Changes of serum VEGF concentration after intravitreal injection of Avastin in treatment of diabetic retinopathy

Davidović, Sofija; Nikolic, Stanislava; Ćurić, Nikola; Latinović, S; Drašković, Dragan; Čabarkapa, Velibor; Stosić, Z

doi:10.5301/ejo.5000118

Cited by 33 publications

(29 citation statements)

References 22 publications

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“…[28][29][30][31] This clearly demonstrates that intravitreally injected IgG can cross the blood-retina barrier. In contrast, systemic plasma concentrations of VEGF were not affected by intravitreal ranibizumab (an anti-VEGF Fab fragment, lacking an Fc domain).…”

Section: Discussionmentioning

confidence: 75%

Expression of Neonatal Fc Receptor in the Eye

Powner

McKenzie

Christianson

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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METHODS. We used qPCR to study mRNA expression of the transmembrane chain of FcRn (FCGRT) in retina, optic nerve, RPE/choroid plexus, ciliary body/iris plexus, lens, cornea, and conjunctiva isolated from mouse, rat, pig, and human postmortem eyes and used immunohistochemistry to determine the pattern of FcRn expression in FCGRT-transgenic mouse and human eyes.RESULTS. In all four tested species, Fcgrt mRNA was expressed in the retina, RPE/choroid, and the ciliary body/iris, while immunohistochemistry documented FcRn protein expression in the ciliary body epithelium, macrophages, and endothelial cells in the retinal and choroidal vasculature.CONCLUSIONS. Our results demonstrate that FcRn has the potential to interact with IgG-Fc domains in the ciliary epithelium and retinal and choroidal vasculature, which might affect the half-life and distribution of intravitreally injected Fc-carrying molecules.

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Section: Discussionmentioning

confidence: 75%

Expression of Neonatal Fc Receptor in the Eye

Powner

McKenzie

Christianson

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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“…Dysregulation of VEGF expression within the glomeruli has been associated with a wide range of renal diseases that may occur within weeks to months after intravitreal administration of VEGF inhibitors [14], [27]. The dose of anti-VEGF agents used in ophthalmology is minute compared with that used intravenously, but there is evidence of systemic absorption and diffuse inhibition of VEGF [14], [17], [38], [39]. Pelle et al ., reported a non diabetic patient with normal kidney function who developed kidney toxicity after four injections of ranibizumab for the treatment of age-related macular degeneration [14].…”

Section: Discussionmentioning

confidence: 99%

Effects of a Single Intravitreal Injection of Aflibercept and Ranibizumab on Glomeruli of Monkeys

et al. 2014

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PurposeIt is known that endothelial cells in the kidney are also strongly VEGF-dependent. Whether intravitreal drugs can be detected within the glomeruli or affect VEGF in glomerular podocytes is not known. Therefore, the aim of this pilot study was to investigate the effects of a single intravitreal injection of aflibercept and ranibizumab on glomeruli of monkeys.MethodsThe kidneys of eight cynomolgus monkeys, which were intravitreally injected either with 2 mg of aflibercept or with 0.5 mg of ranibizumab, were investigated one and seven days after injection. Two animals served as controls. The distribution of aflibercept, ranibizumab and VEGF was evaluated using anti-Fc- or anti-F(ab)-fragment and anti-VEGF antibodies respectively. The ratio of stained area/nuclei was calculated using a semi-quantitative computer assisted method. Glomerular endothelial cell fenestration was quantified in electron microscopy using a systematic uniform random sampling protocol and estimating the ratio of fenestrae per µm.ResultsCompared to the controls, the anti-VEGF stained area/nuclei ratio of the ranibizumab-treated animals showed no significant changes whereas the stained areas of the aflibercept-treated monkeys showed a significant decrease post-treatment. Immune reactivity (IR) against aflibercept or ranibizumab was detected in aflibercept- or ranibizumab treated animals respectively. The number of fenestrations of the glomerular endothelial cells has shown no significant differences except one day after aflibercept injection in which the number was increased.ConclusionSurprisingly, both drugs could be detected within the capillaries of the glomeruli. After a single intravitreal injection of aflibercept, VEGF IR in the podocytes was significantly reduced compared to controls. Ranibizumab injection had no significant effect on the glomeruli's VEGF level. Whether this is caused by aflibercept's higher affinity to VEGF or because it is used in a higher stoichiometric concentration compared to ranibizumab remains to be investigated.

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“…A recent study showed that there is a decline in inflammatory and angiogenic markers namely IL-6 and VEGF with the onset of proliferative diabetic retinopathy changes [12]. The reduction in angiogenic factors with worsening of retinopathy may explain the role of VEGF in initiating the proliferative changes and systemic worsening [13]. However, the final end point is secondary to the sequel arising out of the fibrovascular proliferation.…”

Section: Discussionmentioning

confidence: 99%

Aqueous VEGF and IL-6 Levels in Diabetic Retinopathy

Ahuja¹

2015

OCR

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Changes of serum VEGF concentration after intravitreal injection of Avastin in treatment of diabetic retinopathy

Cited by 33 publications

References 22 publications

Expression of Neonatal Fc Receptor in the Eye

Expression of Neonatal Fc Receptor in the Eye

Effects of a Single Intravitreal Injection of Aflibercept and Ranibizumab on Glomeruli of Monkeys

Aqueous VEGF and IL-6 Levels in Diabetic Retinopathy

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