{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T08:18:50Z","timestamp":1778660330455,"version":"3.51.4"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T00:00:00Z","timestamp":1573084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Corneal neovasculariziation (CNV) is a serious vision-threatening complication; however, all therapeutics have their clinical limitations. The aim of this study is to investigate the efficacy of topical rivoceranib compared with topical bevacizumab in a murine model of corneal neovascularization (CNV). Materials and Methods: Murine CNV was induced by means of total de-epithelization and alkali burn. Mice were divided into five groups according to topical treatment: untreated control, phosphate-buffered saline (PBS), 0.1% and 0.5% rivoceranib, and 0.5% bevacizumab. CNV area and index were measured 7 and 14 days after treatment. After corneal tissues were excised at day 14, the blood and lymphatic vessels were quantified by cluster of differentiation 31 (CD31) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) immunofluorescence, respectively. Results: After 14 days, treatment groups with 0.1% and 0.5% rivoceranib and 0.5% bevacizumab showed a decrease in CNV area and index compared with the untreated and PBS groups (all p &lt; 0.01). Blood and lymphatic vascularization significantly decreased in the 0.5% rivoceranib and 0.5% bevacizumab groups, as measured by CD31 and LYVE1 immunofluorescence. There was no significant difference of vascularization between the 0.5% rivoceranib and bevacizumab groups. Conclusions: Topical application of rivoceranib could effectively decrease CNV equivalent to topical bevacizumab in a murine model.<\/jats:p>","DOI":"10.3390\/medicina55110729","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T11:17:25Z","timestamp":1573125445000},"page":"729","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Comparison of the Therapeutic Efficacies of Topical Rivoceranib and Topical Bevacizumab in a Murine Model of Corneal Neovascularization"],"prefix":"10.3390","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8790-7021","authenticated-orcid":false,"given":"Hyeon Jeong","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Chonnam National University Medical School and Hospital, 42 Jebong-ro, Dong-gu, Gwangju 61469, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Je Moon","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong Sok","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Chonnam National University Medical School and Hospital, 42 Jebong-ro, Dong-gu, Gwangju 61469, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2788-1851","authenticated-orcid":false,"given":"Kyung Chul","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Chonnam National University Medical School and Hospital, 42 Jebong-ro, Dong-gu, Gwangju 61469, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.jtos.2018.06.004","article-title":"Current and emerging therapies for corneal neovascularization","volume":"16","author":"Roshandel","year":"2018","journal-title":"Ocul. Surf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.22336\/rjo.2019.4","article-title":"Corneal neovascularization: Updates on pathophysiology, investigations & management","volume":"63","author":"Sharif","year":"2019","journal-title":"Rom. J. Ophthalmol."},{"key":"ref_3","first-page":"768","article-title":"Molecular underpinnings of corneal angiogenesis: Advances over the past decade","volume":"18","author":"Abdelfattah","year":"2016","journal-title":"Int. J. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.survophthal.2012.01.007","article-title":"Corneal Neovascularization: An Anti-VEGF Therapy Review","volume":"57","author":"Chang","year":"2012","journal-title":"Surv. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1177\/1947601911423031","article-title":"Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies","volume":"2","author":"Shibuya","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/j.1755-3768.2008.01399.x","article-title":"Therapeutic effect of subconjunctival injection of bevacizumab in the treatment of corneal neovascularization","volume":"87","author":"You","year":"2009","journal-title":"Acta Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.vph.2016.05.011","article-title":"VEGF receptor signal transduction\u2014A brief update","volume":"86","year":"2016","journal-title":"Vasc. