Intravitreal injection of conbercept after operation in the treatment of proliferatived diabetic retinophathy complicated with vitreous hemorrhage_Chinese Journal of Ocular Fundus Diseases

Authors：

Zhang Jinping , Ren Xinjun , Zheng Chuanzhen , Wen Dejia , Li Xiaorong ,  Zhang Xiaomin

Tianjin Medical University Hospital, Tianjin Medical University Eye Institute, School of Optometry and Ophthalmology, Tianjin Medical University, Tianjin 300384, China;

Corresponding author：

Zhang Xiaomin, Email: xiaomzh@126.com

Keywords：

Diabetic retinopathy/complications; Vitreous hemorrhage; Angiogenesis inhibitors/therapeutic use; Vitrectomy

DOI：

10.3760/cma.j.issn.1005-1015.2020.02.004

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Objective To observe the efficacy and safety of intravitreal injection of conbercept in the treatment of proliferatived diabetic retinophathy (PDR) complicated with vitreous hemorrhage by minimally invasive vitreoretinal surgery.Methods Prospective clinical study. A total of 50 patients with PDR complicated with vitreous hemorrhage clinically diagnosed in Tianjin Medical University Eye Hospital who needed vitrectomy were recruited in this study. According to the principle of informed consent, the patients were divided into two groups: postoperative injection group and the control group. Twenty-five eyes of 25 patients in each group were examined before operation. No significant proliferative changes in the posterior pole and traction retinal detachment were observed. There was significant difference of age between two groups (t=－24.697, P=0.030), but no significant difference of sex (χ²=0.330, P=0.564), duration of diabetes (t=－1.144, P=0.258), logMAR BCVA (t=－0.148, P=0.883), lens state (χ²=0.397, P=0.529), panretinal laser photocoagulation (χ²=1.333, P=0.248). The postoperative injection group was treated with intravitreous injection of 0.05 ml conbercept (10 mg/ml) immediately after 27G minimally invasive vitrectomy. The other treatment and follow-up were the same as those in the postoperative injection group except for conbercept injection. All patients underwent routine slit-lamp examination, indirect ophthalmoscope and B-ultrasound examination before operation. The main outcome measure included the time of operation, the incidence rate of iatrogenic retinal holes and silicone oil filling. The recurrence of vitreous hemorrhage, BCVA, intraocular pressure, central retinal thickness (CRT), postoperative complications and progression were recorded 1 week, 1 month, 3 months and 6 months after operation.Results At 1 week and 1, 3, 6 months after operation, there was significant difference of logMAR BCVA between the two groups (t=－4.980, －4.840, －4.892, －5.439; P<0.001). At 3 and 6 months after operation, the recurrence of vitreous hemorrhage in the postoperative injection group was lower than that in the control group, but there was no statistical difference between two groups (χ²=3.030, 4.153; P=0.192, 0.103). At 1 week and 1, 3, 6 months after operation, the CRT in the postoperative injection group was lower than that in the control group, the difference was significant (t=－2.622, －2.638, －3.613, －3.037; P=0.012, 0.010, 0.001, 0.004, 0.005). There was no complications such as choroid detachment, proliferative vitreoretinopathy, retinal detachment, iris redness and neovascular glaucoma in all the eyes after operation.Conclusions Intravitreal injection of conbercept in the treatment of PDR after operation is safe and effective. It can reduce the recurrence of vitreous hemorrhage after vitrectomy, improve the BCVA.

Citation： Zhang Jinping, Ren Xinjun, Zheng Chuanzhen, Wen Dejia, Li Xiaorong, Zhang Xiaomin. Intravitreal injection of conbercept after operation in the treatment of proliferatived diabetic retinophathy complicated with vitreous hemorrhage. Chinese Journal of Ocular Fundus Diseases, 2020, 36(2): 105-109. doi: 10.3760/cma.j.issn.1005-1015.2020.02.004 Copy

