{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:10:10Z","timestamp":1790745010073,"version":"4.1.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T00:00:00Z","timestamp":1698624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Neurotrophic Keratopathy (NK) is a neurodegenerative corneal disease that results in diminished corneal sensation. Previous studies have found that Cenegermin 0.002%, a recombinant human nerve growth factor (rhNGF), improves corneal epithelial healing in stage 2 and 3 NK patients. However, rhNGF effect on corneal sensation and nerve regeneration has not been well established. Thus, this study aims to analyze the effect of rhNGF on corneal nerve regeneration using <jats:italic>in vivo<\/jats:italic> confocal microscopy (IVCM) and on corneal sensitivity in NK patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This is a retrospective, longitudinal, case\u2013control study that included patients with NK, treated with rhNGF for at least 4\u2009weeks, with pre- and post-treatment IVCM images available for analysis. Chart reviews were conducted documenting prior medical and surgical history, clinical signs and symptoms, and corneal sensation using Cochet-Bonnet esthesiometry. Corneal nerve parameters were assessed by IVCM. Sex- and age-matched reference controls were selected from a database of healthy subjects for comparison.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study included 25 patients, with 22 (88%) stage 1, two (8%) stage 2, and 1 (4%) stage 3 NK patients, with a median age of 64 years (range: 30\u201393\u2009years). Total, main, and branch nerve densities [median (range) in mm\/mm<jats:sup>2<\/jats:sup>] were lower in the NK group pre-treatment [2.3 (0.0\u201321.1); 1.7 (0.0\u201313.0); 0.5 (0.0\u201310.2); respectively] vs. controls [22.3 (14.9\u201329.0); 10.1 (3.2\u201315.4); and 12.1 (6.2\u201318.4), (<jats:italic>p<\/jats:italic> &amp;lt;\u20090.0001 for all), respectively]. Post-treatment nerve densities increased compared to pre-treatment to 5.3 (0.0\u201319.4, <jats:italic>p<\/jats:italic> =\u20090.0083) for total, 3.5 (0.0\u201313.2, <jats:italic>p<\/jats:italic> =\u20090.0059) for main, and 2.0 (0.0\u201310.4, <jats:italic>p<\/jats:italic> =\u20090.0251) for branch nerves, but remained lower than controls (<jats:italic>p<\/jats:italic> &amp;lt;\u20090.0001 for all). Corneal sensation increased from 2.3\u2009\u00b1\u20091.1\u2009cm pre-treatment to 4.1\u2009\u00b1\u20091.4\u2009cm post-treatment (<jats:italic>p<\/jats:italic> =\u20090.001). Median best corrected visual acuity significantly increased following rhNGF treatment from 0.4 (0.0\u20131.6) to 0.12 (\u22120.1 to 1.6) (<jats:italic>p<\/jats:italic> =\u20090.007).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with NK treated with at least 4\u2009weeks of rhNGF, showed a significant increase in corneal nerve densities after treatment. A significant increase in corneal sensation, as well as best corrected visual acuity, was observed following treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2023.1210179","type":"journal-article","created":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T04:41:40Z","timestamp":1698640900000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Effect of recombinant human nerve growth factor treatment on corneal nerve regeneration in patients with neurotrophic keratopathy"],"prefix":"10.3389","volume":"17","author":[{"given":"Ana","family":"Balbuena-Pareja","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe S.","family":"Bogen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M.","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedram","family":"Hamrah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.jtos.2019.01.009","article-title":"Efficacy of autologous serum tears for treatment of neuropathic corneal pain","volume":"17","author":"Aggarwal","year":"2019","journal-title":"Ocul. 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