Anti-VEGF monoclonal antibody-induced regression of corneal neovascularization and inflammation in a rabbit model of herpetic stromal keratitis

Saravia, Mario; Zapata, Gustavo; Ferraiolo, Paula; Racca, Lourdes; Berra, Alejandro

doi:10.1007/s00417-009-1101-y

Cited by 27 publications

(17 citation statements)

References 38 publications

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“…Consistent with this, Src kinase inhibitors resulted in inhibition of CXCL1 expression. Thus, it is possible that significant reduction in the neutrophils in the treated group may be a consequence of reduced chemokine levels, which is the prominent regulator of neutrophil infiltration into the inflamed cornea (23).…”

Section: Discussionmentioning

confidence: 99%

“…In humans, SK may lead to permanent loss of vision, and the current treatment modalities that are used for the clinical management of SK include anti-VEGF antibody treatment, such as that using bevacizumab (4,23), antivirals, and corticosteroids, but none of them are considered ideal. Antiviral compounds that block virus entry or reduce viral replication can be prophylactic and may not be efficacious against SK.…”

Section: Discussionmentioning

confidence: 99%

“…As a result, small-molecule inhibitors targeting cellular responses that contribute to disease may have a substantial advantage over antiviral approaches. Corticosteroid therapy, on the other hand, when continued for a longer duration, might exhibit several side effects (15), and although anti-VEGF antibody (bevacizumab) was shown to reduce VEGF-induced neovascularization (22,23), abnormal vascular permeability is frequently associated with neovascularization (24). Thus, an antivascular permeability compound that is also antiangiogenic, such as Src kinase inhibitor, should have added therapeutic benefit.…”

Section: Discussionmentioning

confidence: 99%

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An Anti-Inflammatory Role of VEGFR2/Src Kinase Inhibitor in Herpes Simplex Virus 1-Induced Immunopathology

Sharma

Mulik

Kumar

et al. 2011

J Virol

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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An Anti-Inflammatory Role of VEGFR2/Src Kinase Inhibitor in Herpes Simplex Virus 1-Induced Immunopathology

Sharma

Mulik

Kumar

et al. 2011

J Virol

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“…Anti-VEGF antibodies can bind VEGFR1 resulting in macrophage inhibition and neutrophil chemotaxis. Saravia et al (31) reported that subconjunctival administration of bevacizumab abolished the inflammatory response, induced involution of new vessels, and resulted in the return of corneal function in herpes simplex virus type 1-infected rabbits. Furthermore, they demonstrated that a single subconjunctival injection of 10 μl of bevacizumab (25 μg/μl) leads to a significant decrease in neutrophils and blocks the inward flow of inflammatory cells into the stroma.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the effects of subconjunctival and topical anti-VEGF therapy (bevacizumab) on experimental corneal neovascularization

Özdemir¹,

Altıntaş²,

Altıntaş³

et al. 2014

Arquivos Brasileiros De Oftalmologia

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Purpose: To compare the effects of bevacizumab applied either subconjunctivally or topically, in a rat model of corneal neovascularization induced by alkali burn. Methods: The right corneas of 24 Wistar-Albino rats were cauterized with silver nitrate sticks. The rats were divided randomly and equally into three groups: no treatment control (n=8), subconjunctival bevacizumab treatment (n=8), and topical bevacizumab treatment (n=8). Immediately following cauterization, the subconjunctival group was treated with a 0.05 ml (1.25 mg) bevacizumab subconjunctival injection. The topical group was treated with 10 mg/ml bevacizumab twice daily, and the control group received subconjunctival saline injections twice daily. The burn stimulus and neovascularization scores were evaluated using a technique previously described by Mahoney and Waterbury. Digital photographs were obtained before the eyes were enucleated and corneal sections were then analyzed by histopathology. Results: The mean burn stimulus score was 1.86 ± 0.6 and there was no statistical difference between the groups (p=0.730). The mean neovascularization scores in the subconjunctival and topical bevacizumab groups were statistically lower than the control group (p<0.05). The mean percentage area of corneal neovascularization was 82.5 ± 22.1 in the control group, 42.7 ± 15.0 in the subconjunctival group, and 55.8 ± 18.2 in the topical group. The differences between the control and treatment groups were statistically significant (p<0.05). Histopathology showed that the treatment groups presented less neovascularization, inflammation, and fibroblast activity than the control group (p<0.05). Conclusions: This study demonstrates that both subconjunctival and topical administrations of bevacizumab inhibit corneal neovascularization and decrease inflammation and fibroblast activity in a rat model of corneal neovascularization induced by alkali burn.

