Alterations in the intraocular cytokine milieu after intravitreal bevacizumab

Abstract

Purpose: Several complications after intravitreal bevacizumab (IVB) treatment have been described including tears of the retinal pigment epithelium and tractional retinal detachment. The etiology of these complications remains unclear. The purpose of this study was to characterize changes in the intraocular levels of inflammatory cytokines after IVB as a possible explanation for these complications.

Methods: Twenty-nine patients with proliferative diabetic retinopathy (PDR) undergoing pars plana vitrectomy (PPV) for vitreous hemorrhage (VH) with IVB pretreatment were prospectively enrolled. Aqueous humor samples were taken at the time of IVB pretreatment and approximately 1 week later at the time of PPV. Multiplex cytokine arrays were used to assay 20 different cytokines. Multivariate general linear regression was performed to determine differences in cytokine levels between the two study visits. Proportional hazards regression was performed to determine the relationship between cytokine levels at PPV and postoperative outcomes.

Results: After treatment with IVB, vascular endothelial growth factor (VEGF) concentrations in the aqueous humor decreased (P = 0.0003), whereas the concentrations of IL-8 and transforming growth factor (TGF)-beta(2) increased after IVB (P < 0.03). The level of IL-8 at the time of PPV was associated with the occurrence of recurrent VH after surgery (hazard ratio, 1.32; P = 0.02).

Conclusions: Alterations in the intraocular inflammatory cytokine milieu occur after IVB injection, possibly as a compensatory mechanism in response to VEGF inhibition. The increased concentrations of inflammatory cytokines after IVB may be clinically significant and may be responsible for some of the complications after IVB.

Figure 1.

Adjusted mean aqueous humor concentrations of inflammatory cytokines after IVB. Error bars, SEM. *Statistically significant result (P < 0.05). Adjusted for any of the following covariates based on the best-fitting model: age, sex, hemoglobin A1c, presence of TRD, and number of days between the pre and post-bevacizumab injection samples. The mean (± SD) number of days between the date of the pre- and postbevacizumab samples was 10 (5).

Figure 2.

Proportion of patients with recurrent VH after pars plana vitrectomy. Life-table analysis showing proportion of patients with recurrent VH in the upper/lower 50th percentiles of IL-8 concentration at pars plana vitrectomy.