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Therefore, neuroprotection has emerged as a promising therapeutic strategy to prevent disease progression. Topical administration via eyedrops represents a non-invasive approach to deliver neuroprotective agents directly to the retina. This review summarizes the current advances in the field of neuroprotective therapies against early DRD with a special focus on topical delivery, including preclinical and clinical evidence, while discussing the relevance of the transscleral route of absorption in all of them. In this review, the most promising neuroprotective compounds under development will be discussed, highlighting the opportunity that they represent for treating early stages of DRD.<\/jats:p>","DOI":"10.3390\/ijms27125553","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:37:42Z","timestamp":1781879862000},"page":"5553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotection in Early Diabetic Retinal Disease Using Eyedrop Delivery"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6443-7576","authenticated-orcid":false,"given":"Hugo","family":"Ramos","sequence":"first","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Vall d\u2019Hebron Research Institute (VHIR), 08035 Barcelona, Spain"},{"name":"Center for Networked Biomedical Research of Diabetes and Associated Metabolic Diseases (CIBERDEM), Carlos III Health Institute (ICSIII), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3483-652X","authenticated-orcid":false,"given":"Olga","family":"Sim\u00f3-Servat","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Vall d\u2019Hebron Research Institute (VHIR), 08035 Barcelona, Spain"},{"name":"Center for Networked Biomedical Research of Diabetes and Associated Metabolic Diseases (CIBERDEM), Carlos III Health Institute (ICSIII), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3109-1721","authenticated-orcid":false,"given":"Cristina","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Vall d\u2019Hebron Research Institute (VHIR), 08035 Barcelona, Spain"},{"name":"Center for Networked Biomedical Research of Diabetes and Associated Metabolic Diseases (CIBERDEM), Carlos III Health Institute (ICSIII), 28029 Madrid, Spain"},{"name":"Department of Medicine, Autonomous University of Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0475-3096","authenticated-orcid":false,"given":"Rafael","family":"Sim\u00f3","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Vall d\u2019Hebron Research Institute (VHIR), 08035 Barcelona, Spain"},{"name":"Center for Networked Biomedical Research of Diabetes and Associated Metabolic Diseases (CIBERDEM), Carlos III Health Institute (ICSIII), 28029 Madrid, Spain"},{"name":"Department of Medicine, Autonomous University of Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"412","DOI":"10.2337\/dc16-2641","article-title":"Diabetic Retinopathy: A Position Statement by the American Diabetes Association","volume":"40","author":"Solomon","year":"2017","journal-title":"Diabetes Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1007\/s00125-018-4692-1","article-title":"Neurodegeneration in Diabetic Retinopathy: Does It Really Matter?","volume":"61","author":"Stitt","year":"2018","journal-title":"Diabetologia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1056\/NEJMra1005073","article-title":"Diabetic Retinopathy","volume":"366","author":"Antonetti","year":"2012","journal-title":"N. 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