{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T15:49:10Z","timestamp":1776872950438,"version":"3.51.2"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>To explore the relationship between peripapillary atrophy (PPA) and diabetic retinopathy (DR), and to uncover potential mechanisms using swept-source optical coherence tomography (SS-OCT) angiography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This cross-sectional study included 845 patients with type 2 diabetes (T2DM), who underwent detailed systemic and ophthalmic evaluations. A state-of-the-art deep learning method was employed to precisely identify the parapapillary beta and gamma zones. Based on PPA characteristics, eyes were categorized into four groups: without beta or gamma zone (Group A), isolated beta zone (Group B), isolated gamma zone (Group C), and with both beta and gamma zone (Group D). Digital fundus photography was utilized to diagnose and stage DR severity, while SS-OCT angiography quantified retinal and choroidal vasculature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Participants had a mean age of 66 \u00b1 8.8\u00a0years, with 437 (51.7%) male. Beta and gamma PPA zones were observed in 574 (67.9%) and 256 (30.3%) eyes, respectively. Beta zone PPA was associated with older age, whereas gamma zone PPA was correlated with longer axial length (AL), lower vessel density, and reduced choroidal thickness. Adjusted analyses revealed that eyes with isolated (Group C) or concurrent (Group D) gamma zone PPA conferred significantly lower DR grade, independent of known risk factors including systemic diabetes risk factors and AL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study finds that gamma zone PPA is linked to a reduced risk of developing DR. These results imply that the gamma zone may reflect progressive myopia-associated thinning and microvascular depletion in posterior ocular tissues, potentially contributing to structural resilience against DR. This novel insight offers a promising avenue for understanding the interplay between PPA and DR.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcell.2024.1501625","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T10:04:31Z","timestamp":1733306671000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The protective role of gamma zone peripapillary atrophy in diabetic retinopathy: insights from deep learning and SS-OCT angiography"],"prefix":"10.3389","volume":"12","author":[{"given":"Yingying","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinxin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueqiong","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingya","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xixi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinglin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahui","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dandan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juntao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weina","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yitian","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinkang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/s0161-6420(90)32486-7","article-title":"Posterior vitreous detachment and neovascularization in diabetic retinopathy","volume":"97","author":"Akiba","year":"1990","journal-title":"Ophthalmology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.ajo.2016.09.011","article-title":"Myopia is inversely associated with the prevalence of diabetic retinopathy in the South Korean population","volume":"172","author":"Chao","year":"2016","journal-title":"Am. J. Ophthalmol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.diabres.2018.02.023","article-title":"IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045","volume":"138","author":"Cho","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2132","DOI":"10.1016\/j.visres.2011.08.008","article-title":"The relationship between peripapillary crescent and axial length: implications for differential eye growth","volume":"51","author":"Chui","year":"2011","journal-title":"Vis. Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1167\/iovs.12-11255","article-title":"Microstructure of parapapillary atrophy: beta zone and gamma zone","volume":"54","author":"Dai","year":"2013","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1167\/iovs.11-8572","article-title":"Spectral-domain optical coherence tomography of \u03b2-zone peripapillary atrophy: influence of myopia and glaucoma","volume":"53","author":"Hayashi","year":"2012","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41592-020-01008-z","article-title":"nnU-Net: a self-configuring method for deep learning-based biomedical image segmentation","volume":"18","author":"Isensee","year":"2021","journal-title":"Nat. Methods"},{"key":"B8","first-page":"908","article-title":"Parapapillary chorioretinal atrophy in normal and glaucoma eyes. I. Morphometric data","volume":"30","author":"Jonas","year":"1989","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2234.e1","DOI":"10.1016\/j.ophtha.2009.12.006","article-title":"VEGF and refractive error","volume":"117","author":"Jonas","year":"2009","journal-title":"Ophthalmology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1167\/iovs.15-18263","article-title":"Parapapillary gamma zone and axial elongation-associated optic disc rotation: the Beijing eye study","volume":"57","author":"Jonas","year":"2016","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1016\/j.ophtha.2013.02.011","article-title":"Differentiation of parapapillary atrophy using spectral-domain