{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:40:26Z","timestamp":1787755226601,"version":"build-2784847793"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/100019187","name":"HORIZON EUROPE Widening Participation and Strengthening the European Research Area","doi-asserted-by":"publisher","award":["PNRR-MAD-2022-12376008"],"award-info":[{"award-number":["PNRR-MAD-2022-12376008"]}],"id":[{"id":"10.13039\/100019187","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ophthalmol Ther"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1007\/s40123-026-01458-2","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T08:18:10Z","timestamp":1786177090000},"page":"3101-3115","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Macular Pigment Changes in Patients with Diabetes Mellitus and Without Diabetic Retinopathy"],"prefix":"10.1007","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct06582472","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4715-8414","authenticated-orcid":false,"given":"Alessandro","family":"Arrigo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Aragona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianpaolo","family":"Zerbini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Aragona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Bandello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"issue":"1","key":"1458_CR1","doi-asserted-by":"publisher","first-page":"107","DOI":"10.2991\/jegh.k.191028.001","volume":"10","author":"MAB Khan","year":"2020","unstructured":"Khan MAB, et al. Epidemiology of type 2 diabetes\u2014global burden of disease and forecasted trends. J Epidemiol Glob Health. 2020;10(1):107\u201311.","journal-title":"J Epidemiol Glob Health"},{"issue":"10397","key":"1458_CR2","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/S0140-6736(23)01301-6","volume":"402","author":"GBD 2021 Diabetes Collaborators","year":"2023","unstructured":"GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023;402(10397):203\u201334 (Erratum in: Lancet 2023;402(10408):1132. Erratum in: Lancet. 2025;405(10474):202).","journal-title":"Lancet"},{"issue":"11","key":"1458_CR3","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1016\/j.ophtha.2021.04.027","volume":"128","author":"ZL Teo","year":"2021","unstructured":"Teo ZL, et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis. Ophthalmology. 2021;128(11):1580\u201391.","journal-title":"Ophthalmology"},{"issue":"5","key":"1458_CR4","doi-asserted-by":"publisher","first-page":"917","DOI":"10.2337\/dci18-0007","volume":"41","author":"American Diabetes Association","year":"2018","unstructured":"American Diabetes Association. Economic costs of diabetes in the U.S. in 2017. Diabetes Care. 2018;41(5):917\u201328.","journal-title":"Diabetes Care"},{"issue":"1","key":"1458_CR5","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s10384-023-01031-5","volume":"68","author":"H Morita","year":"2024","unstructured":"Morita H, et al. Measuring macular pigment optical density using reflective images of confocal scanning laser system. Jpn J Ophthalmol. 2024;68(1):19\u201325.","journal-title":"Jpn J Ophthalmol"},{"key":"1458_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2024.101326","volume":"105","author":"RL Leit\u00e3o Guerra","year":"2025","unstructured":"Leit\u00e3o Guerra RL, et al. Exploring retinal conditions through blue light reflectance imaging. Prog Retin Eye Res. 2025;105:101326.","journal-title":"Prog Retin Eye Res"},{"issue":"8","key":"1458_CR7","doi-asserted-by":"publisher","first-page":"4852","DOI":"10.1167\/iovs.12-9713","volume":"53","author":"M Zeimer","year":"2012","unstructured":"Zeimer M, et al. Profiles of macular pigment optical density and their changes following supplemental lutein and zeaxanthin: new results from the LUNA study. Invest Ophthalmol Vis Sci. 2012;53(8):4852\u20139.