Downregulation of angiogenic factors in aqueous humor associated with less intraoperative bleeding in PDR patients with NVG receiving conbercept: a randomized controlled trial

Background To analyze the level changes of 28 cytokines in aqueous humor of patients with proliferative diabetic retinopathy (PDR) coexisting neovascular glaucoma (NVG) after intravitreal injection of conbercept (IVC), and to investigate whether these cytokines are associated with intraoperative bleeding (IOB). Methods Totally 34 eyes with NVG secondary to PDR were enrolled. Patients were randomized into two groups, and all of them underwent 25-gauge pars plana vitrectomy (PPV) combined with trabeculectomy. Group I, 18 eyes received IVC 3 days before PPV, and 100 µL aqueous humor was collected at the time of IVC pretreatment and 3 days later at the beginning of PPV respectively. Group II, 16 eyes received IVC after PPV, and 100 µL aqueous humor was collected only at the beginning of PPV. Aqueous humor from 19 eyes with age-matched cataract patients served as controls. Luminex bead-based multiplex array was used to measure the levels of 28 cytokines in aqueous humor. The baseline cytokine levels were compared among the three groups. All NVG patients were divided into IOB and non-bleeding (INB) groups. The cytokine levels of aqueous humor at the beginning of PPV were compared between group I and II, also between IOB and INB groups. IOB in NVG patients was graded according to vitreous bleeding amount. The correlation between cytokine levels and the grades of IOB were analyzed. Results Compared with controls, the baseline levels of 18 cytokines associated with inflammation and angiogenesis showed significantly increased in group I and group II (all, P < 0.0167). The IOB rate as well as the levels of IL-4, IL-22, Ang-2, PLGF and VEGF-A in group I were significantly lower than in group II (all, P < 0.05). The levels of IL-4, IL-22, Ang-2, PLGF and VEGF-A were significantly lower in INB group than in IOB group (all, P < 0.05). The levels of IL-4, Ang-2, PLGF and VEGF-A were positively correlated with the grades of IOB in NVG patients (all, r s > 0.4, P < 0.05). Conclusions IVC 3 days before PPV combined with trabeculectomy reduces IOB in NVG patients, in which the downregulation of IL-4, Ang-2, PLGF and VEGF-A after IVC may be an underlying mechanism. Trial registration ChiCTR2100048118 , retrospectively registered on 2 July 2021.