A Randomized Controlled Trial of Conbercept Pretreatment before Vitrectomy in Proliferative Diabetic Retinopathy

Xiaochun Yang, Jianbiao Xu, Ruili Wang, Yan Mei, Huo Lei, Jun Liu, Ting Zhang, Haiyan Zhao, Xiaochun Yang, Jianbiao Xu, Ruili Wang, Yan Mei, Huo Lei, Jun Liu, Ting Zhang, Haiyan Zhao

Abstract

Purpose. To determine the efficacy and safety of preoperative intravitreal conbercept (IVC) injection before vitrectomy for proliferative diabetic retinopathy (PDR). Methods. 107 eyes of 88 patients that underwent pars plana vitrectomy (PPV) for active PDR were enrolled. All patients were assigned randomly to either preoperative IVC group or control group. Follow-up examinations were performed for three months after surgery. The primary bioactivity measures were severity of intraoperative bleeding, incidence of early and late recurrent VH, vitreous clear-up time, and best-corrected visual acuity (BCVA) levels. The secondary safety measures included intraocular pressure, endophthalmitis, rubeosis, tractional retinal detachment, and systemic adverse events. Results. The incidence and severity of intraoperative bleeding were significantly lower in IVC group than in the control group. The average vitreous clear-up time of early recurrent VH was significantly shorter in IVC group compared with that in control group. There was no significant difference in vitreous clear-up time of late recurrent VH between the two groups. Patients that received pretreatment of conbercept had much better BCVA at 3 days, 1 week, and 1 month after surgery than control group. Moreover, both patients with improved BCVA were greater in IVC group than in control group at each follow-up. Conclusions. Conbercept pretreatment could be an effective adjunct to vitrectomy in accelerating postoperative vitreous clear-up and acquiring stable visual acuity restoration for PDR.

Figures

Figure 1
Figure 1
Chart showing participants flow. IVC: intravitreal conbercept; PPV: pars plana vitrectomy; SO: silicone oil.
Figure 2
Figure 2
Bar graph showing incidence of early and late recurrent VH with or without conbercept pretreatment after surgery. Subgroup pairwise analysis showed significant differences in early recurrent VH incidence between preoperative IVC group and control group. However, there was no statistically significant difference in late recurrent VH in both groups (P < 0.001, P = 0.732, resp.). VH: vitreous hemorrhage; IVC: intravitreal conbercept.
Figure 3
Figure 3
Graph showing vitreous clear-up time of early and late recurrent vitreous hemorrhage in participants with or without conbercept pretreatment. Subgroup pairwise analysis showed significant differences between IVC group and control group in early recurrent VH clear-up time (P < 0.001), but no statistical differences in late recurrent VH clear-up time between the two groups (P > 0.05). VH: vitreous hemorrhage; IVC: intravitreal conbercept.
Figure 4
Figure 4
Bar graph showing best-corrected visual acuity levels in participants with or without conbercept pretreatment preoperatively and at 3 days, 1 week, 1 month, and 3 months after surgery. Subgroup pairwise analysis showed significant differences of visual acuity levels at 3 days (P = 0.025), 1 week (P = 0.012), and 1 month (P = 0.047) after surgery between preoperative IVC group and control group. However, there was no statistically significant difference at 3 months (P = 0.114) after surgery between the two groups. Compared with the preoperative period, visual acuity levels had a significant increase at 3 months after surgery in both groups (P < 0.001, P = 0.010, resp.). IVC: intravitreal conbercept; pre-op: preoperative; post-op: postoperative.

