Safety, penetration and efficacy of topically applied bevacizumab: evaluation of eyedrops in corneal neovascularization after chemical burn

Yoeruek, Efdal; Ziemssen, Focke; Henke-Fahle, Sigrid; Tatar, Olcay; Tura, Aysegül; Grisanti, Salvatore; Bartz‐Schmidt, Karl Ulrich; Szurman, Peter

doi:10.1111/j.1600-0420.2007.01049.x

Cited by 150 publications

(94 citation statements)

References 22 publications

(31 reference statements)

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“…Para a investigação de uma substância antiangiogênica necessita-se de um modelo que permita acessibilidade, visibilidade e acompanhamento temporal do crescimento dos vasos sanguíneos. O coelho foi escolhido por apresentar estas características (17)(18)(19) . De acordo com a análise estatística realizada com os dados obtidos da pesquisa confirmou-se que o método utilizado reproduziu adequadamente o que ocorreu com os vasos.…”

Section: Discussionunclassified

“…Isso se deve possivelmente ao VEGF não ser a única via angiogênica e mesmo como tratamento, outros fatores pró-angiogênicos continuam agindo como TGF-Beta e o fator de crescimento de fibroblasto (19) . Sugere-se que o bevacizumabe não deve ser utilizado como monoterapia e pode ser parte do tratamento para quadros agudos agindo em conjunto com outras drogas como corticóides.…”

Section: Discussionunclassified

“…Estudos com outros quadros devidos a neovasos antigos como a retinopatia diabética (19,29) mostram uma recidiva importante dos vasos após a supressão do medicamento, devendo o tratamento ser realizado seguidamente. Para quadros agudos de neovascularização como queimaduras ou início de neovascularização após um transplante de córnea, o efeito da droga ainda não foi extensivamente estudado e é possível que se diminuirmos o estímulo angiogênico na fase aguda, com o uso de inibidores específicos como o bevacizumabe, podemos ter uma diminuição dos neovasos a longo prazo, já que nesses casos o estímulo angiogênico é de curta duração e não parte da fisiopatologia da doença como na retinopatia diabéti-ca.…”

Section: Discussionunclassified

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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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Section: Discussionunclassified

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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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“…Korneal ödem ve opasitenin de¤erlendirilmesi biyomikroskopik muayeneye göre; Yoeruek ve arkadafllar›n›n tarif ettikleri flekilde yap›ld› (15). Buna göre; korneal ödem varl›¤› 0-2 aras›nda skorland›.…”

Section: Gereç Ve Yöntemunclassified

Alkali Yanığına Bağlı Gelişen Korneal Anjiogenez Modelinde Topikal, Subkonjonktival Bevacizumab ve Florometolon Asetatın Topikal Uygulanması - Özgün Araştırma

