{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:28:45Z","timestamp":1790378925812,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Currently, the gold standard of diabetic macular edema (DME) treatment is anti-vascular endothelial growth factor (VEGF) injections, although a percentage of patients do not respond optimally. Vitrectomy with or without internal limiting membrane (ILM) peeling is a well-established treatment for DME cases with a tractional component while its role for nontractional cases is unclear. The aim of this study is to evaluate the role of vitrectomy with or without ILM peeling in nontractional refractory DME. Methods: We performed a retrospective review of twenty-eight eyes with nontractional refractory DME treated with vitrectomy at San Giuseppe Hospital, Milan, between 2016 and 2018. All surgeries were performed by a single experienced vitreoretinal surgeon. In 43.4% of cases, the ILM was peeled. Best corrected visual acuity and optical coherence tomography (OCT) scans were assessed preoperatively and at 6, 12, and 24 months post-vitrectomy. Results: The mean central macular thickness improved from 413.1 \u00b1 84.4 to 291.3 \u00b1 57.6 \u03bcm at two years (p &lt; 0.0001). The mean logarithm of the minimum angle of resolution logMAR best-corrected visual acuity (BCVA) improved after two years, from 0.6 \u00b1 0.2 to 0.2 \u00b1 0.1 (p &lt; 0.0001). We found no difference between ILM peeling vs. no ILM peeling group in terms of anatomical (p = 0.8) and visual outcome (p = 0.3). Eyes with DME and subfoveal serous retinal detachment (SRD) at baseline had better visual outcomes at the final visit (p = 0.001). Conclusions: We demonstrated anatomical and visual improvement of patients who underwent vitrectomy for nontractional refractory DME with and without ILM peeling. Improvement was greater in patients presenting subretinal fluid preoperatively.<\/jats:p>","DOI":"10.3390\/jcm12062297","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T02:40:11Z","timestamp":1678934411000},"page":"2297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Role of Vitrectomy in Nontractional Refractory Diabetic Macular Edema"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1702-6859","authenticated-orcid":false,"given":"Stefano","family":"Ranno","sequence":"first","affiliation":[{"name":"Ophthalmology Department, Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6773-9967","authenticated-orcid":false,"given":"Stela","family":"Vujosevic","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy"},{"name":"Eye Clinic, IRCCS MultiMedica, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4268-1468","authenticated-orcid":false,"given":"Manuela","family":"Mambretti","sequence":"additional","affiliation":[{"name":"Ophthalmology Department, Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Metrangolo","sequence":"additional","affiliation":[{"name":"Ophthalmology Department, Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5904-8645","authenticated-orcid":false,"given":"Micol","family":"Alkabes","sequence":"additional","affiliation":[{"name":"Eye Clinic, University Hospital Maggiore della Carit\u00e0, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Rabbiolo","sequence":"additional","affiliation":[{"name":"Ophthalmology Department, Ospedale A. Manzoni, 23900 Lecco, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Govetto","sequence":"additional","affiliation":[{"name":"Ophthalmology Department, Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Carini","sequence":"additional","affiliation":[{"name":"Ophthalmology Department, Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4036-703X","authenticated-orcid":false,"given":"Paolo","family":"Nucci","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Radice","sequence":"additional","affiliation":[{"name":"Ophthalmology Department, Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"98","DOI":"10.4239\/wjd.v2.i6.98","article-title":"Managing diabetic macular edema: The leading cause of diabetes blindness","volume":"2","year":"2011","journal-title":"World J. Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.survophthal.2012.10.002","article-title":"Medical management for the prevention and treatment of diabetic macular edema","volume":"58","author":"Kiire","year":"2013","journal-title":"Surv. