility than external fixation (EF). Reproducibility was better in a given eye on a given visit than from visit to visit. Reproducibility as measured by intraclass correlation coefficients were as follows: circle diameter (CD), 2.9 mm, 0.51/0.57 (normal/glaucoma) (IF), 0.43/0.54 (EF); CD, 3.4 mm, 0.56/0.52 (IF), 0.43/0.61 (EF); CD, 4.5 mm, 0.53/0.43 (IF), 0.42/0.49 (EF). Nerve fiber layer thickness can be reproducibly measured using OCT. Internal is superior to external fixation; each circle diameter tested provides adequate reproducibility.
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              Mitochondrial dynamics and disease, OPA1.

              The mitochondria are dynamic organelles that constantly fuse and divide. An equilibrium between fusion and fission controls the morphology of the mitochondria, which appear as dots or elongated tubules depending the prevailing force. Characterization of the components of the fission and fusion machineries has progressed considerably, and the emerging question now is what role mitochondrial dynamics play in mitochondrial and cellular functions. Its importance has been highlighted by the discovery that two human diseases are caused by mutations in the two mitochondrial pro-fusion genes, MFN2 and OPA1. This review will focus on data concerning the function of OPA1, mutations in which cause optic atrophy, with respect to the underlying pathophysiological processes.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                30 March 2017
                2017
                : 12
                : 3
                Affiliations
                [1 ]Ophthalmology Unit, Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, Italy
                [2 ]Laboratory of Biometry, Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy
                [3 ]Molecular Neurogenetics Unit, Neurological Institute C. Besta IRCCS, Milan, Italy
                [4 ]Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
                [5 ]Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell’Immacolata IRCCS, Rome, Italy
                Bascom Palmer Eye Institute, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: MC.

                • Data curation: RPS MC.

                • Formal analysis: RPS.

                • Funding acquisition: FB AC.

                • Investigation: MC JS EC.

                • Methodology: MC EC.

                • Project administration: MC.

                • Resources: FB EL BG.

                • Software: MC JS.

                • Supervision: MC.

                • Validation: MC.

                • Visualization: MC EC.

                • Writing – original draft: MC AC CN FR EC.

                • Writing – review & editing: MC AM.

                Article
                PONE-D-16-45708
                10.1371/journal.pone.0174560
                5373574
                28358911
                6c039da6-0eeb-4aad-9aab-08040f194cbc
                © 2017 Cesareo et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 5, Tables: 5, Pages: 16
                Product
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100004229, Fondazione Pierfranco e Luisa Mariani;
                Award ID: CM23
                Award Recipient :
                Funded by: Mitocon ONLUS
                Award Recipient :
                Funded by: Cell line and DNA Bank of Genetic Movement Disorders and Mitochondrial Diseases” of Telethon Network of Genetics Biobanks
                Award ID: GTB12001
                Award Recipient :
                Funded by: Macula and Genoma Foundation
                Award Recipient :
                This work was supported in part by “Fondazione Pierfranco e Luisa Mariani” (CM23), “Italian Association of Mitochondrial Disease Patients and Families” (Mitocon ONLUS), Italian Ministry of Health, “Cell line and DNA Bank of Genetic Movement Disorders and Mitochondrial Diseases” of Telethon Network of Genetics Biobanks (grant GTB12001) and “Macula & Genoma Foundation”, Rome, Italy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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