{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:52:44Z","timestamp":1791924764796,"version":"4.3.4"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>To review the existing literature to evaluate the utility of insulin eye drops as a treatment for neurotrophic-related epithelial defects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>A comprehensive literature search of Medline, Embase, and Web of Science and additional manual searches were conducted using relevant keywords. All articles published from January 2005 to January 2024 were examined. Studies on the use of topical insulin drops in neurotrophic epithelial defects were included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      A total of 16 articles were found relevant to be discussed in the review. All included patients had neurotrophic-related epithelial defects ranging from 3.8 mm\n                      <jats:sup>2<\/jats:sup>\n                      to 144 mm\n                      <jats:sup>2<\/jats:sup>\n                      . After treatment with topical insulin, most of the epithelial defects showed a complete epithelialization. Various concentrations and types of insulin were used. The studies also varied in the type of vehicle used in the preparation of insulin drops. Two randomized controlled trials demonstrated that topical insulin drops were more effective than conventional treatment with artificial tears or autologous serum. All included studies, except for two, reported the absence of local or systemic side effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Topical insulin is a promising and effective (adjuvant) treatment for neurotrophic keratopathy. It facilitates the healing of neurotrophic epithelial defects and offers many advantages over the current treatment options; insulin is widely available and it is relatively inexpensive. Topical insulin drops do not affect systemic blood glucose levels and are well tolerated. However, further investigation is needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/joco.joco_32_24","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T11:04:09Z","timestamp":1729076649000},"page":"9-22","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":14,"title":["Topical Insulin for Neurotrophic-Related Epithelial Defects: Where do We Stand? A Systematic Review"],"prefix":"10.4103","volume":"36","author":[{"given":"Colette","family":"Wouters","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Saelens","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heleen","family":"Delbeke","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,10,16]]},"reference":[{"key":"R1-20241018","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1159\/000354380","article-title":"Neurotrophic keratitis","volume":"231","author":"Semeraro","year":"2014","journal-title":"Ophthalmologica"},{"key":"R2-20241018","first-page":"692","article-title":"Neurotrophic factors in the human cornea","volume":"41","author":"You","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"R3-20241018","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0014-4835(03)00050-2","article-title":"Corneal nerves:Structure, contents and function","volume":"76","author":"M\u00fcller","year":"2003","journal-title":"Exp Eye Res"},{"key":"R4-20241018","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.jtos.2019.11.008","article-title":"Neurotrophic keratitis:Frequency, etiologies, clinical management and outcomes","volume":"18","author":"Saad","year":"2020","journal-title":"Ocul Surf"},{"key":"R5-20241018","first-page":"571","article-title":"Diagnosis and management of neurotrophic keratitis","volume":"8","author":"Sacchetti","year":"2014","journal-title":"Clin Ophthalmol"},{"key":"R6-20241018","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/0039-6257(87)90102-0","article-title":"Management of noninfectious corneal ulcers","volume":"32","author":"Donzis","year":"1987","journal-title":"Surv Ophthalmol"},{"key":"R7-20241018","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1038\/sj.eye.6700616","article-title":"Neurotrophic keratitis","volume":"17","author":"Bonini","year":"2003","journal-title":"Eye (Lond)"},{"key":"R8-20241018","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s41687-020-00192-y","article-title":"Development of the neurotrophic keratopathy questionnaire:Qualitative research","volume":"4","author":"Murray","year":"2020","journal-title":"J Patient Rep Outcomes"},{"key":"R9-20241018","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.sjopt.2014.06.011","article-title":"Management strategies for persistent epithelial defects of the cornea","volume":"28","author":"Katzman","year":"2014","journal-title":"Saudi J Ophthalmol"},{"key":"R10-20241018","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/S0889-8529(05)70344-3","article-title":"Insulin as a growth factor","volume":"25","author":"Menon","year":"1996","journal-title":"Endocrinol Metab Clin North Am"},{"key":"R11-20241018","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1242\/jcs.110.17.2089","article-title":"Insulin stimulates haptotactic migration of human epidermal keratinocytes through activation of NF-kappa B transcription factor","volume":"110","author":"Benoliel","year":"2017","journal-title":"J cell sci"},{"key":"R12-20241018","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1177\/1099800415592175","article-title":"Effect of topical insulin on second-degree burns in diabetic rats","volume":"18","author":"Azevedo","year":"2016","journal-title":"Biol Res Nurs"},{"key":"R13-20241018","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3109\/03009739709178930","article-title":"Insulin receptors in human ocular tissues. 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