References

    1. Schrey S., Krepler K., Wedrich A. Incidence of rhegmatogenous retinal detachment after vitrectomy in eyes of diabetic patients. Retina. 2006;26(2):149–152. doi: 10.1097/00006982-200602000-00004.
    1. Hershberger V. S., Augsburger J. J., Hutchins R. K., Raymond L. A., Krug S. Fibrovascular ingrowth at sclerotomy sites in vitrectomized diabetic eyes with recurrent vitreous hemorrhage: ultrasound biomicroscopy findings. Ophthalmology. 2004;111(6):1215–1221. doi: 10.1016/j.ophtha.2003.08.043.
    1. Shi L., Huang Y.-F. Postvitrectomy diabetic vitreous hemorrhage in proliferative diabetic retinopathy. Journal of Research in Medical Sciences. 2012;17(9):865–871.
    1. Blum A., Socea D., Ben-Shushan R. S., et al. A decrease in VEGF and inflammatory markers is associated with diabetic proliferative retinopathy. European Cytokine Network. 2012;23(4):158–162. doi: 10.1684/ecn.2012.0321.
    1. Morera Y., González R., Lamdan H., et al. Vaccination with a mutated variant of human Vascular Endothelial Growth Factor (VEGF) blocks VEGF-induced retinal neovascularization in a rabbit experimental model. Experimental Eye Research. 2014;122:102–109. doi: 10.1016/j.exer.2014.03.006.
    1. Wisniewska-Kruk J., Klaassen I., Vogels I. M. C., et al. Molecular analysis of blood-retinal barrier loss in the Akimba mouse, a model of advanced diabetic retinopathy. Experimental Eye Research. 2014;122:123–131. doi: 10.1016/j.exer.2014.03.005.
    1. Ferenchak K., Duval R., Cohen J. A., MacCumber M. W. Intravitreal bevacizumab for postoperative recurrent vitreous hemorrhage after vitrectomy for proliferative diabetic retinopathy. Retina. 2014;34(6):1177–1181. doi: 10.1097/IAE.0000000000000058.
    1. Osaadon P., Fagan X. J., Lifshitz T., Levy J. A review of anti-VEGF agents for proliferative diabetic retinopathy. Eye. 2014;28(5):510–520. doi: 10.1038/eye.2014.13.
    1. Ahn J., Woo S. J., Chung H., Park K. H. The effect of adjunctive intravitreal bevacizumab for preventing postvitrectomy hemorrhage in proliferative diabetic retinopathy. Ophthalmology. 2011;118(11):2218–2226. doi: 10.1016/j.ophtha.2011.03.036.
    1. Takahashi S. Vascular Endothelial Growth Factor (VEGF), VEGF receptors and their inhibitors for antiangiogenic tumor therapy. Biological and Pharmaceutical Bulletin. 2011;34(12):1785–1788. doi: 10.1248/bpb.34.1785.
    1. Wykoff C. C., Hariprasad S. M. Comparing aflibercept, bevacizumab, and ranibizumab for DME: analysis of DRCR Protocol T. Ophthalmic Surgery, Lasers and Imaging Retina. 2015;46(3):302–305. doi: 10.3928/23258160-20150304-01.
    1. Suto K., Yamazaki Y., Morita T., Mizuno H. Crystal structures of novel Vascular Endothelial Growth Factors (VEGF) from snake venoms: insight into selective VEGF binding to kinase insert domain-containing receptor but not to fms-like tyrosine kinase-1. The Journal of Biological Chemistry. 2005;280(3):2126–2131. doi: 10.1074/jbc.m411395200.
    1. Zhang M., Zhang J., Yan M., Li H., Yang C., Yu D. Recombinant anti-vascular endothelial growth factor fusion protein efficiently suppresses choridal neovascularization in monkeys. Molecular Vision. 2008;14:37–49.
    1. Zhang M., Zhang J., Yan M., et al. A phase 1 study of KH902, a vascular endothelial growth factor receptor decoy, for exudative age-related macular degeneration. Ophthalmology. 2011;118(4):672–678. doi: 10.1016/j.ophtha.2010.08.008.
    1. Aiello L. P., Brucker A. J., Chang S., et al. Evolving guidelines for intravitreous injections. Retina. 2004;24(5):S3–S19. doi: 10.1097/00006982-200402000-00003.