1.	Liu L, Wu X, Liu L, et al. Prevalence of diabetic retinopathy in mainland China: a meta-analysis[J/OL]. PLoS One, 2012, 7(9): 45264[2012-09-20].https://doi.org/10.1371/journal.pone.0045264. DOI: 10.1371/journal.pone.0045264.
2.	Ehrlich R, Harris A, Ciulla TA, et al. Diabetic macular oedema: physical, physiological and molecular factors contribute to this pathological process[J]. Acta Ophthalmol, 2010, 88(3): 279-291. DOI: 10.1111/j.1755-3768.2008.01501.x.
3.	Mukhtar A, Khan MS, Junejo M, et al. Effect of pan retinal photocoagulation on central macular thickness and visual acuity in proliferative diabetic retinopathy[J]. Pak J Med Sci, 2016, 32(1): 221-224. DOI: 10.12669/pjms.321.8758.
4.	Yan H, Cui J, Lu Y, et al. Reasons for and management of postvitrectomy vitreous hemorrhage in proliferative diabetic retinopathy[J]. Curr Eye Res, 2010, 35(4): 308-313. DOI: 10.3109/02713680903572491.
5.	Farouk MM, Naito T, Sayed KM, et al. Outcomes of 25-gauge vitrectomy for proliferative diabetic retinopathy[J]. Graefe’s Arch Clin Exp Ophthalmol, 2011, 249(3): 369-376. DOI: 10.1007/s00417-010-1506-7.
6.	Zhang ZH, Liu HY, Hernandez-Da Mota SE, et al. Vitrectomy with or without preoperative intravitreal bevacizumab for proliferative diabetic retinopathy: a meta-analysis of randomized controlled trials[J]. Am J Ophthalmol, 2013, 156(1): 106-115. DOI: 10.1016/j.ajo.2013.02.008.
7.	薛鹏程, 游志鹏, 付书华, 等. 23G玻璃体切割术前、术中辅助玻璃体内注射康柏西普治疗增生型糖尿病视网膜病变(PDR)的疗效分析[J]. 眼科新进展, 2017, 37(5): 458-462. DOI: 10.13389/j.cnki.rao.2017.0116.Xue PC, You ZP, Fu SH, et al. Preoperative and intraoperative adjunctive intravitreal conbercept in 23G vitrectomy for proliferative diabetic retinopathy[J]. Rec Adv Ophthalmol, 2017, 37(5): 458-462. DOI: 10.13389/j.cnki.rao.2017.0116.
8.	Yang W, Lu J, Weng J, et al. Prevalence of diabetes among men and women in China[J]. N Engl J Med, 2010, 362(12): 1090-1101. DOI: 10.1056/NEJMoa0908292.
9.	中华医学会眼科学会眼底病学组. 我国糖尿病视网膜病变临床诊疗指南(2014年)[J]. 中华眼科杂志, 2014, 50(11): 851-865. DOI: 10.3760/cma.j.issn.0412-4081.2014.11.014.Ophthalmology Branch of Chinese Medical Association. Guidelines for clinical diagnosis and treatment of diabetic retinopathy in China[J]. Chin J Ophthalmol, 2014, 50(11): 851-865. DOI: 10.3760/cma.j.issn.0412-4081.2014.11.014.
10.	Vander JF, Duker JS, Benson WE, et al. Long-term stability and visual outcome after favorable initial response of proliferative diabetic retinopathy to panretinal photocoagulation[J]. Ophthalmology, 1991, 98(10): 1575-1579. DOI: 10.1016/s0161-6420(91)32085-2.
11.	Flynn HW Jr, Chew EY, Simons BD, et al. Pars plana vitrectomy in the Early Treatment Diabetic Retinopathy Study. ETDRS report number17: the Early Treatment Diabetic Retinopathy Study Research Group[J]. Ophthalmology, 1992, 99(9): 1351-1357. DOI: 10.1016/s0161-6420(92)31779-8.
12.	di Lanro R, de Ruggiero P, di Lauro R, et al. Intravitreal bevaeizumab for surgical treatment of severe proliferative diabetic retinopathy[J]. Graefe’s Arch Clin Exp Ophthalmol, 2010, 248(6): 785-791. DOI: 10.1007/s00417-010-1303-3.
