{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T23:36:15Z","timestamp":1790120175786,"version":"4.0.1"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum Bonn"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This study aimed to determine whether optical coherence tomography (OCT) with enhanced axial resolution improves structural characterization of the disorganization of the retinal inner layers (DRIL) in diabetic retinal disease (DRD) and its association with functional and vascular alterations. In this prospective cross-sectional study, 55 diabetic patients, 27 with DRIL (age: 57.1\u2009\u00b1\u200914.6 years) and 28 eyes without DRIL with diabetes mellitus (DM) type I\/II (age: 58.2\u2009\u00b1\u200913.0 years), were examined with conventional spectral-domain OCT (SD-OCT), High-Resolution (High-Res)\u00a0OCT, OCT angiography (OCTA), and microperimetry. DRIL areas were significantly smaller on High-Res OCT compared to SD-OCT (mean\u2009\u00b1\u2009standard deviation, 0.3\u2009\u00b1\u20090.3 vs. 1.3\u2009\u00b1\u20091.2\u00a0mm\n                    <jats:sup>2<\/jats:sup>\n                    ,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). OCTA analyses demonstrated persistent group differences in superficial and deep vessel density and FAZ circularity between DRIL eyes and eyes without DRIL, even after adjustment for clinical diabetic retinopathy severity score (DRSS, all\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Within DRIL eyes, intra-eye analysis revealed a stepwise reduction in retinal sensitivity from areas with DRIL detected on both OCT modalities (Zone I: 13.1\u2009\u00b1\u20091.3 dB) to areas with DRIL only on SD-OCT (Zone II: 20.6\u2009\u00b1\u20090.8 dB) and to unaffected retina (Zone III: 23.1\u2009\u00b1\u20090.7 dB, overall\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). OCT with enhanced axial resolution refines DRIL detection, aligning more precisely with localized functional and vascular impairment.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-34931-2","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T14:25:57Z","timestamp":1767795957000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Increased axial resolution OCT improves structure-function correlation of the disorganization of the retinal inner layers in diabetic retinal disease"],"prefix":"10.1038","volume":"16","author":[{"given":"Katharina","family":"Wall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilith P.","family":"Arend","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"von der Emde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Sophia","family":"Jauch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank G.","family":"Holz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Sa\u00dfmannshausen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"34931_CR1","doi-asserted-by":"publisher","first-page":"428","DOI":"10.4103\/0301-4738.100542","volume":"60","author":"Y Zheng","year":"2012","unstructured":"Zheng, Y., He, M. & Congdon, N. The worldwide epidemic of diabetic retinopathy. Indian J. Ophthalmol. 60, 428\u2013431 (2012).","journal-title":"Indian J. Ophthalmol."},{"key":"34931_CR2","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/s41574-020-00451-4","volume":"17","author":"DA Antonetti","year":"2021","unstructured":"Antonetti, D. A., Silva, P. S. & Stitt, A. W. Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nat. Rev. Endocrinol. 17, 195\u2013206 (2021).","journal-title":"Nat. Rev. Endocrinol."},{"key":"34931_CR3","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1111\/aos.12812","volume":"94","author":"S Vujosevic","year":"2016","unstructured":"Vujosevic, S. et al. Proteome analysis of retinal glia cells-related inflammatory cytokines in the aqueous humour of diabetic patients. Acta Ophthalmol. 94, 56\u201364 (2016).","journal-title":"Acta Ophthalmol."},{"key":"34931_CR4","doi-asserted-by":"crossref","unstructured":"Altmann, C. & Schmidt, M. H. H. The role of microglia in diabetic retinopathy: inflammation, microvasculature defects and neurodegeneration. Int. J. Mol. Sci. 19, 586 (2018).","DOI":"10.3390\/ijms19010110"},{"key":"34931_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00417-016-3548-y","volume":"255","author":"TW Gardner","year":"2017","unstructured":"Gardner, T. W. & Davila, J. R. The neurovascular unit and the pathophysiologic basis of diabetic retinopathy. Graefe\u2019s Arch. Clin. Exp. Ophthalmol.  