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      Long-term multimodal imaging in acute posterior multifocal placoid pigment epitheliopathy and association with coxsackievirus exposure

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          Abstract

          The purpose of this study was to evaluate potential insights into the pathogenesis of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) using multimodal diagnostic imaging and laboratory evaluation in long-term follow-up. A retrospective, single-center case series was conducted on seven consecutive patients (14 eyes) who were given a diagnosis of APMPPE from March 1, 2011, through June 30, 2019 with at least three months of follow-up. Clinical characteristics (age, symptoms, visual acuity [VA]), laboratory testing including coxsackievirus titers, and multimodal imaging from fundus photography, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICG) were analyzed for each patient. The initial median VA was 20/71 and final median VA was 20/22. Coxsackievirus B (CVB) titers were elevated (≥ 1:80) in six of seven patients, with a four-fold increase in convalescent titers seen in two patients suggestive of recent infection. All patients were treated with oral corticosteroids, and five patients underwent corticosteroid-sparing immunomodulatory therapy. Initially, multifocal deep choroidal lesions were observed in the posterior pole corresponding to patches of hypocyanescence on ICG. Overlying retinal pigment epithelium (RPE) disease was observed on FAF, although this finding was not universally observed, suggesting that RPE disease may occur as a sequelae to unchecked choroidal inflammation. SD-OCT architectural changes confirmed outer retina and ellipsoid zone disruption. FA of active lesions showed early hypofluorescence and late hyperfluorescence with surrounding leakage while inactive disease showed areas of staining. Long-term follow-up of multimodal diagnostic imaging in APMPPE revealed that choroidal inflammation likely precedes RPE change and photoreceptor damage. Elevation of coxsackievirus titers with seroconversion may be associated with an infectious trigger in concert with immune-mediated disease in this posterior uveitis syndrome.

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          The role of infections in autoimmune disease.

          Autoimmunity occurs when the immune system recognizes and attacks host tissue. In addition to genetic factors, environmental triggers (in particular viruses, bacteria and other infectious pathogens) are thought to play a major role in the development of autoimmune diseases. In this review, we (i) describe the ways in which an infectious agent can initiate or exacerbate autoimmunity; (ii) discuss the evidence linking certain infectious agents to autoimmune diseases in humans; and (iii) describe the animal models used to study the link between infection and autoimmunity.
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            Acute posterior multifocal placoid pigment epitheliopathy.

            J Gass (1968)
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              The white dot syndromes.

              To review the distinctive and shared features of the white dot syndromes, highlighting the clinical findings, diagnostic test results, proposed etiologies, treatments, and prognosis. Review. Review of the literature. Common white dot syndromes are reviewed, including acute posterior multifocal placoid pigment epitheliopathy, birdshot chorioretinopathy, diffuse unilateral subacute neuroretinitis, multiple evanescent white dot syndrome, multifocal choroiditis with panuveitis, serpiginous choroiditis, and acute zonal occult outer retinopathy. The white dot syndromes are a group of disorders characterized by multiple whitish-yellow inflammatory lesions located at the level of the outer retina, retinal pigment epithelium, and choroid. For clinicians and researchers alike, they present significant diagnostic and therapeutic challenges.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                24 August 2020
                2020
                : 15
                : 8
                : e0238080
                Affiliations
                [1 ] Section of Vitreoretinal Disease and Surgery, Department of Ophthalmology, Emory Eye Center, Atlanta, GA, United States of America
                [2 ] Department of Ophthalmology, University of Washington, Seattle, WA, United States of America
                [3 ] Department of Ophthalmology, Bascom Palmer Eye institute, University of Miami Miller School of Medicine, Miami, FL, United States of America
                Massachusetts Eye & Ear Infirmary, Harvard Medical School, UNITED STATES
                Author notes

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

                Author information
                http://orcid.org/0000-0002-5235-6741
                http://orcid.org/0000-0003-1994-7213
                Article
                PONE-D-20-14626
                10.1371/journal.pone.0238080
                7446910
                32834009
                9e377049-e4b0-4c42-864b-9559d992278f
                © 2020 Li 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
                : 16 May 2020
                : 8 August 2020
                Page count
                Figures: 6, Tables: 1, Pages: 16
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000009, Foundation for the National Institutes of Health;
                Award ID: P30EY006360
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000009, Foundation for the National Institutes of Health;
                Award ID: RO1 EY029594
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000009, Foundation for the National Institutes of Health;
                Award ID: K23EY030158
                Award Recipient :
                This work was supported by an unrestricted grant from Research to Prevent Blindness to the Emory Eye Center and National Eye Institute, National Institutes of Health Core Grant to Emory University [SY; P30EY006360]. Research reported in this publication was supported by the National Eye Institute of the National Institutes of Health [SY; award: RO1 EY029594 and JGS; award: K23EY030158]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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