{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T20:22:11Z","timestamp":1770754931539,"version":"3.50.0"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>(1) Background: Diabetic retinopathy and peripheral arterial disease co-occur through shared endothelial pathophysiology. Ankle-brachial index (ABI), the standard peripheral screening tool, demonstrates poor sensitivity (35%) in diabetic cohorts due to medial arterial calcification. We comparatively assessed the association of peak-systolic velocity of posterior\/anterior tibial artery ratio (PT:AT) versus that of traditional pressure-based (ABI) with foveal avascular zone (FAZ), a marker of retinal ischemia, and thus hypothesized that PT:AT would demonstrate stronger association with FAZ compared to ABI in our cohort. (2) Methods: Cross-sectional pilot study of 30 type 2 diabetes mellitus patients. We aimed to enhance the robustness of our results using five convergent statistical methods. (3) Results: PT:AT showed strong association with FAZ (r = 0.471, p = 0.0086, 95% CI [0.13, 0.71]), with convergent evidence across all five analytical methods. ABI showed no effect (r = \u22120.024, p = 0.901, 95% CI [\u22120.38, 0.34]). We showed that velocity-based metrics identify microvascular dysfunction, whereas the pressure-based ABI does not. The mediation analysis showed that the relation of PT:AT to FAZ is not significantly mediated by the resistivity index of ophthalmic artery. (4) Conclusions: In this pilot study, velocity-based tibial hemodynamics showed a stronger cross-sectional relationship with retinal microvascular damage compared to pressure-based ABI. These preliminary findings suggest PT:AT assessment may complement ABI screening in diabetic foot clinics to identify patients requiring intensive retinal surveillance. Multicenter validation is required before clinical implementation.<\/jats:p>","DOI":"10.3390\/diagnostics16040528","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T15:23:14Z","timestamp":1770736994000},"page":"528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tibial Artery Hemodynamics Predict Foveal Avascular Zone Enlargement in Type 2 Diabetes"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1279-540X","authenticated-orcid":false,"given":"Lidia","family":"Ladea","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Clinical Emergency Institute of Ophthalmology Prof. Dr. M. Olteanu, 010464 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5636-0019","authenticated-orcid":false,"given":"Valentin","family":"Dinu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Clinical Emergency Institute of Ophthalmology Prof. Dr. M. Olteanu, 010464 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3623-9813","authenticated-orcid":false,"given":"Ruxandra","family":"Coroleuca","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Ophthalmology Department, Bucharest Emergency University Hospital, 050098 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iulian","family":"Brezean","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"General Surgery Department, Cantacuzino Clinical Hospital, 011437 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0758-6779","authenticated-orcid":false,"given":"Eduard L.","family":"Catrina","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"General Surgery Department, Cantacuzino Clinical Hospital, 011437 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana E.","family":"Nedelcu","sequence":"additional","affiliation":[{"name":"Ponderas Academic Hospital, 014142 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihaela E.","family":"Vilcu","sequence":"additional","affiliation":[{"name":"General Surgery Department, Cantacuzino Clinical Hospital, 011437 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4396-8081","authenticated-orcid":false,"given":"Cristian V.","family":"Toma","sequence":"additional","affiliation":[{"name":"Department of Urology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Urology, Clinical Hospital Prof. Dr. Burghele, 010464 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2710-2280","authenticated-orcid":false,"given":"Adrian I.","family":"Georgevici","sequence":"additional","affiliation":[{"name":"Katholisches Klinikum, Ruhr University Bochum, 44791 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiana M. D.","family":"Dragosloveanu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Clinical Emergency Institute of Ophthalmology Prof. Dr. M. Olteanu, 010464 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.2337\/diabetes.54.6.1615","article-title":"The pathobiology of diabetic complications: A unifying