255, 1\u20136 (2017).","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"34931_CR6","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/s41574-024-01053-0","volume":"21","author":"DA Antonetti","year":"2025","unstructured":"Antonetti, D. A., Silva, P. S. & Stitt, A. W. Publisher Correction: Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nat. Rev. Endocrinol. 21, 62 (2025).","journal-title":"Nat. Rev. Endocrinol."},{"key":"34931_CR7","doi-asserted-by":"crossref","unstructured":"R\u00fcbsam, A., Parikh, S. & Fort, P. E. Role of inflammation in diabetic retinopathy. Int. J. Mol. Sci. 19, 256 (2018).","DOI":"10.3390\/ijms19040942"},{"key":"34931_CR8","doi-asserted-by":"publisher","first-page":"E006","DOI":"10.1017\/S0952523821000031","volume":"38","author":"X Li","year":"2021","unstructured":"Li, X. et al. Retinal microglia polarization in diabetic retinopathy. Vis. Neurosci. 38, E006 (2021).","journal-title":"Vis. Neurosci."},{"key":"34931_CR9","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1136\/bjophthalmol-2021-319587","volume":"107","author":"SK Szeto","year":"2023","unstructured":"Szeto, S. K. et al. OCT-based biomarkers for predicting treatment response in eyes with centre-involved diabetic macular oedema treated with anti-VEGF injections: a real-life retina clinic-based study. Br. J. Ophthalmol. 107, 525\u2013533 (2023).","journal-title":"Br. J. Ophthalmol."},{"key":"34931_CR10","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.ophtha.2006.06.052","volume":"114","author":"DJ Browning","year":"2007","unstructured":"Browning, D. J. et al. Relationship between optical coherence tomography-measured central retinal thickness and visual acuity in diabetic macular edema. Ophthalmology 114, 525\u2013536 (2007).","journal-title":"Ophthalmology"},{"key":"34931_CR11","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1001\/jamaophthalmol.2019.1963","volume":"137","author":"NM Bressler","year":"2019","unstructured":"Bressler, N. M. et al. Association between change in visual acuity and change in central subfield thickness during treatment of diabetic macular edema in participants randomized to aflibercept, bevacizumab, or ranibizumab: a post hoc analysis of the protocol T randomized clinical trial. JAMA Ophthalmol. 137, 977\u2013985 (2019).","journal-title":"JAMA Ophthalmol."},{"key":"34931_CR12","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.ophtha.2008.12.039","volume":"116","author":"M Bolz","year":"2009","unstructured":"Bolz, M. et al. Optical coherence tomographic hyperreflective foci: a morphologic sign of lipid extravasation in diabetic macular edema. Ophthalmology 116, 914\u2013920 (2009).","journal-title":"Ophthalmology"},{"key":"34931_CR13","doi-asserted-by":"publisher","first-page":"e801","DOI":"10.1111\/aos.14390","volume":"98","author":"C Busch","year":"2020","unstructured":"Busch, C. et al. Baseline predictors for visual acuity loss during observation in diabetic macular oedema with good baseline visual acuity. Acta Ophthalmol. 98, e801\u2013e806 (2020).","journal-title":"Acta Ophthalmol."},{"key":"34931_CR14","doi-asserted-by":"publisher","first-page":"3183","DOI":"10.2147\/OPTH.S320948","volume":"15","author":"P Udaondo","year":"2021","unstructured":"Udaondo, P. et al. Challenges in diabetic macular edema management: an expert consensus report. Clin. Ophthalmol. (Auckland N Z). 15, 3183\u20133195 (2021).","journal-title":"Clin. Ophthalmol. (Auckland N Z)"},{"key":"34931_CR15","doi-asserted-by":"publisher","first-page":"251584142095051","DOI":"10.1177\/2515841420950513","volume":"12","author":"A Markan","year":"2020","unstructured":"Markan, A. et al. Novel imaging biomarkers in diabetic retinopathy and diabetic macular edema. Therapeutic Adv. Ophthalmol. 12, 2515841420950513 (2020).","journal-title":"Therapeutic Adv. Ophthalmol."