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1458_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2024.110043","volume":"247","author":"B Li","year":"2024","unstructured":"Li B, et al. Imaging macular carotenoids and their related proteins in the human retina with confocal resonance Raman and fluorescence microscopy. Exp Eye Res. 2024;247:110043.","journal-title":"Exp Eye Res"},{"key":"1458_CR9","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.exer.2017.12.015","volume":"168","author":"A Obana","year":"2018","unstructured":"Obana A, et al. Reliability of a two-wavelength autofluorescence technique by Heidelberg Spectralis to measure macular pigment optical density in Asian subjects. Exp Eye Res. 2018;168:100\u20136.","journal-title":"Exp Eye Res"},{"issue":"5","key":"1458_CR10","doi-asserted-by":"publisher","first-page":"2941","DOI":"10.1167\/iovs.13-13568","volume":"55","author":"C Creuzot-Garcher","year":"2014","unstructured":"Creuzot-Garcher C, et al. Comparison of two methods to measure macular pigment optical density in healthy subjects. Invest Ophthalmol Vis Sci. 2014;55(5):2941\u20136.","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"11","key":"1458_CR11","doi-asserted-by":"publisher","first-page":"5840","DOI":"10.1167\/iovs.09-4695","volume":"51","author":"VC Lima","year":"2010","unstructured":"Lima VC, et al. Macular pigment optical density measured by dual-wavelength autofluorescence imaging in diabetic and nondiabetic patients: a comparative study. Invest Ophthalmol Vis Sci. 2010;51(11):5840\u20135.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1458_CR12","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.biopha.2017.04.057","volume":"91","author":"A Roohbakhsh","year":"2017","unstructured":"Roohbakhsh A, Karimi G, Iranshahi M. Carotenoids in the treatment of diabetes mellitus and its complications: a mechanistic review. Biomed Pharmacother. 2017;91:31\u201342.","journal-title":"Biomed Pharmacother"},{"issue":"9","key":"1458_CR13","doi-asserted-by":"publisher","first-page":"1808","DOI":"10.1097\/IAE.0000000000000551","volume":"35","author":"G Scanlon","year":"2015","unstructured":"Scanlon G, et al. Macular pigment optical density is lower in type 2 diabetes, compared with type 1 diabetes and normal controls. Retina. 2015;35(9):1808\u201316.","journal-title":"Retina"},{"issue":"7","key":"1458_CR14","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin J, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676\u201382.","journal-title":"Nat Methods"},{"issue":"6","key":"1458_CR15","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1364\/JOSAA.18.001212","volume":"18","author":"FC Delori","year":"2001","unstructured":"Delori FC, et al. Macular pigment density measured by autofluorescence spectrometry: comparison with reflectometry and heterochromatic flicker photometry. J Opt Soc Am A Opt Image Sci Vis. 2001;18(6):1212\u201330.","journal-title":"J Opt Soc Am A Opt Image Sci Vis"},{"key":"1458_CR16","doi-asserted-by":"publisher","first-page":"3152","DOI":"10.1167\/iovs.09-3608","volume":"51","author":"R Canovas","year":"2010","unstructured":"Canovas R, et al. Comparison between macular pigment optical density measurements using two-wavelength autofluorescence and heterochromatic flicker photometry techniques. Invest Ophthalmol Vis Sci. 2010;51:3152\u20136.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1458_CR17","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1007\/s00417-006-0289-3","volume":"244","author":"M Trieschmann","year":"2006","unstructured":"Trieschmann M, et al. Macular pigment density measurement in autofluorescence imaging: comparison of one-and two-wavelength methods. Graefes Arch Clin Exp Ophthalmol. 2006;244:1565\u201374.","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"issue":"2","key":"1458_CR18","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1111\/aos.13570","volume":"96","author":"EEB De Clerck","year":"2018","unstructured":"De Clerck EEB, et al. Macular thinning in prediabetes or type 2 diabetes without diabetic retinopathy: the Maastricht Study. Acta Ophthalmol. 2018;96(2):174\u201382.","journal-title":"Acta Ophthalmol"},{"issue":"1","key":"1458_CR19","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1080\/13813455.2017.1361450","volume":"124","author":"M \u015eahin","year":"2018","unstructured":"\u015eahin M, et al. Early detection of macular and peripapillary changes with Spectralis optical coherence tomography in patients with prediabetes. Arch Physiol Biochem. 2018;124(1):75\u20139.","journal-title":"Arch Physiol Biochem"},{"issue":"12","key":"1458_CR20","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1136\/bjophthalmol-2020-317414","volume":"105","author":"J Huru","year":"2021","unstructured":"Huru J, et al. Prediabetes influences the structure of the macula: thinning of the macula in the Northern Finland Birth Cohort. Br J Ophthalmol. 