Recovery of plasma vascular endothelial growth factor concentrations during aflibercept loading phase and after the transition to bimonthly treatment for neovascular age-related macular degeneration

Roald, Anca B; Aass, Hans Christian Dalsbotten; Moe, Morten C.

doi:10.1136/bjophthalmol-2015-306781

Cited by 5 publications

(6 citation statements)

References 13 publications

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“…Roald et al used intravitreal aflibercept to treat 16 individuals with naïve neovascular macular degeneration. 34 To summarize, aflibercept significantly reduced the plasma VEGF levels (which was 56% on the first day) immediately after the treatment. Despite the monthly intravitreal injection of aflibercept, plasma VEGF levels were 87% of baseline in the first month and 90% in the second month.…”

Section: Discussionmentioning

confidence: 82%

“…We found that the mean VEGF level of the control group was statistically higher than those of the injection groups, whereas no statistically significant differences were noted between the injected groups. 34 To summarize, aflibercept significantly reduced the plasma VEGF levels (which was 56% on the first day) immediately after the treatment. Despite the monthly intravitreal injection of aflibercept, plasma VEGF levels were 87% of baseline in the first month and 90% in the second month.…”

Section: Discussionmentioning

confidence: 82%

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The effects of subconjunctival bevacizumab, ranibizumab, and aflibercept on corneal neovascularization

et al. 2022

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Purpose To investigate the effects of subconjunctival bevacizumab, ranibizumab, and aflibercept in an experimental corneal neovascularization model. Materials and methods The eyes of 24 rats were chemically cauterized and randomly divided into four groups: bevacizumab group (0.05 mL/1.25 mg bevacizumab), ranibizumab group (0.05 mL/0.5 mg ranibizumab), aflibercept group (0.05 mL/1.25 mg aflibercept), and control group (0.05 mL saline solution). Plasma vascular endothelial growth factor (VEGF) levels were among the major measurement outcomes to assess corneal neovascularization. The collected plasmas were analyzed using the SIGMA RAB0511 Rat VEGF Elisa kit. The PCR technique and VEGF amplification procedures were used for molecular analysis. Each cornea was removed and histologically examined on day 21. Corneal images were evaluated by image analyzer software. Results In the post-injection period, the number of major corneal arteries decreased significantly in the injection groups when compared to the control group ( p = 0.037), but no statistically significant differences were noted among the injection groups ( p > 0.05). The aflibercept group had the lowest area of neovascularization. Immunohistochemical staining revealed substantially lower VEGF percentages in neovascularized arteries of the injection groups than the control group ( p = 0.015). In TUNEL staining, the mean TUNEL value (number/1hpf) was substantially greater in the control group than in the injection groups, but the mean TUNEL values were similar between the injection groups ( p = 0.019, p > 0.05, respectively). No statistically significant differences were observed between the groups in terms of corneal surface area with increased cellularity, edema, and inflammation ( p = 0.263). The mean plasma VEGF concentration in the control group was statistically greater than those in the injection groups ( p = 0.001). Conclusion Subconjunctival bevacizumab, ranibizumab, and aflibercept crossed the blood and seemed to be effective in inhibiting corneal neovascularization without causing epitheliopathy in an experimental rat model compared to the controls. However, no significant results were noted between these three anti-VEGF molecules.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 82%

The effects of subconjunctival bevacizumab, ranibizumab, and aflibercept on corneal neovascularization

et al. 2022

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“…The mechanism or reason for this underestimation was not determined. A separate study [19], which used a different methodology to measure free VEGF (Bio-Plex Cytokine VEGF-A Luminex assay [Bio-Rad]), reported less impact on circulating VEGF after IVT administration of 2 mg aflibercept, (500 pg/ml) of VEGF with increasing concentrations of each inhibitor, ranging from 72.9 to 2.7 pM, were prepared and incubated at room temperature for approximately 3 days before analysis using the Quantikine VEGF ELISA. At the detection step, the anti-VEGF polyclonal antibody detection antibody in the kit was replaced with an anti-human IgG, Fcγ fragment-specific, polyclonal antibody (for aflibercept and bevacizumab) or an antihuman IgG, F(ab') 2 fragment-specific, polyclonal antibody (for ranibizumab).…”

Section: Discussionmentioning

confidence: 99%

“…In a separate study [19], using a different methodology to measure VEGF, only a modest and temporary decrease in circulating VEGF concentration was observed in 16 patients after IVT administration of 2 mg aflibercept. In this study, the mean free VEGF concentration was 59.6 pg/ml at baseline and only decreased to 32.5 pg/ml after administration of aflibercept.…”

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confidence: 90%

Anti-VEGF Drug Interference with Vegf Quantitation in the R&D Systems Human Quantikine VEGF ELISA Kit

et al. 2019

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To evaluate the accuracy of the Quantikine Human VEGF Immunoassay (R&D Systems) in the presence of VEGF inhibitors. Materials & Methods: Quantikine VEGF ELISA (R&D), anti-VEGF 165 mAb (R&D), VEGF 165 and aflibercept (Regeneron), ranibizumab and bevacizumab (Genentech). Results: Binding affinity of anti-VEGF 165 mAb for VEGF was threefold weaker than aflibercept, but 33-and 40-fold stronger than ranibizumab or bevacizumab. Extended incubation of VEGF complexed with inhibitors led to VEGF dissociation from ranibizumab and bevacizumab, but not aflibercept, and subsequent binding by the immunoassay capture antibody. The immunoassay also detected VEGF:ranibizumab and VEGF:bevacizumab complexes but not VEGF:aflibercept complexes. Conclusion: The immunoassay cannot accurately quantitate VEGF in the presence of these VEGF inhibitors as they interfere with the capture and detection of free VEGF.

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“…Aflibercept was also the most potent of these three drugs in reducing plasma-free VEGF with levels undetectable from 3 hours postdose to greater than 1 week postdose. 71 It is postulated that the Fc fragment present in both the bevacizumab and aflibercept molecules extends their serum half-life, accounting for these differences. 72 The clinical significance of this is, however, yet to be elucidated.…”

Section: Pharmacokineticsmentioning

confidence: 99%

The role of aflibercept in the management of diabetic macular edema

Chang

Hong

Ewe

et al. 2015

DDDT

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Diabetic macular edema (DME) represents one of the leading causes of visual impairment in working-age adults. Although there are several proven treatments available for this condition, pharmacotherapy through the use of intravitreal antivascular endothelial growth factor agents has revolutionized the management of DME over the past decade with superior outcomes compared to laser therapy. This review summarizes the pathophysiology and available treatment options for the management of DME, with an emphasis on the efficacy and safety profile of a single particular intravitreal antivascular endothelial growth factor agent, aflibercept.

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Recovery of plasma vascular endothelial growth factor concentrations during aflibercept loading phase and after the transition to bimonthly treatment for neovascular age-related macular degeneration

Abstract: Identifier no. NCT02125864.

Cited by 5 publications

References 13 publications

The effects of subconjunctival bevacizumab, ranibizumab, and aflibercept on corneal neovascularization

The effects of subconjunctival bevacizumab, ranibizumab, and aflibercept on corneal neovascularization

Anti-VEGF Drug Interference with Vegf Quantitation in the R&D Systems Human Quantikine VEGF ELISA Kit

The role of aflibercept in the management of diabetic macular edema

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