{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:50:55Z","timestamp":1787003455649,"version":"build-2736575974"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Outer retinal tubulations (ORT) are a relatively new finding characterizing outer retinal atrophy. The main aim of the present study was to describe ORT development in advanced age-related macular degeneration (AMD) and to assess its relationship with disease\u2019s severity. Patients with advanced AMD characterized either by macular neovascularization or geographic atrophy, showing signs of outer retinal disruption or retinal pigment epithelium atrophy on structural optical coherence tomography (OCT) at the inclusion examination were prospectively recruited. All the patients underwent complete ophthalmologic evaluation, structural OCT scans and fundus autofluorescence imaging. The planned follow-up was of 3-years. Main outcome measures were ORT prevalence, mechanism of ORT formation, mean time needed for complete ORT formation, best-corrected visual acuity (BCVA), definitely decreased autofluorescence (DDAF) area, questionably decreased autofluorescence (QDAF) area, retinal layer thickness, foveal sparing, number of intravitreal injections. We also assessed the possible role of external limiting membrane (ELM) and M\u00fcller cells in ORT pathogenesis. Seventy eyes (70 patients) were included; 43 showed dry AMD evolving to geographic atrophy, while 27 displayed the features of wet AMD. Baseline BCVA was 0.5\u2009\u00b1\u20090.5 LogMAR, decreasing to 0.9\u2009\u00b1\u20090.5 LogMAR at the 3-year follow-up (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). We detected completely formed ORT in 26\/70 eyes (37%), subdivided as follows: 20 eyes (77%) wet AMD and 6 eyes (23%) dry AMD (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). ORT took 18\u2009\u00b1\u20098\u00a0months (range 3\u201335\u00a0months) to develop fully. We described the steps leading to ORT development, characterized by progressive involvement of, and damage to the photoreceptors, the ELM and the RPE. Eyes displaying ORT were associated with a smaller QDAF area, less retinal layers damage and lower rate of foveal sparing than eyes free of ORT (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). We also described pigment accumulations simulating ORT, which were detected in 16\/70 eyes (23%), associated with a greater loss of foveal sparing, increased DDAF area and smaller QDAF area at the 3-year follow-up (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). In conclusion, this study provided a description of the steps leading to ORT development in AMD. ELM and M\u00fcller cells showed a role in ORT pathogenesis. Furthermore, we described a subtype of pigment hypertrophy mimicking ORT, evaluating its clinical utility.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-94310-5","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T06:03:18Z","timestamp":1626674598000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Outer retinal tubulation formation and clinical course of advanced age-related macular degeneration"],"prefix":"10.1038","volume":"11","author":[{"given":"Alessandro","family":"Arrigo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Aragona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ottavia","family":"Battaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Saladino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Amato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Borghesan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelaide","family":"Pina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Calcagno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashid","family":"Hassan Farah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Bandello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Battaglia Parodi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"issue":"12","key":"94310_CR1","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1001\/archophthalmol.2009.326","volume":"127","author":"SA Zweifel","year":"2009","unstructured":"Zweifel, S. A. et al. Outer retinal tubulation: a novel optical coherence tomography finding. Arch Ophthalmol. 127(12), 1596\u20131602 (2009).","journal-title":"Arch Ophthalmol."},{"issue":"12","key":"94310_CR2","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1001\/archophthalmol.2012.1902","volume":"130","author":"JJ Jung","year":"2012","unstructured":"Jung, J. J. & Freund, K. B. Long-term follow-up of outer retinal tubulation documented by eye-tracked and en face spectral-domain optical coherence tomography. Arch Ophthalmol. 130(12), 1618\u20131619 (2012).","journal-title":"Arch Ophthalmol."},{"issue":"8","key":"94310_CR3","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1097\/IAE.0000000000001810","volume":"38","author":"RC Preti","year":"2018","unstructured":"Preti, R. C. et al. Optical coherence tomography analysis of outer retinal tubulations: Sequential evolution and pathophysiological insights. 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Outer retinal tubulation in diabetic macular edema following anti-VEGF treatment. Eye Vis 2, 9 (2015).","journal-title":"Eye Vis"},{"issue":"9","key":"94310_CR7","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1016\/j.ophtha.2017.03.043","volume":"124","author":"R Dolz-Marco","year":"2017","unstructured":"Dolz-Marco, R., Litts, K. M., Tan, A. C. S., Freund, K. B. & Curcio, C. A. The evolution of outer retinal tubulation, a neurodegeneration and gliosis prominent in macular diseases. Ophthalmology 124(9), 1353\u20131367 (2017).","journal-title":"Ophthalmology"},{"key":"94310_CR8","doi-asserted-by":"crossref","unstructured":"Haensli, C., Sugiura, Y., Freund, K.B. & Zweifel, S.A. Correlation of Outer Retinal Tubulations and Choriocapillaris Flow Signal Deficits surrounding Geographic Atrophy. Retina (2021). [Epub ahead of print].","DOI":"10.1097\/IAE.0000000000003135"},{"key":"94310_CR9","doi-asserted-by":"crossref","unstructured":"Janse van Rensburg, E., et al. 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