Effects of VEGF Inhibitor Conbercept on Corneal Neovascularization Following Penetrating Keratoplasty in Rabbit Model.

PURPOSE: To evaluate the effects of the vascular endothelial growth factor inhibitor conbercept (KH902) on corneal neovascularization and wound healing following penetrating keratoplasty in rabbits. METHODS: Conbercept was administered to New Zealand white rabbits through topical and subconjunctival routes. Corneal neovascularization and wound healing were examined by slit-lamp photography and histological analyses. The expressions of vascular endothelial growth factor inhibitor, α-smooth muscle actin, and keratocan in the corneal grafts were measured by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The anterior segment photographs demonstrated that corneal neovascularization started in the 2nd week. In the 4th week, histologically, the superficial corneal stroma layer showed disordered arrangement, and there were large numbers of dense inflammatory cells and blood vessels in the stroma layer. Vascular endothelial growth factor in the experimental groups was significantly decreased at all time points compared with the control group (both P = 0.001). Expression of α-smooth muscle actin in corneal grafts demonstrated an increase in time even it was lower in experimental groups, but the difference was not statistically significant (P equaled to 0.507 and 0.723, respectively). There were no significant differences with the expression of keratocan in all groups except that it significantly declined at the 4th week as to the second week in all groups and P values were 0.022, 0.020 and 0.014 in control (C), topical (E1), and subconjunctival (E2) group, respectively. CONCLUSION: The study found that conbercept inhibited the formation of corneal neovascularization without affecting keratocan-mediated corneal wound healing and there were no significant differences between topical administration of different doses of conbercept on the rabbit corneal neovascularization after penetrating keratoplasty in this study.

Updates on the Management of Ocular Vasculopathies with VEGF Inhibitor Conbercept.

Purpose: To provide a detailed review on the therapeutic efficacy of conbercept for the management of ocular vasculopathies. Methods: A comprehensive literature search of various electronic databases was performed. Results: Ocular vasculopathy is one of the major causes of visual impairment and blindness which includes a range of disorders. Vascular endothelial growth factor (VEGF) regulates angiogenesis, enhances vascular permeability, and drives the formation of neovascularization. Anti-VEGF therapy has been shown to prevent vision loss or potentially improve vision in patients with exudative or neovascular retinal disease. The most recent anti-VEGF drug in China is conbercept. In the USA and Europe, bevacizumab is the most recently approved anti-VEGF agent. Conclusions: Conbercept serves as another anti-VEGF option for patients with neovascular AMD and other retinal vascular disorders. There have not been many clinical trials that study conbercept as compared with other currently available anti-VEGF drugs. There is a need for large-scale, well-designed, randomized clinical trials to ensure its long-term safety and efficacy and to determine if it has any advantages over other anti-VEGF agents.

Observation of topical tacrolimus on high-risk penetrating keratoplasty patients: a randomized clinical trial study.

BACKGROUND/OBJECTIVES: To evaluate the clinical efficacy of topical tacrolimus 0.1% and cyclosporine 1% on high-risk penetrating keratoplasty (PKP) patients. SUBJECTS/METHODS: A series of 49 high-risk PKP patients (49 eyes), 20 males, 29 females from the age of 4 months to 74 years of age with the mean of 32.5 from 2012 to 2017 were recruited in this study. The patients were randomly divided into two groups by receiving either topical tacrolimus 0.1% or cyclosporine 1% respectively. Twenty five patients were treated with topical tacrolimus 0.1% and 24 patients with topical cyclosporine 1%. The traditional baseline management on these two groups were Tobramycin and Dexamethasone eye drops in the first 3 weeks and then tapered off. Clinical procedures and postoperative follow-up were documented. RESULTS: After 6-54 months follow-up, with the average of 24 months, 11 of 24 high-risk patients (11 eyes) had graft rejection, the rejection rate was 45.8% in topical cyclosporine 1% group. The rejections occurred from 35 days to 20 months after PKP. Three patients had irreversible rejection. On topical tacrolimus 0.1% group, the rejection occurred in four patients (four eyes) with rejection rate of 16%, and no irreversible rejection was observed. The graft rejection episodes were documented between 23 days and 24 months. As compared with the topical cyclosporine 1%, topical tacrolimus 0.1%, a key immunosuppressant, significantly decreased corneal graft rejection rate (p = 0.02). CONCLUSIONS: Topical tacrolimus 01% on high-risk PKP patients significantly prevented corneal graft rejection, and it had less adverse effects and was very safe to high-risk patients as to topical cyclosporine 1%. Further case controlled randomized clinical trial studies are needed to establish the best management option for these high-risk patients.