{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T23:18:57Z","timestamp":1793488737726,"version":"4.5.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neural Regen Res"],"published-print":{"date-parts":[[2017]]},"DOI":"10.4103\/1673-5374.213534","type":"journal-article","created":{"date-parts":[[2017,8,22]],"date-time":"2017-08-22T03:08:06Z","timestamp":1503371286000},"page":"1220","source":"Crossref","is-referenced-by-count":119,"title":["Neurotrophic factors and corneal nerve regeneration"],"prefix":"10.4103","volume":"12","author":[{"given":"Alessandro","family":"Lambiase","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Sacchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"key-10.4103\/1673-5374.213534-1","doi-asserted-by":"crossref","unstructured":"Aifa A, Gueudry J, Portmann A, Delcampe A, Muraine M (2012) Topical treatment with a new matrix therapy agent (RGTA) for the treatment of corneal neurotrophic ulcers. Invest Ophthalmol Vis Sci 53:8181-8185.","DOI":"10.1167\/iovs.12-10476"},{"key":"key-10.4103\/1673-5374.213534-2","doi-asserted-by":"crossref","unstructured":"Alino AM, Perry HD, Kanellopoulos AJ, Donnenfeld ED, Rahn EK (1998) Conjunctival flaps. Ophthalmology 105:1120-1123.","DOI":"10.1016\/S0161-6420(98)96017-1"},{"key":"key-10.4103\/1673-5374.213534-3","doi-asserted-by":"crossref","unstructured":"Arvola RP, Robciuc A, Holopainen JM (2016) Matrix regeneration therapy: a case series of corneal neurotrophic ulcers. Cornea 35:451-455.","DOI":"10.1097\/ICO.0000000000000759"},{"key":"key-10.4103\/1673-5374.213534-4","doi-asserted-by":"crossref","unstructured":"Belmonte C, Aracil A, Acosta MC, Luna C, Gallar J (2004) Nerves and sensations from the eye surface. Ocul Surf 2:248-253.","DOI":"10.1016\/S1542-0124(12)70112-X"},{"key":"key-10.4103\/1673-5374.213534-5","doi-asserted-by":"crossref","unstructured":"Bonini S, Lambiase A, Rama P, Caprioglio G, Aloe L (2000) Topical treatment with nerve growth factor for neurotrophic keratitis. Ophthalmology 107:1347-1351; discussion 1351-1342.","DOI":"10.1016\/S0161-6420(00)00163-9"},{"key":"key-10.4103\/1673-5374.213534-6","doi-asserted-by":"crossref","unstructured":"Chen HJ, Pires RT, Tseng SC (2000) Amniotic membrane transplantation for severe neurotrophic corneal ulcers. Br J Ophthalmol 84:826-833.","DOI":"10.1136\/bjo.84.8.826"},{"key":"key-10.4103\/1673-5374.213534-7","doi-asserted-by":"crossref","unstructured":"Cruzat A, Qazi Y, Hamrah P (2016) In vivo confocal microscopy of corneal nerves in health and disease. Ocul Surf 15:15-47.","DOI":"10.1016\/j.jtos.2016.09.004"},{"key":"key-10.4103\/1673-5374.213534-8","doi-asserted-by":"crossref","unstructured":"Culver DA, Dahan A, Bajorunas D, Jeziorska M, van Velzen M, Aarts L, Tavee J, Tannemaat MR, Dunne AN, Kirk RI, Petropoulos IN, Cerami A, Malik RA, Brines M (2017) Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain. Invest Ophthalmol Vis Sci 58:BIO52-BIO60.","DOI":"10.1167\/iovs.16-21291"},{"key":"key-10.4103\/1673-5374.213534-9","doi-asserted-by":"crossref","unstructured":"Dai Y, Zhao X, Chen P, Yu Y, Wang Y, Xie L (2015) Neuropeptide FF promotes recovery of corneal nerve injury associated with hyperglycemia. Invest Ophthalmol Vis Sci 