{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:45:46Z","timestamp":1774975546353,"version":"3.50.1"},"reference-count":22,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T00:00:00Z","timestamp":1621900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AIBILI","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"COMPETE Portugal2020","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"name":"Fundo de Inova\u00e7\u00e3o, Tecnologia e Economia Circular (FITEC) \u2013 Programa Interface","award":["FITEC\/CIT\/2018\/2"],"award-info":[{"award-number":["FITEC\/CIT\/2018\/2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>To examine retinal vessel closure metrics and neurodegenerative changes occurring in the initial stages of nonproliferative diabetic retinopathy (NPDR) and severity progression in a three-year period. Methods: Three-year prospective longitudinal observational cohort of individuals with type 2 diabetes (T2D), one eye per person, using spectral domain-optical coherence tomography (SD-OCT) and OCT-Angiography (OCTA). Eyes were examined four times with one-year intervals. OCTA vessel density maps of the retina were used to quantify vessel closure. Thickness of the ganglion cell + inner plexiform layer (GCL + IPL) was examined to identify retinal neurodegenerative changes. Diabetic retinopathy ETDRS classification was performed using the seven-field ETDRS protocol. Results: A total of 78 eyes\/patients, aged 52 to 80 years, with T2D and ETDRS grades from 10 to 47 were followed for 3 years with annual examinations. A progressive increase in retinal vessel closure was observed. Vessel density (VD) showed higher decreases with retinopathy worsening demonstrated by step-changes in ETDRS severity scale (p &lt; 0.001). No clear correlation was observed between neurodegenerative changes and retinopathy progression. Conclusions: Retinal vessel closure in NPDR correlates with DR severity progression. Our findings provide supporting evidence that OCTA metrics of vessel closure may be used as a surrogate for DR severity progression.<\/jats:p>","DOI":"10.3390\/jcm10112296","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T13:14:21Z","timestamp":1621948461000},"page":"2296","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Optical Coherence Tomography Angiography Metrics Monitor Severity Progression of Diabetic Retinopathy\u20143-Year Longitudinal Study"],"prefix":"10.3390","volume":"10","author":[{"given":"In\u00eas P.","family":"Marques","sequence":"first","affiliation":[{"name":"AIBILI\u2014Association for Innovation and Biomedical Research on Light and Image, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Sophie","family":"Kubach","sequence":"additional","affiliation":[{"name":"Research and Development, Carl Zeiss Meditec, Dublin, CA 94568, USA"}]},{"given":"Torcato","family":"Santos","sequence":"additional","affiliation":[{"name":"AIBILI\u2014Association for Innovation and Biomedical Research on Light and Image, 3000-548 Coimbra, Portugal"}]},{"given":"Lu\u00eds","family":"Mendes","sequence":"additional","affiliation":[{"name":"AIBILI\u2014Association for Innovation and Biomedical Research on Light and Image, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6282-3553","authenticated-orcid":false,"given":"Maria H.","family":"Madeira","sequence":"additional","affiliation":[{"name":"AIBILI\u2014Association for Innovation and Biomedical Research on Light and Image, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Luis","family":"de Sisternes","sequence":"additional","affiliation":[{"name":"Research and Development, Carl Zeiss Meditec, Dublin, CA 94568, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1791-4768","authenticated-orcid":false,"given":"Diana","family":"Tavares","sequence":"additional","affiliation":[{"name":"AIBILI\u2014Association for Innovation and Biomedical Research on Light and Image, 3000-548 Coimbra, Portugal"}]},{"given":"Ana Rita","family":"Santos","sequence":"additional","affiliation":[{"name":"AIBILI\u2014Association for Innovation and Biomedical Research on Light and Image, 3000-548 Coimbra, Portugal"},{"name":"Department of Orthoptics, School of Health, Polytechnic of Porto, 4200-072 Porto, Portugal"}]},{"given":"Warren","family":"Lewis","sequence":"additional","affiliation":[{"name":"Research and Development, Carl Zeiss Meditec, Dublin, CA 94568, USA"}]},{"given":"Concei\u00e7\u00e3o","family":"Lobo","sequence":"additional","affiliation":[{"name":"AIBILI\u2014Association for Innovation and Biomedical Research on Light and Image, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Department of Ophthalmology, Centro Hospitalar e Universit\u00e1rio de Coimbra (CHUC), 3000-075 Coimbra, Portugal"}]},{"given":"Mary K.","family":"Durbin","sequence":"additional","affiliation":[{"name":"Research and Development, Carl Zeiss Meditec, Dublin, CA 94568, USA"}]},{"given":"Jos\u00e9","family":"Cunha-Vaz","sequence":"additional","affiliation":[{"name":"AIBILI\u2014Association for Innovation and Biomedical Research on Light and Image, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e339","DOI":"10.1016\/S2214-109X(13)70113-X","article-title":"Causes of vision loss worldwide, 1990\u20132010: A systematic analysis","volume":"1","author":"Bourne","year":"2013","journal-title":"Lancet Glob. 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