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.biopha.2018.12.022","article-title":"Therapeutic targeting of angiogenesis molecular pathways in angiogenesis-dependent diseases","volume":"110","author":"Fallah","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e153","DOI":"10.1038\/oncsis.2015.14","article-title":"Compensatory angiogenesis and tumor refractoriness","volume":"4","author":"Gacche","year":"2015","journal-title":"Oncogenesis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s10792-017-0786-x","article-title":"Effectiveness of photodynamic therapy with verteporfin combined with intrastromal bevacizumab for corneal neovascularization in Stevens\u2013Johnson syndrome","volume":"39","author":"Yoon","year":"2019","journal-title":"Int. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Dugel, P.U., Koh, A., Ogura, Y., Jaffe, G.J., Schmidt-Erfurth, U., Brown, D.M., Gomes, A.V., Warburton, J., Weichselberger, A., and Holz, F.G. (2019). HAWK and HARRIER: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration. Ophthalmology, (ahead of print).","DOI":"10.1016\/j.ophtha.2019.04.017"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e246","DOI":"10.1111\/j.1755-3768.2012.02540.x","article-title":"The effect of topical bevacizumab as an adjunctive therapy for corneal neovascularization","volume":"91","author":"Asena","year":"2013","journal-title":"Acta Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1159\/000499165","article-title":"Comparison of Subconjunctival Aflibercept and Betamethasone for the Treatment of Formed Corneal Neovascularization in a Rabbit Model","volume":"62","author":"Livny","year":"2019","journal-title":"Ophthalmic Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.ajo.2010.04.024","article-title":"Inhibition of Corneal Neovascularization by Topical Bevacizumab (Anti-VEGF) and Sunitinib (Anti-VEGF and Anti-PDGF) in an Animal Model","volume":"150","author":"Javaloy","year":"2010","journal-title":"Am. J. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1136\/bjophthalmol-2012-302137","article-title":"Subconjunctival bevacizumab induces regression of corneal neovascularisation: A pilot randomised placebo-controlled double-masked trial","volume":"97","author":"Petsoglou","year":"2013","journal-title":"Br. J. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.sjopt.2017.02.008","article-title":"Topical versus subconjunctival anti-vascular endothelial growth factor therapy (Bevacizumab, Ranibizumab and Aflibercept) for treatment of corneal neovascularization","volume":"31","author":"Mansour","year":"2017","journal-title":"Saudi J. Ophthalmol."},{"key":"ref_17","first-page":"1","article-title":"Emerging roles of FGF signaling in hepatocellular carcinoma","volume":"5","author":"Zheng","year":"2016","journal-title":"Transl. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s40265-018-0903-9","article-title":"Apatinib: A Review in Advanced Gastric Cancer and Other Advanced Cancers","volume":"78","author":"Scott","year":"2018","journal-title":"Drugs"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.2147\/OTT.S172305","article-title":"Progress in the treatment of solid tumors with apatinib: A systematic review","volume":"11","author":"Zhao","year":"2018","journal-title":"OncoTargets Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e16967","DOI":"10.1097\/MD.0000000000016967","article-title":"Apatinib is effective as third-line and more treatment of advanced metastatic non-small-cell lung cancer: A retrospective analysis in a real-world setting","volume":"98","author":"Leng","year":"2019","journal-title":"Medicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17220","DOI":"10.18632\/oncotarget.7948","article-title":"Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma","volume":"7","author":"Peng","year":"2016","journal-title":"Oncotarget"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/07357907.2016.1276185","article-title":"Targeting VEGFR-2 in Metastatic Gastric Cancer: Results from a Literature-Based Meta-Analysis","volume":"35","author":"Roviello","year":"2017","journal-title":"Cancer Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4813","DOI":"10.2147\/IJN.S135133","article-title":"Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization","volume":"12","author":"Lee","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1634\/theoncologist.11-7-753","article-title":"Tyrosine Kinase Inhibitors of Vascular Endothelial Growth Factor Receptors in Clinical Trials: Current Status and Future Directions","volume":"11","author":"Morabito","year":"2006","journal-title":"Oncologist"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1097\/ICO.0000000000002012","article-title":"Comparison of the Effects of Dovitinib and Bevacizumab on Reducing Neovascularization in an Experimental