56:7754-7765.","DOI":"10.1167\/iovs.15-16513"},{"key":"key-10.4103\/1673-5374.213534-10","doi-asserted-by":"crossref","unstructured":"Daniele S, Gilbard JP, Schepens CL (1992) Treatment of persistent epithelial defects in neurotrophic keratitis with epidermal growth factor: a preliminary open study. Graefes Arch Clin Exp Ophthalmol 230:314-317.","DOI":"10.1007\/BF00165937"},{"key":"key-10.4103\/1673-5374.213534-11","doi-asserted-by":"crossref","unstructured":"Dunn SP, Heidemann DG, Chow CY, Crockford D, Turjman N, Angel J, Allan CB, Sosne G (2010) Treatment of chronic nonhealing neurotrophic corneal epithelial defects with thymosin beta4. Ann N Y Acad Sci 1194:199-206.","DOI":"10.1111\/j.1749-6632.2010.05471.x"},{"key":"key-10.4103\/1673-5374.213534-12","doi-asserted-by":"crossref","unstructured":"Ferrari MP, Mantelli F, Sacchetti M, Antonangeli MI, Cattani F, D'Anniballe G, Sinigaglia F, Ruffini PA, Lambiase A (2014) Safety and pharmacokinetics of escalating doses of human recombinant nerve growth factor eye drops in a double-masked, randomized clinical trial. BioDrugs 28:275-283.","DOI":"10.1007\/s40259-013-0079-5"},{"key":"key-10.4103\/1673-5374.213534-13","unstructured":"Geremicca W, Fonte C, Vecchio S (2010) Blood components for topical use in tissue regeneration: evaluation of corneal lesions treated with platelet lysate and considerations on repair mechanisms. Blood Transfus 8:107-112."},{"key":"key-10.4103\/1673-5374.213534-14","doi-asserted-by":"crossref","unstructured":"Giannaccare G, Fresina M, Vagge A, Versura P (2015) Synergistic effect of regenerating agent plus cord blood serum eye drops for the treatment of resistant neurotrophic keratitis: a case report and a hypothesis for pathophysiologic mechanism. Int Med Case Rep J 8:277-281.","DOI":"10.2147\/IMCRJ.S89968"},{"key":"key-10.4103\/1673-5374.213534-15","doi-asserted-by":"crossref","unstructured":"Golebiowski B, Papas E, Stapleton F (2011) Assessing the sensory function of the ocular surface: implications of use of a non-contact air jet aesthesiometer versus the Cochet-Bonnet aesthesiometer. Exp Eye Res 92:408-413.","DOI":"10.1016\/j.exer.2011.02.016"},{"key":"key-10.4103\/1673-5374.213534-16","doi-asserted-by":"crossref","unstructured":"Guadilla AM, Balado P, Baeza A, Merino M (2013) Effectiveness of topical autologous serum treatment in neurotrophic keratopathy. Arch Soc Esp Oftalmol 88:302-306.","DOI":"10.1016\/j.oftal.2012.09.033"},{"key":"key-10.4103\/1673-5374.213534-17","doi-asserted-by":"crossref","unstructured":"He J, Cortina MS, Kakazu A, Bazan HE (2015) The PEDF neuroprotective domain plus DHA induces corneal nerve regeneration after experimental surgery. Invest Ophthalmol Vis Sci 56:3505-3513.","DOI":"10.1167\/iovs.15-16755"},{"key":"key-10.4103\/1673-5374.213534-18","doi-asserted-by":"crossref","unstructured":"Hick S, Demers PE, Brunette I, La C, Mabon M, Duchesne B (2005) Amniotic membrane transplantation and fibrin glue in the management of corneal ulcers and perforations: a review of 33 cases. Cornea 24:369-377.","DOI":"10.1097\/01.ico.0000151547.08113.d1"},{"key":"key-10.4103\/1673-5374.213534-19","doi-asserted-by":"crossref","unstructured":"Hsu HY, Modi D (2015) Etiologies, quantitative hypoesthesia, and clinical outcomes of neurotrophic keratopathy. Eye Contact Lens 