optical coherence tomography","volume":"120","author":"Kim","year":"2013","journal-title":"Ophthalmology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1016\/j.ophtha.2014.01.008","article-title":"Microstructure of \u03b2-zone parapapillary atrophy and rate of retinal nerve fiber layer thinning in primary open-angle glaucoma","volume":"121","author":"Kim","year":"2014","journal-title":"Ophthalmology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"4020","DOI":"10.1167\/iovs.18-24775","article-title":"Change of \u03b2-zone parapapillary atrophy during axial elongation: boramae myopia cohort study report 3","volume":"59","author":"Lee","year":"2018","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1459040","DOI":"10.3389\/fcell.2024.1459040","article-title":"Unveiling the hidden: a deep learning approach to unraveling subzone-specific changes in peripapillary atrophy in type 2 diabetes","volume":"12","author":"Li","year":"2024","journal-title":"Front. Cell Dev. Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1167\/iovs.10-6184","article-title":"Influence of refractive error and axial length on retinal vessel geometric characteristics","volume":"52","author":"Lim","year":"2011","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.ophtha.2009.07.044","article-title":"Are myopic eyes less likely to have diabetic retinopathy?","volume":"117","author":"Lim","year":"2010","journal-title":"Ophthalmology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e157","DOI":"10.1111\/aos.14885","article-title":"Optic disc morphology and peripapillary atrophic changes in diabetic children and adults without diabetic retinopathy or visual impairment","volume":"100","author":"Lin","year":"2022","journal-title":"Acta Ophthalmol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"7691","DOI":"10.1167\/iovs.13-12412","article-title":"Axial length, retinal function, and oxygen consumption: a potential mechanism for a lower risk of diabetic retinopathy in longer eyes","volume":"54","author":"Man","year":"2013","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1016\/j.ophtha.2012.03.021","article-title":"Longer axial length is protective of diabetic retinopathy and macular edema","volume":"119","author":"Man","year":"2012","journal-title":"Ophthalmology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1111\/j.1600-0420.2007.01139.x","article-title":"Longterm findings in peripapillary crescent formation in eyes with mild or moderate myopia","volume":"86","author":"Nakazawa","year":"2008","journal-title":"Acta Ophthalmol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1038\/s41433-019-0541-9","article-title":"Morphological features of parapapillary beta zone and gamma zone in chronic primary angle-closure glaucoma","volume":"33","author":"Shang","year":"2019","journal-title":"Eye (Lond)."},{"key":"B22","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.oret.2017.09.019","article-title":"Associations of peripapillary atrophy and fundus tessellation with diabetic retinopathy","volume":"2","author":"Tan","year":"2018","journal-title":"Ophthalmol. Retina"},{"key":"B23","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1111\/ceo.12696","article-title":"Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review","volume":"44","author":"Ting","year":"2016","journal-title":"Clin. Exp. Ophthalmol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1167\/iovs.61.4.29","article-title":"Choroidal thickness in diabetes and diabetic retinopathy: a swept source OCT study","volume":"61","author":"Wang","year":"2020","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"122212","DOI":"10.1016\/j.eswa.2023.122212","article-title":"E-YOLO: recognition of estrus cow based on improved YOLOv8n model","volume":"238","author":"Wang","year":"2024","journal-title":"Expert Syst. Appl."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1016\/S0161-6420(03)00475-5","article-title":"Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales","volume":"110","author":"Wilkinson","year":"2003","journal-title":"Ophthalmology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1016\/j.ophtha.2015.10.061","article-title":"Microstructure of peripapillary atrophy and subsequent visual field progression in treated primary open-angle glaucoma","volume":"123","author":"Yamada","year":"2016","journal-title":"Ophthalmology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1159\/000083019","article-title":"Concentration of transforming growth factor beta2 in aqueous humor","volume":"37","author":"Yamamoto","year":"2005","journal-title":"Ophthalmic Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"556","DOI":"10.2337\/dc11-1909","article-title":"Global prevalence and major risk factors of diabetic retinopathy","volume":"35","author":"Yau","year":"2012","journal-title":"Diabetes Care"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3320","DOI":"10.1167\/iovs.18-24141","article-title":"Parapapillary beta zone and gamma zone in a healthy population: the Beijing eye study 2011","volume":"59","author":"Zhang","year":"2018","journal-title":"Invest Ophthalmol. Vis. Sci."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2024.1501625\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T10:04:34Z","timestamp":1733306674000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2024.1501625\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,4]]},"references-count":30,"alternative-id":["10.3389\/fcell.2024.1501625"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2024.1501625","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,4]]},"article-number":"1501625"}}