{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T02:28:48Z","timestamp":1786328928232,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"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\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Arterial hypertension is a major cause of systemic microvascular damage involving target organs such as the kidneys and retina. Because the retinal and renal microcirculations share common pathogenic mechanisms, retinal imaging may provide non-invasive biomarkers of hypertensive microvascular injury. This study investigated the association between the renal resistive index (RRI), systemic oxidative stress biomarkers, and retinal abnormalities in patients with essential hypertension. Retinal structural and microvascular parameters were evaluated using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Materials and Methods: In this cross-sectional exploratory study, 32 patients with essential hypertension (64 eyes) underwent comprehensive ophthalmic examination, OCT\/OCTA imaging, renal Doppler ultrasonography for RRI assessment, and evaluation of systemic oxidative stress biomarkers. Associations between renal, ocular, and biochemical parameters were analyzed. Results: No significant differences were observed in most global OCT\/OCTA parameters. However, higher RRI values were associated with localized macular thinning and reduced optic nerve head perfusion metrics. Patients with RRI values \u2265 the 75th percentile showed significantly increased hydrogen peroxide levels (p = 0.004) and reduced nitric oxide bioavailability (p = 0.033), together with thinning of selected inner macular sectors. A trend toward reduced optic nerve head flow index was also observed, suggesting early microvascular impairment that may not be detected by conventional global OCT measurements. Conclusions: These exploratory findings suggest a possible association among increased renal vascular resistance, oxidative stress, and localized retinal structural alterations in patients with essential hypertension. The coexistence of systemic redox imbalance and sectorial retinal changes supports the hypothesis of an eye\u2013kidney\u2013redox interplay and indicates that advanced retinal imaging, particularly detailed sectorial OCT analysis, may represent a complementary non-invasive tool for the early detection of subclinical microvascular damage. Larger prospective studies are warranted to validate these findings.<\/jats:p>","DOI":"10.3390\/medicina62081526","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:20:03Z","timestamp":1786324803000},"page":"1526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating Retinal Microvascular Changes Using OCT-Angiography: The Role of Oxidative Stress and Endothelial Dysfunction in Hypertensive Nephropathy"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1190-9733","authenticated-orcid":false,"given":"Mariaelena","family":"Malvasi","sequence":"first","affiliation":[{"name":"Department of Sense Organs, Faculty of Medicine and Dentistry, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1929-3044","authenticated-orcid":false,"given":"Luca","family":"Salomone","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Azzara","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1966-5945","authenticated-orcid":false,"given":"Vittoria","family":"Cammisotto","sequence":"additional","affiliation":[{"name":"Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6455-4828","authenticated-orcid":false,"given":"Valentina","family":"Castellani","sequence":"additional","affiliation":[{"name":"Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2265-7455","authenticated-orcid":false,"given":"Pasquale","family":"Pignatelli","sequence":"additional","affiliation":[{"name":"Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Paola","family":"Mitterhofer","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Department of Systems Medicine, Tor Vergata University of Rome, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7199-2954","authenticated-orcid":false,"given":"Silvia","family":"Lai","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8867-3979","authenticated-orcid":false,"given":"Francesca","family":"Tinti","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Department of Molecular Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6542-6235","authenticated-orcid":false,"given":"Lorenzo","family":"Loffredo","sequence":"additional","affiliation":[{"name":"Department of Medical and Cardiovascular Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5431-6399","authenticated-orcid":false,"given":"Elena","family":"Pacella","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Faculty of Medicine and Dentistry, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Salomone, L., Menichelli, D., Azzara, I., Damosso, P.M., Cammisotto, V., Castellani, V., Pignatelli, P., Pacella, E., Mitterhofer, A.P., and Tinti, F. (2026). Oxidative Stress and Endothelial Dysfunction in Patients with Hypertensive Nephropathy: Role of the Mediterranean Diet. