Intravitreal Bevacizumab for Subfoveal Choroidal Neovascularization in Age-Related Macular Degeneration at Twenty-four Months: The Pan-American Collaborative Retina Study

Arévalo, J. Fernando; Sánchez, J. García; Wu, Lihteh; Berrocal, María H.; Alezzandrini, Arturo; Restrepo, Natalia; Maia, Maurício; Farah, Michel Eid; Brito, Miguel; Díaz-Llopis, M.; Rodriguez, Francisco J.; Reategui, Guillermo; Iturralde-Iraola, Juan; Udaondo, Patricia

doi:10.1016/j.ophtha.2010.01.056

Cited by 66 publications

(71 citation statements)

References 35 publications

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“…Intravenous and intravitreous bevacizumab (IVB) administration decreases central retinal thickness and improves vision, respectively (Michels et al 2005;Rosenfeld et al 2005a,b). The therapeutic effect of bevacizumab on CNV has been previously confirmed (Bashshur et al 2009), and a recent study involving primary IVB demonstrated stability or improvement of visual acuity in patients with subfoveal CNV secondary to AMD at 24 months post-IVB (Arevalo et al 2010). However, the mechanism of action of bevacizumab on CNV has not been fully determined.…”

Section: Introductionmentioning

confidence: 87%

Bevacizumab modulates epithelial‐to‐mesenchymal transition in the retinal pigment epithelial cells via connective tissue growth factor up‐regulation

Chen

Liang

Chen

et al. 2012

Acta Ophthalmologica

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ABSTRACT.Purpose: To investigate the effect of bevacizumab treatment on connective tissue growth factor (CTGF) expression and the induction of epithelial-to-mesenchymal transition in ARPE-19 cells and human donor retinal pigment epithelium (HRPE) cells in vitro. Methods: We quantitated the protein and gene expression level of CTGF by ELISA. The effect of Fc-Fc receptor (Fc-FcR) interaction on CTGF expression was evaluated by CD64 siRNA silencing. Expression of epithelial-to-mesenchymal transition markers, alpha-smooth muscle actin (a-SMA) and zona occludens protein (ZO-1) was evaluated by Western blot. Cell migration and collagen gel contraction assay were examined by light microscopy, and collagen production was measured by ELISA. Results: Bevacizumab stimulation increased CTGF expression in ARPE-19 and HRPE cells in a dose-dependent manner. CD64 gene silencing inhibited the effect of bevacizumab-induced CTGF up-regulation. Bevacizumab increased the expression of a-SMA and decreased the expression of ZO-1 in ARPE-19 cells. Bevacizumab also caused the release of type-1 collagen and increased cell migration and contraction of collagen. Conclusions: Bevacizumab exerts pro-fibrotic effects on human RPE cells at clinical doses by up-regulation of CTGF expression via an Fc-FcR interaction. This effect of bevacizumab may be one of the underlying mechanisms involved in age-related macular degeneration therapy or intravitreal bevacizumab-associated complications.

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Section: Introductionmentioning

confidence: 87%

Bevacizumab modulates epithelial‐to‐mesenchymal transition in the retinal pigment epithelial cells via connective tissue growth factor up‐regulation

Chen

Liang

Chen

et al. 2012

Acta Ophthalmologica

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“…A retrospective study demonstrated the effectiveness of bevacizumab in the treatment of AMD, with average vision improving from 20/235 to 20/172. 47 To circumvent the theoretical concerns associated with the intravitreal injection of full-length antibodies, bevacizumab was cleaved into a smaller Fab fragment (48 kDa compared with the original 148 kDa) 48 and was affinity-enhanced by 5-to 20-fold 49 tion (ANCHOR) study improved more than patients treated with photodynamic therapy (10.7 letters vs loss of 9.8 letters). 51 Despite the ranibizumab trials, however, bevacizumab quickly became the drug of first choice among the majority (58%) of retina surgeons 52 …”

Section: Ocular Conditions and Therapiesmentioning

confidence: 99%

The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology

Stewart

2012

Mayo Clinic Proceedings

167

105

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Vascular endothelial growth factor (VEGF) plays an important role in both physiologic and pathologic angiogenesis and contributes to increased permeability across both the blood-retinal and blood-brain barriers. After 2 decades of extensive research into the VEGF families and receptors, specific molecules have been targeted for drug development, and several medications have received US Food and Drug Administration approval. Bevacizumab, a full-length antibody against VEGF approved for the intravenous treatment of advanced carcinomas, has been used extensively in ophthalmology for exudative age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, retinopathy of prematurity, and other chorioretinal vascular disorders. Pegaptanib and ranibizumab have been developed specifically for intraocular use, whereas the soon-to-be-introduced aflibercept (VEGF Trap-Eye) is moving through clinical trials for both intraocular and systemic use. Although these drugs exhibit excellent safety profiles, ocular and systemic complications, particularly thromboembolic events, remain a concern in patients receiving therapy. Patients experiencing adverse events that may be related to VEGF suppression should be carefully evaluated by both the ophthalmologist and the medical physician to reassess the need for intraocular therapy and explore the feasibility of changing medications. For this review a search of PubMed from January 1, 1985 through April 15, 2011, was performed using the following terms (or combination of terms): vascular endothelial growth factors, VEGF, age-related macular degeneration, diabetic retinopathy, retina vein occlusions, retinopathy of prematurity, intravitreal injections, bevacizumab, ranibizumab, and VEGF Trap. Studies were limited to those published in English. Other articles were identified from bibliographies of retrieved articles and archives of the author.

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“…Despite its large molecular weight, bevacizumab showed satisfying penetration into subretinal space, without any harmful neurophysiologic effects (25). Many clinical trials confirmed later the efficacy of bevacizumab in improving the visual acuity, reducing the retinal exudation and the acceptable safety profile (26,27,28,29,30).…”

Section: Bevacizumabmentioning

confidence: 94%

Treatment of Neovascular Age Related Macular Degeneration

Lazić¹,

Gabrić²

2012

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Intravitreal Bevacizumab for Subfoveal Choroidal Neovascularization in Age-Related Macular Degeneration at Twenty-four Months: The Pan-American Collaborative Retina Study

Cited by 66 publications

References 35 publications

Bevacizumab modulates epithelial‐to‐mesenchymal transition in the retinal pigment epithelial cells via connective tissue growth factor up‐regulation

Bevacizumab modulates epithelial‐to‐mesenchymal transition in the retinal pigment epithelial cells via connective tissue growth factor up‐regulation

The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology

Treatment of Neovascular Age Related Macular Degeneration

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