},{"key":"34931_CR16","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.2337\/db14-0782","volume":"64","author":"JK Sun","year":"2015","unstructured":"Sun, J. K. et al. Neural retinal disorganization as a robust marker of visual acuity in current and resolved diabetic macular edema. Diabetes 64, 2560\u20132570 (2015).","journal-title":"Diabetes"},{"key":"34931_CR17","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1001\/jamaophthalmol.2015.0972","volume":"133","author":"SH Radwan","year":"2015","unstructured":"Radwan, S. H. et al. Association of disorganization of retinal inner layers with vision after resolution of center-involved diabetic macular edema. JAMA Ophthalmol. 133, 820\u2013825 (2015).","journal-title":"JAMA Ophthalmol."},{"key":"34931_CR18","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1001\/jamaophthalmol.2018.4484","volume":"137","author":"AS Babiuch","year":"2019","unstructured":"Babiuch, A. S. et al. Association of disorganization of retinal inner layers with visual acuity response to anti-vascular endothelial growth factor therapy for macular edema secondary to retinal vein occlusion. JAMA Ophthalmol. 137, 38\u201346 (2019).","journal-title":"JAMA Ophthalmol."},{"key":"34931_CR19","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1001\/jamaophthalmol.2014.2350","volume":"132","author":"JK Sun","year":"2014","unstructured":"Sun, J. K. et al. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. JAMA Ophthalmol. 132, 1309\u20131316 (2014).","journal-title":"JAMA Ophthalmol."},{"key":"34931_CR20","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1167\/iovs.10-6293","volume":"52","author":"AJ Barber","year":"2011","unstructured":"Barber, A. J., Gardner, T. W. & Abcouwer, S. F. The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy. Investig. Ophthalmol. Vis. Sci. 52, 1156\u20131163 (2011).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"34931_CR21","doi-asserted-by":"publisher","first-page":"5481","DOI":"10.1167\/iovs.18-24955","volume":"59","author":"KA Joltikov","year":"2018","unstructured":"Joltikov, K. A. et al. Disorganization of retinal inner layers (DRIL) and neuroretinal dysfunction in early diabetic retinopathy. Investig. Ophthalmol. Vis. Sci. 59, 5481\u20135486 (2018).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"34931_CR22","doi-asserted-by":"crossref","unstructured":"Midena, E. et al. The disorganization of retinal inner layers is correlated to m\u00fcller cells impairment in diabetic macular edema: an imaging and omics study. Int. J. Mol. Sci. 24, 569 (2023).","DOI":"10.3390\/ijms24119607"},{"key":"34931_CR23","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1097\/IAE.0000000000002179","volume":"39","author":"AC Onishi","year":"2019","unstructured":"Onishi, A. C., Ashraf, M., Soetikno, B. T. & Fawzi, A. A. Multilevel ischemia in disorganization of the retinal inner layers on projection-resolved optical coherence tomography angiography. Retina (Philadelphia Pa). 39, 1588\u20131594 (2019).","journal-title":"Retina (Philadelphia Pa)"},{"key":"34931_CR24","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1097\/IAE.0000000000002721","volume":"40","author":"ASH Tsai","year":"2020","unstructured":"Tsai, A. S. H. et al. Diabetic macular ischemia: correlation of retinal vasculature changes by optical coherence tomography angiography and functional deficit. Retina (Philadelphia Pa). 40, 2184\u20132190 (2020).","journal-title":"Retina (Philadelphia Pa)"},{"key":"34931_CR25","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ajo.2023.09.007","volume":"257","author":"WS Tsai","year":"2023","unstructured":"Tsai, W. S. et al. Topographic correlation of microperimetry with structural characteristics in diabetic macular ischemia. Am. J. Ophthalmol. 257, 25\u201333 (2023).","journal-title":"Am. J. Ophthalmol."},{"key":"34931_CR26","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.oret.2022.07.010","volume":"7","author":"WS Tsai","year":"2023","unstructured":"Tsai, W. S. et al. Characterization of the structural and functional alteration in eyes with diabetic macular ischemia. Ophthalmol. Retina. 