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The aim of this study was to determine if ultrasound can be applied to increase transcorneal drug delivery of macromolecules without dangerously overheating surrounding ocular tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Dissected corneas of adult rabbits were placed in a diffusion cell between a donor compartment filled with a solution of macromolecules (40, 70\u2009kDa, or 150\u2009kDa) and a receiver compartment. Each cornea was exposed to the drug solution for 60\u2009minutes, with the experimental group receiving 5\u2009minutes of continuous ultrasound or 10\u2009minutes of pulsed ultrasound at a 50% duty cycle (pulse repetition frequency of 500\u2009ms on, 500\u2009ms off) at the beginning of treatment. Unfocused circular ultrasound transducers were operated at 0.5 to 1\u2009W\/cm<jats:sup>2<\/jats:sup> intensity and at 600\u2009kHz frequency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The greatest increase in transcorneal drug delivery seen was 1.2 times (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05) with the application of pulsed ultrasound at 0.5\u2009W\/cm<jats:sup>2<\/jats:sup> and 600\u2009kHz for 10\u2009minutes with 40\u2009kDa macromolecules. Histological analysis revealed structural damage mostly in the corneal epithelium, with most damage occurring at the epithelial surface.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study suggests that ultrasound may be used for enhancing transcorneal delivery of macromolecules of lower molecular weights. Further research is needed on the long\u2010term effects of ultrasound parameters used in this study on human ocular tissues.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jum.16346","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T11:20:21Z","timestamp":1697455221000},"page":"127-136","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Therapeutic Ultrasound for Enhanced Corneal Permeability to Macromolecules"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2125-2169","authenticated-orcid":false,"given":"Claire","family":"Allison","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering The George Washington University  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The George 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