{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:10:32Z","timestamp":1788441032201,"version":"build-2803163510"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T00:00:00Z","timestamp":1601942400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T00:00:00Z","timestamp":1601942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"COMPETE Portugal2020"},{"name":"Fundo de Inova\u00e7\u00e3o, Tecnologia e Economia Circular","award":["Programa Interface (FITEC\/CIT\/2018\/2)"],"award-info":[{"award-number":["Programa Interface (FITEC\/CIT\/2018\/2)"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Diabetol"],"published-print":{"date-parts":[[2021,2]]},"abstract":"Abstract<\/jats:title>\n \n Purpose<\/jats:title>\n To characterize the progression in retinopathy severity of different phenotypes of mild nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes.<\/jats:p>\n <\/jats:sec>\n \n Design and methods<\/jats:title>\n Patients with type 2 diabetes and mild NPDR (ETDRS 20 or 35) were followed in a 5-year longitudinal study. Examinations, including color fundus photography (CFP) and optical coherence tomography (OCT and OCTA), were performed at baseline, 6 months and then annually. Phenotype classification was performed based on microaneurysm turnover (MAT, on CFP) and central retinal thickness (CRT, on OCT). Phenotype A is characterized by low MAT (<\u20096) and normal CRT; Phenotype B by low MAT (<\u20096) and increased CRT; and Phenotype C by higher MAT (\u2265\u20096) with or without increased CRT. ETDRS grading of seven fields CFP was performed at the initial and last visits.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Analysis of ETDRS grade step changes showed significant differences in diabetic retinopathy (DR) progression between the different phenotypes (\n p<\/jats:italic>\n \u2009<\u20090.001). Of the 66 participants with phenotype A only 2 eyes (3%) presented 2-or-more-step worsening. None of the 50 participants characterized as phenotype B developed 2-step worsening, whereas 13 eyes (23.2%) characterized as phenotype C had 2-or-more-steps worsening. Phenotype C presents the higher risk for 2-or-more step worsening (OR: 15.94 95% CI: 3.45\u201373.71;\n p<\/jats:italic>\n \u2009<\u20090.001) and higher sensitivity, correctly identifying 86.7% of cases at risk (AUC: 0.84 95% CI: 0.72\u20130.96;\n p<\/jats:italic>\n \u2009<\u20090.001). Diabetic retinopathy severity progression was associated with HbA\n 1c<\/jats:sub>\n (\n p<\/jats:italic>\n \u2009=\u20090.019), LDL levels (\n p<\/jats:italic>\n \u2009=\u20090.043), and ocular factors as MAT (\n p<\/jats:italic>\n \u2009=\u20090.010), MA formation rate (\n p<\/jats:italic>\n \u2009=\u20090.014) and MA disappearance rate (\n p<\/jats:italic>\n \u2009=\u20090.005). Capillary closure at 5-year follow-up, identified by lower vessel density (VD) on OCTA, was also associated with diabetic DR severity progression (\n p<\/jats:italic>\n \u2009=\u20090.035).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Different DR phenotypes in type 2 diabetes show different risks of retinopathy progression. Phenotype C is associated with increased HbA\n 1c<\/jats:sub>\n values and presents a higher risk of a 2-or-more-step worsening of the ETDRS severity score.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1007\/s00592-020-01602-9","type":"journal-article","created":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T14:04:25Z","timestamp":1601993065000},"page":"197-205","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Different retinopathy phenotypes in type 2 diabetes predict retinopathy progression"],"prefix":"10.1007","volume":"58","author":[{"given":"In\u00eas P.","family":"Marques","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria H.","family":"Madeira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana L.","family":"Messias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f3nio C.-V.","family":"Martinho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torcato","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o","family":"Figueira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0947-9850","authenticated-orcid":false,"given":"Jos\u00e9","family":"Cunha-Vaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,6]]},"reference":[{"key":"1602_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(13)70113-X","author":"RRA Bourne","year":"2013","unstructured":"Bourne RRA, Stevens GA, White RA et al (2013) Causes of vision loss worldwide, 1990\u20132010: a systematic analysis. 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A.C.-V.M and DS. do not have financial disclosures. J.F.: member of Advisory board for Alimera, Allergan, Bayer, Boehringer, and Novartis; J.C.-V. reports grants from Carl Zeiss Meditec outside the submitted work and is consultant for Alimera Sciences, Allergan, Bayer, Gene Signal, Novartis, Pfizer, Precision Ocular Ltd., Roche, Sanofi-Aventis, Vifor Pharma, and Carl Zeiss Meditec.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"PROGRESS was approved by the Institutional Ethical Review Board and registered at ClinicalTrials.gov (#NCT03010397).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standard statement"}},{"value":"Each participant signed a written informed consent before the beginning of the study, agreeing to participate in the study, after all procedures were explained.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}