Inhibition of Corneal Neovascularization by Subconjunctival Bevacizumab in an Animal Model

Purpose To evaluate the effect of subconjunctival injection of bevacizumab on experimentally induced corneal neovascularization. Design Experimental animal study. Methods Twelve New Zealand white rabbits were involved, divided equally into four groups. Only one eye per rabbit was used. Topical insti...

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Veröffentlicht in:American journal of ophthalmology 2008-03, Vol.145 (3), p.424-431.e1
Hauptverfasser: Papathanassiou, Miltiadis, Theodossiadis, Panagiotis G, Liarakos, Vasilios S, Rouvas, Alexandros, Giamarellos-Bourboulis, Evaggelos J, Vergados, Ioannis A
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container_end_page 431.e1
container_issue 3
container_start_page 424
container_title American journal of ophthalmology
container_volume 145
creator Papathanassiou, Miltiadis
Theodossiadis, Panagiotis G
Liarakos, Vasilios S
Rouvas, Alexandros
Giamarellos-Bourboulis, Evaggelos J
Vergados, Ioannis A
description Purpose To evaluate the effect of subconjunctival injection of bevacizumab on experimentally induced corneal neovascularization. Design Experimental animal study. Methods Twelve New Zealand white rabbits were involved, divided equally into four groups. Only one eye per rabbit was used. Topical instillation of 10 μl 5% NaOH solution was used, under general anesthesia, to induce corneal neovascularization secondary to corneal alkali burn in groups 2, 3, and 4. A single dose of 3.75 mg (25 mg/ml) bevacizumab was injected subconjunctivally. Group 1 (control group 1) was neither cauterized nor treated. Group 2 (control group 2) received a sham injection of balanced salt solution on day 14. Group 3 was treated on day 14 (after corneal neovascularization had been established). Group 4 was treated on day 1. Digital photographs were obtained and analyzed during the entire 28-day procedure. The area of neovascularization and scarring were measured in terms of the percentage of corneal surface affected. Results On day 28, the difference of neovascularization between groups 2, 3, and 4 was found to be statistically significant at the .05 level (one-way analysis of variance [ANOVA]): group 4 (4.7% ± 3.1%) < group 3 (13.3% ± 2.3%) < group 2 (41.0% ± 3.6%; P < .05, Mann–Whitney U test). In group 3, the area of neovascularization decreased 14 days after treatment by 42%. Neovascularization was almost completely absent in group 4. The development of scarring was unaffected by bevacizumab ( P > .1, one-way ANOVA). No side effects were noted. Conclusions Subconjunctival administration of bevacizumab inhibits corneal neovascularization effectively in the rabbit experimental model, especially if administered early.
doi_str_mv 10.1016/j.ajo.2007.11.003
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Design Experimental animal study. Methods Twelve New Zealand white rabbits were involved, divided equally into four groups. Only one eye per rabbit was used. Topical instillation of 10 μl 5% NaOH solution was used, under general anesthesia, to induce corneal neovascularization secondary to corneal alkali burn in groups 2, 3, and 4. A single dose of 3.75 mg (25 mg/ml) bevacizumab was injected subconjunctivally. Group 1 (control group 1) was neither cauterized nor treated. Group 2 (control group 2) received a sham injection of balanced salt solution on day 14. Group 3 was treated on day 14 (after corneal neovascularization had been established). Group 4 was treated on day 1. Digital photographs were obtained and analyzed during the entire 28-day procedure. The area of neovascularization and scarring were measured in terms of the percentage of corneal surface affected. Results On day 28, the difference of neovascularization between groups 2, 3, and 4 was found to be statistically significant at the .05 level (one-way analysis of variance [ANOVA]): group 4 (4.7% ± 3.1%) &lt; group 3 (13.3% ± 2.3%) &lt; group 2 (41.0% ± 3.6%; P &lt; .05, Mann–Whitney U test). In group 3, the area of neovascularization decreased 14 days after treatment by 42%. Neovascularization was almost completely absent in group 4. The development of scarring was unaffected by bevacizumab ( P &gt; .1, one-way ANOVA). No side effects were noted. Conclusions Subconjunctival administration of bevacizumab inhibits corneal neovascularization effectively in the rabbit experimental model, especially if administered early.