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Markus van der Giet, Mirjam Schuchardt, Nicole Pruefer, Jasmin Pruefer; Plasma VEGF-levels are variable in patients with persistent renal dysfunction and diabetes: possible implications and risks for ophthalmic anti-VEGF therapy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4653. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Ophthalmic anti-VEGF therapies are used commonly without monitoring of systemic risks and their intraocular application might cause unexpected effects to systemic VEGF-dependent regulatory mechanisms. Our study aims at quantifying systemic VEGF-levels in situations commonly found in the target population of ocular anti-VEGFs
Blood was drawn form 30 healthy controls (age 28-78 years), 30 patients with type I or II diabetes without renal dysfunction (24-84 years, DM), 30 patients with chronic kidney disease (CKD) stage III-V (incl. hemodialysis patients) and 30 patients with type I/II diabetes and renal dysfunction (CKD III-V, CKD/DM). VEGF A-D were quantified using 96-well ELISA (Cusabio, Wuhan, China) according to manufacturer’s protocol. VEGF levels were quantified by comparison to standard concentration curves; all values are given as means.
Mean plasma VEGF A levels were 85.8 pg/ml in healthy controls and 77.6 pg/ml in DM patients. These levels were moderately elevated in CKD (129.92pg/ml) and CKD/DM (111.9 pg/ml) patients (p<0.05). Levels of VEGF-B were significantly elevated in DM (169.3 pg/ml), CKD (271.4 p/ml) and CKD/DM patients (697.1 pg/ml) in comparison to controls (105.6 pg/ml). Changes of VEGF C levels were massive and significant in CKD (1187.4 pg/ml), DM (214.7 pg/ml), and CKD/DM (3939.1pg/ml) patients compared to controls (162.2pg/ml). VEGF D levels were very similar to VEGF A, with no significant differences between controls (89,3 pg/ml) and DM patients (61.0 pg/ml) while there was a significant increase in CKD (209,4 pg/ml) and CKD/DM (208.2pg/ml).
Our data show that the plasma VEGF levels in elderly patients (target population for ophthalmic anti-VEGF treatment) are affected by disease status as seen in Diabetes Mellitus and even more in Chronic Kidney Disease, especially for the VEGF B and C isoforms. The physiopathology and relevance of these changes remain unclear but caution should be taken in risk patients when injecting ophthalmic anti-VEGFs with a long plasma half-life, implying a high systemic exposure.
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