7, 142\u2013152 (2023).","journal-title":"Ophthalmol. Retina"},{"key":"34931_CR27","doi-asserted-by":"publisher","first-page":"100519","DOI":"10.1016\/j.xops.2024.100519","volume":"4","author":"AR Glassman","year":"2024","unstructured":"Glassman, A. R. et al. Visual function measurements in eyes with diabetic retinopathy: an expert opinion on available measures. Ophthalmol. Sci. 4, 100519 (2024).","journal-title":"Ophthalmol. Sci."},{"key":"34931_CR28","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1136\/bjophthalmol-2015-307064","volume":"100","author":"L Gella","year":"2016","unstructured":"Gella, L. et al. Retinal sensitivity in subjects with type 2 diabetes mellitus: Sankara Nethralaya diabetic retinopathy epidemiology and molecular genetics study (SN-DREAMS II, report 4). Br. J. Ophthalmol. 100, 808\u2013813 (2016).","journal-title":"Br. J. Ophthalmol."},{"key":"34931_CR29","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1038\/eye.2017.27","volume":"31","author":"G Montesano","year":"2017","unstructured":"Montesano, G. et al. Structure-function relationship in early diabetic retinopathy: a spatial correlation analysis with OCT and microperimetry. Eye (Lond. Engl.) 31, 931\u2013939 (2017).","journal-title":"Eye (Lond. Engl.)"},{"key":"34931_CR30","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1038\/s41433-020-1054-2","volume":"35","author":"AR Santos","year":"2021","unstructured":"Santos, A. R. et al. Microperimetry and MfERG as functional measurements in diabetic macular oedema undergoing intravitreal Ranibizumab treatment. Eye (Lond. Engl.) 35, 1384\u20131392 (2021).","journal-title":"Eye (Lond. Engl.)"},{"key":"34931_CR31","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1016\/S0140-6736(23)01520-9","volume":"402","author":"JS Heier","year":"2023","unstructured":"Heier, J. S. et al. Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials. Lancet (Lond. Engl.) 402, 1434\u20131448 (2023).","journal-title":"Lancet (Lond. Engl.)"},{"key":"34931_CR32","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ajo.2023.09.007","volume":"257","author":"WS Tsai","year":"2024","unstructured":"Tsai, W. S. et al. Topographic correlation of microperimetry with structural characteristics in diabetic macular ischemia. Am. J. Ophthalmol. 257, 25\u201333 (2024).","journal-title":"Am. J. Ophthalmol."},{"key":"34931_CR33","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.2147\/OPTH.S220877","volume":"13","author":"M Alonso-Plasencia","year":"2019","unstructured":"Alonso-Plasencia, M., Abreu-Gonz\u00e1lez, R. & G\u00f3mez-Culebras, M. A. Structure-function correlation using OCT angiography and microperimetry in diabetic retinopathy. Clin. Ophthalmol. (Auckland N Z). 13, 2181\u20132188 (2019).","journal-title":"Clin. Ophthalmol. (Auckland N Z)"},{"key":"34931_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.oret.2024.04.005","author":"S Vujosevic","year":"2024","unstructured":"Vujosevic, S. et al. Severity of disorganization of retinal layers and visual function impairment in diabetic retinopathy. Ophthalmol. Retina. https:\/\/doi.org\/10.1016\/j.oret.2024.04.005 (2024).","journal-title":"Ophthalmol. Retina"},{"key":"34931_CR35","unstructured":"Heidelberg Engineering. HighRes-OCT user manual software version SP-X1904. 1\u2013162 (2021)."},{"key":"34931_CR36","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1167\/tvst.13.12.19","volume":"13","author":"L Goerdt","year":"2024","unstructured":"Goerdt, L. et al. Band visibility in high-resolution optical coherence tomography assessed with a custom review tool and updated, histology-derived nomenclature. Transl. Vis. Sci. Technol. 13, 19 (2024).","journal-title":"Transl. Vis. Sci. Technol."},{"key":"34931_CR37","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1167\/tvst.14.1.12","volume":"14","author":"K Wall","year":"2025","unstructured":"Wall, K. et al. Characterization of the disorganization of the inner retinal layers in diabetics using increased axial resolution optical coherence tomography. Transl. Vis. Sci. Technol. 14, 12 (2025).","journal-title":"Transl. Vis. Sci. Technol."},{"key":"34931_CR38","unstructured":"Frank, S. et al. Advances in photoreceptor quantification moving from conventional to high-resolution SPECTRALIS optical coherence tomography. Investig. Ophthalmol.  Vis. Sci. 63, 1023 \u2013 F0270-1023 \u2013 F0270  (2022)."