{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:03:27Z","timestamp":1789963407752,"version":"4.0.1"},"reference-count":54,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471103"],"award-info":[{"award-number":["82471103"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404266"],"award-info":[{"award-number":["82404266"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YC2510803"],"award-info":[{"award-number":["2024YC2510803"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"abstract":"ABSTRACT<\/jats:title>\n \n Purpose<\/jats:title>\n This exploratory study integrates aqueous humour metabolomic data with clinical and imaging features to examine candidate biomarkers and characterize multimodal patterns associated with persistent diabetic macular edema (pDME).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In this prospective cohort study, DME patients were treated with monthly anti\u2010VEGF injections over 3\u2009months and categorized as pDME and non\u2010pDME groups based on central subfield thickness and best\u2010corrected visual acuity. We then carried out a nested case\u2013control comparison of these groups, performing untargeted metabolomic analysis on aqueous humour samples. Comparison of clinical data, OCT parameters, and metabolites was performed. Logistic regression models were constructed to explore associations between multimodal features and pDME in the metabolomics subset.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 103 patients (146 eyes) were finally included in the analysis. The pDME patients had significantly higher BMI (25.20 vs. 23.27,\n p<\/jats:italic>\n \u2009=\u20090.004) and triglyceride (1.80 vs. 1.50,\n p<\/jats:italic>\n \u2009=\u20090.003) levels when compared with non\u2010pDME patients. A higher rate of disorganization of retinal inner layers (DRIL,\n p<\/jats:italic>\n \u2009=\u20090.026) and vitreoretinal interface abnormality (\n p<\/jats:italic>\n \u2009=\u20090.009), but a lower rate of SRF (\n p<\/jats:italic>\n \u2009=\u20090.019), was found in the pDME group. Metabolomics analysis revealed 405 differentially expressed metabolites, and purine metabolism (\n p<\/jats:italic>\n \u2009=\u20090.001,\n Q<\/jats:italic>\n \u2009=\u20090.024) and DNA repair pathway (\n p<\/jats:italic>\n \u2009<\u20090.001,\n Q<\/jats:italic>\n \u2009=\u20090.013) were significantly enriched. Purine score and DNA repair score were both significantly higher in the pDME group compared with the non\u2010pDME group (\n p<\/jats:italic>\n \u2009<\u20090.001). ROC analysis demonstrated metabolomic markers, particularly the purine score, showed stronger group\u2010wise separation for pDME than clinical and OCT features (LOOCV AUC 0.963 vs. 0.716 and 0.505). Additionally, vitreoretinal interface abnormality was associated with purine metabolism (OR\u2009=\u20095.820, 95% CI: 1.136\u201329.811) and DNA repair score (OR\u2009=\u20093.790, 95% CI: 1.096\u201313.109), while DRIL (OR\u2009=\u20090.214, 95% CI: 0.046\u20130.990) was associated with DNA repair score.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n PDME is characterized by elevated BMI, serum triglyceride, low SRF incidence, but a higher rate of DRIL and vitreoretinal interface abnormality. Purine metabolism and DNA repair pathways were associated with treatment response and correlated with OCT structural changes. Metabolomic signatures, particularly the purine score, emerged as promising candidate markers associated with pDME in this exploratory cohort, warranting further validation in independent studies. A novel mechanism of pDME, the purine metabolism\u2013DNA repair axis, was proposed and needs further verification.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.71173","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T03:35:58Z","timestamp":1789961758000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multimodal Exploratory Analysis of Persistent Diabetic Macular Edema: Integrating Aqueous Humour Metabolomics, Clinical and\n OCT<\/scp>\n Features"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7390-5164","authenticated-orcid":false,"given":"Yunhan","family":"Tao","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Hubei Key Laboratory of Otolaryngologic and Ophthalmic Diseases Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China"},{"name":"Department of Ophthalmology West China Second University Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hubei Key Laboratory of Otolaryngologic and Ophthalmic Diseases Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxi","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hubei Key Laboratory of Otolaryngologic and Ophthalmic Diseases Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhu","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hubei Key Laboratory of Otolaryngologic and Ophthalmic Diseases Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guochong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, School of Public Health Suzhou Medical College of Soochow University Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hubei Key Laboratory of Otolaryngologic and Ophthalmic Diseases Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health Tongji Medical College, Huazhong University of Science and Technology Wuhan China"},{"name":"Section of Statistical Multi\u2010Omics, Discipline of Clinical Medicine, School of Bioscience and Medicine University of Surrey Guildford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3499-1725","authenticated-orcid":false,"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hubei Key Laboratory of Otolaryngologic and Ophthalmic Diseases Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7133-4508","authenticated-orcid":false,"given":"Xufang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hubei Key Laboratory of Otolaryngologic and Ophthalmic Diseases Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"issue":"1","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41572-025-00646-x","article-title":"Diabetic Retinal Disease","volume":"11","author":"Sivaprasad S.","year":"2025","journal-title":"Nature Reviews. 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