Penetration of Bevacizumab through the Retina after Intravitreal Injection in the Monkey

Heiduschka, Peter; Fietz, Heike; Hofmeister, Sabine; Schultheiss, Sigrid; Mack, Andreas F.; Peters, Swaantje; Ziemssen, Focke; Niggemann, Birgit; Julien, Sylvie; Bartz‐Schmidt, Karl Ulrich; Schraermeyer, Ulrich

doi:10.1167/iovs.06-1171

Cited by 242 publications

(177 citation statements)

References 23 publications

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“…Accordingly, ranibizumab was developed as a cleaved Fab lacking an Fc region as the smaller size was thought to enhance its diffusion from the vitreous into the retina and choroid (Ferrara et al 2006). Contrary to this original hypothesis, immunohistochemistry studies and findings of systemic VEGF blockade after intravitreal injection of bevacizumab proved the effective penetration of the larger molecule through all retinal layers and the choroid, despite its bigger molecule size (Heiduschka et al 2007). The ease of penetrating the retina and passing into the systemic blood circulation across the blood-retina barrier is thought to be mediated by the presence of FcRn receptors (Kim et al 2009).…”

Section: Discussionmentioning

confidence: 78%

Systemic levels of vascular endothelial growth factor before and after intravitreal injection of aflibercept or ranibizumab in patients with age‐related macular degeneration: a randomised, prospective trial

Zehetner

Kralinger

Modi

et al. 2014

Acta Ophthalmologica

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ABSTRACT.Purpose: To evaluate the changes of vascular endothelial growth factor (VEGF) plasma levels after intravitreal injections of aflibercept or ranibizumab in patients with exudative age-related macular degeneration (AMD). Methods: Thirty-eight patients with exudative AMD were included in this randomised, prospective study. Nineteen patients were randomised to treatment with intravitreal aflibercept (2.0 mg) and 19 to intravitreal ranibizumab (0.5 mg). The concentration of VEGF was measured by ELISA just before the injection, after 7 days and 1 month. Twenty-two age-and sex-matched healthy patients without chorioretinal diseases served as control. Results: The median baseline plasma VEGF concentration was 61.0 pg/ml in the control group, 43.0 pg/ml in the aflibercept group and 59.0 pg/ml in the ranibizumab group (p = 0.127). Seven days after intravitreal injection of aflibercept plasma levels were significantly reduced to values below the minimum detectable dose (MDD) in 17 of 19 patients (89.5%) resulting in a median VEGF concentration of <9 pg/ml (p < 0.001). The reduction persisted throughout 1 month with values below the MDD in 5 of 19 patients (26.3%) and a median measurement of 17.0 pg/ml (p < 0.001). In patients treated with ranibizumab no significant effects could be observed with a baseline VEGF of 59.0 pg/ml, 54.0 pg/ ml at 7 days (p = 0.776) and 58.5 pg/ml at 4 weeks of follow-up (p = 0.670). Conclusion: After intravitreal aflibercept injection, the systemic VEGF levels were significantly reduced throughout the observational period of 4 weeks. No significant systemic effects of intravitreal ranibizumab on plasma VEGF were observed.

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Section: Discussionmentioning

confidence: 78%

Systemic levels of vascular endothelial growth factor before and after intravitreal injection of aflibercept or ranibizumab in patients with age‐related macular degeneration: a randomised, prospective trial

Zehetner

Kralinger

Modi

et al. 2014

Acta Ophthalmologica

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“…[1][2][3][22][23][24]28,30,32,33,[41][42][43] Bevacizumab is a recombinant humanized full-length monoclonal antibody of VEGF that penetrates the retina and is transported into the photoreceptor outer segments, RPE, and choroid after intravitreal injection. 44 The half-life of bevacizumab in the vitreous is 5.6 days, and it remains in the eye for 4 to 6 weeks. 45 Many studies of other macular diseases have reported that the CMT starts decreasing or stabilizes in most eyes at 3-6 weeks.…”

Section: Discussionmentioning

confidence: 99%

Lack of positive effect of intravitreal bevacizumab in central serous chorioretinopathy: meta-analysis and review