41:314-317.","DOI":"10.1097\/ICL.0000000000000133"},{"key":"key-10.4103\/1673-5374.213534-20","doi-asserted-by":"crossref","unstructured":"Ilic D, Vicovac L, Nikolic M, Lazic Ilic E (2016) Human amniotic membrane grafts in therapy of chronic non-healing wounds. Br Med Bull 117:59-67.","DOI":"10.1093\/bmb\/ldv053"},{"key":"key-10.4103\/1673-5374.213534-21","doi-asserted-by":"crossref","unstructured":"Jeng BH, Dupps WJ, Jr. (2009) Autologous serum 50% eyedrops in the treatment of persistent corneal epithelial defects. Cornea 28:1104-1108.","DOI":"10.1097\/ICO.0b013e3181a2a7f6"},{"key":"key-10.4103\/1673-5374.213534-22","doi-asserted-by":"crossref","unstructured":"Khokhar S, Natung T, Sony P, Sharma N, Agarwal N, Vajpayee RB (2005) Amniotic membrane transplantation in refractory neurotrophic corneal ulcers: a randomized, controlled clinical trial. Cornea 24:654-660.","DOI":"10.1097\/01.ico.0000153102.19776.80"},{"key":"key-10.4103\/1673-5374.213534-23","doi-asserted-by":"crossref","unstructured":"Lambiase A, Rama P, Aloe L, Bonini S (1999) Management of neurotrophic keratopathy. Curr Opin Ophthalmol 10:270-276.","DOI":"10.1097\/00055735-199908000-00009"},{"key":"key-10.4103\/1673-5374.213534-24","doi-asserted-by":"crossref","unstructured":"Lambiase A, Sacchetti M, Mastropasqua A, Bonini S (2013) Corneal changes in neurosurgically induced neurotrophic keratitis. JAMA Ophthalmol 131:1547-1553.","DOI":"10.1001\/jamaophthalmol.2013.5064"},{"key":"key-10.4103\/1673-5374.213534-25","doi-asserted-by":"crossref","unstructured":"Lambiase A, Rama P, Bonini S, Caprioglio G, Aloe L (1998) Topical treatment with nerve growth factor for corneal neurotrophic ulcers. N Engl J Med 338:1174-1180.","DOI":"10.1056\/NEJM199804233381702"},{"key":"key-10.4103\/1673-5374.213534-26","doi-asserted-by":"crossref","unstructured":"Lambiase A, Micera A, Sacchetti M, Cortes M, Mantelli F, Bonini S (2011) Alterations of tear neuromediators in dry eye disease. Arch Ophthalmol 129:981-986.","DOI":"10.1001\/archophthalmol.2011.200"},{"key":"key-10.4103\/1673-5374.213534-27","doi-asserted-by":"crossref","unstructured":"Leckelt J, Guimaraes P, Kott A, Ruggeri A, Stachs O, Baltrusch S (2016) Early detection of diabetic neuropathy by investigating CNFL and IENFD in thy1-YFP mice. J Endocrinol 231:147-157.","DOI":"10.1530\/JOE-16-0284"},{"key":"key-10.4103\/1673-5374.213534-28","doi-asserted-by":"crossref","unstructured":"Lee HK, Ryu IH, Seo KY, Hong S, Kim HC, Kim EK (2006) Topical 0.1% prednisolone lowers nerve growth factor expression in keratoconjunctivitis sicca patients. Ophthalmology 113:198-205.","DOI":"10.1016\/j.ophtha.2005.09.033"},{"key":"key-10.4103\/1673-5374.213534-29","doi-asserted-by":"crossref","unstructured":"Lee YC, Kim SY (2015) Treatment of neurotrophic keratopathy with nicergoline. Cornea 34:303-307.","DOI":"10.1097\/ICO.0000000000000348"},{"key":"key-10.4103\/1673-5374.213534-30","doi-asserted-by":"crossref","unstructured":"Lewis EJH, Perkins BA, Lovblom LE, Bazinet RP, Wolever TMS, Bril V (2017) Effect of omega-3 supplementation on neuropathy in type 1 diabetes: A 12-month pilot trial. Neurology 88:2294-2301.","DOI":"10.1212\/WNL.0000000000004033"},{"key":"key-10.4103\/1673-5374.213534-31","doi-asserted-by":"crossref","unstructured":"Lugo M, Arentsen JJ (1987) Treatment