</description><identifier>ISSN: 0002-9394</identifier><identifier>EISSN: 1879-1891</identifier><identifier>DOI: 10.1016/j.ajo.2007.11.003</identifier><identifier>PMID: 18207123</identifier><identifier>CODEN: AJOPAA</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Angiogenesis ; Angiogenesis Inhibitors - administration &amp; dosage ; Animals ; Antibodies, Monoclonal - administration &amp; dosage ; Antibodies, Monoclonal, Humanized ; Bevacizumab ; Biological and medical sciences ; Conjunctiva ; Cornea - blood supply ; Corneal Neovascularization - drug therapy ; Corneal Neovascularization - pathology ; Diabetic retinopathy ; Disease Models, Animal ; Injections ; Male ; Medical sciences ; Miscellaneous ; Ophthalmology ; Rabbits ; Rodents ; Steroids ; Studies ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - antagonists &amp; inhibitors</subject><ispartof>American journal of ophthalmology, 2008-03, Vol.145 (3), p.424-431.e1</ispartof><rights>Elsevier Inc.</rights><rights>2008 Elsevier Inc.</rights><rights>2008 INIST-CNRS</rights><rights>Copyright Elsevier Limited Mar 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c530t-ed9d346b31847bfe6006042925f5dc0f408845c1b4aa5619f17e6dfed402802b3</citedby><cites>FETCH-LOGICAL-c530t-ed9d346b31847bfe6006042925f5dc0f408845c1b4aa5619f17e6dfed402802b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ajo.2007.11.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=20122217$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18207123$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Papathanassiou, Miltiadis</creatorcontrib><creatorcontrib>Theodossiadis, Panagiotis G</creatorcontrib><creatorcontrib>Liarakos, Vasilios S</creatorcontrib><creatorcontrib>Rouvas, Alexandros</creatorcontrib><creatorcontrib>Giamarellos-Bourboulis, Evaggelos J</creatorcontrib><creatorcontrib>Vergados, Ioannis A</creatorcontrib><title>Inhibition of Corneal Neovascularization by Subconjunctival Bevacizumab in an Animal Model</title><title>American journal of ophthalmology</title><addtitle>Am J Ophthalmol</addtitle><description>Purpose To evaluate the effect of subconjunctival injection of bevacizumab on experimentally induced corneal neovascularization. Design Experimental animal study. Methods Twelve New Zealand white rabbits were involved, divided equally into four groups. Only one eye per rabbit was used. Topical instillation of 10 μl 5% NaOH solution was used, under general anesthesia, to induce corneal neovascularization secondary to corneal alkali burn in groups 2, 3, and 4. A single dose of 3.75 mg (25 mg/ml) bevacizumab was injected subconjunctivally. Group 1 (control group 1) was neither cauterized nor treated. Group 2 (control group 2) received a sham injection of balanced salt solution on day 14. Group 3 was treated on day 14 (after corneal neovascularization had been established). Group 4 was treated on day 1. Digital photographs were obtained and analyzed during the entire 28-day procedure. The area of neovascularization and scarring were measured in terms of the percentage of corneal surface affected. Results On day 28, the difference of neovascularization between groups 2, 3, and 4 was found to be statistically significant at the .05 level (one-way analysis of variance [ANOVA]): group 4 (4.7% ± 3.1%) &lt; group 3 (13.3% ± 2.3%) &lt; group 2 (41.0% ± 3.6%; P &lt; .05, Mann–Whitney U test). In group 3, the area of neovascularization decreased 14 days after treatment by 42%. Neovascularization was almost completely absent in group 4. The development of scarring was unaffected by bevacizumab ( P &gt; .1, one-way ANOVA). No side effects were noted. 