Efficacy and Safety of Intravitreal Conbercept, Ranibizumab, and Triamcinolone on 23-Gauge Vitrectomy for Patients with Proliferative Diabetic Retinopathy

Jinglin Cui, Hong Chen, Hang Lu, Fangtian Dong, Dongmei Wei, Yan Jiao, Steve Charles, Weikuan Gu, Lin Wang, Jinglin Cui, Hong Chen, Hang Lu, Fangtian Dong, Dongmei Wei, Yan Jiao, Steve Charles, Weikuan Gu, Lin Wang

Abstract

Introduction: To compare the effect and safety of intravitreal conbercept (IVC), intravitreal ranibizumab (IVR), or intravitreal triamcinolone acetonide (IVTA) injection on 23-gauge (23-G) pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR).

Methods: Fifty patients (60 eyes) of varying degrees of PDR were randomly grouped into 3 groups (1 : 1 : 1) (n = 20 in each group). The 23-G PPV was performed with intravitreal conbercept or ranibizumab injection 3-7 days before surgery or intravitreal TA injection during surgery. The experiment was randomized controlled, with a noninferiority limit of five letters. Main outcome measures included BCVA, operation time, incidence of iatrogenic retinal breaks, endodiathermy rate, and silicone oil tamponade.

Results: At 6 months after surgery, there were no significant differences of BCVA improvements, operation time, incidence of iatrogenic retinal breaks, endodiathermy rate, silicone oil tamponade, vitreous clear-up time, and the incidence of intraoperative bleeding between the IVC and IVR groups (all P values ≥ 0.05), but they were significantly different from the IVTA group (all P values < 0.05). IOP increases did not show significant differences between the IVC and IVR groups, but both were significantly different with the IVTA group. More patients had higher postoperative IOP in the IVTA group.

Conclusions: The intravitreal injection of conbercept, ranibizumab, or TA for PDR had a significant different effect on outcomes of 23-G PPV surgery. Conbercept and ranibizumab can reduce difficulty of the operation, improve the success rate of PPV surgery, and decrease the incidence of postoperative complications.

Figures

Figure 1
Figure 1
Study flow chart.
Figure 2
Figure 2
The mean changes in BCVA from baseline in IVC, IVR, and IVTA groups over 6 m were as indicated by the ETDRS chart letters. BCVA gradually increased after treatments in all three groups. The increases of BCVA were the most at the end of the first month. At the end of 6 m, the mean BCVA was improved by 25.10 ± 3.73, 26.32 ± 4.06, and 17.16 ± 2.87 letters in IVC, IVR, and IVTA groups, respectively (all P values < 0.05).
Figure 3
Figure 3
Comparison of outcomes of IVC, IVR, and IVTA groups at 6 m. There were no significant differences in operation time, incidence of iatrogenic retinal breaks, endodiathermy rate, and silicone oil tamponade between IVC and IVR groups. However, each of these two groups showed significant difference with the IVTA group.
Figure 4
Figure 4
Secondary outcomes and adverse events of the IVC, IVR, and IVTA groups at 6 m. There were no significant differences in vitreous clear-up time and the incidence of intraoperative bleeding between IVC and IVR groups, while both of these groups were significantly different from IVTA group. More patients were at high IOP level in the IVTA group than the other two groups after surgeries. However, there were no statistically significant differences in the incidence of postoperative bleeding, PRP completion rate, and reoperation probability among 3 groups.