13.	Ahmadieh H, Shoeibi N, Entezari M, et al. Intravitreal bevacizumab for prevention of early postvitrectomy hemorrhage in diabetic patients:arandomized clinical trial[J]. Ophthalmology, 2009, 116(10): 1943-1948. DOI: 10.1016/j.ophtha.2009.07.001.
14.	Kohno R, Hata Y, Moehizuki Y, et al. Histopathology of neovaseular tissue from eyes with proliferative diabetic retinopathy after intravitreal bevacizumab injection[J]. Am J Ophthalmol, 2010, 150(2): 223-229. DOI: 10.1016/j.ajo.2010.03.016.
15.	丁国鹏, 丁国龙, 雷姝, 等. 康柏西普联合577 nm微脉冲激光治疗糖尿病性黄斑水肿临床观察[J]. 国际眼科杂志, 2015, 15(11): 1942-1944. DOI: 10.3980/j.issn.1672-5123.2015.11.28.Ding GP, Ding GL, Lei S, et al. Clinical effect of Conbercept intravitreal injection combined with 577 nm micro-pulse laser on the treatment of diabetic macular edema[J]. Int Eye Sci, 2015, 15(11): 1942-1944. DOI: 10.3980/j.issn.1672-5123.2015.11.28.
16.	Su L, Ren X, Wei H, et al. Intravitreal conbercept (KH902) for surgical treatment of severe proliferative diabetic retinopathy[J]. Retina, 2016, 36(5): 938-943. DOI: 10.1097/IAE.0000000000000900.
17.	Spaide RF, Fisher YL. Intravitreal IVB (Avastin) treatment of proliferative diabetic retinopathy complicated by vitreous hemorrhage[J]. Retina, 2006, 26(3): 275-278. DOI: 10.1097/00006982-200603000-00004.
18.	Huang YH, Yeh PT, Chen MS, et al. Intravitreal IVB and panretinal photocoagulation for proliferative diabetic retinopathy associated with vitreous hemorrhage[J]. Retina, 2009, 29(8): 1134-1140. DOI: 10.1097/IAE.0b013e3181b094b7.
19.	Ip MS, Domalpally A, Hopkins JJ, et al. Long - term effects of ranibizumab on diabetic retinopathy severity and progression[J]. Arch Ophthalmol, 2012, 130(9): 1145-1152. DOI: 10.1001/archophthalmol.2012.1043.
20.	Moradian S, Ahmadieh H, Malihi M, et al. Intravitreal bevacizumab in active progressive proliferative diabetic retinopathy[J]. Garaefe’s Arch Clin Exp Ophthalmol, 2008, 246(12): 1699-1705. DOI: 10.1007/s00417-008-0914-4.
21.	Arevalo JF, Maia M, Flynn HW Jr, et al. Tractional retinal detachment following intravitreal bevacizumab in patients with severe proliferative diabetic retinopathy[J]. Br J Ophthalmol, 2008, 92(2): 213-216. DOI: 10.1136/bjo.2007.127142.
22.	Yeh PT, Yang CM, Lin YC, et al. IVB pretreatment in vitrectomy with silicone oil for severe diabetic retinopathy[J]. Retina, 2009, 29(6): 768-774. DOI: 10.1097/IAE.0b013e3181a3b7ef.
23.	Ishikawa K, Honda S, Tsukahara Y, et al. Preferable use of intravitreal bevacizumab as a pretreatment of vitrectomy for severe proliferative diabetic retinopathy[J]. Eye (Lond), 2009, 23(1): 108-111. DOI: 10.1038/sj.eye.6702983.
24.	El-Sabagh HA, Abdelghaffar W, Labib AM, et al. Preoperative intravitreal bevacizumab use as an adjuvant to diabetic vitrectomy: histopathologic findings and clinical implication[J]. Ophthalmology, 2011, 118(4): 636-641. DOI: 10.1016/j.ophtha.2010.08.038.
25.	Gupta A, Bansal R, Gupta V, et al. Six-month visual outome after pars plana vitrectomy in proliferative diabetic retinopathy with or without a single preoperative injection of intravitreal bevacizumab[J]. Int Ophthalmol, 2012, 32(2): 135-144. DOI: 10.1007/s10792-012-9541-5.

