The influence of intravitreal ranibizumab on aqueous cytokines in diabetic macular oedema (DMO)

Session Details

Session Title: Free Paper Session 19: Vascular Diseases & Diabetic Retinopathy V

Session Date/Time: Saturday 09/09/2017 | 16:30-18:00

Paper Time: 17:48

Venue: Room 120

First Author: : S.Lim AUSTRALIA

Co Author(s): :    E. Bandala Sanchez   M. Kolic   L. Lim   S. Wickremasinghe                    

Abstract Details


To evaluate the effect of monthly intravitreal ranibizumab injections on aqueous concentrations of angiogenic or inflammatory cytokines in patients with DMO.


This prospective, interventional study included 30 eyes of 26 participants with type 1 or type 2 diabetes mellitus who were treated with intravitreal ranibizumab.


At baseline visit (week 0 ± 7 days), all patients received a paracentesis to remove 0.1ml of aqueous with a 30-gauge needle. Following this, 0.5mg/ 0.05ml ranibizumab was injected 3.5-4.0mm from the limbus. At week 4 (± 7 days), all patients received a second dose of intravitreal ranibizumab and at week 8 (± 7 days), a second aqueous sample was obtained prior to the third dose of intravitreal ranibizumab. The patients were then treated with “as required” dosing according to the RESTORE protocol up to 48 weeks. Angiogenic and inflammatory cytokine concentrations were assessed at baseline and at week 8 using Multiplex analysis based on Luminex xMAP® technology.


30 eyes of 26 participants were included in this study. The mean (± standard deviation [SD]) age of participants was 63.3 (± 9.6) years, and study participants included 6 females and 20 males. There were significant changes in cytokine measurements during the study. Following two consecutive ranibizumab injections compared to baseline measurements, pairwise comparisons revealed there was a statistically significant reduction in vascular endothelial growth factor (VEGF) (p<0.001), as well as interleukin (IL)-1, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-17, eotaxin, granulocyte colony-stimulating factor (GCSF), granulocyte macrophage colony-stimulating factor (GMCSF), monocyte chemoattractant protein-1 (MCP-1), platelet-derived growth factor subunit b (PDGFb) and tumour necrosis factor alpha (TNF-) (p<0.05). Concentrations of some cytokines however, did not show any change following ranibizumab injections. These included IL-1RA, IL-9, IL-13, IL-15, basic fibroblast growth factor (FGFb), interferon gamma (IFNg), interferon gamma-induced protein 10 (IP-10), macrophage inflammatory protein (MIP)-1a, MIP-1b and epidermal growth factor (EGF) (p>0.10).


This study revealed that intravitreal ranibizumab not only reduces VEGF levels but also influences aqueous inflammatory cytokine concentrations. Current data suggests that there is an overlap in pathways of VEGF and cytokines in DMO, and targeting VEGF alone does not always lead to a consistent and permanent reduction in DMO. This is the first study to demonstrate a significant impact of ranibizumab on various inflammatory cytokines. Elevated concentrations of certain inflammatory cytokines in the eye may be a possible reason for poor response to anti-VEGF monotherapy.

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