of neurotrophic ulcers with conjunctival flaps. Am J Ophthalmol 103:711-712.","DOI":"10.1016\/S0002-9394(14)74337-5"},{"key":"key-10.4103\/1673-5374.213534-32","doi-asserted-by":"crossref","unstructured":"Mantelli F, Lambiase A, Sacchetti M, Orlandi V, Rosa A, Casella P, Bonini S (2015) Cocaine snorting may induce ocular surface damage through corneal sensitivity impairment. Graefes Arch Clin Exp Ophthalmol 253:765-772.","DOI":"10.1007\/s00417-015-2938-x"},{"key":"key-10.4103\/1673-5374.213534-33","doi-asserted-by":"crossref","unstructured":"Mastropasqua L, Massaro-Giordano G, Nubile M, Sacchetti M (2017) Understanding the pathogenesis of neurotrophic keratitis: the role of corneal nerves. J Cell Physiol 232:717-724.","DOI":"10.1002\/jcp.25623"},{"key":"key-10.4103\/1673-5374.213534-34","doi-asserted-by":"crossref","unstructured":"Muller LJ, Marfurt CF, Kruse F, Tervo TM (2003) Corneal nerves: structure, contents and function. Exp Eye Res 76:521-542.","DOI":"10.1016\/S0014-4835(03)00050-2"},{"key":"key-10.4103\/1673-5374.213534-35","doi-asserted-by":"crossref","unstructured":"Nishida T, Chikama T, Morishige N, Yanai R, Yamada N, Saito J (2007) Persistent epithelial defects due to neurotrophic keratopathy treated with a substance p-derived peptide and insulin-like growth factor 1. Jpn J Ophthalmol 51:442-447.","DOI":"10.1007\/s10384-007-0480-z"},{"key":"key-10.4103\/1673-5374.213534-36","unstructured":"Rajak S, Rajak J, Selva D (2015) Performing a tarsorrhaphy. Community Eye Health 28:10-11."},{"key":"key-10.4103\/1673-5374.213534-37","doi-asserted-by":"crossref","unstructured":"Rama P, Ferrari G, Pellegrini G (2017) Cultivated limbal epithelial transplantation. Curr Opin Ophthalmol 28:387-389.","DOI":"10.1097\/ICU.0000000000000382"},{"key":"key-10.4103\/1673-5374.213534-38","doi-asserted-by":"crossref","unstructured":"Reichard M, Hovakimyan M, Guthoff RF, Stachs O (2014) In vivo visualisation of murine corneal nerve fibre regeneration in response to ciliary neurotrophic factor. Exp Eye Res 120:20-27.","DOI":"10.1016\/j.exer.2013.12.015"},{"key":"key-10.4103\/1673-5374.213534-39","unstructured":"Sacchetti M, Lambiase A (2014) Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol 8:571-579."},{"key":"key-10.4103\/1673-5374.213534-40","unstructured":"Sacchetti M, Micera A, Lambiase A, Speranza S, Mantelli F, Petrachi G, Bonini S, Bonini S (2011) Tear levels of neuropeptides increase after specific allergen challenge in allergic conjunctivitis. Mol Vis 17:47-52."},{"key":"key-10.4103\/1673-5374.213534-41","doi-asserted-by":"crossref","unstructured":"Sanchez-Avila RM, Merayo-Lloves J, Riestra AC, Fernandez-Vega Cueto L, Anitua E, Begona L, Muruzabal F, Orive G (2017) Treatment of patients with neurotrophic keratitis stages 2 and 3 with plasma rich in growth factors (PRGF-Endoret) eye-drops. Int Ophthalmol doi:10.1007\/s10792-017-0582-7.","DOI":"10.1007\/s10792-017-0582-7"},{"key":"key-10.4103\/1673-5374.213534-42","doi-asserted-by":"crossref","unstructured":"Shaheen BS, Bakir M, Jain S (2014) Corneal nerves in health and disease. Surv Ophthalmol 59:263-285.","DOI":"10.1016\/j.survophthal.2013.09.002"},{"key":"key-10.4103\/1673-5374.213534-43","doi-asserted-by":"crossref","unstructured":"Tavakoli M, Mitu-Pretorian