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27031320"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1161\/01.HYP.34.4.655","article-title":"Rarefaction of skin capillaries in borderline essential hypertension suggests an early structural abnormality","volume":"34","author":"Antonios","year":"1999","journal-title":"Hypertension"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1007\/s11033-024-09425-5","article-title":"The role of oxidative stress in the pathogenesis of ocular diseases: An overview","volume":"51","author":"Zhang","year":"2024","journal-title":"Mol. Biol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"102967","DOI":"10.1016\/j.redox.2023.102967","article-title":"Oxidative stress in the eye and its role in the pathophysiology of ocular diseases","volume":"68","author":"Buonfiglio","year":"2023","journal-title":"Redox Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9208489","DOI":"10.1155\/2017\/9208489","article-title":"Retinal diseases associated with oxidative stress and the effects of a free radical scavenger (Edaravone)","volume":"2017","author":"Masuda","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"108255","DOI":"10.1016\/j.exer.2020.108255","article-title":"The role of reactive oxygen species in the pathogenesis and treatment of retinal diseases","volume":"201","author":"Chan","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1161\/ATVBAHA.116.308351","article-title":"NADPH Oxidase-2 and Atherothrombosis: Insight from Chronic Granulomatous Disease","volume":"37","author":"Violi","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kellner, R.L., Harris, A., Ciulla, L., Guidoboni, G., Verticchio Vercellin, A., Oddone, F., Carnevale, C., Zaid, M., Antman, G., and Kuvin, J.T. (2024). The Eye as the Window to the Heart: Optical Coherence Tomography Angiography Biomarkers as Indicators of Cardiovascular Disease. J. Clin. Med., 13.","DOI":"10.3390\/jcm13030829"},{"key":"ref_9","first-page":"e1","article-title":"Optical coherence tomography angiography changes in cardiovascular systemic diseases and risk factors: A Review","volume":"100","year":"2022","journal-title":"Acta Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1469-7580.2005.00395.x","article-title":"Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: A rationale based on homology between cerebral and retinal microvasculatures","volume":"206","author":"Patton","year":"2005","journal-title":"J. Anat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S0140-6736(07)60198-6","article-title":"The eye in hypertension","volume":"369","author":"Wong","year":"2007","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1177\/11206721251335060","article-title":"Implementing potential biomarkers for early detection of retinal changes in Parkinson\u2019s disease: Preliminary study on BDNF role","volume":"35","author":"Malvasi","year":"2025","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2017.11.003","article-title":"Optical coherence tomography angiography","volume":"64","author":"Spaide","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1093\/eurheartj\/ehy339","article-title":"2018 ESC\/ESH Guidelines for the management of arterial hypertension","volume":"39","author":"Williams","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1016\/j.kint.2023.10.018","article-title":"2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","volume":"105","author":"Stevens","year":"2024","journal-title":"Kidney Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"713","DOI":"10.5603\/KP.a2018.0071","article-title":"Oxidative stress and cardiovascular disease: New insights","volume":"76","author":"Pignatelli","year":"2018","journal-title":"Kardiol. Pol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1152\/physrev.00034.2023","article-title":"NADPH oxidases: Redox regulation of cell homeostasis and disease","volume":"105","author":"Lopes","year":"2025","journal-title":"Physiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12814","DOI":"10.1073\/pnas.221381098","article-title":"Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action","volume":"98","author":"Lauer","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bilha, I.M., Bilha, S.C., Akad, N., Covic, A., Branisteanu, D.C., Sandu, C.A., Donica, V.C., Bogdanici, C.M., Giusca, S.E., and Caruntu, I.D. (2026). Optical Coherence Tomography and Optical Coherence Tomography-Angiography Chronic Changes in End-Stage Renal Disease: A Systematic Review. Diagnostics, 16.","DOI":"10.3390\/diagnostics16030459"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1097\/IAE.0000000000004377","article-title":"Systematic Review and Meta-Analysis of Optical Coherence Tomography Measurements in Patients with Chronic Kidney Disease","volume":"45","author":"Bineshfar","year":"2025","journal-title":"Retina"},{"key":"ref_21","first-page":"199","article-title":"Renal resistive index and cardiovascular organ damage in hypertension","volume":"50","author":"Tedesco","year":"2007","journal-title":"Hypertension"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1038\/s41401-024-01295-8","article-title":"Endothelial dysfunction: Mechanisms and contribution to diseases","volume":"45","author":"Ajoolabady","year":"2024","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9580","DOI":"10.1038\/s41598-020-66736-w","article-title":"Systemic hypertension associated retinal microvascular changes can be detected with optical coherence tomography angiography","volume":"10","author":"Sun","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101292","DOI":"10.1016\/j.preteyeres.2024.101292","article-title":"Optical coherence tomography angiography of the retina and choroid in systemic diseases","volume":"103","author":"Chua","year":"2024","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103969","DOI":"10.1016\/j.mvr.2019.103969","article-title":"Use of optical coherence tomography angiography for assessment of microvascular changes in the macula and optic nerve head in hypertensive patients without hypertensive retinopathy","volume":"129","author":"Hua","year":"2020","journal-title":"Microvasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Verma, N., Khare, D., Poe, A.J., Amador, C., Ghiam, S., Fealy, A., Ebrahimi, S., Shadrokh, O., Song, X.Y., and Santiskulvong, C. (2023). MicroRNA and Protein Cargos of Human Limbal Epithelial Cell-Derived Exosomes and Their Regulatory Roles in Limbal Stromal Cells of Diabetic and Non-Diabetic Corneas. Cells, 12.","DOI":"10.3390\/cells12212524"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1212\/WNL.0000000000002774","article-title":"The APOSTEL recommendations for reporting quantitative optical coherence tomography studies","volume":"86","author":"Balk","year":"2016","journal-title":"Neurology"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Tewarie, P., Balk, L., Costello, F., Green, A., Martin, R., Schippling, S., and Petzold, A. (2012). The OSCAR-IB consensus criteria for retinal OCT quality assessment. