Multiphasic changes in systemic VEGF following intravitreal injections of ranibizumab in a child

Abstract

Purpose To investigate whether intravitreal ranibizumab injections administered to a child alter systemic plasma levels of total and free VEGF 165. Methods A 9-year-old child sustained a choroidal rupture from blunt trauma. He subsequently developed a secondary choroidal neovascular membrane, which was treated with five ranibizumab injections over a period of 8 months. Peripheral venous blood samples were taken at each visit over a period of 12 months and plasma was extracted. Plasma VEGF 165 levels were determined using enzyme-linked immunosorbent assay and were assayed both pre-and post-immunodepletion to remove complexed VEGF. Results Plasma VEGF 165 levels proved labile following intravitreal injection of ranibizumab. Levels increased by 30% above baseline following the first intravitreal ranibizumab injection, but then returned to baseline despite two subsequent injections. There was then a rebound increase of 67% in total plasma VEGF levels following a further injection, which remained above baseline for 12 weeks despite two further intravitreal ranibizumab injections. Baseline levels were re-attained 26 weeks after the final injection. Conclusions These results suggest intravitreal ranibizumab injections can cause significant, multiphasic changes in systemic VEGF levels. This may be of particular clinical significance in children as VEGF is known to be vital in the development of major organs, in addition to its role in the maintenance of normal organ function in adults.

Choroidal neovascular membrane in paediatric patients: clinical characteristics and outcomes

“…While bevacizumab was the most frequently used anti-VEGF agent at study locations 1 and 3, ranibizumab, bevacizumab and pegaptanib accounted for 40%, 40% and 20% of cases, respectively, receiving anti-VEGF treatment at study location 2. Ocular delivery of anti-VEGF agents has been shown to cause rapid and sustained systemic VEGF suppression in adult and paediatric patients 12. This has raised serious concerns, as VEGF is known to be vital in the development of major organs in children and the maintenance of normal organ function in adults 13.…”

Short-term impact of glycaemic control and intravitreal ranibizumab treatment on serum cytokine levels and diabetic macular edema in patients with unregulated blood glucose

“…Shao et al reported significant multiphasic changes of total and free plasma VEGF in a child following intravitreal ranibizumab injections. (19) As a result of two ranibizumab injections for DME, Gnanasekaran et al found an increase in VEGF levels in serum samples collected before and four weeks after administration. (20) Since this increase was seen only in the participants who received intravitreal injection, contrary to the hypothesis that hypoglycaemia induces the release of VEGF, it is more likely that this effect is due to an increase in VEGF synthesis, (21) and its release from the tissues into the circulation, (22) as mentioned in studies on cancer, which was the first field of use of anti-VEGF drugs.…”

A novel anti-TNF scFv constructed with human antibody frameworks and antagonistic peptides

“…Furthermore, small antibody molecules can be produced more economically and provide rapid biodistribution, which make them be potentially superior therapeutic molecules [12,13]. Several such small antibody molecules have been proved for the treatment of human diseases including ranibizumab (Fab, anti-VEGF), certolizumab(Fab, anti-TNF), blinatumomab (bispecific-scFv, anti-CD19/CD3) (www.fda.gov) or in clinical and preclinical development, such as scFv Efungumab, pexelizumab, DLX105, and Fab Digibind, abciximab, ranibizumab [14][15][16][17].…”