抗血管内皮生长因子时代糖尿病视网膜病变的治疗演变_West China Medical Journal

Authors：

闵晓雪 , 牟佳 , 刘依琳 , 任湘 , 周思睿 ,  张明

四川大学华西医院眼科（成都 610041）;

Corresponding author：

张明, Email: zhangmingscu@126.com

Keywords：

糖尿病; 视网膜病变; 抗血管内皮生长因子; 激光; 玻璃体切除术

DOI：

10.7507/1002-0179.201708076

Video：

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糖尿病视网膜病变（diabetic retinopathy，DR）是糖尿病常见的眼部并发症，其治疗包括眼部治疗及系统综合性治疗。眼部治疗手段有视网膜激光光凝术、玻璃体腔注射激素类药物、玻璃体切除术、玻璃体腔注射抗血管内皮生长因子（vascular endothelial growth factor，VEGF）类药物，如今最为热门的是玻璃体腔注射抗 VEGF 类药物。以上不同的治疗手段在 DR 不同病程阶段的应用处于不断的更新和探索中。该文就抗 VEGF 时代 DR 的治疗演变及目前存在的争议进行综述。

Citation： 闵晓雪, 牟佳, 刘依琳, 任湘, 周思睿, 张明. 抗血管内皮生长因子时代糖尿病视网膜病变的治疗演变. West China Medical Journal, 2017, 32(10): 1615-1619. doi: 10.7507/1002-0179.201708076 Copy