References

    1. Boscia F. Current approaches to the management of diabetic retinopathy and diabetic macular oedema. Drugs. 2010;70(16):2171–2200. doi: 10.2165/11538130-000000000-00000.
    1. Yang W., Lu J., Weng J., et al. Prevalence of diabetes among men and women in China. The New England Journal of Medicine. 2010;362(12):1090–1101. doi: 10.1056/NEJMoa0908292.
    1. Liu L., Wu X., Liu L., et al. Prevalence of diabetic retinopathy in mainland China: a meta-analysis. PLoS One. 2012;7(9, article e45264) doi: 10.1371/journal.pone.0045264.
    1. Fong D. S., Aiello L., Gardner T. W., et al. Retinopathy in diabetes. Diabetes Care. 2004;27(Supplement 1):S84–S87. doi: 10.2337/diacare.27.2007.S84.
    1. Tseng V. L., Greenberg P. B., Scott I. U., Anderson K. L. Compliance with the American Academy of Ophthalmology Preferred Practice Pattern for Diabetic Retinopathy in a resident ophthalmology clinic. Retina. 2010;30(5):787–794. doi: 10.1097/IAE.0b013e3181cd47a2.
    1. Li F. M. Systemic disease and retinopathy; Part1, diabetic retinopathy. Vol. 2. Beijing: People’s Medical Publishing House; 2005. Chinese ophthalmology; pp. 2165–2171.
    1. Bressler S. B., Qin H., Melia M., et al. Exploratory analysis of the effect of intravitreal ranibizumab or triamcinolone on worsening of diabetic retinopathy in a randomized clinical trial. JAMA Ophthalmology. 2013;131(8):1033–1040. doi: 10.1001/jamaophthalmol.2013.4154.
    1. Googe J., Brucker A. J., Bressler N. M., et al. Randomized trial evaluating short-term effects of intravitreal ranibizumab or triamcinolone acetonide on macular edema after focal/grid laser for diabetic macular edema in eyes also receiving panretinal photocoagulation. Retina. 2011;31(6):1009–1027. doi: 10.1097/IAE.0b013e318217d739.
    1. Liu T., Xie A. M., Tian X. Y., Chen M., Wei J. Drug assisted vitrectomy for the treatment of proliferative diabetic retinopathy. International Journal of Ophthalmology. 2008;8:1681–1684.
    1. Peyman G. A., Cheema R., Conway M. D., Fang T. Triamcinolone acetonide as an aid to visualization of the vitreous and the posterior hyaloid during pars plana vitrectomy. Retina. 2000;20(5):554–555. doi: 10.1097/00006982-200005000-00024.
    1. Sakamoto T., Miyazaki M., Hisatomi T., et al. Triamcinolone-assisted pars plana vitrectomy improves the surgical procedures and decreases the postoperative blood–ocular barrier breakdown. Graefe's Archive for Clinical and Experimental Ophthalmology. 2002;240(6):423–429. doi: 10.1007/s00417-002-0454-2.
    1. Enaida H., Hata Y., Ueno A., et al. Possible benefits of triamcinolone-assisted pars plana vitrectomy for retinal diseases. Retina. 2003;23(6):764–770. doi: 10.1097/00006982-200312000-00003.
    1. Zhu J., Wang Y. S., Hui Y. N. Growth and inhibition of choroidal neovascularization. Recent Advances in Ophthalmology. 2004;24:57–60.
    1. Nguyen Q. D., Tatlipinar S., Shah S. M., et al. Vascular endothelial growth factor is a critical stimulus for diabetic macular edema. American Journal of Ophthalmology. 2006;142(6):961–969.e4. doi: 10.1016/j.ajo.2006.06.068.
    1. Kroll P., Büchele Rodrigues E., Hoerle S. Pathogenesis and classification of proliferative diabetic vitreoretinopathy. Ophthalmologica. 2007;221(2):78–94. doi: 10.1159/000098253.
    1. Simunovic M. P., Maberley D. A. L. Anti-vascular endothelial growth factor therapy for proliferative diabetic retinopathy: a systematic review and meta-analysis. Retina. 2015;35(10):1931–1942. doi: 10.1097/IAE.0000000000000723.
    1. Lu H., Cui J., Dong H., Luo B., Xiu W., Li H. Clinical observation of a new anti-VEGF drugs conbercept for wet age-related macular degeneration. Chinese Journal of Ophthalmology. 2015;51(11):818–821.
