Article | Published:

Safety and efficacy of intravitreal conbercept injection after vitrectomy for the treatment of proliferative diabetic retinopathy

Abstract

Background/objectives

The aim of this study was to evaluate the safety and efficacy of intravitreal conbercept (a recombinant fusion protein that primarily targets vascular endothelial growth factors) after vitrectomy for the management of proliferative diabetic retinopathy without tractional retinal detachment (TRD).

Subjects/methods

Fifty patients with non-clearing vitreous haemorrhage (VH) due to proliferative diabetic retinopathy without TRD were enroled. They were randomly divided into control and treatment groups (25 eyes to each group) after they provided informed consent. The treatment group received intravitreal conbercept (10 mg/mL, 0.5 mg) immediately after surgery, while the control group did not. The best corrected visual acuity (BCVA) and the central retinal thickness were measured.

Results

There were no significant between-group differences in baseline characteristics (P > 0.05), except in age (P = 0.003). Improvement in BCVA was significantly greater at 1, 4, 12, and 24 weeks post surgery in the treatment group than it was in the control group (P < 0.001). There were more cases in the control group who developed recurrent VH, but the recurrence rate of VH was not significantly different between the two groups at 12 and 24 weeks post surgery (P = 0.192 and  0.103). Central retinal thickness was lower in the treatment group than in the control group at 1 week (P = 0.012), 4 weeks (P = 0.01), 12 weeks (P = 0.001), and 24 weeks (P = 0.004) post surgery, which were statistically significant.

Conclusions

An intravitreal injection of conbercept after vitrectomy improved visual acuity and seemed to reduce the recurrence of VH resulting in prompt visual recovery in the PDR patients.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Crawford TN, Alfaro DV, Kerrison JB, Jablon EP. Diabetic retinopathy and angiogenesis. Curr Diabetes Rev. 2009;5:8–13.

  2. 2.

    Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, et al. Prevalence of diabetes among men and women in China. N Engl J Med. 2010;362:1090–101.

  3. 3.

    Ehrlich R, Harris A, Ciulla TA, Kheradiya N, Winston DM, Wirostko B. Diabetic macular oedema: physical, physiological and molecular factors contribute to this pathological process. Acta Ophthalmol. 2010;88:279–91.

  4. 4.

    Liu L, Wu X, Liu L, Geng J, Yuan Z, Shan Z, et al. Prevalence of diabetic retinopathy in mainland China: a meta-analysis. PLoS ONE. 2012;7:e45264.

  5. 5.

    Subash M, Comyn O, Samy A, Qatarneh D, Antonakis S, Mehat M, et al. The effect of multispot laser panretinal photocoagulation on retinal sensitivity and driving eligibility in patients with diabetic retinopathy. JAMA Ophthalmol. 2016;134:666–72.

  6. 6.

    The Diabetic Retinopathy Vitrectomy Study Research Group. Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Two-year results of a randomized trial. Diabetic Retinopathy Vitrectomy Study report 2. Arch Ophthalmol. 1985;103(11):1644–52.

  7. 7.

    Farouk MM, Naito T, Sayed KM, Nagasawa T, Katome T, Radwan G, et al. Outcomes of 25-gauge vitrectomy for proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2011;249:369–76.

  8. 8.

    Aoki Y, Tomith M, Sato T, Watanabe M, Kase H, Fujita K, et al. Neoadjuvant chemotherapy for patients younger than 50 years with high-risk squamous cell carcinoma of the cervix. Gynecol Oncol. 2001;83:263–7.

  9. 9.

    Martinez-Zapata MJ, Marti-Carvajal AJ, Solà I, Pijoán JI, Buil-Calvo JA, Cordero JA, et al. Anti-vascular endothelial growth factor for proliferative diabetic retinopathy. Cochrane Database Syst Rev. 2014;11:CD008721.

  10. 10.

    Pakzad-Vaezi K, Albiani DA, Kirker AW, Merkur AB, Kertes PJ, Eng KT, et al. A randomized study comparing the efficacy of bevacizumab and ranibizumab as pre-treatment for pars plana vitrectomy in proliferative diabetic retinopathy. Ophthalmic Surg Lasers Imaging Retin. 2014;45:521–4.

  11. 11.

    Storkebaum E, Lambrechts D, Canneliet P. VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection. Bioessays. 2004;26:943–54.

  12. 12.

    El-Batarny AM. Intravitreal bevacizumab as an adjunctive therapy before diabetic vitrectomy. Clin Ophthalmol. 2008;2:709–16.

  13. 13.

    Farahvash MS, Majidi AR, Roohipoor R, Ghassemi F. Preoperative injection of intravitreal bevacizumab in dense diabetic vitreous hemorrhage. Retina. 2011;31:1254–60.

