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Josephine V. Glenn, Shrobona Bhattycharya, Barnaby C. Reeves, Cyril McMaster, Chris A. Rogers, Alan W. Stitt, Usha Chakravarthy; Fluctuating Levels Of Circulating VEGF In A Subset Of Patients As Part Of The Multicentre IVAN Study. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5930.
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To report longitudinal changes in circulating levels of vascular endothelial growth factor (VEGF) in patients with neovascular AMD, who are enrolled in the Inhibition of VEGF in Age-related choroidal neovascularisation trial (IVAN) and randomised to ranibizumab or bevacizumab and to more or less frequent treatment.
Serum samples were obtained at 0, 1, 11 and 12, 23 and 24 months. We analysed circulating VEGF in subset comprising the first 91 participants over the first year of enrolment. Anonymised samples taken at each of the specified visits were sent to the independent laboratory where ELISA analyses were performed using the R&D systems commercial Duoset ELISA with manual plate coating. The data was transformed to the logarithmic scale for analysis and results are presented as geometric means and as a ratio of means. The data was analysed using a mixed repeated measures regression model.
Assay detection limits were 30 pg to 2000 pg/ml and cross reactivity with a range of recombinant human factors (PlGF, hVEGF165/ PlGF, VEGF-C and VEGF-D) was 23%. All serum samples had VEGF concentrations below the upper limit but 90 samples (including all samples from one patient) had undetectable VEGF concentrations. Mean VEGF concentrations were 182.7 pg/ml at Visit 0 (range 33 to 1326); 117.5 pg/ml at Visit 1 (range 29 to 506); 136.2 pg/ml at Visit 11 (range 37 to 849) and 155.8 pg/ml at Visit 12 (range 34 to 764). The mean VEGF concentration was significantly higher at Visit 0 than at Visit 1 (ratio 1.55, 95%CI 1.30 to 1.85, p<0.01) and at Visit 11 (ratio 1.34, 95%CI 1.07 to 1.68, p=0.01) but a difference between Visit 0 and Visit 12 was not seen (ratio 1.17, 95%CI 0.94 to 1.46, p=0.16).
The findings raise the possibility that anti VEGF agents administered through the intraocular route egress into the circulation and bind to circulating VEGF.
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