{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:51:06Z","timestamp":1790628666677,"version":"4.1.0"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["2024A03J0333"],"award-info":[{"award-number":["2024A03J0333"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970807"],"award-info":[{"award-number":["81970807"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271099"],"award-info":[{"award-number":["82271099"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ajo.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["American Journal of Ophthalmology"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.ajo.2025.09.025","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T07:09:11Z","timestamp":1758265751000},"page":"201-210","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Longitudinal Neural and Microvascular Changes in Type 2 Diabetic Patients Without Retinopathy: A 2-Year Prospective Cohort Study"],"prefix":"10.1016","volume":"281","author":[{"given":"Yiran","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayi","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7662-7359","authenticated-orcid":false,"given":"Pan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1636-6393","authenticated-orcid":false,"given":"Likun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6682-4768","authenticated-orcid":false,"given":"Yuntong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5636-962X","authenticated-orcid":false,"given":"Ching-Kit","family":"Tsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8540-1828","authenticated-orcid":false,"given":"Kaiqun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3167-0851","authenticated-orcid":false,"given":"Wenyong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2772-030X","authenticated-orcid":false,"given":"Andina","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"9735","key":"10.1016\/j.ajo.2025.09.025_bib0001","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/S0140-6736(09)62124-3","article-title":"Diabetic retinopathy","volume":"376","author":"Cheung","year":"2010","journal-title":"Lancet"},{"issue":"3","key":"10.1016\/j.ajo.2025.09.025_bib0002","doi-asserted-by":"crossref","first-page":"301","DOI":"10.4155\/fmc.12.206","article-title":"Microvascular complications and diabetic retinopathy: recent advances and future implications","volume":"5","author":"Barot","year":"2013","journal-title":"Future Medicin Chem"},{"issue":"12","key":"10.1016\/j.ajo.2025.09.025_bib0003","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1167\/iovs.65.12.5","article-title":"Initial retinal nerve fiber layer loss and risk of diabetic retinopathy over a four-year period","volume":"65","author":"Zhong","year":"2024","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"5 suppl","key":"10.1016\/j.ajo.2025.09.025_bib0004","first-page":"823","article-title":"Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12","volume":"98","year":"1991","journal-title":"Ophthalmology"},{"issue":"4","key":"10.1016\/j.ajo.2025.09.025_bib0005","first-page":"161","article-title":"Digital ocular fundus imaging: a review","volume":"226","author":"Bernardes","year":"2011","journal-title":"Ophthalmol J Int d'Ophtalmol Int J Ophthalmol Zeitschrift fur Augenheilkunde"},{"key":"10.1016\/j.ajo.2025.09.025_bib0006","doi-asserted-by":"crossref","DOI":"10.1155\/2018\/3082893","article-title":"Analysis of changes in retinal thickness in type 2 diabetes without diabetic retinopathy","volume":"2018","author":"Jiang","year":"2018","journal-title":"J Diabetes Res"},{"issue":"4","key":"10.1016\/j.ajo.2025.09.025_bib0007","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1136\/bjophthalmol-2020-317322","article-title":"Longitudinal analysis of microvascular perfusion and neurodegenerative changes in early type 2 diabetic retinal disease","volume":"106","author":"Aschauer","year":"2022","journal-title":"Br J Ophthalmol"},{"issue":"7","key":"10.1016\/j.ajo.2025.09.025_bib0008","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1016\/j.ophtha.2015.03.024","article-title":"Diabetic macular edema: pathophysiology and novel therapeutic targets","volume":"122","author":"Das","year":"2015","journal-title":"Ophthalmology"},{"issue":"9","key":"10.1016\/j.ajo.2025.09.025_bib0009","doi-asserted-by":"crossref","first-page":"3330","DOI":"10.1167\/iovs.04-0247","article-title":"Death of retinal neurons in streptozotocin-induced