mechanism","volume":"54","author":"Brownlee","year":"2005","journal-title":"Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cmet.2012.11.012","article-title":"Vascular complications of diabetes: Mechanisms of injury and protective factors","volume":"17","author":"King","year":"2013","journal-title":"Cell Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.2337\/dbi17-0044","article-title":"Microvascular dysfunction and hyperglycemia: A vicious cycle with widespread consequences","volume":"67","author":"Stehouwer","year":"2018","journal-title":"Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.2337\/dc20-1085","article-title":"Relationship between diabetic retinopathy stages and risk of major lower-extremity arterial disease in patients with type 2 diabetes","volume":"43","author":"Foussard","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.2337\/dc16-0588","article-title":"Microvascular and macrovascular disease and risk for major peripheral arterial disease in patients with type 2 diabetes","volume":"39","author":"Mohammedi","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1016\/j.ophtha.2019.06.016","article-title":"OCT angiography metrics predict progression of diabetic retinopathy and development of diabetic macular edema: A prospective study","volume":"126","author":"Sun","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ophtha.2016.10.008","article-title":"Quantification of diabetic macular ischemia using optical coherence tomography angiography and its relationship with visual acuity","volume":"124","author":"Samara","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103799","DOI":"10.1016\/j.pdpdt.2023.103799","article-title":"Optical coherence tomography angiography metrics in diabetes: Focusing on diabetic retinopathy and carotid atherosclerosis","volume":"42","author":"Yang","year":"2023","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_9","first-page":"376","article-title":"Retinal vascular abnormalities predict progression of peripheral arterial disease: The atherosclerosis risk in communities (ARIC) study","volume":"127","author":"Yang","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12933-020-01023-6","article-title":"The relationship between carotid disease and retinopathy in diabetes: A systematic review","volume":"19","author":"Drinkwater","year":"2020","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Pappelis, K., Risi-Koziona, A., Agapitou, C., Korakas, E., Thymis, J., Pavlidis, G., Lampsas, S., Kountouri, A., Pliouta, L., and Georgalas, I. (2024). Retinal microvascular changes in association with endothelial glycocalyx damage and arterial stiffness in patients with retinal vein occlusion: A cross-sectional study. Biomedicines, 12.","DOI":"10.3390\/biomedicines12112564"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.jacc.2021.06.049","article-title":"Medial arterial calcification: JACC state-of-the-art review","volume":"78","author":"Lanzer","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_13","first-page":"e726","article-title":"2016 AHA\/ACC guideline on the management of patients with lower extremity peripheral artery disease","volume":"135","author":"Gornik","year":"2017","journal-title":"Circulation"},{"key":"ref_14","first-page":"2497","article-title":"2024 ACC\/AHA\/AACVPR\/APMA\/ABC\/SCAI\/SVM\/SVN\/SVS\/SIR\/VESS guideline for the management of lower extremity peripheral artery disease","volume":"83","author":"Gornik","year":"2024","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.jvs.2015.08.112","article-title":"Characterization of tibial velocities by duplex ultrasound in severe peripheral arterial disease and controls","volume":"63","author":"Crawford","year":"2016","journal-title":"J. Vasc. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Boulton, A.J.M., Connor, H., and Cavanagh, P.R. (2000). The Foot in Diabetes, John Wiley & Sons. [3rd ed.].","DOI":"10.1002\/0470846399"},{"key":"ref_17","first-page":"68","article-title":"Screening for lower extremity arterial disease","volume":"33","author":"Moneta","year":"2020","journal-title":"Semin. Vasc. Surg."},{"key":"ref_18","unstructured":"American Diabetes Association Professional Practice Committee (2024). Standards of care in diabetes\u20142025. Diabetes Care, 48, S27\u2013S49."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2890","DOI":"10.1161\/CIR.0b013e318276fbcb","article-title":"Measurement and interpretation of the ankle-brachial index: A scientific statement from the american heart association","volume":"126","author":"Aboyans","year":"2012","journal-title":"Circulation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B (Methodol.)"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/00031305.2019.1583913","article-title":"Moving to a world beyond \u201cp < 0.05\u201d","volume":"73","author":"Wasserstein","year":"2019","journal-title":"Am. Stat."