    1. Yang X., Xu J., Wang R., et al. A randomized controlled trial of conbercept pretreatment before vitrectomy in proliferative diabetic retinopathy. Journal of Ophthalmology. 2016;2016:8. doi: 10.1155/2016/2473234.2473234
    1. Li T., Zheng Z., Zheng B. Q., Zhao S. Z., Chen W., Ni L. S. Effect of bevacizumab combined 23G vitrectomy in the treatment of severe proliferative diabetic retinopathy. Progress in Modern Biomedicine. 2013;13:4488–4491.
    1. Zhang X., Wu C., Zhou L. J., Dai R. P. Observation of optic disc neovascularization using OCT angiography in proliferative diabetic retinopathy after intravitreal conbercept injections. Scientific Reports. 2018;8, article e3972 doi: 10.1038/s41598-018-22363-0.
    1. Dong F., Yu C., Ding H., Shen L., Lou D. Evaluation of intravitreal ranibizumab on the surgical outcome for diabetic retinopathy with tractional retinal detachment. Medicine. 2016;95(8):p. e2731. doi: 10.1097/MD.0000000000002731.
    1. Munir W. M., Pulido J. S., Sharma M. C., Buerk B. M. Intravitreal triamcinolone for treatment of complicated proliferative diabetic retinopathy and proliferative vitreoretinopathy. Canadian Journal of Ophthalmology. 2005;40(5):598–604. doi: 10.1016/S0008-4182(05)80052-3.
    1. Su L., Ren X., Wei H., et al. Intravitreal conbercept (kh902) for surgical treatment of severe proliferative diabetic retinopathy. Retina. 2016;36(5):938–943. doi: 10.1097/IAE.0000000000000900.
    1. di Lauro R., De Ruggiero P., di Lauro R., di Lauro M. T., Romano M. R. Intravitreal bevacizumab for surgical treatment of severe proliferative diabetic retinopathy. Graefe's Archive for Clinical and Experimental Ophthalmology. 2010;248(6):785–791. doi: 10.1007/s00417-010-1303-3.
    1. Keshavamurthy R., Venkatesh P., Garg S. Ultrasound biomicroscopy findings of 25 G transconjuctival sutureless (TSV) and conventional (20G) pars plana sclerotomy in the same patient. BMC Ophthalmology. 2006;6(1):p. 7. doi: 10.1186/1471-2415-6-7.
    1. Durham J. T., Herman I. M. Microvascular modifications in diabetic retinopathy. Current Diabetes Reports. 2011;11(4):253–264. doi: 10.1007/s11892-011-0204-0.
    1. Van Geest R. J., Lesnik-Oberstein S. Y., Tan H. S., et al. A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy. British Journal of Ophthalmology. 2012;96(4):587–590. doi: 10.1136/bjophthalmol-2011-301005.
    1. Fong D. S., Ferris F. L., III, Davis M. D., Chew E. Y., Early Treatment Diabetic Retinopathy Study Research Group Causes of severe visual loss in the early treatment diabetic retinopathy study: ETDRS report no. 24. American Journal of Ophthalmology. 1999;127(2):137–141. doi: 10.1016/S0002-9394(98)00309-2.
    1. Ribeiro J. A. S., Messias A., Jorge R. Antiangiogenic drugs and advanced proliferative diabetic retinopathy. Arquivos Brasileiros de Oftalmologia. 2011;74(2):143–146. doi: 10.1590/S0004-27492011000200017.
    1. Avery R. L., Pearlman J., Pieramici D. J., et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology. 2006;113(10):1695–1705.e6. doi: 10.1016/j.ophtha.2006.05.064.
    1. Kohno R.-I., Hata Y., Mochizuki Y., et al. Histopathology of neovascular tissue from eyes with proliferative diabetic retinopathy after intravitreal bevacizumab injection. American Journal of Ophthalmology. 2010;150(2):223–229.e1. doi: 10.1016/j.ajo.2010.03.016.
    1. Chen E., Park C. H. Use of intravitreal bevacizumab as a preoperative adjunct for tractional retinal detachment repair in severe proliferative diabetic retinopathy. Retina. 2006;26(6):699–700. doi: 10.1097/01.iae.0000225351.87205.69.
    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. 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. Arevalo J. F., Maia M., Flynn H. W., et al. Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy. British Journal of Ophthalmology. 2008;92(2):213–216. doi: 10.1136/bjo.2007.127142.
