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Subretinal injection is the preferred method of delivery for retinal gene and stem\u2010cell therapies, but its invasive and complex surgical procedure is a major limiting factor in clinical investigations and practice. Here, we engineered a novel trans\u2010scleral injection technique to safely administer to the subretinal space in a simple, non\u2010surgical, and minimally invasive procedure. Subretinal injection using this technique in rodents and rabbits took &lt;1\u2009min per injection and did not require a surgical microscope. Extensive safety examinations in rats showed that the injection technique reliably administered into the subretinal space with no incidence of retinal perforation, little or no choroidal bleeding, and no evidence of retinal toxicity. We further found that repeated subretinal injection in the same eye, in rats, was well tolerated. The developed technique may enable non\u2010surgical subretinal injection without vitrectomy, potentially increasing safety, efficacy, and access to ocular therapies.<\/jats:p>","DOI":"10.1002\/btm2.10755","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T07:09:17Z","timestamp":1738048157000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A non\u2010surgical method for subretinal delivery by trans\u2010scleral microneedle injection"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-4886","authenticated-orcid":false,"given":"Amir","family":"Hejri","sequence":"first","affiliation":[{"name":"School of Chemical and Biomolecular Engineering Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah A.","family":"Chrenek","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nolan T.","family":"Goehring","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomolecular Engineering Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella I.","family":"Bowland","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomolecular Engineering Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Noel","sequence":"additional","affiliation":[{"name":"Department of Animal Resources Georgia Institute of Technology  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiong","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Emory University  Atlanta Georgia 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