{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:32:58Z","timestamp":1787758378612,"version":"build-2784847793"},"reference-count":173,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Age-related macular degeneration (AMD) represents a leading cause of irreversible vision loss worldwide, driven by intricate interactions among oxidative stress, low-degree chronic inflammation, and macular pigment depletion in aging retinas. Lutein, a component of the macular pigment, has attracted significant attention in AMD management for its antioxidant and blue-light filtering properties. Its oral supplementation, however, although showing potential in slowing AMD progression, requires daily intake and results in variable macular absorption. Trans-scleral iontophoresis (TSI) is a non-invasive technique using low-intensity electric currents to deliver charged molecules into biological tissues and represents an innovative method to deliver lutein into the retina. Methods: The present narrative review synthesizes and discusses the results of lutein supplementation in AMD patients; the ocular iontophoresis basal principles, efficacy, safety and limitations in treating different ophthalmic pathologies; and the evolving clinical evidence supporting lutein TSI in the AMD management. Results: Ex-vivo studies have shown that lutein TSI may provide efficient, localized, rapid, and sustained retinal supplementation of macular pigment, overcoming oral intake limitations. Recent preliminary clinical studies have demonstrated that this technique is well-tolerated and effective in enhancing macular pigment optical density and improving some visual functions in AMD patients. Conclusions: Ex-vivo and pilot clinical studies highlight the capacity of TSI to deliver lutein inside the retina, overcoming physiological barriers that may limit the efficacy of lutein oral administration. The demonstration of the efficacy of the procedure in preserving\/improving visual functions and delaying disease progression in AMD patients requires further long-term randomized controlled clinical studies.<\/jats:p>","DOI":"10.3390\/diseases14090310","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:04:32Z","timestamp":1787756672000},"page":"310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Iontophoresis Drug Delivery to the Macula of Lutein for Age Related Macular Degeneration"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6566-1075","authenticated-orcid":false,"given":"Maria Letizia","family":"Salvetat","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Azienda Sanitaria Friuli Occidentale, 33170 Pordenone, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Azienda Sanitaria Friuli Occidentale, 33170 Pordenone, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-5545","authenticated-orcid":false,"given":"Marco","family":"Zeppieri","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy"},{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34129 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2969-8610","authenticated-orcid":false,"given":"Matteo","family":"Capobianco","sequence":"additional","affiliation":[{"name":"Eye Clinic, Catania University, Policlinico G. Rodolico, 95121 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1051-876X","authenticated-orcid":false,"given":"Alessandro","family":"Avitabile","sequence":"additional","affiliation":[{"name":"Biomedicine, Neuroscience and Advance Diagnostic (BIND) Department, University of Palermo, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7556-6952","authenticated-orcid":false,"given":"Ludovica","family":"Cannizaro","sequence":"additional","affiliation":[{"name":"Biomedicine, Neuroscience and Advance Diagnostic (BIND) Department, University of Palermo, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0059-5253","authenticated-orcid":false,"given":"Giuseppe","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Eye Clinic, Catania University, Policlinico G. Rodolico, 95121 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6807-9455","authenticated-orcid":false,"given":"Francesco","family":"Cappellani","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, Piazza dell \u2019Universit\u00e0, 94100 Enna, Italy"},{"name":"Mediterranean Foundation \u201cG.B. Morgagni\u201d, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-0068","authenticated-orcid":false,"given":"Caterina","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, Piazza dell \u2019Universit\u00e0, 94100 Enna, Italy"},{"name":"Mediterranean Foundation \u201cG.B. Morgagni\u201d, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/S0140-6736(22)02609-5","article-title":"Age-related macular degeneration","volume":"401","author":"Guymer","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1001\/jama.2023.26074","article-title":"Age-Related Macular Degeneration: A Review","volume":"331","author":"Fleckenstein","year":"2024","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-030-66014-7_1","article-title":"Age-Related Macular Degeneration: Epidemiology and Clinical Aspects","volume":"1256","author":"Keenan","year":"2021","journal-title":"Adv. Exp. Med. 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