2021;105(12):1731\u20137.","journal-title":"Br J Ophthalmol"},{"issue":"11","key":"1458_CR21","doi-asserted-by":"publisher","first-page":"2364","DOI":"10.1097\/IAE.0000000000000882","volume":"35","author":"TE de Carlo","year":"2015","unstructured":"de Carlo TE, et al. Detection of microvascular changes in eyes of patients with diabetes but not clinical diabetic retinopathy using optical coherence tomography angiography. Retina. 2015;35(11):2364\u201370.","journal-title":"Retina"},{"issue":"3","key":"1458_CR22","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.3.50","volume":"61","author":"Y Dai","year":"2020","unstructured":"Dai Y, et al. Microvascular changes in the choriocapillaris of diabetic patients without retinopathy investigated by swept-source OCT angiography. Invest Ophthalmol Vis Sci. 2020;61(3):50.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1458_CR23","doi-asserted-by":"publisher","first-page":"8676091","DOI":"10.1155\/2017\/8676091","volume":"2017","author":"MM Goudot","year":"2017","unstructured":"Goudot MM, et al. Parafoveal OCT angiography features in diabetic patients without clinical diabetic retinopathy: a qualitative and quantitative analysis. J Ophthalmol. 2017;2017:8676091.","journal-title":"J Ophthalmol"},{"issue":"3","key":"1458_CR24","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.66.3.53","volume":"66","author":"H Albertos-Arranz","year":"2025","unstructured":"Albertos-Arranz H, et al. Neuronal degeneration and glial activation in the absence of vascular changes in human retinas of patients with diabetes. Invest Ophthalmol Vis Sci. 2025;66(3):53.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1458_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2022.101111","volume":"92","author":"A Arrigo","year":"2023","unstructured":"Arrigo A, et al. Quantitative approaches in multimodal fundus imaging: state of the art and future perspectives. Prog Retin Eye Res. 2023;92:101111.","journal-title":"Prog Retin Eye Res"},{"key":"1458_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2025.101357","volume":"106","author":"A Arrigo","year":"2025","unstructured":"Arrigo A, et al. M\u00fcller cells trophism and pathology as the next therapeutic targets for retinal diseases. Prog Retin Eye Res. 2025;106:101357.","journal-title":"Prog Retin Eye Res"},{"issue":"1","key":"1458_CR27","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1080\/07853890.2022.2095010","volume":"54","author":"Q Chai","year":"2022","unstructured":"Chai Q, et al. Structural and functional retinal changes in patients with type 2 diabetes without diabetic retinopathy. Ann Med. 2022;54(1):1816\u201325.","journal-title":"Ann Med"},{"issue":"1","key":"1458_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-68552-y","volume":"14","author":"J Shah","year":"2024","unstructured":"Shah J, et al. Evaluation of thickness of individual macular retinal layers in diabetic eyes from optical coherence tomography. Sci Rep. 2024;14(1):17909.","journal-title":"Sci Rep"},{"issue":"1","key":"1458_CR29","volume":"17","author":"P Ganne","year":"2025","unstructured":"Ganne P, et al. Modular architecture of retinal layers in diabetic patients without retinopathy. Cureus. 2025;17(1):e77657.","journal-title":"Cureus"},{"issue":"8","key":"1458_CR30","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.8.46","volume":"61","author":"D Kar","year":"2020","unstructured":"Kar D, et al. Local abundance of macular xanthophyll pigment is associated with rod- and cone-mediated vision in aging and age-related macular degeneration. Invest Ophthalmol Vis Sci. 2020;61(8):46.","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"13","key":"1458_CR31","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241310702","volume":"24","author":"W Grudzinski","year":"2023","unstructured":"Grudzinski W, et al. Physiological significance of the heterogeneous distribution of zeaxanthin and lutein in the retina of the human eye. Int J Mol Sci. 2023;24(13):10702.","journal-title":"Int J Mol Sci"},{"issue":"2","key":"1458_CR32","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1017\/S095442241900012X","volume":"32","author":"G