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"The Early Treatment Diabetic Retinopathy Study Research Group (1985). Photocoagulation for diabetic macular edema. Early treatment diabetic retinopathy study report number 1. Arch Ophthalmol., 103, 1796e1806.","DOI":"10.1001\/archopht.1985.01050120030015"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1097\/IAE.0b013e3181a2c07a","article-title":"Diabetic Retinopathy Clinical Research Network. Effect of focal\/grid photocoagulation on visual acuity and retinal thickening in eyes with non-center-involved diabetic macular edema","volume":"29","author":"Scott","year":"2009","journal-title":"Retina"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.2337\/db07-0982","article-title":"Intravitreal triamcinolone acetonide inhibits breakdown of the blood-retinal barrier through differential regulation of VEGF-A and its receptors in early diabetic rat retinas","volume":"57","author":"Zhang","year":"2008","journal-title":"Diabetes"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000458539","article-title":"Guidelines for the Management of Diabetic Macular Edema by the European Society of Retina Specialists (EURETINA)","volume":"237","author":"Bandello","year":"2017","journal-title":"Ophthalmologica"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1016\/j.ophtha.2010.12.034","article-title":"Economic Considerations of macular edema therapies","volume":"118","author":"Smiddy","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/S0161-6420(92)31901-3","article-title":"Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction","volume":"99","author":"Lewis","year":"1992","journal-title":"Ophthalmology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1007\/s00417-006-0456-6","article-title":"Comparative evaluation of vitrectomy and dye-enhanced ILM peel with grid laser in diffuse diabetic macular edema","volume":"245","author":"Kumar","year":"2007","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1159\/000355487","article-title":"Degree of decrease in central retinal thickness predicts visual acuity response to intravitrealranibizumab in diabetic macular edema","volume":"231","author":"Santos","year":"2014","journal-title":"Ophthalmologica"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/S0002-9394(02)01548-9","article-title":"A controlled study of vitrectomy for diabetic macular edema","volume":"134","author":"Otani","year":"2002","journal-title":"Am. J. Ophthalmol."},{"key":"ref_12","first-page":"352487","article-title":"Strategy for the management of diabetic macular edema: The European vitreo-retinal society macular edema study","volume":"2015","author":"Adelman","year":"2015","journal-title":"Biomed Res. Int."},{"key":"ref_13","first-page":"590","article-title":"Internal limiting membrane peeling in vitreous surgery for diabetic macular edema","volume":"106","author":"Kumagai","year":"2002","journal-title":"Nippon Ganka Gakkai Zasshi"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1097\/IAE.0000000000000497","article-title":"Effect of Internal Limiting Membrane Peeling on Long-Term Visual Outcomes for Diabetic Macular Edema","volume":"35","author":"Kumagai","year":"2015","journal-title":"Retina"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1097\/IAE.0000000000000433","article-title":"Vitrectomy with internal limiting membrane peeling for tractional and nontractional diabetic macular edema: Long-term Results of a Comparative Study","volume":"35","author":"Bonnin","year":"2015","journal-title":"Retina"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Diabetic Retinopathy Clinical Research Network Writing Committee (2010). Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. Ophthalmology, 117, 1087\u20131093.e3.","DOI":"10.1016\/j.ophtha.2009.10.040"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.survophthal.2006.04.005","article-title":"Ocular oxygenation and the treatment of diabetic retinopathy","volume":"51","year":"2006","journal-title":"Surv. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/S0002-9394(00)00575-4","article-title":"Perifoveal microcirculation before and after vitrectomy for diabetic cystoid macular edema","volume":"130","author":"Kadonosono","year":"2000","journal-title":"Am. J. Ophthalmol."},{"key":"ref_19","first-page":"1953","article-title":"Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: Vascular endothelial growth factor decreases occludin in retinal endothelial cells","volume":"47","author":"Antonetti","year":"1998","journal-title":"Penn State Retina Research Group. Diabetes"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1097\/00004397-200404410-00015","article-title":"Surgical and other treatments of diabetic macular edema: An update","volume":"44","author":"Christoforidis","year":"2004","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1097\/00006982-200002000-00004","article-title":"Resolution of diabetic macular edema after surgical removal of the posterior hyaloid and the inner limiting membrane","volume":"20","author":"Gandorfer","year":"2000","journal-title":"Retina"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1097\/IAE.0b013e31819c632f","article-title":"Long-term follow-up of vitrectomy for diffuse nontractional diabetic macular edema","volume":"29","author":"Kumagai","year":"2009","journal-title":"Retina"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1007\/s004170000251","article-title":"Vitrectomy results in diabetic macular oedema without evident vitreomacular traction","volume":"239","author":"Hendrikse","year":"2001","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S0002-9394(02)01819-6","article-title":"Early postoperative retinal thickness changes and complications after vitrectomy for diabetic macular edema","volume":"135","author":"Yamamoto","year":"2003","journal-title":"Am. J. