Changes in level of circulating vascular endothelial growth factor-A and proteinuria after intravitreal injections of ranibizumab or aflibercept in patients with retinal vascular diseases

Poster Details

First Author: S.Ozawa JAPAN

Co Author(s):    R. Kikuchi   S. Nakamura                          

Abstract Details


The incidence of adverse systemic events after intravitreal aflibercept (IVA) is similar to those after intravitreal ranibizumab (IVR). However, studies that targeted their nephrotoxicity including periodic monitoring of the blood pressure and renal parameters before and after the injections are lacking. Thus, the nephrotoxic risks between IVA and IVR might have been underestimated. We evaluated the changes of circulating levels of pan VEGF-A, VEGF-A165b (an anti-angiogenic isoform of VEGF-A), blood pressure, and proteinuria before and after IVA or IVR in patients with retinal vascular diseases.


Prospective, interventional case series.


We studied 32 consecutive patients treated with three monthly injections of IVA or IVR for retinal vascular diseases. Four cases of age-related macular degeneration (AMD), 6 of diabetic macular edema (DME), and 5 of retinal vascular occlusion (RVO) were included in the IVR group, and 4 cases of AMD, 8 of DME, and 5 of RVO were included in the IVA group. Blood and spot urine samples were collected before and at 1 week, 1month (just before the second injection), 2 months (just before the third injection), and 3months after starting the treatment. The blood pressure was also measured at each follow-up visit. Serum pan VEGF-A and VEGF-A165b levels were measured by enzyme-linked immunosorbent assay (ELISA). The urine albumin to creatinine ratio (ACR, mg/g) was calculated and the patients were divided into 3 grades: normal, ACR<30;, microalbuminuria, 30 ACR<300; and macroalbuminuria, ACR 300.


In the IVR group, the mean serum pan VEGF-A and VEGF-A165b were not significantly changed from 199.9 pg/ml and 92.1pg/ml at the baseline to 198.6pg/ml (P=0.65) and 57.2 pg/ml (P=0.13) at 3 months, respectively. In the IVA group, the mean serum pan VEGF-A and VEGF-A165b levels were significantly decreased from 293.3 pg/ml and 90.5pg/ml at the baseline to 22.8pg/ml (P<0.001) and 11.2 pg/ml (P<0.001) at 3 months, respectively. No significant increases in the systolic and diastolic blood pressures were found at any time in both groups. At three month, the percentage of the patients who developed a worsening of the alubuminuria grade compared with baseline was 20% in the IVR group and 18% in the IVA group (P=0.87).


These short-term results demonstrate that there are no significant differences between the IVR and IVA groups in the hypertension and proteinuria, although three monthly intravitreal aflibercept significantly reduced the systemic VEGF-A levels throughout the 3-month period.

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