{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:49:57Z","timestamp":1790628597999,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T00:00:00Z","timestamp":1696464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Diabetic retinopathy (DR) is both a microangiopathy and a neurodegenerative disease. However, the connections between both changes are not well known.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To characterise the longitudinal retinal ganglion cell layer\u2009+\u2009inner plexiform layer (GCL\u2009+\u2009IPL) changes and their association with microvascular changes in type\u20102 diabetes (T2D) patients with nonproliferative diabetic retinopathy (NPDR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This two\u2010year prospective study (CORDIS, NCT03696810) included 122 T2D individuals with NPDR identified as risk phenotypes B and C, which present a more rapid progression. Phenotype C was identified by decreased VD\u2009\u2265\u20092SD in healthy controls, and phenotype B, identified by subclinical macular oedema with only minimal vascular closure. The GCL\u2009+\u2009IPL thickness, vessel density, perfusion density and area of intercapillary spaces (AIS) were assessed by optical coherence tomography (OCT) and OCT angiography (OCTA). Linear mixed effects models were employed to evaluate the retinal GCL\u2009+\u2009IPL progression and its associations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Regarding GCL\u2009+\u2009IPL thickness, T2D individuals presented on average 80.1\u2009\u00b1\u20097.49\u2009\u03bcm, statistically significantly lower than the healthy control group, 82.5\u2009\u00b1\u20095.71 (<jats:italic>p<\/jats:italic>\u2009=\u20090.022), with only phenotype C differing significantly from controls (<jats:italic>p<\/jats:italic>\u2009=\u20090.006). GCL\u2009+\u2009IPL thickness steadily decreased during the two\u2010year period in both risk phenotypes, with an annual decline rate of \u22120.372\u2009\u03bcm\/year (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Indeed, phenotype C showed a higher rate of progression (\u22120.459\u2009\u03bcm\/year, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) when compared to phenotype B (\u22120.296\u2009\u03bcm\/year, <jats:italic>p<\/jats:italic>\u2009=\u20090.036). Eyes with ETDRS grade 20 showed GCL\u2009+\u2009IPL thickness values comparable to those of healthy control group (83.3\u2009\u00b1\u20095.80 and 82.7\u2009\u00b1\u20095.50\u2009\u03bcm, respectively, <jats:italic>p<\/jats:italic>\u2009=\u20090.880), whereas there was a progressive decrease in GCL\u2009+\u2009IPL thickness in ETDRS grades 35 and 43\u201347 associated with the increase in severity of the retinopathy (\u22120.276\u2009\u03bcm\/year, <jats:italic>p<\/jats:italic>\u2009=\u20090.004; \u22120.585\u2009\u03bcm\/year, <jats:italic>p<\/jats:italic>\u2009=\u20090.013, respectively). Furthermore, the study showed statistically significant associations between the progressive thinning of GCL\u2009+\u2009IPL and the progressive increase in retinal capillary non\u2010perfusion, with particular relevance for AIS (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings showed that, in eyes with NPDR and at risk for progression, retinal neurodegeneration occurs at different rates in different risk phenotypes, and it is associated with retinal microvascular non\u2010perfusion.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aos.15787","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T17:35:30Z","timestamp":1696613730000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Retinal neurodegeneration in eyes with <scp>NPDR<\/scp> risk phenotypes: A two\u2010year longitudinal study"],"prefix":"10.1111","volume":"102","author":[{"given":"D\u00e9bora","family":"Reste\u2010Ferreira","sequence":"first","affiliation":[{"name":"AIBILI \u2013 Association for Innovation and Biomedical Research on Light and Image  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00eas Pereira","family":"Marques","sequence":"additional","affiliation":[{"name":"AIBILI \u2013 Association for Innovation and Biomedical Research on Light and Image  Coimbra Portugal"},{"name":"CORC \u2013 Coimbra Ophthalmology Reading Center  Coimbra Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine University of Coimbra  Coimbra Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB) University of Coimbra  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torcato","family":"Santos","sequence":"additional","affiliation":[{"name":"AIBILI \u2013 Association for 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Biomedical Research on Light and Image  Coimbra Portugal"},{"name":"CORC \u2013 Coimbra Ophthalmology Reading Center  Coimbra Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine University of Coimbra  Coimbra Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB) University of Coimbra  Coimbra Portugal"},{"name":"Department of Orthoptics School of Health, Polytechnic of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concei\u00e7\u00e3o","family":"Lobo","sequence":"additional","affiliation":[{"name":"AIBILI \u2013 Association for Innovation and Biomedical Research on Light and Image  Coimbra Portugal"},{"name":"CORC \u2013 Coimbra Ophthalmology Reading Center  Coimbra Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine University of Coimbra  Coimbra Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology 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