Monitoring intraocular proangiogenic and profibrotic cytokines within 7 days after adjunctive anti-vascular endothelial growth factor therapy for proliferative diabetic retinopathy

Abstract

Purpose: To monitor the intraocular proangiogenic and profibrotic cytokine profiles within 7 days after intravitreous injection of conbercept (IVC) for patients with proliferative diabetic retinopathy (PDR).

Methods: This prospective, randomized controlled, consecutive, comparative study included 157 eyes with PDR. Participant eyes underwent sham IVC or IVC and subsequent vitrectomy at days 2, 3, 4, 5, 6, 7 postinjection. The intraocular cytokines profiles were measured using beaded assay methods.

Results: After IVC, the vascular endothelial growth factor (VEGF)-A level in PDR vitreous decreased rapidly by approximately 10 times at day 2 (p = 0.00001) and kept at a low level at days 3, 4, 5, 6, 7 (p < 0.001, each compared with IVC-sham group). Similar tendency of the change in VEGF-A was observed in aqueous humour. The level of placenta growth factor (PIGF) in aqueous humour decreased 2 days after IVC whereas returned to baseline level after 5 days. The vitreous profibrotic cytokines, tissue growth factor (TGF)-β1, TGF-β2, TGF-β3 and connective tissue growth factor did not increase after IVC in each group.

Conclusion: We observed a remarkable and rapid decrease in intraocular VEGF-A, temporal decrease in PIGF from day 2 to day 4, increase in VEGF-C and VEGF-D from day 2 onwards, but no profibrotic switch in PDR eyes after IVC. The findings might suggest that ideal vitrectomy timing might be around 3 days after IVC.

Keywords: PIGF; VEGF; anti-VEGF; aqueous humour; conbercept; cytokines; proliferative diabetic retinopathy; vitrectomy; vitreous.