1.	World Health Organization. Global report on diabetes. (2016-04-01)[2017-08-10]. http://www.who.int/diabetes/publications/grd-2016/en/.
2.	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) 中华眼科杂志, 2014, 50(11): 851-865.
3.	Association AD. Executive summary: standards of medical care in diabetes--2009. Diabetes Care, 2009, 32(Suppl 1): S6-S12.
4.	Boyer DS, Hopkins JJ, Sorof J, et al. Anti-vascular endothelial growth factor therapy for diabetic macular edema. Ther Adv Endocrinol Metab, 2013, 4(6): 151-169.
5.	Nguyen QD, Shah SM, Heier JS, et al. Primary end point (six months) results of the ranibizumab for edema of the macula in Diabetes (READ-2) study. Ophthalmology, 2009, 116(11): 2175-2181.
6.	Michaelides M, Kaines A, Hamilton RD, 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): 1076-1078.
7.	Mitchell P, Bandello F, Schmidt-Erfurth UA, et al. The RESTORE study ranibizumab monotherapy or combined with laser <italic>versus</italic> laser monotherapy for diabetic macular edema. Ophthalmology, 2011, 118(4): 615-625.
8.	Brown DM, Schmidt-Erfurth U, Do DV, et al. Intravitreal aflibercept for diabetic macular edema: 100-week results from the VISTA and VIVID studies. Ophthalmology, 2015, 122(10): 2044-2052.
9.	Barteselli G, Kozak I, El-Emam S, et al. 12-month results of the standardised combination therapy for diabetic macular oedema: intravitreal bevacizumab and navigated retinal photocoagulation. Br J Ophthalmol, 2014, 98(8): 1036-1041.
10.	Hirano T, Toriyama Y, Iesato Y, et al. Effect of leaking perifoveal microaneurysms on resolution of diabetic macular edema treated by combination therapy using anti-vascular endothelial growth factor and short pulse focal/grid laser photocoagulation. Jpn J Ophthalmol, 2017, 61(1): 51-60.
11.	Yu AK, Merrill KD, Truong SN, et al. The comparative histologic effects of subthreshold 532- and 810-nm diode micropulse laser on the retina. Invest Ophthalmol Vis Sci, 2013, 54(3): 2216-2224.
12.	Writing Committee for the Diabetic Retinopathy Clinical Research Network, Gross JG, Glassman AR, et al. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA, 2015, 314(20): 2137-2146.
13.	Ulrich JN. Pars plana vitrectomy with internal limiting membrane peeling for nontractional diabetic macular edema. Open Ophthalmol J, 2017, 11(1): 5-10.
14.	Figueroa MS, Contreras I, Noval S. Surgical and anatomical outcomes of pars plana vitrectomy for diffuse nontractional diabetic macular edema. Retina, 2008, 28(3): 420-426.
15.	Hoerauf H, Brüggemann A, Muecke M, et al. Pars plana vitrectomy for diabetic macular edema. Internal limiting membrane delamination <italic>vs</italic> posterior hyaloid removal. A prospective randomized trial. Graefes Arch Clin Exp Ophthalmol, 2011, 249(7): 997-1008.
16.	Kumar A, Sinha S, Azad R, et al. Comparative evaluation of vitrectomy and dye-enhanced ILM peel with grid laser in diffuse diabetic macular edema. Graefes Arch Clin Exp Ophthalmol, 2007, 245(3): 360-368.
17.	Patel JI, Hykin PG, Schadt M, et al. Diabetic macular oedema: pilot randomised trial of pars plana vitrectomy <italic>vs</italic> macular Argon photocoagulation. Eye (Lond), 2006, 20(8): 873-881.
18.	刘大川, 吴航, 杨惠青. 玻璃体手术治疗弥漫性非牵引性糖尿病性黄斑水肿的临床效果. 中华眼科杂志, 2011, 47(6): 492-496.
19.	Banerjee PJ, Quartilho A, Bunce C, et al. Slow-release dexamethasone in proliferative vitreoretinopathy: a prospective, randomized controlled clinical trial. Ophthalmology, 2017, 124(6): 757-767.
20.	El-Remessy AB, Behzadian MA, Abou-mohamed G, et al. Experimental diabetes causes breakdown of the blood-retina barrier by a mechanism involving tyrosine nitration and increases in expression of vascular endothelial growth factor and urokinase plasminogen activator receptor. Am J Pathol, 2003, 162(6): 1995-2004.