Rat Corneal Neovascularization Model","volume":"38","author":"Sahan","year":"2019","journal-title":"Cornea"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1080\/02713683.2019.1584320","article-title":"Efficacy of Sunitinib, Sunitinib-Hesperetin, and Sunitinib-Doxycycline Combinations on Experimentally-Induced Corneal Neovascularization","volume":"44","author":"Ekim","year":"2019","journal-title":"Curr. Eye Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1111\/ceo.13333","article-title":"Topical axitinib is a potent inhibitor of corneal neovascularization","volume":"46","year":"2018","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1167\/iovs.12-11032","article-title":"Safety and Efficacy of the Multitargeted Receptor Kinase Inhibitor Pazopanib in the Treatment of Corneal Neovascularization","volume":"54","author":"Amparo","year":"2013","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/gt.2009.50","article-title":"Subconjunctival gene delivery of the transcription factor GA-binding protein delays corneal neovascularization in a mouse model","volume":"16","author":"Yoon","year":"2009","journal-title":"Gene Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1167\/iovs.17-23198","article-title":"Substance P Modulation of Human and Murine Corneal Neovascularization","volume":"59","author":"Barbariga","year":"2018","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4082","DOI":"10.1073\/pnas.91.9.4082","article-title":"Thalidomide is an inhibitor of angiogenesis","volume":"91","author":"Loughnan","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","first-page":"769","article-title":"Xanthatin inhibits corneal neovascularization by inhibiting the VEGFR2-mediated STAT3\/PI3K\/Akt signaling pathway","volume":"42","author":"Shen","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/ICO.0b013e3181dc81a0","article-title":"Photodynamic Therapy with Verteporfin Combined with Subconjunctival Injection of Bevacizumab for Corneal Neovascularization","volume":"30","author":"You","year":"2011","journal-title":"Cornea"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1167\/iovs.16-20926","article-title":"Subconjunctival Bevacizumab Injection Impairs Corneal Innervations and Epithelial Wound Healing in Mice","volume":"58","author":"Dong","year":"2017","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1167\/iovs.07-1129","article-title":"Safety Profile of Topical VEGF Neutralization at the Cornea","volume":"50","author":"Bock","year":"2009","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/j.biochi.2013.03.002","article-title":"Mechanisms of resistance to anti-angiogenesis therapies","volume":"95","author":"Giuliano","year":"2013","journal-title":"Biochimie"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1167\/iovs.18-24024","article-title":"Anti-CD160, Alone or in Combination with Bevacizumab, Is a Potent Inhibitor of Ocular Neovascularization in Rabbit and Monkey Models","volume":"59","author":"Menguy","year":"2018","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.sjopt.2010.05.002","article-title":"Regression of aggressive corneal vascularization after photodynamic therapy, subconjunctival Avastin injections and topical cyclosporin-A 1% drops: A case report","volume":"24","author":"Kirat","year":"2010","journal-title":"Saudi J. Ophthalmol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"126","DOI":"10.5301\/ejo.5000050","article-title":"Triple Therapy for Corneal Neovascularization: A Case Report","volume":"22","author":"Vergallo","year":"2012","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1159\/000324994","article-title":"Inhibitory effects of SU5416, a selective vascular endothelial growth factor receptor tyrosine kinase inhibitor, on experimental corneal neovascularization","volume":"47","author":"Keskin","year":"2012","journal-title":"Ophthalmic Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kong, D.-H., Kim, M.R., Jang, J.H., Na, H.-J., Lee, S., Lee, S., and Lee, S. (2017). A Review of Anti-Angiogenic Targets for Monoclonal Antibody Cancer Therapy. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081786"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/55\/11\/729\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:32:35Z","timestamp":1760189555000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/55\/11\/729"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,7]]},"references-count":41,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["medicina55110729"],"URL":"https:\/\/doi.org\/10.3390\/medicina55110729","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,7]]}}}