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“…A ação na inflamação aguda ainda não havia sido estudada mais profundamente, sendo sugerido uma diminuição na invasão de neutrófilos na ferida (23) . Os resultados mostraram que a droga não tem um efeito anti-inflamatório clinicamente significativo.…”

Section: Discussionunclassified

Ação do bevacizumabe subconjuntival na neovascularização e re-epitelização corneana 25 dias após queimadura química

Mello¹,

Lupion²,

Oliveira³

et al. 2011

Arq. Bras. Oftalmol.

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Nota Editorial: Depois de concluída a análise do artigo sob sigilo editorial e com a anuência do Dr. Vinícius Coral Ghanem e Procópio Miguel dos Santos sobre a divulgação de seu nome como revisor, agradecemos sua participação neste processo.Ação do bevacizumabe subconjuntival na neovascularização e re-epitelização corneana 25 dias após queimadura química ABSTRACT Purposes:To evaluate the effect of subconjunctival bevacizumab in an experimental model of neovascularization in rabbit cornea. Determine its effect on vessels extension, inflammation, epithelialization of the cornea and whether the evaluation method used is appropriate to compare neovascular models. Methods: Experimental, prospective, randomized, blinded study in twenty rabbits subjected to chemical trauma with sodium hydroxide at 1N divided into two groups. The study group received subconjunctival injection of 0.15 ml (3.75 mg) of bevacizumab and was compared with the control group that received subconjunctival injection of 0.15 ml saline solution. After 25 days, digital photographic analysis was performed to assess the vessel's extension and inflammation/diameter according to pre-established criteria. Histopathology of the cornea, which evaluated the state of the epithelium and the number of polymorphonuclear cells was also studied. Results:The length of the neovessels was greater in the control group compared to the study group (P=<0.001). There was no difference in inflammation/vessel diameter between groups. Histopathology analysis showed that there was no difference between groups for the variables state of the epithelium and number of polymorphonuclear cells. The concordance analysis for the variable extension of the vessels and the variable inflammation/vessel diameter was estimated with Kappa coefficients of 0.705 and 0.500 respectively, indicating a good level of agreement in different evaluations and validating the method. Conclusions:The experimental model is adequate and can be reproduced to evaluate other drugs in the cornea. Bevacizumab inhibit the neovessels' growth but was not effective in preventing the inflammatory response. The drug did not delay the reepithelialization of the cornea.

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Anti-VEGF monoclonal antibody-induced regression of corneal neovascularization and inflammation in a rabbit model of herpetic stromal keratitis

Abstract: Subconjunctival administration of bevacizumab induced involution of new vessels, abolished inflammatory response, and resulted in return of corneal function. Furthermore, bevacizumab is a novel approach for the treatment of herpetic stromal keratitis.

Cited by 27 publications

References 38 publications

An Anti-Inflammatory Role of VEGFR2/Src Kinase Inhibitor in Herpes Simplex Virus 1-Induced Immunopathology

An Anti-Inflammatory Role of VEGFR2/Src Kinase Inhibitor in Herpes Simplex Virus 1-Induced Immunopathology

Comparison of the effects of subconjunctival and topical anti-VEGF therapy (bevacizumab) on experimental corneal neovascularization

Ação do bevacizumabe subconjuntival na neovascularização e re-epitelização corneana 25 dias após queimadura química

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