21.	Qaum T, Xu Q, Joussen AM, et al. VEGF-initiated blood-retinal barrier breakdown in early diabetes. Invest Ophthalmol Vis Sci, 2001, 42(10): 2408-2413.
22.	Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema two-year results from a comparative effectiveness randomized clinical trial. Ophthalmology, 2016, 123(6): 1351-1359.
23.	Chen YY, Chang PY, Wang JK. Intravitreal aflibercept for patients with diabetic macular edema refractory to bevacizumab or ranibizumab: analysis of response to aflibercept. Asia Pac J Ophthalmol (Phila), 2017, 6(3): 250-255.
24.	Kiss S, Liu Y, Brown J, et al. Clinical utilization of anti-vascular endothelial growth-factor agents and patient monitoring in retinal vein occlusion and diabetic macular edema. Clin Ophthalmol, 2014, 8: 1611-1621.
25.	Blinder KJ, Dugel PU, Chen S, et al. Anti-VEGF treatment of diabetic macular edema in clinical practice: effectiveness and patterns of use (ECHO Study Report 1). Clin Ophthalmol, 2017, 11: 393-401.
26.	Distefano LN, Garcia-Arumi J, Martinez-Castillo V, et al. Combination of Anti-VEGF and laser photocoagulation for diabetic macular edema: a review. J Ophthalmol, 2017: 2407037.
27.	Solaiman KA, Diab MM, Dabour SA. Repeated intravitreal bevacizumab injection with and without macular grid photocoagulation for treatment of diffuse diabetic macular edema. Retina, 2013, 33(8): 1623-1629.
28.	Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group, Lachin JM, White NH, et al. Effect of intensive diabetes therapy on the progression of diabetic retinopathy in patients with type 1 diabetes: 18 years of follow-up in the DCCT/EDIC. Diabetes, 2015, 64(2): 631-642.
29.	UKPDS Group. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ, 2000, 321:405-412.
30.	中华医学会内分泌学分会. 中国成人 2 型糖尿病 HbA1c 控制目标的专家共识. 中华内分泌代谢杂志, 2011, 27(5): 371-374.
31.	Klein BE, Moss SE, Klein R, et al. The Wisconsin epidemiologic study of diabetic retinopathy. ⅩⅢ. relationship of serum cholesterol to retinopathy and hard exudate. Ophthalmology, 1991, 98(8): 1261-1265.
32.	Chew EY, Klein ML, Ferris FL, et al. Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Arch Ophthalmol, 1996, 114(9): 1079-1084.
33.	Papavasileiou E, Davoudi S, Roohipoor R, et al. Association of serum lipid levels with retinal hard exudate area in African Americans with type 2 diabetes. Graefes Arch Clin Exp Ophthalmol, 2017, 255(3): 509-517.
34.	罗向霞, 陈浩, 段俊国. 血脂代谢异常与糖尿病视网膜病变的关系探讨. 眼科新进展, 2007, 27(11): 833-835.
35.	Abcouwer SF. Direct effects of PPARα agonists on retinal inflammation and angiogenesis may explain how fenofibrate lowers risk of severe proliferative diabetic retinopathy. Diabetes, 2013, 62(1): 36-38.
36.	ACCORD Study Group, ACCORD Eye Study Group, Chew EY, et al. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med, 2010, 363(3): 233-244.
37.	Keech AC, Mitchell P, Summanen PA, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet, 2007, 370(960): 1687-1697.
38.	Wong TY, Simó R, Mitchell P. Fenofibrate - A potential systemic treatment for diabetic retinopathy? Am J Ophthalmol, 2012, 154(1): 6-12.
39.	Wright AD, Dodson PM. Medical management of diabetic retinopathy: fenofibrate and ACCORD Eye studies. Eye (Lond), 2011, 25(7): 843-849.
40.	Aroca PR, Salvat M, Fernández J, et al. Risk factors for diffuse and focal macular edema. J Diabetes Complications, 2004, 18(4): 211-215.
41.	刘爱玲, 闫俊茹, 李成龙. 血脂、血压对早期糖尿病视网膜病变进展的影响. 临床眼科杂志, 2012, 20(3): 238-240.
42.	Do DV, Wang X, Vedula SS, et al. Blood pressure control for diabetic retinopathy. Cochrane Database Syst Rev, 2015, 1: CD006127.
43.	王玉洁, 周慧超, 孙兰芳, 等. 糖尿病合并高尿酸血症与糖尿病视网膜病变相关性研究. 中国医药科学, 2012, 2(6): 16-17.

