Abstract
Purpose :
Vascular endothelial growth factor (VEGF) has become a major target for the treatment of retinal disease. However, the systemic effects of intraocular administration of anti-VEGF drugs remain controversial and this may be particularly important in patients with coexistent diabetic maculopathy and nephropathy, as VEGF is essential for the maintenance of normal renal function. Monocyte chemoattractant protein 1 (MCP1) is a key chemokine that regulates migration and infiltration of monocytes/ macrophages. It also mediates acute ischaemic and toxic kidney injury and is a major marker of acute kidney injury. In this study we analysed systemic changes in VEGF and MCP-1 levels in diabetic patients with diabetic macular oedema who was treated with a course of bevacizumab, ranibizumab and aflibercept injections for diabetic macular oedema.
Methods :
Serum samples were obtained from thirty patients with diabetic macular oedema, randomised to bevacizumab, ranibizumab and aflibercept treatment. They were each treated with 3 intravitreal injections over a period of 3 months. Peripheral venous blood samples were taken at each visit and centrifuged at 3,000 rpm for 10 minutes followed by being stored at – 70°C until analysis. Serum VEGF 165 and MCP-1 levels were determined using enzyme-linked immunosorbent assay (R&D systems, UK) both pre and post immunodepletion to remove complexed VEGF.
Results :
There were greater suppression of serum VEGF 165 levels was suppressed by intravitreal bevacizumab in comparison to ranibizumab and aflibercept (p=0.03). Serum MCP-1 levels conversely increased with intravitreal anti-VEGF therapy, after the end of the first course of three injections (p=0.04). Patients with poorer initial renal function had a significantly greater increase in systemic MCP-1 levels following intravitreal Bevacizumab relative to patients with normal baseline renal function.
Conclusions :
These results suggest that repeated intravitreal anti-VEGF therapy lead to a decrease in systemic VEGF levels, with corresponding increase in MCP-1 levels in diabetic patients. Patients with poor baseline renal function were the most affected, suggesting that the systemic decrease in VEGF levels with intravitreal Bevacizumab may be of particular significance in diabetic patients with coexistent nephropathy.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.