    1. Wiedemann P. Growth factors in retinal diseases: proliferative vitreoretinopathy, proliferative diabetic retinopathy, and retinal degeneration. Survey of Ophthalmology. 1992;36(5):373–384. doi: 10.1016/0039-6257(92)90115-A.
    1. Glaser B. M., Cardin A., Biscoe B. Prolieferative vitreoretinopathy: the mechanism of development of vitreoretinal traction. Ophthalmology. 1987;94(4):327–332. doi: 10.1016/S0161-6420(87)33443-8.
    1. Tano Y., Chandler D. B., McCuen B. W., Machemer R. Glucocorticosteroid inhibition of intraocular proliferation after injury. American Journal of Ophthalmology. 1981;91(2):184–189. doi: 10.1016/0002-9394(81)90171-9.
    1. Tano Y., Chandler D., Machemer R. Treatment of intraocular proliferation with intravitreal injection of triamcinolone acetonide. American Journal of Ophthalmology. 1980;90(6):810–816. doi: 10.1016/S0002-9394(14)75196-7.
    1. Meyer C. N. Current treatment approaches in diabetic macular edema. Ophthalmologica. 2007;221(2):118–131. doi: 10.1159/000098257.
    1. Ueno A., Enaida H., Hata Y., et al. Long-term clinical outcomes and therapeutic benefits of triamcinolone-assisted pars plana vitrectomy for proliferative vitreoretinopathy: a case study. European Journal of Ophthalmology. 2007;17(3):392–398. doi: 10.1177/112067210701700320.
    1. Mańkowska A., Rejdak R., Nowomiejska K., Zagórski Z. Efficacy of intravitreal triamcinolone acetonide in the visualization of the vitreous during pars plana vitrectomy. Klinika Oczna. 2006;108(1-3):24–27.
    1. Brown D. M., Kaiser P. K., Michels M., et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. The New England Journal of Medicine. 2006;355(14):1432–1444. doi: 10.1056/NEJMoa062655.
    1. Sun X., Lu X. Profile of conbercept in the treatment of neovascular age-related macular degeneration. Drug Design, Development and Therapy. 2015;9:2311–2320. doi: 10.2147/DDDT.S67536.
    1. CATT Research Group, Martin D. F., Maguire M. G., et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. The New England Journal of Medicine. 2011;364(20):1897–1908. doi: 10.1056/NEJMoa1102673.
    1. Campochiaro P. A., Heier J. S., Feiner L., et al. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010;117(6):1102–1112.e1. doi: 10.1016/j.ophtha.2010.02.021.
    1. Michaelides M., Kaines A., Hamilton R. D., et al. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study): 12-month data: report 2. Ophthalmology. 2010;117(6):1078–1086.e2. doi: 10.1016/j.ophtha.2010.03.045.
    1. Gross J. G., Glassman A. R. A Novel Treatment for Proliferative Diabetic Retinopathy: Anti-Vascular Endothelial Growth Factor Therapy. JAMA Ophthalmology. 2016;134(1):13–14. doi: 10.1001/jamaophthalmol.2015.5079.
    1. Peyman G. A. Vitreoretinal Surgical Techniques. London, UK: MartinDunitz; 2001.
    1. Tangjai P., Chingchana P., Taweerutchana R. Glycated haemoglobin and diabetic retinopathy in type 2 diabetic patients in HRH Princess Maha Chakri Sirindhorn Medical Center. Journal of the Medical Association of Thailand. 2015;98:135–42m.
    1. Moreira C. A., Jr, Arana L. A., Zago R. J. Long-term results of repeated anti–vascular endothelial growth factor therapy in eyes with retinal pigment epithelial tears. Retina. 2013;33(2):277–281. doi: 10.1097/IAE.0b013e318263d139.
    1. Cunningham E. T., Jr, Feiner L., Chung C., Tuomi L., Ehrlich J. S. Incidence of retinal pigment epithelial tears after intravitreal ranibizumab injection for neovascular age-related macular degeneration. Ophthalmology. 2011;118(12):2447–2452. doi: 10.1016/j.ophtha.2011.05.026.

Source: PubMed

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