},{"key":"ref_22","unstructured":"R Core Team (2024). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1097\/IAE.0000000000000849","article-title":"Enlargement of foveal avascular zone in diabetic eyes evaluated by en face optical coherence tomography angiography","volume":"35","author":"Takase","year":"2015","journal-title":"Retina"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1167\/iovs.62.1.9","article-title":"Diabetic macular ischemia: Influence of optical coherence tomography angiography parameters on changes in functional outcomes over one year","volume":"62","author":"Tsai","year":"2021","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1038\/s41598-018-37969-7","article-title":"Correlation of systemic arterial stiffness with changes in retinal and choroidal microvasculature in type 2 diabetes","volume":"9","author":"Kim","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11458","DOI":"10.1038\/s41598-021-90900-5","article-title":"Retinal and choriocapillaris perfusion are associated with ankle-brachial-pressure-index and fontaine stage in peripheral arterial disease","volume":"11","author":"Wintergerst","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1177\/1358863X231210866","article-title":"Role of noninvasive ocular imaging as a biomarker in peripheral artery disease (PAD): A systematic review","volume":"29","author":"Senthil","year":"2024","journal-title":"Vasc. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s11883-020-0834-2","article-title":"Association between caliber of retinal vessels and cardiovascular disease: A systematic review and meta-analysis","volume":"22","author":"Guo","year":"2020","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3922398","DOI":"10.1155\/2022\/3922398","article-title":"Diabetic retinopathy and the risk of diabetic kidney disease: A systematic review and meta-analysis","volume":"2022","author":"Gupta","year":"2022","journal-title":"Int. J. Nephrol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1210\/endrev\/bnaa025","article-title":"Microvascular dysfunction in diabetes mellitus and cardiometabolic disease","volume":"42","author":"Horton","year":"2020","journal-title":"Endocr. Rev."},{"key":"ref_31","first-page":"108348","article-title":"Diabetes mellitus: The linkage between oxidative stress, inflammation, hypercoagulability and vascular complications","volume":"37","author":"Domingueti","year":"2023","journal-title":"J. Diabetes Its Complicat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1161\/ATVBAHA.118.310839","article-title":"Endothelial glycocalyx as a shield against diabetic vascular complications","volume":"38","author":"Flamion","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"480","DOI":"10.2337\/diabetes.55.02.06.db05-1103","article-title":"Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo","volume":"55","author":"Nieuwdorp","year":"2006","journal-title":"Diabetes"},{"key":"ref_34","first-page":"823","article-title":"Measuring endothelial glycocalyx dimensions in humans: A potential novel tool to monitor vascular vulnerability","volume":"100","author":"Nieuwdorp","year":"2006","journal-title":"J. Appl. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.jvs.2014.02.008","article-title":"Ankle-brachial index, toe-brachial index, and cardiovascular mortality in persons with and without diabetes mellitus","volume":"60","author":"Hyun","year":"2014","journal-title":"J. Vasc. Surg."},{"key":"ref_36","first-page":"602","article-title":"Ankle-brachial index in diabetic patients: Beware of calcified vessels","volume":"27","author":"Abouhamda","year":"2019","journal-title":"Vascular"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13098-024-01291-2","article-title":"Toe brachial index and not ankle brachial index is appropriate in initial evaluation of peripheral arterial disease in type 2 diabetes","volume":"16","author":"Singhania","year":"2024","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_38","first-page":"723","article-title":"Interpretation of peripheral arterial and venous Doppler waveforms: A consensus statement","volume":"35","author":"Kim","year":"2020","journal-title":"Phlebology"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/4\/528\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T15:34:53Z","timestamp":1770737693000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/4\/528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,10]]},"references-count":38,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["diagnostics16040528"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16040528","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,10]]}}}