M, Petropoulos IN, Fadavi H, Asghar O, Alam U, Ponirakis G, Jeziorska M, Marshall A, Efron N, Boulton AJ, Augustine T, Malik RA (2013) Corneal confocal microscopy detects early nerve regeneration in diabetic neuropathy after simultaneous pancreas and kidney transplantation. Diabetes 62:254-260.","DOI":"10.2337\/db12-0574"},{"key":"key-10.4103\/1673-5374.213534-44","doi-asserted-by":"crossref","unstructured":"Tervo TM, Mertaniemi P, Ylatupa S, Tervo K, Virtanen T, Partanen P (1995) Release of calcitonin gene-related peptide in tears after excimer laser photorefractive keratectomy. J Refract Surg 11:126-128.","DOI":"10.3928\/1081-597X-19950301-13"},{"key":"key-10.4103\/1673-5374.213534-45","doi-asserted-by":"crossref","unstructured":"Turkoglu E, Celik E, Alagoz G (2014) A comparison of the efficacy of autologous serum eye drops with amniotic membrane transplantation in neurotrophic keratitis. Semin Ophthalmol 29:119-126.","DOI":"10.3109\/08820538.2013.768678"},{"key":"key-10.4103\/1673-5374.213534-46","doi-asserted-by":"crossref","unstructured":"Uhlig CE, Frings C, Rohloff N, Harmsen-Aasman C, Schmitz R, Kiesel L, Eter N, Busse H, Alex AF (2015) Long-term efficacy of glycerine-processed amniotic membrane transplantation in patients with corneal ulcer. Acta Ophthalmol 93:e481-487.","DOI":"10.1111\/aos.12671"},{"key":"key-10.4103\/1673-5374.213534-47","doi-asserted-by":"crossref","unstructured":"Yamada M, Ogata M, Kawai M, Mashima Y (2000) Decreased substance P concentrations in tears from patients with corneal hypesthesia. Am J Ophthalmol 129:671-672.","DOI":"10.1016\/S0002-9394(00)00415-3"},{"key":"key-10.4103\/1673-5374.213534-48","doi-asserted-by":"crossref","unstructured":"Yamada N, Matsuda R, Morishige N, Yanai R, Chikama TI, Nishida T, Ishimitsu T, Kamiya A (2008) Open clinical study of eye-drops containing tetrapeptides derived from substance P and insulin-like growth factor-1 for treatment of persistent corneal epithelial defects associated with neurotrophic keratopathy. Br J Ophthalmol 92:896-900.","DOI":"10.1136\/bjo.2007.130013"},{"key":"key-10.4103\/1673-5374.213534-49","doi-asserted-by":"crossref","unstructured":"Yanai R, Nishida T, Chikama T, Morishige N, Yamada N, Sonoda KH (2015) Potential new modes of treatment of neurotrophic keratopathy. Cornea 34 Suppl 11:S121-127.","DOI":"10.1097\/ICO.0000000000000587"},{"key":"key-10.4103\/1673-5374.213534-50","doi-asserted-by":"crossref","unstructured":"Yu CQ, Rosenblatt MI (2007) Transgenic corneal neurofluorescence in mice: a new model for in vivo investigation of nerve structure and regeneration. Invest Ophthalmol Vis Sci 48:1535-1542.","DOI":"10.1167\/iovs.06-1192"}],"container-title":["Neural Regeneration Research"],"original-title":[],"language":"en","deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T13:39:46Z","timestamp":1786714786000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/1673-5374.213534"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017]]},"references-count":50,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2017]]}},"alternative-id":["213534"],"URL":"https:\/\/doi.org\/10.4103\/1673-5374.213534","relation":{},"ISSN":["1673-5374"],"issn-type":[{"value":"1673-5374","type":"print"}],"subject":[],"published":{"date-parts":[[2017]]}}}