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      Distribution of cone density, spacing and arrangement in adult healthy retinas with adaptive optics flood illumination

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          Abstract

          The aim of this article is to analyse cone density, spacing and arrangement using an adaptive optics flood illumination retina camera (rtx1 ) on a healthy population. Cone density, cone spacing and packing arrangements were measured on the right retinas of 109 subjects at 2°, 3°, 4°, 5° and 6° of eccentricity along 4 meridians. The effects of eccentricity, meridian, axial length, spherical equivalent, gender and age were evaluated. Cone density decreased on average from 28 884 ± 3 692 cones/mm 2, at 2° of eccentricity, to 15 843 ± 1 598 cones/mm 2 at 6°. A strong inter-individual variation, especially at 2°, was observed. No important difference of cone density was observed between the nasal and temporal meridians or between the superior and inferior meridians. However, the horizontal and vertical meridians differed by around 14% (T-test, p<0.0001). Cone density, expressed in units of area, decreased as a function of axial length (r 2 = 0.60), but remained constant (r 2 = 0.05) when cone density is expressed in terms of visual angle supporting the hypothesis that the retina is stretched during the elongation of the eyeball. Gender did not modify the cone distribution. Cone density was slightly modified by age but only at 2°. The older group showed a smaller density (7%). Cone spacing increased from 6,49 ± 0,42 μm to 8,72 ± 0,45 μm respectively between 2° and 6° of eccentricity. The mosaic of the retina is mainly triangularly arranged (i.e. cells with 5 to 7 neighbors) from 2° to 6°. Around half of the cells had 6 neighbors.

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          Most cited references32

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          Adaptive noise smoothing filter for images with signal-dependent noise.

          In this paper, we consider the restoration of images with signal-dependent noise. The filter is noise smoothing and adapts to local changes in image statistics based on a nonstationary mean, nonstationary variance (NMNV) image model. For images degraded by a class of uncorrelated, signal-dependent noise without blur, the adaptive noise smoothing filter becomes a point processor and is similar to Lee's local statistics algorithm [16]. The filter is able to adapt itself to the nonstationary local image statistics in the presence of different types of signal-dependent noise. For multiplicative noise, the adaptive noise smoothing filter is a systematic derivation of Lee's algorithm with some extensions that allow different estimators for the local image variance. The advantage of the derivation is its easy extension to deal with various types of signal-dependent noise. Film-grain and Poisson signal-dependent restoration problems are also considered as examples. All the nonstationary image statistical parameters needed for the filter can be estimated from the noisy image and no a priori information about the original image is required.
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            Aging of the human photoreceptor mosaic: evidence for selective vulnerability of rods in central retina.

            Because previous studies suggested degeneration and loss of photoreceptors in aged human retina, the spatial density of cones and rods subserving the central 43 degrees of vision as a function of age was determined. Cones and rods were counted in 27 whole mounted retinas from donors aged 27 to 90 years with macroscopically normal fundi. Photoreceptor topography was analyzed with new graphic and statistical techniques. Changes in cone density throughout this age span showed no consistent relationship to age or retinal location, and the total number of foveal cones was remarkably stable. In contrast, rod density decreased by 30%, beginning inferior to the fovea in midlife and culminating in an annulus of deepest loss at 0.5 to 3 mm eccentricity by the ninth decade. Space vacated by dying rods was filled in by larger rod inner segments, resulting in a similar rod coverage at all ages. At the temporal equator, cone density declined by 23%, but rods were stable throughout adulthood. The stability of both rod coverage and rhodopsin content despite decreasing cell number suggests plasticity of the adult rod system and that age-related declines in scotopic sensitivity may be due to postreceptoral factors. There is no evidence for the massive loss of foveal cones required to explain even modest decrements in acuity, consistent with evidence that visual deficits at high photopic levels may be largely due to optical factors. Why the rods of central retina, which share a common support system and light exposure with the neighboring cones, are preferentially vulnerable to aging remains to be determined.
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              Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic factor treatment.

              To study cone photoreceptor structure and function in patients with inherited retinal degenerations treated with sustained-release ciliary neurotrophic factor (CNTF). Two patients with retinitis pigmentosa and one with Usher syndrome type 2 who participated in a phase 2 clinical trial received CNTF delivered by an encapsulated cell technology implant in one eye and sham surgery in the contralateral eye. Patients were followed longitudinally over 30 to 35 months. Adaptive optics scanning laser ophthalmoscopy (AOSLO) provided high-resolution images at baseline and at 3, 6, 12, 18, and 24 months. AOSLO measures of cone spacing and density and optical coherence tomography measures of retinal thickness were correlated with visual function, including visual acuity (VA), visual field sensitivity, and full-field electroretinography (ERG). No significant changes in VA, visual field sensitivity, or ERG responses were observed in either eye of the three patients over 24 months. Outer retinal layers were significantly thicker in CNTF-treated eyes than in sham-treated eyes (P < 0.005). Cone spacing increased by 2.9% more per year in sham-treated eyes than in CNTF-treated eyes (P < 0.001, linear mixed model), and cone density decreased by 9.1%, or 223 cones/degree(2) more per year in sham-treated than in CNTF-treated eyes (P = 0.002, linear mixed model). AOSLO images provided a sensitive measure of disease progression and treatment response in patients with inherited retinal degenerations. Larger studies of cone structure using high-resolution imaging techniques are urgently needed to evaluate the effect of CNTF treatment in patients with inherited retinal degenerations.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Methodology
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                16 January 2018
                2018
                : 13
                : 1
                : e0191141
                Affiliations
                [1 ] Laboratoire Aimé Cotton, CNRS, Université Paris-Sud, ENS Paris-Saclay, Université Paris-Saclay, Orsay, France
                [2 ] Université Paris Diderot - APHP Hôpital Lariboisière, Paris, France
                Instituto Murciano de Investigacion y Desarrollo Agrario y Alimentario, SPAIN
                Author notes

                Competing Interests: We received funds from Imagine Eyes (Orsay, France) to conduct the experiment described in this manuscript. The funds permitted to partially acquire the rtx1 device manufactured by Imagine Eyes. Imagine Eyes had no other role. They did not participate to the study design; collection, analysis, and interpretation of data; writing of the paper; and/or decision to submit for publication. We claim that this does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0002-1430-3649
                Article
                PONE-D-17-37573
                10.1371/journal.pone.0191141
                5770065
                29338027
                9c2e35e0-70ff-4c6d-89c1-a1bdda20f832
                © 2018 Legras 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.

                History
                : 20 October 2017
                : 28 December 2017
                Page count
                Figures: 5, Tables: 4, Pages: 13
                Funding
                Funded by: Conseil Geéneéral de l’Essonne
                Award Recipient :
                Funded by: Initiative Doctorale Interdisciplinaire
                Award Recipient :
                This project was founded by the Conseil Général de l’Essonne (Action de Soutien à la Technologie et à la Recherche en Essonne) and by Imagine Eyes, Orsay, France. This research was supported by an Initiative Doctorale Interdisciplinaire grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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