1. World Health Organization. Global report on diabetes. (2016-04-01)[2017-08-10]. http://www.who.int/diabetes/publications/grd-2016/en/.
2. 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) 中华眼科杂志, 2014, 50(11): 851-865.
3. Association AD. Executive summary: standards of medical care in diabetes--2009. Diabetes Care, 2009, 32(Suppl 1): S6-S12.
4. Boyer DS, Hopkins JJ, Sorof J, et al. Anti-vascular endothelial growth factor therapy for diabetic macular edema. Ther Adv Endocrinol Metab, 2013, 4(6): 151-169.
5. Nguyen QD, Shah SM, Heier JS, et al. Primary end point (six months) results of the ranibizumab for edema of the macula in Diabetes (READ-2) study. Ophthalmology, 2009, 116(11): 2175-2181.
6. Michaelides M, Kaines A, Hamilton RD, 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): 1076-1078.
7. Mitchell P, Bandello F, Schmidt-Erfurth UA, et al. The RESTORE study ranibizumab monotherapy or combined with laser <italic>versus</italic> laser monotherapy for diabetic macular edema. Ophthalmology, 2011, 118(4): 615-625.
8. Brown DM, Schmidt-Erfurth U, Do DV, et al. Intravitreal aflibercept for diabetic macular edema: 100-week results from the VISTA and VIVID studies. Ophthalmology, 2015, 122(10): 2044-2052.
9. Barteselli G, Kozak I, El-Emam S, et al. 12-month results of the standardised combination therapy for diabetic macular oedema: intravitreal bevacizumab and navigated retinal photocoagulation. Br J Ophthalmol, 2014, 98(8): 1036-1041.
10. Hirano T, Toriyama Y, Iesato Y, et al. Effect of leaking perifoveal microaneurysms on resolution of diabetic macular edema treated by combination therapy using anti-vascular endothelial growth factor and short pulse focal/grid laser photocoagulation. Jpn J Ophthalmol, 2017, 61(1): 51-60.
11. Yu AK, Merrill KD, Truong SN, et al. The comparative histologic effects of subthreshold 532- and 810-nm diode micropulse laser on the retina. Invest Ophthalmol Vis Sci, 2013, 54(3): 2216-2224.
12. Writing Committee for the Diabetic Retinopathy Clinical Research Network, Gross JG, Glassman AR, et al. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA, 2015, 314(20): 2137-2146.
13. Ulrich JN. Pars plana vitrectomy with internal limiting membrane peeling for nontractional diabetic macular edema. Open Ophthalmol J, 2017, 11(1): 5-10.
14. Figueroa MS, Contreras I, Noval S. Surgical and anatomical outcomes of pars plana vitrectomy for diffuse nontractional diabetic macular edema. Retina, 2008, 28(3): 420-426.
15. Hoerauf H, Brüggemann A, Muecke M, et al. Pars plana vitrectomy for diabetic macular edema. Internal limiting membrane delamination <italic>vs</italic> posterior hyaloid removal. A prospective randomized trial. Graefes Arch Clin Exp Ophthalmol, 2011, 249(7): 997-1008.
16. Kumar A, Sinha S, Azad R, et al. Comparative evaluation of vitrectomy and dye-enhanced ILM peel with grid laser in diffuse diabetic macular edema. Graefes Arch Clin Exp Ophthalmol, 2007, 245(3): 360-368.
17. Patel JI, Hykin PG, Schadt M, et al. Diabetic macular oedema: pilot randomised trial of pars plana vitrectomy <italic>vs</italic> macular Argon photocoagulation. Eye (Lond), 2006, 20(8): 873-881.
18. 刘大川, 吴航, 杨惠青. 玻璃体手术治疗弥漫性非牵引性糖尿病性黄斑水肿的临床效果. 中华眼科杂志, 2011, 47(6): 492-496.
19. Banerjee PJ, Quartilho A, Bunce C, et al. Slow-release dexamethasone in proliferative vitreoretinopathy: a prospective, randomized controlled clinical trial. Ophthalmology, 2017, 124(6): 757-767.
20. El-Remessy AB, Behzadian MA, Abou-mohamed G, et al. Experimental diabetes causes breakdown of the blood-retina barrier by a mechanism involving tyrosine nitration and increases in expression of vascular endothelial growth factor and urokinase plasminogen activator receptor. Am J Pathol, 2003, 162(6): 1995-2004.