diabetic mice","volume":"45","author":"Martin","year":"2004","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"9","key":"10.1016\/j.ajo.2025.09.025_bib0010","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.2337\/db05-1635","article-title":"Diabetic retinopathy: seeing beyond glucose-induced microvascular disease","volume":"55","author":"Antonetti","year":"2006","journal-title":"Diabetes"},{"issue":"2","key":"10.1016\/j.ajo.2025.09.025_bib0011","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0278-5846(03)00023-X","article-title":"A new view of diabetic retinopathy: a neurodegenerative disease of the eye","volume":"27","author":"Barber","year":"2003","journal-title":"Prog Neuro-psychopharmacol Biol Psychiatry"},{"key":"10.1016\/j.ajo.2025.09.025_bib0012","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ajo.2016.02.018","article-title":"In vivo assessment of macular vascular density in healthy human eyes using optical coherence tomography angiography","volume":"165","author":"Shahlaee","year":"2016","journal-title":"Am J Ophthalmol"},{"key":"10.1016\/j.ajo.2025.09.025_bib0013","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ajo.2022.07.011","article-title":"Rates of choroidal and neurodegenerative changes over time in diabetic patients without retinopathy: a 3-year prospective study","volume":"246","author":"Huang","year":"2023","journal-title":"Am J Ophthalmol"},{"issue":"1","key":"10.1016\/j.ajo.2025.09.025_bib0014","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1038\/s41598-020-58465-x","article-title":"Ganglion cell\u2013inner plexiform layer damage in diabetic patients: 3-year prospective, longitudinal, observational study","volume":"10","author":"Lim","year":"2020","journal-title":"Sci Rep"},{"issue":"5","key":"10.1016\/j.ajo.2025.09.025_bib0015","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.oret.2017.09.011","article-title":"Quantifying microvascular changes using OCT angiography in diabetic eyes without clinical evidence of retinopathy","volume":"2","author":"Yasin Alibhai","year":"2018","journal-title":"Ophthalmol Retina"},{"issue":"2","key":"10.1016\/j.ajo.2025.09.025_bib0016","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/s41433-019-0513-0","article-title":"Optical coherence tomography angiography study of the retinal vascular plexuses in type 1 diabetes without retinopathy","volume":"34","author":"Sousa","year":"2020","journal-title":"Eye (London, England)"},{"key":"10.1016\/j.ajo.2025.09.025_bib0017","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.ajo.2020.09.032","article-title":"Early detection of microvascular impairments with optical coherence tomography angiography in diabetic patients without clinical retinopathy: a meta-analysis","volume":"222","author":"Zhang","year":"2021","journal-title":"Am J Ophthalmol"},{"issue":"7","key":"10.1016\/j.ajo.2025.09.025_bib0018","doi-asserted-by":"crossref","DOI":"10.3390\/jcm12072687","article-title":"Early retinal microvascular changes assessed with swept-source OCT angiography in type 1 diabetes patients without retinopathy","volume":"12","author":"Eid","year":"2023","journal-title":"J Clin Med"},{"issue":"12","key":"10.1016\/j.ajo.2025.09.025_bib0019","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1136\/bjophthalmol-2018-313582","article-title":"Early retinal neurovascular impairment in patients with diabetes without clinically detectable retinopathy","volume":"103","author":"Zeng","year":"2019","journal-title":"Br J Ophthalmol"},{"issue":"3","key":"10.1016\/j.ajo.2025.09.025_bib0020","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1167\/iovs.62.3.35","article-title":"Evidence for structural and functional damage of the inner retina in diabetes with no diabetic retinopathy","volume":"62","author":"Montesano","year":"2021","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"7","key":"10.1016\/j.ajo.2025.09.025_bib0021","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1097\/IAE.0000000000002576","article-title":"Changes in total and inner retinal thicknesses in type 1 diabetes with no retinopathy after 8 years of follow-up","volume":"40","author":"Pinilla","year":"2020","journal-title":"Retina (Philadelphia, Pa)"},{"issue":"11","key":"10.1016\/j.ajo.2025.09.025_bib0022","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.2522\/ptj.20080020","article-title":"Epidemiology of diabetes and diabetes-related