1. Liu L, Wu X, Liu L, et al. Prevalence of diabetic retinopathy in mainland China: a meta-analysis[J/OL]. PLoS One, 2012, 7(9): 45264[2012-09-20].https://doi.org/10.1371/journal.pone.0045264. DOI: 10.1371/journal.pone.0045264.
2. Ehrlich R, Harris A, Ciulla TA, et al. Diabetic macular oedema: physical, physiological and molecular factors contribute to this pathological process[J]. Acta Ophthalmol, 2010, 88(3): 279-291. DOI: 10.1111/j.1755-3768.2008.01501.x.
3. Mukhtar A, Khan MS, Junejo M, et al. Effect of pan retinal photocoagulation on central macular thickness and visual acuity in proliferative diabetic retinopathy[J]. Pak J Med Sci, 2016, 32(1): 221-224. DOI: 10.12669/pjms.321.8758.
4. Yan H, Cui J, Lu Y, et al. Reasons for and management of postvitrectomy vitreous hemorrhage in proliferative diabetic retinopathy[J]. Curr Eye Res, 2010, 35(4): 308-313. DOI: 10.3109/02713680903572491.
5. Farouk MM, Naito T, Sayed KM, et al. Outcomes of 25-gauge vitrectomy for proliferative diabetic retinopathy[J]. Graefe’s Arch Clin Exp Ophthalmol, 2011, 249(3): 369-376. DOI: 10.1007/s00417-010-1506-7.
6. Zhang ZH, Liu HY, Hernandez-Da Mota SE, et al. Vitrectomy with or without preoperative intravitreal bevacizumab for proliferative diabetic retinopathy: a meta-analysis of randomized controlled trials[J]. Am J Ophthalmol, 2013, 156(1): 106-115. DOI: 10.1016/j.ajo.2013.02.008.
7. 薛鹏程, 游志鹏, 付书华, 等. 23G玻璃体切割术前、术中辅助玻璃体内注射康柏西普治疗增生型糖尿病视网膜病变(PDR)的疗效分析[J]. 眼科新进展, 2017, 37(5): 458-462. DOI: 10.13389/j.cnki.rao.2017.0116.Xue PC, You ZP, Fu SH, et al. Preoperative and intraoperative adjunctive intravitreal conbercept in 23G vitrectomy for proliferative diabetic retinopathy[J]. Rec Adv Ophthalmol, 2017, 37(5): 458-462. DOI: 10.13389/j.cnki.rao.2017.0116.
8. Yang W, Lu J, Weng J, et al. Prevalence of diabetes among men and women in China[J]. N Engl J Med, 2010, 362(12): 1090-1101. DOI: 10.1056/NEJMoa0908292.
9. 中华医学会眼科学会眼底病学组. 我国糖尿病视网膜病变临床诊疗指南(2014年)[J]. 中华眼科杂志, 2014, 50(11): 851-865. DOI: 10.3760/cma.j.issn.0412-4081.2014.11.014.Ophthalmology Branch of Chinese Medical Association. Guidelines for clinical diagnosis and treatment of diabetic retinopathy in China[J]. Chin J Ophthalmol, 2014, 50(11): 851-865. DOI: 10.3760/cma.j.issn.0412-4081.2014.11.014.
10. Vander JF, Duker JS, Benson WE, et al. Long-term stability and visual outcome after favorable initial response of proliferative diabetic retinopathy to panretinal photocoagulation[J]. Ophthalmology, 1991, 98(10): 1575-1579. DOI: 10.1016/s0161-6420(91)32085-2.
11. Flynn HW Jr, Chew EY, Simons BD, et al. Pars plana vitrectomy in the Early Treatment Diabetic Retinopathy Study. ETDRS report number17: the Early Treatment Diabetic Retinopathy Study Research Group[J]. Ophthalmology, 1992, 99(9): 1351-1357. DOI: 10.1016/s0161-6420(92)31779-8.
12. di Lanro R, de Ruggiero P, di Lauro R, et al. Intravitreal bevaeizumab for surgical treatment of severe proliferative diabetic retinopathy[J]. Graefe’s Arch Clin Exp Ophthalmol, 2010, 248(6): 785-791. DOI: 10.1007/s00417-010-1303-3.
13. Ahmadieh H, Shoeibi N, Entezari M, et al. Intravitreal bevacizumab for prevention of early postvitrectomy hemorrhage in diabetic patients:arandomized clinical trial[J]. Ophthalmology, 2009, 116(10): 1943-1948. DOI: 10.1016/j.ophtha.2009.07.001.
