Intravitreal bevacizumab increases intraocular interleukin-6 levels at 1 day after injection in patients with proliferative diabetic retinopathy.

In the present investigation, we evaluated the acute changes in intraocular cytokines after intravitreal injection of an anti-vascular endothelial growth factor (VEGF) in diabetic retinopathy (DR). This analysis may contribute to the understanding of changes in intraocular cytokines after intravitreal bevacizumab (IVB), which is frequently used to reduce permeability and neovascularization in DR. This study was a prospective, open-label, controlled, randomized clinical trial. Eyes of 30 consecutive patients who were scheduled for pars plana vitrectomy (PPV) for proliferative DR (PDR) were prospectively enrolled. All patients were randomly assigned to receive IVB either at 1 (group 1) or 7 (group 2) days before PPV, and aqueous humor samples were taken from the anterior chamber just prior to IVB and PPV. The levels of VEGF, interleukin (IL)-2, IL-6, IL-8, tumor necrosis factor (TNF)-α, and transforming growth factor-β(2) (TGF-β(2)) in aqueous humor were evaluated at each time point-baseline and after IVB. VEGF levels were significantly decreased at day 1 (p=0.003) and the decrease sustained through day 7 (p=0.004). IL-6 increased from 23.26 ± 26.68 to 1992.88 ± 2266.87 pg/mL at day 1 (p<0.001) and from 17.13 ± 19.61 to 207.83 ± 269.59 pg/mL at day 7 (p=0.001). IL-6 levels were significantly higher at day 1 compared to day 7 (p=0.002). IL-8 showed an increase at days 1 (p=0.003) and 7 (p=0.002) compared to baseline, with no significant differences between the groups (p=0.157). TGF-β(2) also showed a tendency for an increase at day 7 compared to day 1, but missed statistical significance (p=0.084). No remarkable differences were detected between the 2 groups for IL-2 or for TNF-α at both time points. These results suggest that IVB aggravates intraocular inflammatory cytokines, and IL-6 may mediate those inflammatory changes after IVB in the acute period. These findings also suggest a role for IL-6 as an acute mediator for inflammatory changes in pathologic hypoxic conditions.

RCT Entities:   Population Interventions Outcomes