Scanlon","year":"2019","unstructured":"Scanlon G, et al. A review of the putative causal mechanisms associated with lower macular pigment in diabetes mellitus. Nutr Res Rev. 2019;32(2):247\u201364.","journal-title":"Nutr Res Rev"},{"issue":"7","key":"1458_CR33","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1017\/S0007114510004721","volume":"105","author":"ML Kirby","year":"2011","unstructured":"Kirby ML, et al. Changes in macular pigment optical density and serum concentrations of lutein and zeaxanthin in response to weight loss. Br J Nutr. 2011;105(7):1036\u201346.","journal-title":"Br J Nutr"},{"key":"1458_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2021.105932","volume":"133","author":"N Wang","year":"2021","unstructured":"Wang N, et al. Lutein attenuates excessive lipid accumulation in differentiated 3T3-L1 cells and abdominal adipose tissue of rats by the SIRT1-mediated pathway. Int J Biochem Cell Biol. 2021;133:105932.","journal-title":"Int J Biochem Cell Biol"},{"issue":"8","key":"1458_CR35","doi-asserted-by":"publisher","first-page":"2475","DOI":"10.1007\/s00394-016-1283-0","volume":"56","author":"G Sharavana","year":"2017","unstructured":"Sharavana G, et al. Lutein attenuates oxidative stress markers and ameliorates glucose homeostasis through polyol pathway in heart and kidney of STZ-induced hyperglycemic rat model. Eur J Nutr. 2017;56(8):2475\u201385.","journal-title":"Eur J Nutr"},{"issue":"4","key":"1458_CR36","doi-asserted-by":"crossref","DOI":"10.4081\/ejh.2015.2576","volume":"58","author":"AC Croce","year":"2014","unstructured":"Croce AC, Bottiroli G. Autofluorescence spectroscopy and imaging: a tool for biomedical research and diagnosis. Eur J Histochem. 2014;58(4):2461.","journal-title":"Eur J Histochem"},{"issue":"11","key":"1458_CR37","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.1097\/IAE.0000000000000205","volume":"34","author":"U De Benedetto","year":"2014","unstructured":"De Benedetto U, et al. Macular dysfunction is common in both type 1 and type 2 diabetic patients without macular edema. Retina. 2014;34(11):2171\u20137.","journal-title":"Retina"},{"key":"1458_CR38","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.ajo.2023.04.005","volume":"253","author":"F Bandello","year":"2023","unstructured":"Bandello F, et al. Imaging biomarkers of mesopic and dark-adapted macular functions in eyes with treatment-na\u00efve mild diabetic retinopathy. Am J Ophthalmol. 2023;253:56\u201364.","journal-title":"Am J Ophthalmol"}],"container-title":["Ophthalmology and Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40123-026-01458-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40123-026-01458-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40123-026-01458-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T13:39:41Z","timestamp":1787751581000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40123-026-01458-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,8]]},"references-count":38,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["1458"],"URL":"https:\/\/doi.org\/10.1007\/s40123-026-01458-2","relation":{},"ISSN":["2193-8245","2193-6528"],"issn-type":[{"value":"2193-8245","type":"print"},{"value":"2193-6528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,8]]},"assertion":[{"value":"20 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Alessandro Arrigo, Emanuela Aragona, Gianpaolo Zerbini MD, Pasquale Aragona MD, PhD, and Francesco Bandello declare no conflict of interest.","order":1,"name":"Ethics","label":"Conflict of Interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All the patients were recruited at the Ophthalmology Unit of IRCCS San Raffaele Scientific Institute in Milan and signed an informed consent before the inclusion. IRCCS San Raffaele Scientific Institute is the ethics committee that approved the study. The entire study was performed in accordance with good clinical practice and Helsinki Declaration, receiving the approval by the local ethical committee (protocol ID: PNRR-MAD-2022\u201312376008; ClinicalTrials.gov Identifier: NCT06582472). We thank the ethical committee of the IRCCS San Raffaele Scientific Institute in Milan, Italy.","order":2,"name":"Ethics","label":"Ethical Approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}