21. Qaum T, Xu Q, Joussen AM, et al. VEGF-initiated blood-retinal barrier breakdown in early diabetes. Invest Ophthalmol Vis Sci, 2001, 42(10): 2408-2413.
22. Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema two-year results from a comparative effectiveness randomized clinical trial. Ophthalmology, 2016, 123(6): 1351-1359.
23. Chen YY, Chang PY, Wang JK. Intravitreal aflibercept for patients with diabetic macular edema refractory to bevacizumab or ranibizumab: analysis of response to aflibercept. Asia Pac J Ophthalmol (Phila), 2017, 6(3): 250-255.
24. Kiss S, Liu Y, Brown J, et al. Clinical utilization of anti-vascular endothelial growth-factor agents and patient monitoring in retinal vein occlusion and diabetic macular edema. Clin Ophthalmol, 2014, 8: 1611-1621.
25. Blinder KJ, Dugel PU, Chen S, et al. Anti-VEGF treatment of diabetic macular edema in clinical practice: effectiveness and patterns of use (ECHO Study Report 1). Clin Ophthalmol, 2017, 11: 393-401.
26. Distefano LN, Garcia-Arumi J, Martinez-Castillo V, et al. Combination of Anti-VEGF and laser photocoagulation for diabetic macular edema: a review. J Ophthalmol, 2017: 2407037.
27. Solaiman KA, Diab MM, Dabour SA. Repeated intravitreal bevacizumab injection with and without macular grid photocoagulation for treatment of diffuse diabetic macular edema. Retina, 2013, 33(8): 1623-1629.
28. Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group, Lachin JM, White NH, et al. Effect of intensive diabetes therapy on the progression of diabetic retinopathy in patients with type 1 diabetes: 18 years of follow-up in the DCCT/EDIC. Diabetes, 2015, 64(2): 631-642.
29. UKPDS Group. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ, 2000, 321:405-412.
30. 中华医学会内分泌学分会. 中国成人 2 型糖尿病 HbA1c 控制目标的专家共识. 中华内分泌代谢杂志, 2011, 27(5): 371-374.
31. Klein BE, Moss SE, Klein R, et al. The Wisconsin epidemiologic study of diabetic retinopathy. ⅩⅢ. relationship of serum cholesterol to retinopathy and hard exudate. Ophthalmology, 1991, 98(8): 1261-1265.
32. Chew EY, Klein ML, Ferris FL, et al. Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Arch Ophthalmol, 1996, 114(9): 1079-1084.
33. Papavasileiou E, Davoudi S, Roohipoor R, et al. Association of serum lipid levels with retinal hard exudate area in African Americans with type 2 diabetes. Graefes Arch Clin Exp Ophthalmol, 2017, 255(3): 509-517.
34. 罗向霞, 陈浩, 段俊国. 血脂代谢异常与糖尿病视网膜病变的关系探讨. 眼科新进展, 2007, 27(11): 833-835.
35. Abcouwer SF. Direct effects of PPARα agonists on retinal inflammation and angiogenesis may explain how fenofibrate lowers risk of severe proliferative diabetic retinopathy. Diabetes, 2013, 62(1): 36-38.
36. ACCORD Study Group, ACCORD Eye Study Group, Chew EY, et al. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med, 2010, 363(3): 233-244.
37. Keech AC, Mitchell P, Summanen PA, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet, 2007, 370(960): 1687-1697.
38. Wong TY, Simó R, Mitchell P. Fenofibrate - A potential systemic treatment for diabetic retinopathy? Am J Ophthalmol, 2012, 154(1): 6-12.
39. Wright AD, Dodson PM. Medical management of diabetic retinopathy: fenofibrate and ACCORD Eye studies. Eye (Lond), 2011, 25(7): 843-849.
40. Aroca PR, Salvat M, Fernández J, et al. Risk factors for diffuse and focal macular edema. J Diabetes Complications, 2004, 18(4): 211-215.
41. 刘爱玲, 闫俊茹, 李成龙. 血脂、血压对早期糖尿病视网膜病变进展的影响. 临床眼科杂志, 2012, 20(3): 238-240.
42. Do DV, Wang X, Vedula SS, et al. Blood pressure control for diabetic retinopathy. Cochrane Database Syst Rev, 2015, 1: CD006127.
43. 王玉洁, 周慧超, 孙兰芳, 等. 糖尿病合并高尿酸血症与糖尿病视网膜病变相关性研究. 中国医药科学, 2012, 2(6): 16-17.

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抗血管内皮生长因子时代糖尿病视网膜病变的治疗演变

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