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034823"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1039\/D5PM00097A","article-title":"Unlocking the potential of exosomes \u201cextracellular vesicles\u201d: Drug delivery advancements and therapeutics in ocular diseases","volume":"2","author":"Verma","year":"2025","journal-title":"RSC Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1007\/s00125-025-06558-5","article-title":"Oxidative stress-regulatory role of miR-10b-5p in the diabetic human cornea revealed through integrated multi-omics analysis","volume":"69","author":"Zha","year":"2026","journal-title":"Diabetologia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1097\/HJH.0b013e328365b29c","article-title":"Ultrasound Doppler renal resistive index: A useful tool for the management of the hypertensive patient","volume":"32","author":"Viazzi","year":"2014","journal-title":"J. Hypertens."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1093\/eurheartj\/ehr304","article-title":"Nitric oxide synthases: Regulation and function","volume":"33","author":"Sessa","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"42","DOI":"10.2174\/157016112798829823","article-title":"Hypertension and endothelial dysfunction: Therapeutic approach","volume":"10","author":"Ghiadoni","year":"2012","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7803","DOI":"10.21037\/qims-24-2113","article-title":"Quantitative analysis of macular and optic disc microvascular parameters in patients with immunoglobulin A nephropathy using optical coherence tomography angiography","volume":"15","author":"Qiu","year":"2025","journal-title":"Quant. Imaging Med. Surg."},{"key":"ref_35","first-page":"720","article-title":"Multimodal ophthalmic imaging in the search for the association between subretinal drusenoid deposits and systemic vascular comorbidity with metabolic dysregulation in age-related macular degeneration progression","volume":"177","author":"Malvasi","year":"2026","journal-title":"Clin. Ter."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1111\/aos.14392","article-title":"Microvascular damage assessed by optical coherence tomography angiography for glaucoma diagnosis: A systematic review of the most discriminative regions","volume":"98","author":"Bekkers","year":"2020","journal-title":"Acta Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"105513","DOI":"10.1016\/j.isci.2022.105513","article-title":"Spatio-temporal optical coherence tomography provides full thickness imaging of the chorioretinal complex","volume":"25","author":"Auksorius","year":"2022","journal-title":"iScience"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.preteyeres.2011.06.003","article-title":"Polarization sensitive optical coherence tomography in the human eye","volume":"30","author":"Pircher","year":"2011","journal-title":"Prog. Retin Eye Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Longo, R., Gusson, E., Lorenzetto, E., Polinelli, L., Malvasi, M., Panozzo, G., and Marchini, G. (2025). Retinal vascular density and vessel diameter in Sturge\u2013Weber syndrome assessed by OCT-angiography. J. Clin. Med., 14.","DOI":"10.3390\/jcm14197061"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e89173","DOI":"10.1172\/jci.insight.89173","article-title":"Chorioretinal thinning in chronic kidney disease links to inflammation and endothelial dysfunction","volume":"1","author":"Balmforth","year":"2016","journal-title":"JCI Insight"},{"key":"ref_41","first-page":"25158414221132825","article-title":"Choroidal thickness in patients with systemic arterial hypertension: A systematic review and meta-analysis","volume":"14","author":"Papathanasiou","year":"2022","journal-title":"Ther. Adv. Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Nassisi, M., Baghdasaryan, E., Tepelus, T., Asanad, S., Borrelli, E., and Sadda, S.R. (2018). Topographic distribution of choriocapillaris flow deficits in healthy eyes. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0207638"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1097\/HJH.0000000000001916","article-title":"Impact of hypertension on retinal capillary microvasculature using optical coherence tomographic angiography","volume":"37","author":"Chua","year":"2019","journal-title":"J. Hypertens."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.ophtha.2019.12.030","article-title":"Ganglion cell complex thickness and macular vessel density loss in primary open-angle glaucoma","volume":"127","author":"Hou","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1161\/CIRCULATIONAHA.105.602532","article-title":"Endothelial nitric oxide synthase in vascular disease: From marvel to menace","volume":"113","year":"2006","journal-title":"Circulation"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"98","DOI":"10.4103\/2008-322X.200162","article-title":"Optical coherence tomography angiography of the optic disc; an overview","volume":"12","author":"Akil","year":"2017","journal-title":"J. Ophthalmic Vis. Res."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/8\/1526\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:48:25Z","timestamp":1786326505000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/8\/1526"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,8]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["medicina62081526"],"URL":"https:\/\/doi.org\/10.3390\/medicina62081526","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,8]]}}}