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      Peripapillary Retinoschisis in Glaucoma: Association With Progression and OCT Signs of Müller Cell Involvement

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          Abstract

          Purpose

          To examine demographic and clinical factors associated with glaucomatous peripapillary retinoschisis (PPRS) and assess its association with glaucoma progression.

          Methods

          Using a case control study design and longitudinal data from a cohort of 166 subjects with a diagnosis of glaucoma or glaucoma suspect, we compared functional, structural, clinical, and demographic characteristics between PPRS cases and controls.

          Results

          The frequency of PPRS was 6.0% (12 eyes from 10/166 subjects) with two eyes having PPRS in different sectors for a total of 15 retinoschisis events. There were no significant differences ( P > 0.05) in age, sex, visual acuity, central corneal thickness, intraocular pressure, or presence of vitreous adhesion between PPRS and controls. However, eyes with PPRS tended to have a higher cup-to-disc ratio ( P = 0.06), thinner RNFL ( P = 0.02), and worse visual field mean deviation (MD, P = 0.06) than controls. The rate of RNFL thinning was faster in PPRS (average: −2.8%/year; range: −7.4% to 0.0%/year) than controls (−1.3%/year; range: −4.4% to 0.6%/year; P = 0.021). The rate of visual field MD change was faster in PPRS (−0.49 dB/year; range: −2.0 to 0.9 dB/year) than controls (−0.06 dB/year; range: −0.8 to 0.3 dB/year; P = 0.030). OCT scans showed hyperreflective structures spanning the PPRS whose morphology and spacing (50 ± 7 μm) are consistent with Müller glia, causing signal attenuation casting “shadows” onto distal retina.

          Conclusions

          This is the first report showing that glaucomatous PPRS is associated with a faster overall rate of RNFL thinning and visual field deterioration and to specifically identify OCT signs of Müller cell involvement.

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          Most cited references46

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          Muller cells are living optical fibers in the vertebrate retina.

          Although biological cells are mostly transparent, they are phase objects that differ in shape and refractive index. Any image that is projected through layers of randomly oriented cells will normally be distorted by refraction, reflection, and scattering. Counterintuitively, the retina of the vertebrate eye is inverted with respect to its optical function and light must pass through several tissue layers before reaching the light-detecting photoreceptor cells. Here we report on the specific optical properties of glial cells present in the retina, which might contribute to optimize this apparently unfavorable situation. We investigated intact retinal tissue and individual Müller cells, which are radial glial cells spanning the entire retinal thickness. Müller cells have an extended funnel shape, a higher refractive index than their surrounding tissue, and are oriented along the direction of light propagation. Transmission and reflection confocal microscopy of retinal tissue in vitro and in vivo showed that these cells provide a low-scattering passage for light from the retinal surface to the photoreceptor cells. Using a modified dual-beam laser trap we could also demonstrate that individual Müller cells act as optical fibers. Furthermore, their parallel array in the retina is reminiscent of fiberoptic plates used for low-distortion image transfer. Thus, Müller cells seem to mediate the image transfer through the vertebrate retina with minimal distortion and low loss. This finding elucidates a fundamental feature of the inverted retina as an optical system and ascribes a new function to glial cells.
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            X-linked juvenile retinoschisis: clinical diagnosis, genetic analysis, and molecular mechanisms.

            X-linked juvenile retinoschisis (XLRS, MIM 312700) is a common early onset macular degeneration in males characterized by mild to severe loss in visual acuity, splitting of retinal layers, and a reduction in the b-wave of the electroretinogram (ERG). The RS1 gene (MIM 300839) associated with the disease encodes retinoschisin, a 224 amino acid protein containing a discoidin domain as the major structural unit, an N-terminal cleavable signal sequence, and regions responsible for subunit oligomerization. Retinoschisin is secreted from retinal cells as a disulphide-linked homo-octameric complex which binds to the surface of photoreceptors and bipolar cells to help maintain the integrity of the retina. Over 190 disease-causing mutations in the RS1 gene are known with most mutations occurring as non-synonymous changes in the discoidin domain. Cell expression studies have shown that disease-associated missense mutations in the discoidin domain cause severe protein misfolding and retention in the endoplasmic reticulum, mutations in the signal sequence result in aberrant protein synthesis, and mutations in regions flanking the discoidin domain cause defective disulphide-linked subunit assembly, all of which produce a non-functional protein. Knockout mice deficient in retinoschisin have been generated and shown to display most of the characteristic features found in XLRS patients. Recombinant adeno-associated virus (rAAV) mediated delivery of the normal RS1 gene to the retina of young knockout mice result in long-term retinoschisin expression and rescue of retinal structure and function providing a 'proof of concept' that gene therapy may be an effective treatment for XLRS. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Optic disc pit: a review.

              Since Wiethe first described the clinical presentation of two optic disc depressions in a 62-year-old woman in 1882, there have been many studies addressing what later become known as the "optic disc pit." The main complication of this condition, termed optic disc pit maculopathy, is associated with visual deterioration. Treatment of optic disc pit maculopathy remains challenging. Here we review the body of literature that documents the clinical findings, pathophysiology, histology, main complications, treatment options, special features and presentations, and differential diagnosis of optic disc pit. The source of the intraretinal fluid in optic disc pit maculopathy remains controversial. Four possible sources of this fluid have been proposed: fluid from the vitreous cavity; cerebrospinal fluid originating from the subarachnoid space; fluid from leaky blood vessels at the base of the pit; and fluid from the orbital space surrounding the dura. Optic disc pits are a very rare clinical entity, affecting approximately one in 11,000 people. Patients with congenital optic disc pit sometimes remain asymptomatic, but 25% to 75% present with visual deterioration in their 30s or 40s after developing macular schisis and detachment. The most widely accepted treatment for such patients is a surgical approach involving pars plana vitrectomy with or without internal limiting membrane peeling, with or without endolaser photocoagulation and C3F8 endotamponade.
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                Author and article information

                Journal
                Invest Ophthalmol Vis Sci
                Invest. Ophthalmol. Vis. Sci
                iovs
                Invest Ophthalmol Vis Sci
                IOVS
                Investigative Ophthalmology & Visual Science
                The Association for Research in Vision and Ophthalmology
                0146-0404
                1552-5783
                June 2018
                : 59
                : 7
                : 2818-2827
                Affiliations
                [1 ]Discoveries in Sight Research Laboratories, Devers Eye Institute and Legacy Research Institute, Legacy Health, Portland, Oregon, United States
                [2 ]Northwest Permanente, Portland, Oregon, United States
                Author notes
                Correspondence: Brad Fortune, Discoveries in Sight Research Laboratories, Devers Eye Institute and Legacy Research Institute, 1225 NE Second Avenue, Portland, OR 97232, USA; bfortune@ 123456deverseye.org .
                Article
                iovs-59-06-52 IOVS-18-24160R1
                10.1167/iovs.18-24160
                5983909
                29860466
                b4a1aa73-79ab-44c3-91c0-713a06c62486
                Copyright 2018 The Authors

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

                History
                : 20 February 2018
                : 29 April 2018
                Categories
                Glaucoma

                glaucoma,peripapillary retinoschisis,optical coherence tomography,retinal nerve fiber layer,optic nerve head,müller glia

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