},{"key":"34931_CR39","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.1097\/IAE.0000000000001902","volume":"38","author":"HR Moein","year":"2018","unstructured":"Moein, H. R. et al. Optical coherence tomography angiography to detect macular capillary ischemia in patients with inner retinal changes after resolved diabetic macular edema. Retina (Philadelphia Pa). 38, 2277\u20132284 (2018).","journal-title":"Retina (Philadelphia Pa)"},{"key":"34931_CR40","doi-asserted-by":"publisher","first-page":"2352","DOI":"10.1016\/j.ophtha.2016.07.008","volume":"123","author":"C Balaratnasingam","year":"2016","unstructured":"Balaratnasingam, C. et al. Visual acuity is correlated with the area of the foveal avascular zone in diabetic retinopathy and retinal vein occlusion. Ophthalmology 123, 2352\u20132367 (2016).","journal-title":"Ophthalmology"},{"key":"34931_CR41","doi-asserted-by":"publisher","DOI":"10.1016\/j.oret.2024.12.015","author":"BV Duffy","year":"2024","unstructured":"Duffy, B. V. et al. Foveal avascular zone enlargement correlates with visual acuity decline in patients with diabetic retinopathy. Ophthalmol. Retina. https:\/\/doi.org\/10.1016\/j.oret.2024.12.015 (2024).","journal-title":"Ophthalmol. Retina"},{"key":"34931_CR42","doi-asserted-by":"publisher","first-page":"103555","DOI":"10.1016\/j.pdpdt.2023.103555","volume":"42","author":"Y Gong","year":"2023","unstructured":"Gong, Y., Wang, M., Li, Q., Shao, Y. & Li, X. Evaluating the effect of vitreomacular interface abnormalities on anti-vascular endothelial growth factor treatment outcomes in diabetic macular edema by optical coherence tomography: A systematic review and meta-analysis. Photodiagn. Photodyn. Ther. 42, 103555 (2023).","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"34931_CR43","doi-asserted-by":"publisher","first-page":"e529","DOI":"10.1111\/aos.12153","volume":"91","author":"L Reznicek","year":"2013","unstructured":"Reznicek, L. et al. Functional and morphological changes in diabetic macular edema over the course of anti-vascular endothelial growth factor treatment. Acta Ophthalmol. 91, e529\u2013e536 (2013).","journal-title":"Acta Ophthalmol."},{"key":"34931_CR44","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1111\/j.1755-3768.1994.tb02787.x","volume":"72","author":"T Bek","year":"1994","unstructured":"Bek, T. Transretinal histopathological changes in capillary-free areas of diabetic retinopathy. Acta Ophthalmol. 72, 409\u2013415 (1994).","journal-title":"Acta Ophthalmol."},{"issue":"Pt 1","key":"34931_CR45","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1046\/j.1469-7580.1999.19410089.x","volume":"194","author":"J Moore","year":"1999","unstructured":"Moore, J., Bagley, S., Ireland, G., McLeod, D. & Boulton, M. E. Three dimensional analysis of microaneurysms in the human diabetic retina. J. Anat. 194 (Pt 1), 89\u2013100 (1999).","journal-title":"J. Anat."},{"key":"34931_CR46","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.1167\/iovs.17-23304","volume":"59","author":"AC Onishi","year":"2018","unstructured":"Onishi, A. C. et al. Importance of considering the middle capillary plexus on OCT angiography in diabetic retinopathy. Investig. Ophthalmol. Vis. Sci. 59, 2167\u20132176 (2018).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"34931_CR47","doi-asserted-by":"publisher","first-page":"3785","DOI":"10.1167\/iovs.17-21461","volume":"58","author":"Q Chen","year":"2017","unstructured":"Chen, Q. et al. Macular vascular fractal dimension in the deep capillary layer as an early indicator of microvascular loss for retinopathy in type 2 diabetic patients. Investig. Ophthalmol. Vis. Sci. 58, 3785\u20133794 (2017).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"34931_CR48","doi-asserted-by":"publisher","first-page":"2575","DOI":"10.1038\/s41598-017-02767-0","volume":"7","author":"FY Tang","year":"2017","unstructured":"Tang, F. Y. et al. Determinants of quantitative optical coherence tomography angiography metrics in patients with diabetes. Sci. Rep. 7, 2575 (2017).","journal-title":"Sci. Rep."