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1097\/00006982-200002000-00023","article-title":"Improved visual acuity following pars plana vitrectomy for diabetic cystoid macular edema and detached posterior hyaloid","volume":"20","author":"Ikeda","year":"2000","journal-title":"Retina"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1007\/s00417-003-0849-8","article-title":"Vitrectomy with removal of the internal limiting membrane in chronic diabetic macular oedema","volume":"242","author":"Dillinger","year":"2004","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1097\/IAE.0b013e318159e7d2","article-title":"Surgical and anatomical outcomes of pars plana vitrectomy for diffuse nontractional diabetic macular edema","volume":"28","author":"Figueroa","year":"2008","journal-title":"Retina"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1007\/s00417-010-1610-8","article-title":"Pars plana vitrectomy for diabetic macular edema. Internal limiting membrane delamination vs posterior hyaloid removal. A prospective randomized trial","volume":"249","author":"Hoerauf","year":"2011","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/sj.eye.6702012","article-title":"Diabetic macular oedema: Pilot randomised trial of pars plana vitrectomy vs macular argon photocoagulation","volume":"20","author":"Patel","year":"2006","journal-title":"Eye"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Iglicki, M., Lavaque, A., Ozimek, M., Negri, H.P., Okada, M., Chhablani, J., Busch, C., Loewenstein, A., and Zur, D. (2018). Biomarkers and predictors for functional and anatomic outcomes for small gauge pars plana vitrectomy and peeling of the internal limiting membrane in na\u00efve diabetic macular edema: The VITAL Study. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200365"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.jcjo.2017.10.011","article-title":"Vitrectomy in the management of diabetic macular edema in treatment-na\u00efve patients","volume":"53","author":"Michalewska","year":"2017","journal-title":"Can. J. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1007\/s00417-015-3251-4","article-title":"The effectiveness of vitrectomy for diffuse diabetic macular edema may depend on its preoperative optical coherence tomography pattern","volume":"254","author":"Ichiyama","year":"2016","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Guerra, M.H., Yumnamcha, T., Ebrahim, A.S., Berger, E.A., Singh, L.P., and Ibrahim, A.S. (2021). Real-Time Monitoring the Effect of Cytopathic Hypoxia on Retinal Pigment Epithelial Barrier Functionality Using Electric Cell-Substrate Impedance Sensing (ECIS) Biosensor Technology. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094568"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00592-019-01424-4","article-title":"Diabetic macular edema with neuroretinal detachment: OCT and OCT-angiography biomarkers of treatment response to anti-VEGF and steroids","volume":"57","author":"Vujosevic","year":"2020","journal-title":"Acta Diabetol."},{"key":"ref_35","first-page":"872978","article-title":"Usefulness of the vitreous fluid analysis in the translational research of diabetic retinopathy","volume":"2012","year":"2012","journal-title":"Mediat. Inflamm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1007\/s10792-017-0761-6","article-title":"ILM peeling in nontractional diabetic macular edema: Review and metanalysis","volume":"38","author":"Rinaldi","year":"2018","journal-title":"Int. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s10792-006-0008-4","article-title":"Visual acuity comparison of vitrectomy with and without internal limiting membrane removal in the treatment of diabetic macular edema","volume":"26","author":"Bahadir","year":"2005","journal-title":"Int. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1097\/00006982-200504000-00010","article-title":"Histopathologic evaluation of the internal limiting membrane surgically excised from eyes with diabetic maculopathy","volume":"25","author":"Matsunaga","year":"2005","journal-title":"Retina"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/6\/2297\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:56:01Z","timestamp":1760122561000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/6\/2297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,15]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["jcm12062297"],"URL":"https:\/\/doi.org\/10.3390\/jcm12062297","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,15]]}}}