complications","volume":"88","author":"Deshpande","year":"2008","journal-title":"Phys Ther"},{"issue":"4","key":"10.1016\/j.ajo.2025.09.025_bib0023","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1159\/000522527","article-title":"Association between neurodegeneration and macular perfusion in the progression of diabetic retinopathy: a 3-year longitudinal study","volume":"245","author":"Marques","year":"2022","journal-title":"Ophthalmol J Int d'Ophtalmologie Int J Ophthalmol Zeitschrift fur Augenheilkunde"},{"issue":"1","key":"10.1016\/j.ajo.2025.09.025_bib0024","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-72813-x","article-title":"Density-based classification in diabetic retinopathy through thickness of retinal layers from optical coherence tomography","volume":"10","author":"Mohammed","year":"2020","journal-title":"Sci Rep"},{"issue":"9","key":"10.1016\/j.ajo.2025.09.025_bib0025","doi-asserted-by":"crossref","first-page":"3804","DOI":"10.1167\/iovs.17-21460","article-title":"Age-related alterations in the retinal microvasculature, microcirculation, and microstructure","volume":"58","author":"Wei","year":"2017","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"2","key":"10.1016\/j.ajo.2025.09.025_bib0026","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ophtha.2019.09.013","article-title":"Differential effects of aging in the macular retinal layers, neuroretinal rim, and peripapillary retinal nerve fiber layer","volume":"127","author":"Chauhan","year":"2020","journal-title":"Ophthalmology"},{"key":"10.1016\/j.ajo.2025.09.025_bib0027","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.ajo.2024.02.034","article-title":"Macular neural and microvascular alterations in type 2 diabetes without retinopathy: a SS-OCT study","volume":"262","author":"Dai","year":"2024","journal-title":"Am J Ophthalmol"},{"issue":"1","key":"10.1016\/j.ajo.2025.09.025_bib0028","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1136\/bjo-2022-321603","article-title":"Rates of choroidal loss and ganglion cell-inner plexiform layer thinning in type 2 diabetes mellitus and healthy individuals: a 2-year prospective study","volume":"108","author":"Hui","year":"2023","journal-title":"Br J Ophthalmol"},{"issue":"14","key":"10.1016\/j.ajo.2025.09.025_bib0029","doi-asserted-by":"crossref","DOI":"10.3390\/jcm11143982","article-title":"Retinal microvascular and neuronal changes are also present, even if differently, in adolescents with type 1 diabetes without clinical diabetic retinopathy","volume":"11","author":"Pilotto","year":"2022","journal-title":"J Clin Med"},{"issue":"1","key":"10.1016\/j.ajo.2025.09.025_bib0030","article-title":"Microperimetry and optical coherence tomography changes in type-1 diabetes mellitus without retinopathy","volume":"11","author":"Orduna-Hospital","year":"2021","journal-title":"Diagnostics (Basel, Switzerland)"},{"issue":"1","key":"10.1016\/j.ajo.2025.09.025_bib0031","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.tem.2013.09.005","article-title":"Neurodegeneration in the diabetic eye: new insights and therapeutic perspectives","volume":"25","author":"Sim\u00f3","year":"2014","journal-title":"Trends Endocrinol Metab"},{"issue":"6865","key":"10.1016\/j.ajo.2025.09.025_bib0032","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/414813a","article-title":"Biochemistry and molecular cell biology of diabetic complications","volume":"414","author":"Brownlee","year":"2001","journal-title":"Nature"},{"issue":"19","key":"10.1016\/j.ajo.2025.09.025_bib0033","doi-asserted-by":"crossref","first-page":"E2655","DOI":"10.1073\/pnas.1522014113","article-title":"Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus","volume":"113","author":"Sohn","year":"2016","journal-title":"Proc Natl Acad Sci U S Am."