},{"key":"34931_CR49","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1016\/j.ajo.2013.05.033","volume":"156","author":"DA Sim","year":"2013","unstructured":"Sim, D. A. et al. Predictive factors for the progression of diabetic macular ischemia. Am. J. Ophthalmol. 156, 684\u2013692 (2013).","journal-title":"Am. J. Ophthalmol."},{"key":"34931_CR50","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.ophtha.2016.10.008","volume":"124","author":"WA Samara","year":"2017","unstructured":"Samara, W. A. et al. Quantification of diabetic macular ischemia using optical coherence tomography angiography and its relationship with visual acuity. Ophthalmology 124, 235\u2013244 (2017).","journal-title":"Ophthalmology"},{"key":"34931_CR51","doi-asserted-by":"publisher","first-page":"5031","DOI":"10.1167\/iovs.16-20007","volume":"57","author":"MB Powner","year":"2016","unstructured":"Powner, M. B. et al. Evaluation of nonperfused retinal vessels in ischemic retinopathy. Investig. Ophthalmol. Vis. Sci. 57, 5031\u20135037 (2016).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"34931_CR52","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1167\/iovs.15-18034","volume":"57","author":"PD Bradley","year":"2016","unstructured":"Bradley, P. D. et al. The evaluation of diabetic macular ischemia using optical coherence tomography angiography. Investig. Ophthalmol. Vis. Sci. 57, 626\u2013631 (2016).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"34931_CR53","doi-asserted-by":"publisher","first-page":"4292","DOI":"10.1167\/iovs.18-24142","volume":"59","author":"M Ashraf","year":"2018","unstructured":"Ashraf, M., Nesper, P. L., Jampol, L. M., Yu, F. & Fawzi, A. A. Statistical model of optical coherence tomography angiography parameters that correlate with severity of diabetic retinopathy. Investig. Ophthalmol. Vis. Sci. 59, 4292\u20134298 (2018).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"34931_CR54","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1111\/ceo.12557","volume":"43","author":"L Nicholson","year":"2015","unstructured":"Nicholson, L. et al. Diagnostic accuracy of disorganization of the retinal inner layers in detecting macular capillary non-perfusion in diabetic retinopathy. Clin. Exp. Ophthalmol. 43, 735\u2013741 (2015).","journal-title":"Clin. Exp. Ophthalmol."},{"key":"34931_CR55","doi-asserted-by":"crossref","unstructured":"Tsai, W. S. et al. Correlation of optical coherence tomography angiography characteristics with visual function to define vision-threatening diabetic macular ischemia. Diagn. (Basel Switzerl.) 2022, 12 (2022).","DOI":"10.3390\/diagnostics12051050"},{"key":"34931_CR56","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1016\/j.ophtha.2019.06.016","volume":"126","author":"Z Sun","year":"2019","unstructured":"Sun, Z. et al. OCT angiography metrics predict progression of diabetic retinopathy and development of diabetic macular edema: a prospective study. Ophthalmology 126, 1675\u20131684 (2019).","journal-title":"Ophthalmology"},{"key":"34931_CR57","doi-asserted-by":"publisher","first-page":"e0244789","DOI":"10.1371\/journal.pone.0244789","volume":"16","author":"G Cennamo","year":"2021","unstructured":"Cennamo, G., Montorio, D., Fossataro, F., Fossataro, C. & Tranfa, F. Evaluation of vessel density in disorganization of retinal inner layers after resolved diabetic macular edema using optical coherence tomography angiography. PloS One. 16, e0244789 (2021).","journal-title":"PloS One"},{"key":"34931_CR58","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1016\/j.ophtha.2009.12.044","volume":"117","author":"E Midena","year":"2010","unstructured":"Midena, E., Vujosevic, S. & Cavarzeran, F. Normal values for fundus perimetry with the microperimeter MP1. Ophthalmology 117, 1571\u20131576 (2010).","journal-title":"Ophthalmology"},{"key":"34931_CR59","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1016\/j.ophtha.2004.11.051","volume":"112","author":"C Springer","year":"2005","unstructured":"Springer, C., B\u00fcltmann, S., V\u00f6lcker, H. E. & Rohrschneider, K. Fundus perimetry with the micro perimeter 1 in normal individuals: comparison with conventional threshold perimetry. Ophthalmology 112, 848\u2013854 (2005).","journal-title":"Ophthalmology"},{"key":"34931_CR60","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/S0161-6420(13)38012-9","volume":"98","author":"Grading