{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:15:43Z","timestamp":1783574143303,"version":"3.55.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Ophthalmol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To identify optical coherence tomography angiography (OCTA)-derived biomarkers correlating with diabetic retinopathy (DR) severity and characterize longitudinal retinal microvascular changes across DR stages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this 3-year prospective study, we analyzed OCTA images from 328 eyes of 164 adults with type II diabetes and 33 eyes from 17 healthy controls. Patients were categorized as no DR, mild, moderate, or severe nonproliferative DR (NPDR), or proliferative DR (PDR) at baseline. Bilateral OCTA scans were obtained at each visit and processed with a validated pipeline to extract seven microvascular indices from the superficial and deep capillary plexuses: vessel density, skeleton density, acircularity index, average vessel caliber, foveal avascular zone (FAZ) area, FAZ perimeter, and fractal dimensions. Linear regression quantified changes over time, and intergroup comparisons were made using ANOVA and\n                      <jats:italic>post-hoc<\/jats:italic>\n                      testing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 361 eyes (328 diabetic eyes and 33 control eyes) were followed for a mean of 3 years. Longitudinal analysis demonstrated stage-dependent microvascular changes across DR severity groups. In the deep capillary plexus, eyes with severe NPDR exhibited greater annual declines in vessel density (-0.563 \u00b1 0.39% per year) and skeleton density (-0.296 \u00b1 0.23% per year) compared with controls. Acircularity index increased over time, with greater annual increases observed in severe NPDR relative to mild NPDR (0.16 \u00b1 0.12% per year), consistent with progressive macular ischemia. In the superficial plexus, eyes with severe NPDR showed greater annual reductions in average vessel caliber (-4.5e-4 \u00b1 0.0005% per year) compared with earlier disease stages. Across the cohort, most OCTA metrics demonstrated small but statistically significant longitudinal trends, reflecting gradual microvascular remodeling detectable over repeated measurements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Longitudinal OCTA analysis reveals stage-specific microvascular changes in DR. These dynamic biomarkers may provide early indicators of DR progression and offer a quantitative foundation for individualized monitoring and timely intervention strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Translational Relevance<\/jats:title>\n                    <jats:p>OCTA-derived biomarkers offer a noninvasive tool for detecting early DR changes and guiding personalized care strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fopht.2026.1860036","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:21:39Z","timestamp":1783570899000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal changes in anatomic biomarkers on optical coherence tomography angiography in diabetic retinopathy"],"prefix":"10.3389","volume":"6","author":[{"given":"Rachel","family":"Liu","sequence":"first","affiliation":[{"name":"Vanderbilt University School of Medicine","place":["Nashville, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Bakis","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine","place":["Nashville, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Steinkerchner","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute","place":["Nashville, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Sun","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine","place":["Nashville, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sapna","family":"Gangaputra","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute","place":["Nashville, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Kim","sequence":"additional","affiliation":[{"name":"Vanderbilt Eye Institute","place":["Nashville, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lok Hin","family":"Lee","sequence":"additional","affiliation":[{"name":"Vanderbilt University School of Medicine","place":["Nashville, TN, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9100905","article-title":"Diabetic retinopathy: the role of mitochondria in the neural retina and microvascular disease","volume":"9","author":"Miller","year":"2020","journal-title":"Antioxidants"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3362","DOI":"10.3390\/ijms19113362","article-title":"Reactive Oxygen Species-Mediated Damage of Retinal Neurons: Drug Development Targets for Therapies of Chronic Neurodegeneration of the Retina","volume":"19","author":"Rohowetz","year":"2018","journal-title":"Int. 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