Topalkara¹,

Toker²,

Dursun³

et al. 2010

tjo

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ÖzetAmaç: Alkali yan›¤a ba¤l› geliflen korneal anjiogenez modelinde kornea neovaskülarizasyonu üzerine bevacizumab›n etkisini araflt›rmak. Gereç ve Yöntem: Çal›flmada 24 adet Wistar-Albino cinsi rat kullan›ld›. Kornealarda kimyasal koterizasyonu takiben ratlar tesadüfi olarak 4 gruba ayr›ld›. Grup 1'e (kontrol grubu) suni gözyafl› günde iki kez, grup 2'ye topikal florometolon asetat günde iki kez, Grup 3'e subkonjonktival bevacizumab 2,5 mg olarak tek doz, grup 4'e ise topikal bevacizumab günde iki kez 5 mg/ml konsantrasyonunda uyguland›. Üç hafta sonra rat kornealar› biyomikroskopla muayene edildi ve kornea foto¤raflar› çekilip denekler sakrifiye edildi. Neovaskülarize alan oran›, geliflen en uzun damar›n boyu, korneal ödem ve opasite skoru de¤erlendirildi. Sonuçlar: Dijital foto¤raflar analiz edildi¤inde korneal neovaskülarizasyon, geliflen en uzun damar›n boyu, korneal ödem ve opasite skorunun her 3 grupta kontrol grubundan daha düflük oldu¤u görüldü (p<0,05). Korneal neovaskülarizasyon Grup 3 ve 4'de, grup 2'den daha düflüktü (p=0,035, p=0,027). Topikal ve subkonjonktival bevacizumab gruplar› aras›nda korneal neovaskülarizasyon, korneal ödem ve opasite skoru aç›s›ndan anlaml› bir fark saptanmad›. Bununla birlikte geliflen en uzun damar›n boyu topikal bevacizumab grubunda anlaml› olarak daha düflük bulundu (p=0,029). Material and Method: Twenty-four Wistar albino rats were used in our study. After chemical cauterization of the cornea, the rats were divided randomly into four groups. Group 1 (control group) received artificial tears twice a day, group 2 received topical fluorometholone acetate twice a day, in group 3, a single dose of bevacizumab (2.5 mg) was administered by a subconjunctival injection, and group 4 received topical bevacizumab 5mg/ml twice a day. Three weeks later, the rat corneas were evaluated by slit-lamp biomicroscopy and corneal photographs were taken with a digital camera, followed by sacrifice of the subjects. The proportional area of vascularized cornea, length of the longest neovascular sprout, corneal oedema and corneal opacity score were assessed. Result: The analysis of digital photographs showed less corneal neovascularization, corneal oedema, corneal opacity score and shorter length of the longest neovascular sprout in the three drug groups than in the control one (p<0.05). The area of corneal neovascularization in groups 3 and 4 was less than in group 2 (p=0.035 and p=0.027, respectively). Corneal neovascularization, corneal oedema and corneal opacity did not differ significantly between the subconjunctival and topical bevacizumab groups. However, statistically significant decrease was observed in the length of the longest neovascular sprout in the topical bevacizumab group (p=0.029). Discussion: Subconjunctival/topical bevacizumab treatment is an effective method in reducing corneal neovascularization. However, we observed that topical bevacizumab is more efficient than subconjunctival bevacizumab and fluorometholone acetate in preventing corneal neovascularization. (Turk J Oph...

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“…Corneal opacity was scored using a 0-to-4 scaling system (27), where 0 = no opacity, completely clear cornea; 1 = slightly hazy, iris and lens visible; 2 = moderately opaque; iris and lens still detectable, 3 = severely opaque, iris and lens hardly visible and 4 = completely opaque, with no view of iris and lens. Corneal haze was graded in increments of 0.5.…”

Section: Assessment Of Corneal Haze and Neovascularizationmentioning

confidence: 99%

Bevacizumab accelerates corneal wound healing by inhibiting TGF-βexpression in alkali-burned mouse cornea

Lee

Leem²,

Jeong³

et al. 2009

BMB Reports

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This study investigated the effect of subconjunctival injections of bevacizumab, an anti-VEGF antibody, on processes involved in corneal wound healing after alkali burn injury. Mice were divided into three groups: Group 1 was the saline-treated control, group 2 received subconjunctival injection of bevacizumab 1hr after injury and group 3 received bevacizumab 1 hr and 4 days after injury. Cornea neovascularization and opacity were observed using a slit lamp microscope. Corneal repair was assessed through histological analysis and immunostaining for CD31, α-SMA, collagen I, and TGF-β2 7 days post-injury. In

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Safety, penetration and efficacy of topically applied bevacizumab: evaluation of eyedrops in corneal neovascularization after chemical burn

Cited by 150 publications

References 22 publications

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

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

Alkali Yanığına Bağlı Gelişen Korneal Anjiogenez Modelinde Topikal, Subkonjonktival Bevacizumab ve Florometolon Asetatın Topikal Uygulanması - Özgün Araştırma

Bevacizumab accelerates corneal wound healing by inhibiting TGF-βexpression in alkali-burned mouse cornea

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