diabetic retinopathy","year":"1991","unstructured":"Grading diabetic retinopathy. From stereoscopic color fundus photographs\u2013an extension of the modified airlie house classification. ETDRS report number 10. Early treatment diabetic retinopathy study research group. Ophthalmology 98, 786\u2013806 (1991).","journal-title":"Ophthalmology"},{"key":"34931_CR61","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","volume":"76","author":"GA Roth","year":"2020","unstructured":"Roth, G. A. et al. Global burden of cardiovascular diseases and risk factors, 1990\u20132019: update from the GBD 2019 study. J. Am. Coll. Cardiol. 76, 2982\u20133021 (2020).","journal-title":"J. Am. Coll. Cardiol."},{"key":"34931_CR62","doi-asserted-by":"crossref","unstructured":"Ameln, J. et al. Assessment of local sensitivity in incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) lesions in intermediate age-related macular degeneration (iAMD). BMJ Open. Ophthalmol. 2024, 9 (2024).","DOI":"10.1136\/bmjophth-2024-001638"},{"key":"34931_CR63","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1167\/iovs.65.12.27","volume":"65","author":"M Pfau","year":"2024","unstructured":"Pfau, M. et al. Multicenter normative data for mesopic microperimetry. Investig. Ophthalmol. Vis. Sci. 65, 27 (2024).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"34931_CR64","doi-asserted-by":"publisher","first-page":"1572","DOI":"10.1016\/j.ophtha.2014.02.023","volume":"121","author":"G Staurenghi","year":"2014","unstructured":"Staurenghi, G., Sadda, S., Chakravarthy, U. & Spaide, R. F. Proposed lexicon for anatomic landmarks in normal posterior segment spectral-domain optical coherence tomography: the IN OCT consensus. Ophthalmology 121, 1572\u20131578 (2014).","journal-title":"Ophthalmology"},{"key":"34931_CR65","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. 9, 676\u2013682 (2012).","journal-title":"Nat. Methods"},{"key":"34931_CR66","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider, C. A., Rasband, W. S. & Eliceiri, K. W. NIH image to imageJ: 25 years of image analysis. Nat. Methods. 9, 671\u2013675 (2012).","journal-title":"Nat. Methods"},{"key":"34931_CR67","doi-asserted-by":"publisher","first-page":"10143","DOI":"10.1038\/s41598-018-28530-7","volume":"8","author":"H Shiihara","year":"2018","unstructured":"Shiihara, H. et al. Objective evaluation of size and shape of superficial foveal avascular zone in normal subjects by optical coherence tomography angiography. Sci. Rep. 8, 10143 (2018).","journal-title":"Sci. Rep."},{"key":"34931_CR68","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.jcjo.2020.03.011","volume":"55","author":"F Corvi","year":"2020","unstructured":"Corvi, F., Sadda, S. R., Staurenghi, G. & Pellegrini, M. Thresholding strategies to measure vessel density by optical coherence tomography angiography. Can. J. Ophthalmol. 55, 317\u2013322 (2020).","journal-title":"Can. J. Ophthalmol."},{"key":"34931_CR69","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.ajo.2016.08.035","volume":"171","author":"AY Kim","year":"2016","unstructured":"Kim, A. Y. et al. Quantifying retinal microvascular changes in uveitis using spectral-domain optical coherence tomography angiography. Am. J. Ophthalmol. 171, 101\u2013112 (2016).","journal-title":"Am. J. Ophthalmol."},{"key":"34931_CR70","doi-asserted-by":"crossref","unstructured":"Munk, M. R. et al. The role of intravitreal corticosteroids in the treatment of DME: predictive OCT biomarkers. Int. J. Mol. Sci. 23, 256 (2022).","DOI":"10.3390\/ijms23147585"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-34931-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-34931-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-34931-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:02:26Z","timestamp":1767916946000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-34931-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["34931"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-34931-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]},"assertion":[{"value":"6 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"889"}}