14. Kohno R, Hata Y, Moehizuki Y, et al. Histopathology of neovaseular tissue from eyes with proliferative diabetic retinopathy after intravitreal bevacizumab injection[J]. Am J Ophthalmol, 2010, 150(2): 223-229. DOI: 10.1016/j.ajo.2010.03.016.
15. 丁国鹏, 丁国龙, 雷姝, 等. 康柏西普联合577 nm微脉冲激光治疗糖尿病性黄斑水肿临床观察[J]. 国际眼科杂志, 2015, 15(11): 1942-1944. DOI: 10.3980/j.issn.1672-5123.2015.11.28.Ding GP, Ding GL, Lei S, et al. Clinical effect of Conbercept intravitreal injection combined with 577 nm micro-pulse laser on the treatment of diabetic macular edema[J]. Int Eye Sci, 2015, 15(11): 1942-1944. DOI: 10.3980/j.issn.1672-5123.2015.11.28.
16. Su L, Ren X, Wei H, et al. Intravitreal conbercept (KH902) for surgical treatment of severe proliferative diabetic retinopathy[J]. Retina, 2016, 36(5): 938-943. DOI: 10.1097/IAE.0000000000000900.
17. Spaide RF, Fisher YL. Intravitreal IVB (Avastin) treatment of proliferative diabetic retinopathy complicated by vitreous hemorrhage[J]. Retina, 2006, 26(3): 275-278. DOI: 10.1097/00006982-200603000-00004.
18. Huang YH, Yeh PT, Chen MS, et al. Intravitreal IVB and panretinal photocoagulation for proliferative diabetic retinopathy associated with vitreous hemorrhage[J]. Retina, 2009, 29(8): 1134-1140. DOI: 10.1097/IAE.0b013e3181b094b7.
19. Ip MS, Domalpally A, Hopkins JJ, et al. Long - term effects of ranibizumab on diabetic retinopathy severity and progression[J]. Arch Ophthalmol, 2012, 130(9): 1145-1152. DOI: 10.1001/archophthalmol.2012.1043.
20. Moradian S, Ahmadieh H, Malihi M, et al. Intravitreal bevacizumab in active progressive proliferative diabetic retinopathy[J]. Garaefe’s Arch Clin Exp Ophthalmol, 2008, 246(12): 1699-1705. DOI: 10.1007/s00417-008-0914-4.
21. Arevalo JF, Maia M, Flynn HW Jr, et al. Tractional retinal detachment following intravitreal bevacizumab in patients with severe proliferative diabetic retinopathy[J]. Br J Ophthalmol, 2008, 92(2): 213-216. DOI: 10.1136/bjo.2007.127142.
22. Yeh PT, Yang CM, Lin YC, et al. IVB pretreatment in vitrectomy with silicone oil for severe diabetic retinopathy[J]. Retina, 2009, 29(6): 768-774. DOI: 10.1097/IAE.0b013e3181a3b7ef.
23. Ishikawa K, Honda S, Tsukahara Y, et al. Preferable use of intravitreal bevacizumab as a pretreatment of vitrectomy for severe proliferative diabetic retinopathy[J]. Eye (Lond), 2009, 23(1): 108-111. DOI: 10.1038/sj.eye.6702983.
24. El-Sabagh HA, Abdelghaffar W, Labib AM, et al. Preoperative intravitreal bevacizumab use as an adjuvant to diabetic vitrectomy: histopathologic findings and clinical implication[J]. Ophthalmology, 2011, 118(4): 636-641. DOI: 10.1016/j.ophtha.2010.08.038.
25. Gupta A, Bansal R, Gupta V, et al. Six-month visual outome after pars plana vitrectomy in proliferative diabetic retinopathy with or without a single preoperative injection of intravitreal bevacizumab[J]. Int Ophthalmol, 2012, 32(2): 135-144. DOI: 10.1007/s10792-012-9541-5.

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Chinese Journal of Ocular Fundus Diseases

Intravitreal injection of conbercept after operation in the treatment of proliferatived diabetic retinophathy complicated with vitreous hemorrhage

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