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The IHRF were counted in a series of 5 sequential en face slabs from outer to inner retina. The number of IHRF in each slab at baseline and the change in IHRF from baseline to year 2 were correlated with progression to late AMD at 2 years.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Among 120 eyes from 71 patients with iAMD, 52 eyes (43.3%) of 42 patients had evidence of both iAMD and IHRF at baseline. Twenty-three eyes (19.0%) showed progression to late AMD after 2 years. The total IHRF count increased from 243 at baseline to 604 at 2 years, with a significant increase in the IHRF number in each slab, except for the innermost slab 5 which had no IHRF at baseline or follow-up. The IHRF count increased from 121 to 340 in eyes that showed progression to late AMD. The presence of IHRF in the outermost retinal slabs 1 and 2 was independently associated with a significant risk of progression to late AMD. A greater increase in IHRF count over 2 years in these same slabs 1 and 2 was also associated with a higher risk of conversion to late AMD.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The risk of progression to late AMD appears to be significantly associated with the distribution and extent of IHRF in the outermost retinal layers. This observation may point to significant pathophysiologic differences of IHRF in inner versus outer layers of the retina.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00417-023-06180-4","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T09:02:41Z","timestamp":1691744561000},"page":"3437-3447","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Relationship between the distribution of intra-retinal hyper-reflective foci and the progression of intermediate age-related macular degeneration"],"prefix":"10.1007","volume":"261","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3778-8834","authenticated-orcid":false,"given":"Aditya","family":"Verma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Corradetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muneeswar G.","family":"Nittala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Nassisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swetha B.","family":"Velaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan L.","family":"Haines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A.","family":"Pericak-Vance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwight","family":"Stambolian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4939-3306","authenticated-orcid":false,"given":"SriniVas R.","family":"Sadda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,11]]},"reference":[{"issue":"12","key":"6180_CR1","doi-asserted-by":"publisher","first-page":"2656","DOI":"10.1016\/j.ophtha.2013.05.029","volume":"120","author":"Y Ouyang","year":"2013","unstructured":"Ouyang Y, Heussen FM, Hariri A, Keane PA, Sadda SR (2013) Optical coherence tomography-based observation of the natural history of drusenoid lesion in eyes with dry age-related macular degeneration. 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Institutional Review Board approval was obtained from the following: University of Pennsylvania, University of Miami, Case Western Reserve University, and University of California\u2014Los Angeles.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"AV, YH, MNG, MN, JLH, MAP-V, DS: none; GC: Nidek (speaker fee); SRS: 4DMT consultant\/advisor; Alexion consultant\/advisor; Allergan, Inc. consultant\/advisor; Alnylam Pharmaceuticals consultant\/advisor; Amgen Inc. consultant\/advisor; Apellis Pharmaceuticals, Inc. consultant\/advisor; Astellas consultant\/advisor; Bayer Healthcare Pharmaceuticals consultant\/advisor; Carl Zeiss Meditec consultant\/advisor, lecture fees\/speakers bureau, grant support; Catalyst Pharmaceuticals Inc. consultant\/advisor; Centervue, Inc. consultant\/advisor; GENENTECH consultant\/advisor; Gyroscope Therapeutics consultant\/advisor; Heidelberg Engineering consultant\/advisor, lecture fees\/speakers bureau, grant support; Iveric Bio consultant\/advisor; Janssen Pharmaceuticals, Inc. consultant\/advisor; Merck & Co., Inc. consultant\/advisor; Nanoscope consultant\/advisor; Nidek Incorporated lecture fees\/speakers bureau; Novartis Pharma AG consultant\/advisor, lecture fees\/speakers bureau; Optos, Inc. consultant\/advisor; Oxurion\/Thrombogenics consultant\/advisor; Pfizer, Inc. consultant\/advisor; Regeneron Pharmaceuticals, Inc. consultant\/advisor; Samsung Bioepis consultant\/advisor; Topcon Medical Systems Inc. lecture fees\/speakers bureau; Vertex Pharmaceuticals Incorporated consultant\/advisor.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Although the co-author (Vas Sadda) is an editor of the journal, there was no involvement with the peer-review process for this article.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclaimer"}}]}}