Younghae

et al. 2013

Eye

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Purpose To review and evaluate the effects of intravitreal bevacizumab injection (IVB) in centralserous chorioretinopathy (CSC) by meta-analysis. Patients and methods Clinical controlled studies that evaluated the effect of IVB in CSC were identified through systematic searches of Embase, PubMed, and the Cochrane Central Register of Controlled Trials. Data on the bestcorrected visual acuity (BCVA) in logMAR and central macular thickness (CMT) in mm at baseline and 6 months after IVB were extracted and compared with those treated by simple observation.Results Four clinical controlled studies were included in the meta-analysis. The IVB injection group achieved better BCVA at a follow-up of 6 months. However, the analysis showed that there were no significant differences of BCVA at 6 months after injection between IVB group and the observation group ( À 0.02 logMAR, 95% CI À 0.14 to 0.11, P ¼ 0.80). The analysis of the reduction in CMT revealed that the difference between groups was not statistically significant ( À 8.37 lm, 95% CI À 97.26 to 80.52, P ¼ 0.85). No report assessed severe complications or side effects of IVB in patients with CSC. Conclusions Meta-analysis failed to verify the positive effect of IVB in CSC based on the epidemiological literature published to date.

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“…This result may be attributable to the findings that both full-length antibody (bevacizumab) and Fab fragment (ranibizumab) drugs are able to penetrate into all retinal layers, reach the choroid, and accumulate in the wall of the choroidal vessel (26)(27)(28) . As VEGF functions by inducing vessel dilation and increasing ocular blood flow, which is mediated by increased nitric oxide production (29) , VEGF inhibition by these drugs may cause constriction of the choroidal vessels.…”

Section: Discussionmentioning

confidence: 99%

Effect of intravitreal anti-VEGF on choroidal thickness in patients with diabetic macular edema using spectral domain OCT

Kniggendorf¹,

Novais²,

Kniggendorf³

et al. 2016

Arquivos Brasileiros De Oftalmologia

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Approved by the following research ethics committee: UNIFESP (#1.093.853). ABSTRACTPurpose: To evaluate choroidal thickness (CT) using spectral domain optical coherence tomography (SD-OCT) imaging at baseline and 6 months after intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with diabetic macular edema (DME). Methods: A retrospective chart review was performed to identify patients with DME who underwent intravitreal injection of anti-VEGF (bevacizumab or ranibizumab) in a pro re nata (PRN) regimen. Subfoveal choroidal thickness was compared between values obtained at baseline and at 6-month follow-up visits. Results: Thirty-nine eyes (15 females, 24 males) from 39 patients were enrolled (mean age, 62.43 ± 8.7 years; range, 44-79 years). Twenty-three and 16 eyes were treated with ranibizumab and bevacizumab respectively. The mean number of anti-VEGF injections was 2.28 ± 1.27 (range, 1-5). Mean nasal, subfoveal, and temporal choroidal thickness (CT) measurements at baseline were 234.10 ± 8.63 μm, 246.89 ± 8.94 μm, and 238.12 ± 8.20 μm, respectively, and those at 6 months post-treatment were 210.46 ± 8.00 μm, 215.66 ± 8.29 μm, and 212.43 ± 8.14 μm, respectively. Significant differences in CT were observed between baseline and the 6-month follow-up at all measured points (p=0.0327). Conclusions: Over a 6-month period, the use of intravitreal anti-VEGF was associated with significant thinning of the choroid in patients with DME. The clinical significance of a thinner choroid in DME is currently unknown; however, it may contribute to long-term adverse effects on choroidal and retinal function, representing an area requiring future investigation.

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Penetration of Bevacizumab through the Retina after Intravitreal Injection in the Monkey

Cited by 242 publications

References 23 publications

Systemic levels of vascular endothelial growth factor before and after intravitreal injection of aflibercept or ranibizumab in patients with age‐related macular degeneration: a randomised, prospective trial

Systemic levels of vascular endothelial growth factor before and after intravitreal injection of aflibercept or ranibizumab in patients with age‐related macular degeneration: a randomised, prospective trial

Lack of positive effect of intravitreal bevacizumab in central serous chorioretinopathy: meta-analysis and review

Effect of intravitreal anti-VEGF on choroidal thickness in patients with diabetic macular edema using spectral domain OCT

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