    1. Cheng Y., Liu X.-H., Shen X., Zhong Y.-S. Ahmed valve implantation for neovascular glaucoma after 23-gauge vitrectomy in eyes with proliferative diabetic retinopathy. International Journal of Ophthalmology. 2013;6(3):316–320. doi: 10.3980/j.issn.2222-3959.2013.03.11.
    1. Yang C.-M., Yeh P.-T., Yang C.-H., Chen M.-S. Bevacizumab pretreatment and long-acting gas infusion on vitreous clear-up after diabetic vitrectomy. American Journal of Ophthalmology. 2008;146(2):211.e1–217.e1. doi: 10.1016/j.ajo.2008.04.028.
    1. Yeh P.-T., Yang C.-M., Lin Y.-C., Chen M.-S., Yang C.-H. Bevacizumab pretreatment in vitrectomy with silicone oil for severe diabetic retinopathy. Retina. 2009;29(6):768–774. doi: 10.1097/IAE.0b013e3181a3b7ef.
    1. Ramezani A. R., Ahmadieh H., Ghaseminejad A. K., Yazdani S., Golestan B. Effect of tranexamic acid on early postvitrectomy diabetic haemorrhage; a randomised clinical trial. British Journal of Ophthalmology. 2005;89(8):1041–1044. doi: 10.1136/bjo.2004.062638.
    1. Wang F., Bai Y., Yu W., et al. Anti-angiogenic effect of KH902 on retinal neovascularization. Graefe's Archive for Clinical and Experimental Ophthalmology. 2013;251(9):2131–2139. doi: 10.1007/s00417-013-2392-6.
    1. Peyman G. A. Vitreoretinal Surgical Techniques. London, UK: Martin Dunitz; 2001.
    1. Williams D. F., Burke J. M., Williams G. A. Clearance of experimental vitreous hemorrhage after panretinal cryotherapy is related to macrophage influx. Archives of Ophthalmology. 1990;108(4):595–597. doi: 10.1001/archopht.1990.01070060143065.
    1. Li T., Hu J., Du S., Chen Y., Wang S., Wu Q. ERK1/2/COX-2/PGE2 signaling pathway mediates GPR91-dependent VEGF release in streptozotocin-induced diabetes. Molecular Vision. 2014;20:1109–1121.
    1. Saint-Geniez M., Maharaj A. S. R., Walshe T. E., et al. Endogenous VEGF is required for visual function: evidence for a survival role on Müller cells and photoreceptors. PLoS ONE. 2008;3(11) doi: 10.1371/journal.pone.0003554.e3554
    1. Li H., Lei N., Zhang M., Li Y., Xiao H., Hao X. Pharmacokinetics of a long-lasting anti-VEGF fusion protein in rabbit. Experimental Eye Research. 2012;97(1):154–159. doi: 10.1016/j.exer.2011.09.002.
    1. Chu K. O., Liu D. T. L., Chan K. P., et al. Quantification and structure elucidation of in vivo bevacizumab modification in rabbit vitreous humor after intravitreal injection. Molecular Pharmaceutics. 2012;9(12):3422–3433. doi: 10.1021/mp3005403.
    1. Sinapis C. I., Routsias J. G., Sinapis A. I., et al. Pharmacokinetics of intravitreal bevacizumab (Avastin®) in rabbits. Clinical Ophthalmology. 2011;5(1):697–704. doi: 10.2147/opth.s19555.
    1. Krohne T. U., Eter N., Holz F. G., Meyer C. H. Intraocular pharmacokinetics of bevacizumab after a single intravitreal injection in humans. American Journal of Ophthalmology. 2008;146(4):508–512. doi: 10.1016/j.ajo.2008.05.036.
    1. Krohne T. U., Liu Z., Holz F. G., Meyer C. H. Intraocular pharmacokinetics of ranibizumab following a single intravitreal injection in humans. American Journal of Ophthalmology. 2012;154(4):682–686. doi: 10.1016/j.ajo.2012.03.047.
    1. Meyer C. H., Krohne T. U., Holz F. G. Intraocular pharmacokinetics after a single intravitreal injection of 1.5 mg versus 3.0 mg of bevacizumab in humans. Retina. 2011;31(9):1877–1884. doi: 10.1097/iae.0b013e318217373c.
    1. Krohne T. U., Muether P. S., Stratmann N. K., et al. Influence of ocular volume and lens status on pharmacokinetics and duration of action of intravitreal vascular endothelial growth factor inhibitors. Retina. 2015;35(1):69–74. doi: 10.1097/IAE.0000000000000265.

Source: PubMed

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