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Theodossiadis, Panagiotis G ; Liarakos, Vasilios S ; Rouvas, Alexandros ; Giamarellos-Bourboulis, Evaggelos J ; Vergados, Ioannis A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c530t-ed9d346b31847bfe6006042925f5dc0f408845c1b4aa5619f17e6dfed402802b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Angiogenesis</topic><topic>Angiogenesis Inhibitors - administration &amp; dosage</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - administration &amp; dosage</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Bevacizumab</topic><topic>Biological and medical sciences</topic><topic>Conjunctiva</topic><topic>Cornea - blood supply</topic><topic>Corneal Neovascularization - drug therapy</topic><topic>Corneal Neovascularization - pathology</topic><topic>Diabetic retinopathy</topic><topic>Disease Models, Animal</topic><topic>Injections</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Ophthalmology</topic><topic>Rabbits</topic><topic>Rodents</topic><topic>Steroids</topic><topic>Studies</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - antagonists &amp; inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Papathanassiou, Miltiadis</creatorcontrib><creatorcontrib>Theodossiadis, Panagiotis G</creatorcontrib><creatorcontrib>Liarakos, Vasilios S</creatorcontrib><creatorcontrib>Rouvas, Alexandros</creatorcontrib><creatorcontrib>Giamarellos-Bourboulis, Evaggelos J</creatorcontrib><creatorcontrib>Vergados, Ioannis A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of ophthalmology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Papathanassiou, Miltiadis</au><au>Theodossiadis, Panagiotis G</au><au>Liarakos, Vasilios S</au><au>Rouvas, Alexandros</au><au>Giamarellos-Bourboulis, Evaggelos J</au><au>Vergados, Ioannis A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Corneal Neovascularization by Subconjunctival Bevacizumab in an Animal Model</atitle><jtitle>American journal of ophthalmology</jtitle><addtitle>Am J Ophthalmol</addtitle><date>2008-03-01</date><risdate>2008</risdate><volume>145</volume><issue>3</issue><spage>424</spage><epage>431.e1</epage><pages>424-431.e1</pages><issn>0002-9394</issn><eissn>1879-1891</eissn><coden>AJOPAA</coden><abstract>Purpose To evaluate the effect of subconjunctival injection of bevacizumab on experimentally induced corneal neovascularization. Design Experimental animal study. Methods Twelve New Zealand white rabbits were involved, divided equally into four groups. Only one eye per rabbit was used. Topical instillation of 10 μl 5% NaOH solution was used, under general anesthesia, to induce corneal neovascularization secondary to corneal alkali burn in groups 2, 3, and 4. A single dose of 3.75 mg (25 mg/ml) bevacizumab was injected subconjunctivally. Group 1 (control group 1) was neither cauterized nor treated. Group 2 (control group 2) received a sham injection of balanced salt solution on day 14. Group 3 was treated on day 14 (after corneal neovascularization had been established). Group 4 was treated on day 1. Digital photographs were obtained and analyzed during the entire 28-day procedure. The area of neovascularization and scarring were measured in terms of the percentage of corneal surface affected. Results On day 28, the difference of neovascularization between groups 2, 3, and 4 was found to be statistically significant at the .05 level (one-way analysis of variance [ANOVA]): group 4 (4.7% ± 3.1%) &lt; group 3 (13.3% ± 2.3%) &lt; group 2 (41.0% ± 3.6%; P &lt; .05, Mann–Whitney U test). In group 3, the area of neovascularization decreased 14 days after treatment by 42%. Neovascularization was almost completely absent in group 4. The development of scarring was unaffected by bevacizumab ( P &gt; .1, one-way ANOVA). No side effects were noted. Conclusions Subconjunctival administration of bevacizumab inhibits corneal neovascularization effectively in the rabbit experimental model, especially if administered early.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>18207123</pmid><doi>10.1016/j.ajo.2007.11.003</doi><tpages>8</tpages></addata></record>
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subjects Angiogenesis
Angiogenesis Inhibitors - administration & dosage
Animals
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal, Humanized
Bevacizumab
Biological and medical sciences
Conjunctiva
Cornea - blood supply
Corneal Neovascularization - drug therapy
Corneal Neovascularization - pathology
Diabetic retinopathy
Disease Models, Animal
Injections
Male
Medical sciences
Miscellaneous
Ophthalmology
Rabbits
Rodents
Steroids
Studies
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - antagonists & inhibitors
title Inhibition of Corneal Neovascularization by Subconjunctival Bevacizumab in an Animal Model
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