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In this retrospective case\u2013control study, we collected data from 35 eyes with intermediate AMD from 35 patients who had swept source optical coherence tomography structural and angiography imaging obtained. A control group of 35 eyes from 35 healthy subjects was included for comparison. Our main outcome measure for comparison between groups was the normalized reflectivity of <jats:italic>en face<\/jats:italic> image segmented at the ellipsoid zone (EZ) level, which was calculated to quantify the photoreceptor damage. OCTA metrics to quantify CC flow signal were also computed. These metrics were measured in a circle centered on the fovea and with a diameter of 5\u00a0mm. In intermediate AMD eyes, the macular area occupied by drusen was identified. Therefore, the EZ reflectivity and CC flow signal were separately measured in regions without drusen (\u201cdrusen-free\u201d region). Measurements were generated using previously published algorithms. Mean\u2009\u00b1\u2009SD age was 74.1\u2009\u00b1\u20096.8\u00a0years in the intermediate AMD group and 72.1\u2009\u00b1\u20096.0\u00a0years in the control group (p\u2009=\u20090.206). The normalized EZ reflectivity was 0.76\u2009\u00b1\u20090.10 in the intermediate AMD group and 0.85\u2009\u00b1\u20090.08 in the control group (p\u2009&lt;\u2009.0001). In the \u201cdrusen-free\u201d region, the normalized EZ reflectivity was 0.77\u2009\u00b1\u20090.10 (p\u2009&lt;\u2009.0001   \u00a0vs. healthy controls) and was positively correlated with the CC flow signal density (\u03c1\u2009=\u2009\u2212\u00a00.340 and p\u2009=\u20090.020). In conclusion, eyes with intermediate AMD exhibit a diffuse reduced EZ normalized reflectivity, and this reduction is correlated with CC flow signal in the regions without drusen. This study supports the concept of the damage of the unit comprised of photoreceptor, CC, and intervening tissues as an early event in AMD.<\/jats:p>","DOI":"10.1038\/s41598-020-78201-9","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T11:04:47Z","timestamp":1606993487000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Photoreceptor alteration in intermediate age-related macular degeneration"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-5031","authenticated-orcid":false,"given":"Enrico","family":"Borrelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2891-2012","authenticated-orcid":false,"given":"Riccardo","family":"Sacconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biancamaria","family":"Zuccaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Cavalleri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Bordato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Zucchiatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Querques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Bandello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3292-9581","authenticated-orcid":false,"given":"Giuseppe","family":"Querques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"key":"78201_CR1","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1001\/archopht.122.7.1019","volume":"122","author":"DS Friedman","year":"2004","unstructured":"Friedman, D. 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Francesco Bandello is a consultant for: Alcon (Fort Worth,Texas,USA), Alimera Sciences (Alpharetta, Georgia, USA), Allergan Inc (Irvine, California,USA), Farmila-Thea (Clermont-Ferrand, France), Bayer Shering-Pharma (Berlin, Germany), Bausch And Lomb (Rochester, New York, USA), Genentech (San Francisco, California, USA), Hoffmann-La-Roche (Basel, Switzerland), Novagali Pharma (\u00c9vry, France), Novartis (Basel, Switzerland), Sanofi-Aventis (Paris, France), Thrombogenics (Heverlee,Belgium), Zeiss (Dublin, USA). Giuseppe Querques is a consultant for: Alimera Sciences (Alpharetta, Georgia, USA), Allergan Inc (Irvine, California, USA), Amgen (Thousand Oaks ,USA), Bayer Shering-Pharma (Berlin, Germany), Heidelberg (Germany), KBH (Chengdu; China), LEH Pharma (London, UK), Lumithera (Poulsbo; USA), Novartis (Basel, Switzerland), Sandoz (Berlin, Germany), Sifi (Catania, Italy), Sooft-Fidea (Abano, Italy), Zeiss (Dublin, USA). The other authors have no disclosures.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21036"}}