Abstract
Purpose :
To report the levels of 39 cytokines in the vitreous and plasma of subjects enrolled in a randomised controlled trial investigating the impact of ranibizumab pre-treatment on subjects with advanced proliferative diabetic retinopathy undergoing vitrectomy/delamination surgery.
Methods :
Thirty subjects were randomised 1:1 to receive either intravitreal ranibizumab 0.5mg or subconjunctival 0.9% saline 0.05ml one week before planned vitrectomy for advanced proliferative diabetic retinopathy. At initiation of 20G pars plana vitrectomy an undiluted sample of vitreous up to 1ml was placed into EDTA coated tubes, centrifuged and frozen. Venous blood samples were collected simultaneously and centrifuged to obtain plasma. The 30 paired vitreous and plasma samples obtained in the trial were analysed with seven paired samples from non-diabetic subjects. Samples were subjected to multiplex bead analysis using a Milliplex 39 cytokine kit. Concentrations were determined by comparison to standard curves prepared on the same plate and run in parallel to quality control samples.
Results :
Elevated concentrations of IL-1α, IL-4, IL-6, IL8, IP-10, MCP-1 and VEGF (P<0.05, Kruskal-Wallis test with correction for multiple comparisons) were detected in the vitreous of diabetic subjects compared to non-diabetic controls. Of these, only IL-1α and VEGF had significantly lower levels in the ranibizumab-treated diabetic patients than in the saline-treated diabetic controls. Levels of MDC and Flt-3 ligand showed no difference between non-diabetic controls and saline-treated diabetic controls but were reduced in the group treated with ranibizumab. In plasma, no significant differences were found in the levels of any cytokine between the diabetic groups treated with saline and ranibizumab, although there was a trend towards a reduction in plasma VEGF level from 65.4 pg/ml to 29.0 pg/ml in ranibizumab-treated subjects.
Conclusions :
Cytokine analysis in this study has found elevated vitreous levels of cytokines previously found to be raised in proliferative diabetic retinopathy. Treatment with ranibizumab significantly reduced vitreous VEGF levels at one week and also levels of the pro-fibrotic cytokine IL-1α, suggesting a possible inhibitory effect of ranibizumab. No significant reduction in plasma VEGF levels was detected after ranibizumab administration.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.