},{"issue":"5","key":"10.1016\/j.ajo.2025.09.025_bib0034","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/eye.2016.13","article-title":"Neuroretinal alterations in the early stages of diabetic retinopathy in patients with type 2 diabetes mellitus","volume":"30","author":"Carpineto","year":"2016","journal-title":"Eye (London, England)"},{"issue":"2","key":"10.1016\/j.ajo.2025.09.025_bib0035","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1167\/iovs.10-5931","article-title":"Multifocal electroretinograms predict onset of diabetic retinopathy in adult patients with diabetes","volume":"52","author":"Harrison","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.ajo.2025.09.025_bib0036","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2021.800004","article-title":"Retinal neurodegeneration in different risk phenotypes of diabetic retinal disease","volume":"15","author":"Madeira","year":"2021","journal-title":"Front Neurosci"},{"issue":"16","key":"10.1016\/j.ajo.2025.09.025_bib0037","doi-asserted-by":"crossref","first-page":"5977","DOI":"10.1007\/s00018-021-03893-9","article-title":"Neurovascular regulation in diabetic retinopathy and emerging therapies","volume":"78","author":"Ji","year":"2021","journal-title":"Cell Mol Life Sci"},{"issue":"11","key":"10.1016\/j.ajo.2025.09.025_bib0038","doi-asserted-by":"crossref","DOI":"10.3390\/jcm9113523","article-title":"Reversed neurovascular coupling on optical coherence tomography angiography is the earliest detectable abnormality before clinical diabetic retinopathy","volume":"9","author":"Zhang","year":"2020","journal-title":"J Clin Med"},{"issue":"4","key":"10.1016\/j.ajo.2025.09.025_bib0039","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1055\/s-0032-1304571","article-title":"Crosstalk in the retinal neurovascular unit\u2014lessons for the diabetic retina","volume":"120","author":"Feng","year":"2012","journal-title":"Exp Clin Endocrinol Diabetes"},{"issue":"9","key":"10.1016\/j.ajo.2025.09.025_bib0040","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1097\/IJG.0000000000001598","article-title":"Comparison of peripapillary retinal nerve fiber layer thickness, functional subzones, and macular ganglion cell-inner plexiform layer in differentiating patients with mild, moderate, and severe open-angle glaucoma","volume":"29","author":"Huo","year":"2020","journal-title":"J Glaucoma"},{"issue":"8","key":"10.1016\/j.ajo.2025.09.025_bib0041","doi-asserted-by":"crossref","first-page":"e650","DOI":"10.1111\/aos.12438","article-title":"Severity-dependent association between ganglion cell inner plexiform layer thickness and macular mean sensitivity in open-angle glaucoma","volume":"92","author":"Kim","year":"2014","journal-title":"Acta Ophthalmol"},{"issue":"11","key":"10.1016\/j.ajo.2025.09.025_bib0042","doi-asserted-by":"crossref","first-page":"5152","DOI":"10.1167\/iovs.07-0427","article-title":"Effect of memantine on neuroretinal function and retinal vascular changes of streptozotocin-induced diabetic rats","volume":"48","author":"Kusari","year":"2007","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"4","key":"10.1016\/j.ajo.2025.09.025_bib0043","first-page":"819","article-title":"The relation between expression of vascular endothelial growth factor and breakdown of the blood-retinal barrier in diabetic rat retinas","volume":"74","author":"Murata","year":"1996","journal-title":"Lab Invest"},{"issue":"2","key":"10.1016\/j.ajo.2025.09.025_bib0044","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1159\/000450958","article-title":"Development of a normative database for multifocal electroretinography in the context of a multicenter clinical trial","volume":"57","author":"Sim\u00e3o","year":"2017","journal-title":"Ophthalmic Res"},{"issue":"5","key":"10.1016\/j.ajo.2025.09.025_bib0045","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s00592-017-0970-5","article-title":"Cognitive impairment and dementia: a new emerging complication of type 2 diabetes\u2014the diabetologist's perspective","volume":"54","author":"Sim\u00f3","year":"2017","journal-title":"Acta Diabetol"}],"container-title":["American Journal of Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002939425005033?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002939425005033?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T01:20:25Z","timestamp":1778635225000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002939425005033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":45,"alternative-id":["S0002939425005033"],"URL":"https:\/\/doi.org\/10.1016\/j.ajo.2025.09.025","relation":{},"ISSN":["0002-9394"],"issn-type":[{"value":"0002-9394","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Longitudinal Neural and Microvascular Changes in Type 2 Diabetic Patients Without Retinopathy: A 2-Year Prospective Cohort Study","name":"articletitle","label":"Article Title"},{"value":"American Journal of Ophthalmology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajo.2025.09.025","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}