Rate of serious adverse effects in a series of bevacizumab and ranibizumab injections

Sharma, Sanjay; Johnson, Davin; Abouammoh, Marwan; Hollands, Simon; Brissette, Ashley

doi:10.1016/j.jcjo.2012.03.026

Cited by 56 publications

(44 citation statements)

References 33 publications

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“…Most case series reported no specific complications, although there is always some risk of postinjection endophthalmitis. 49 Most studies reported that IVB might be effective in terms of improving visual acuity and reducing CMT without significant complications and can be considered an optional intervention, 1,2,23,24,28,32,33 but these conclusions should be interpreted cautiously owing to the self-limiting nature of acute and even in chronic CSC. Moreover, it should be noted that the aqueous humor and plasma levels of VEGF were not significantly increased in patients with CSC compared with the healthy control group.…”

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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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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“…In comparison studies using intravitreal injection of bevacizumab versus ranibizumab, bevacizumab was 12 times more likely to cause severe intraocular inflammation (odds ratio [OR] ¼ 11.71; 95% confidence interval [CI] ¼ 1.5-93). 33 No apparent cellular toxicity was observed after application of ranibizumab.…”

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confidence: 98%

Modulation of Bevacizumab-Induced Toxicity for Cultured Human Corneal Fibroblasts

Kim

Kang²,

Kim

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…In studies comparing ranibizumab and bevacizumab treatment, the incidence of ATEs either did not differ significantly between groups [41] or showed a trend toward an increased risk for ATEs in patients receiving bevacizumab [43,44]. However, the IVAN (Inhibit VEGF in Age-related Choroidal Neovascularization) study reported significantly more ATEs with ranibizumab (bevacizumab vs. ranibizumab: 0.7 vs. 2.9%), but only at 1 year [45,46].…”

Section: Discussionmentioning

confidence: 99%

“…Intravitreal injections of bevacizumab are used off-label in AMD and other ocular diseases associated with macular edema and retinal or choroidal neovascularization [8]. However, the elimination of intravitreally administered full-length IgG across the blood-retinal barrier into the blood system has raised concerns about a possible increased risk of systemic effects [9,10,11]. In addition, it is well known that combination treatment with bevacizumab and chemotherapy increases the risk of arterial thromboembolic events (ATEs) in cancer patients by approximately 2-fold [8,12,13].…”

Section: Introductionmentioning

confidence: 99%

Different Effects of Ranibizumab and Bevacizumab on Platelet Activation Profile

Sobolewska

Grimmel

Gatsiou³

et al. 2015

Ophthalmologica

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Purpose: The aim of the study was to evaluate the potential influence of ranibizumab and bevacizumab on platelet activation and aggregation, which are critical processes in the pathogenesis of arterial thromboembolic events (ATEs). Methods: For the assessment of platelet function, flow cytometry and aggregometry were employed. Platelets were isolated from healthy volunteers and exposed to ranibizumab (1 mg/ml and 150 ng/ml) and bevacizumab (2.5 mg/ml and 3 μg/ml) or their solvents for 10 and 30 min prior to the addition of TRAP (25 μM), PAR-4-AP (25 μM) or thrombin (0.02 U/ml). The surface expression of activated GP IIb/IIIa, P-selectin (CD62P) and platelet-bound stromal cell-derived factor-1 (SDF-1) was measured on resting (nonactivated) and activated platelets by flow cytometry. The platelet aggregation capacity was examined using light transmission aggregometry. Results: The expression of surface activation markers did not differ significantly between nonstimulated and TRAP-, PAR-4-AP- or thrombin-activated platelets after incubating with ranibizumab. However, GP IIb/IIIa, CD62P and SDF-1 were significantly downregulated in PAR-4-AP- and thrombin-activated platelets after exposure to bevacizumab 2.5 mg/ml. In addition, ranibizumab- and bevacizumab-FITC were significantly increased in all activated platelets. No significant differences were observed in the aggregation of activated platelets after incubation with ranibizumab or bevacizumab. Conclusion: All ranibizumab concentrations as well as the bevacizumab concentration of 3 μg/ml had no influence on platelet activation and aggregation. Therefore, this in vitro study did not show any relationship between the exposition of activated platelets to ranibizumab or bevacizumab and the development of ATEs. However, the highest level of bevacizumab interfered with platelet activation, leading to downregulation of platelet activation markers. This observation might explain why the systemic treatment with high-dose bevacizumab could be associated with an increased risk of bleeding. Regarding the use of lower intravitreal dosages, further research should focus on the complex interactions between platelets and other cells, such as endothelial cells, which might stronger relate to a potentially increased risk of ATEs and depend on systemic vascular endothelial growth factor levels. Facing the different activation profiles, the diverse effects of the drugs on the cellular level have to be critically scrutinized for their clinical relevance.

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Rate of serious adverse effects in a series of bevacizumab and ranibizumab injections

Cited by 56 publications

References 33 publications

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

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

Modulation of Bevacizumab-Induced Toxicity for Cultured Human Corneal Fibroblasts

Different Effects of Ranibizumab and Bevacizumab on Platelet Activation Profile

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