{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:45:44Z","timestamp":1782711944130,"version":"3.54.5"},"reference-count":26,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      To describe the radial outer retina reflectivity (RORR) sign in patients carrying pathogenic variants in the X\u2010linked lysosome\u2010associated membrane protein\u20102 (\n                      <jats:italic>LAMP2<\/jats:italic>\n                      ) gene and to review the histologic characteristics of LAMP2 expression in the human retina.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      International multicentre observational case series and experimental laboratory study of patients with\n                      <jats:italic>LAMP2<\/jats:italic>\n                      deficiency. Baseline demographics and multimodal retinal imaging including colour and fundus autofluorescence (FAF), optical coherence tomography (OCT) with en face reconstruction and fluorescein angiography were obtained. Sections through the retina of a human donor eye were processed for immunofluorescence combining antibodies against\n                      <jats:italic>LAMP2<\/jats:italic>\n                      with markers for M\u00fcller glia, rod and cone photoreceptors. Sections were imaged using high\u2010resolution multichannel confocal microscopy. Assessment of en face OCT reflectivity profiles at 5\u201350\u2009\u03bcm internal to the plane of external limiting membrane (ELM) was performed as well as histologic localisation of LAMP2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We recruited 11 cases with pathogenic variants in\n                      <jats:italic>LAMP2<\/jats:italic>\n                      across five countries. Six cases demonstrated peripheral radial streaks of hyper\u2010 and hypopigmentation with UWF imaging. The RORR sign was best visualised 10\u201325\u2009\u03bcm internal to ELM in 9 cases. We hypothesise the radial pattern to be secondary to X\u2010chromosome inactivation. LAMP2 immunoreactivity was observed internal and external to the ELM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings expand the phenotypic spectrum of\n                      <jats:italic>LAMP2<\/jats:italic>\n                      \u2010associated retinopathy by demonstrating the RORR sign using en face OCT. Histologic sections revealed LAMP2 expression in the neuroretina.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aos.70178","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:13:13Z","timestamp":1782709993000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Radial outer retina reflectivity (\n                    <scp>RORR<\/scp>\n                    ) sign in\n                    <scp>\n                      <i>LAMP2<\/i>\n                    <\/scp>\n                    \u2010associated retinopathy"],"prefix":"10.1111","author":[{"given":"Rachael C.","family":"Heath Jeffery","sequence":"first","affiliation":[{"name":"Centre for Ophthalmology and Visual Science, the University of Western Australia  Perth Western Australia Australia"},{"name":"Ocular Tissue Engineering Laboratory, Lions Eye Institute  Nedlands Western Australia Australia"},{"name":"Royal Victorian Eye and Ear Hospital  East Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bohdan","family":"Kousal","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, First Faculty of Medicine Charles University and General University Hospital in Prague  Prague Czech Republic"},{"name":"First Faculty of Medicine, Department of Pediatrics and Inherited Metabolic Disorders, Research Unit for Rare Diseases Charles University and General University Hospital in Prague  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9595-8152","authenticated-orcid":false,"given":"Ulrike","family":"Gr\u00fcnert","sequence":"additional","affiliation":[{"name":"The University of Sydney, Faculty of Medicine, Save Sight Institute  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A.","family":"Curcio","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Heersink School of Medicine, University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Cherepanoff","sequence":"additional","affiliation":[{"name":"Sydpath, St Vincent's Hospital  Darlinghurst New South Wales Australia"},{"name":"Institute of Health Research, UNSW  Darlinghurst New South Wales Australia"},{"name":"St Vincent's Clinical School, UNSW  Darlinghurst New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina M.","family":"Lamey","sequence":"additional","affiliation":[{"name":"Australian Inherited Retinal Disease Registry and DNA Bank, Department of Medical Technology and Physics Sir Charles Gairdner Hospital  Nedlands Western Australia 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Eye Hospital NHS Foundation Trust  London UK"},{"name":"UCL Institute of Ophthalmology, University College London  London UK"},{"name":"Section of Ophthalmology and Department of Twin Research and Genetic Epidemiology King's College London, St Thomas' Hospital Campus  London UK"},{"name":"Department of Physiology, Development and Neuroscience University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6213-3250","authenticated-orcid":false,"given":"Seungmin","family":"Lee","sequence":"additional","affiliation":[{"name":"Pusan National University Hospital  Busan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Meliska","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, First Faculty of Medicine Charles University and General University Hospital in Prague  Prague Czech 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