  14. 14.

    Jorge R, Costs RA, Calucci D, Cintra LP, Scott IU. Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy (IBEPE study). Retina. 2006;26:1006–13.

  15. 15.

    Bakri SJ, Donaldson MJ, Link TP. Rapid regression of disc neovascularization in a patient with proliferative diabetic retinopathy following adjunctive intravitreal bevacizumab. Eye. 2006;20:1474–5.

  16. 16.

    Diabetic Retinopathy Clinical Research N, Wells JA, Glassman AR, Ayala AR, Jampol LM, Aiello LP, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015;372:1193–203.

  17. 17.

    Shinkai A, Ito M, Anazawa H, Yamaguchi S, Shitara K, Shibuya M. Mapping of the sites involved in ligand association and dissociation at the extracellular domain of the kinase insert domain-containing receptor for vascular endothelial growth factor. J Biol Chem. 1998;273:31283–8.

  18. 18.

    Zhang ZH, Liu HY, Hernandez-Da Mota SE, Romano MR, Falavarjani KG, Ahmadieh H, et al. Vitrectomy with or without preoperative intravitreal bevacizumab for proliferative diabetic retinopathy: a meta-analysis of randomized controlled trials. Am J Ophthalmol. 2013;156:106–15.

  19. 19.

    Su L, Ren X, Wei H, Zhao L, Zhang X, Liu J, et al. Intravitreal conbercept (KH902) for surgical treatment of severe proliferative diabetic retinopathy. Retina. 2016;36:938–43.

  20. 20.

    Li F, Zhang L, Wang Y, et al. One-year outcome of conbercept therapy for diabetic macular edema. Curr Eye Res. 2018;43(2):218–23.

  21. 21.

    di Lauro R, De Ruggiero P, di Lauro R, di Lauro MT, Romano MR. Intravitreal bevacizumab for surgical treatment of severe proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2010;248:785–91.

  22. 22.

    Holladay JT. Proper method for calculating average visual acuity. J Refract Surg. 1997;13:388–91.

  23. 23.

    Ajvazi H. Proliferative diabetic retinopathy-results of the microsurgical and laser treatment. Med Arch. 2010;64:165–7.

  24. 24.

    Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010;376:124–36.

  25. 25.

    Ahmadieh H, Shoeibi N, Entezari M, Monshizadeh R. Intravitreal bevacizumab for prevention of early postvitrectomy hemorrhage in diabetic patients: a randomized clinical trial. Ophthalmology. 2009;116:1943–8.

  26. 26.

    Kohno R, Hata Y, Moehizuki Y, Arita R, Kawahara S, Kita T, et al. Histopathology of neovascular tissue from eyes with proliferative diabetic retinopathy after intravitreal bevacizumab injection. Am J Ophthalmol. 2010;150:223–9.

  27. 27.

    Ip MS, Domalpally A, Hopkins JJ, Wong P, Ehrlich JS. Long-term effects of ranibizumab on diabetic retinopathy severity and progression. Arch Ophthalmol. 2012;130:1145–52.

  28. 28.

    Moradian S, Ahmadieh H, Malihi M, Soheilian M, Dehghan MH, Azarmina M. Intravitreal bevacizumab in active progressive proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2008;246:1699–705.

  29. 29.

    Yeh PT, Yang CM, Lin YC, Chen MS, Yang CH. Bevacizumab pretreatment in vitrectomy with silicone oil for severe diabetic retinopathy. Retina. 2009;29:768–74.

  30. 30.

    Arevalo JF, Maia M, Flynn HW Jr, Saravia M, Avery RL, Wu L, et al. Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy. Br J Ophthalmol. 2008;92:213–6.

  31. 31.

    Ishikawa K, Honda S, Tsukahara Y, Negi A. Preferable use of intravitreal bevacizumab as a pretreatment of vitrectomy for severe proliferative diabetic retinopathy. Eye (Lond). 2009;23:108–11.

  32. 32.

    El-Sabagh HA, Abdelghaffar W, Labib AM, Mateo C, Hashem TM, Al-Tamimi DM, et al. Preoperative intravitreal bevacizumab use as an adjuvant to diabetic vitrectomy: histopathologic findings and clinical implication. Ophthalmology. 2011;118:636–41.

  33. 33.

    Gupta A, Bansal R, Gupta V, Dogra MR. Six-month visual outcome after pars plana vitrectomy in proliferative diabetic retinopathy with or without a single preoperative injection of intravitreal bevacizumab. Int Ophthalmol. 2012;32:135–44.

Download references

Acknowledgements

The authors thank Fuhua Yang for help with the statistical analysis.

Funding

This article is supported by National Natural Science Foundation of China (81600723).

Author information

Correspondence to Xiaorong Li.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark