抗血管內皮生長因子時代糖尿病視網膜病變的治療演變_West China Medical Journal

Authors：

閔曉雪 , 牟佳 , 劉依琳 , 任湘 , 周思睿 ,  張明

四川大學華西醫院眼科（成都 610041）;

Corresponding?author：

張明, Email: zhangmingscu@126.com

Keywords：

糖尿病; 視網膜病變; 抗血管內皮生長因子; 激光; 玻璃體切除術

DOI：

10.7507/1002-0179.201708076

Video：

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糖尿病視網膜病變（diabetic retinopathy，DR）是糖尿病常見的眼部并發癥，其治療包括眼部治療及系統綜合性治療。眼部治療手段有視網膜激光光凝術、玻璃體腔注射激素類藥物、玻璃體切除術、玻璃體腔注射抗血管內皮生長因子（vascular endothelial growth factor，VEGF）類藥物，如今最為熱門的是玻璃體腔注射抗 VEGF 類藥物。以上不同的治療手段在 DR 不同病程階段的應用處于不斷的更新和探索中。該文就抗 VEGF 時代 DR 的治療演變及目前存在的爭議進行綜述。

Citation： 閔曉雪, 牟佳, 劉依琳, 任湘, 周思睿, 張明. 抗血管內皮生長因子時代糖尿病視網膜病變的治療演變. 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.	中華醫學會眼科學會眼底病學組. 我國糖尿病視網膜病變臨床診療指南 (2014 年) 中華眼科雜志, 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.	劉大川, 吳航, 楊惠青. 玻璃體手術治療彌漫性非牽引性糖尿病性黃斑水腫的臨床效果. 中華眼科雜志, 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.	中華醫學會內分泌學分會. 中國成人 2 型糖尿病 HbA1c 控制目標的專家共識. 中華內分泌代謝雜志, 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.	羅向霞, 陳浩, 段俊國. 血脂代謝異常與糖尿病視網膜病變的關系探討. 眼科新進展, 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.	劉愛玲, 閆俊茹, 李成龍. 血脂、血壓對早期糖尿病視網膜病變進展的影響. 臨床眼科雜志, 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.	王玉潔, 周慧超, 孫蘭芳, 等. 糖尿病合并高尿酸血癥與糖尿病視網膜病變相關性研究. 中國醫藥科學, 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. 中華醫學會眼科學會眼底病學組. 我國糖尿病視網膜病變臨床診療指南 (2014 年) 中華眼科雜志, 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. 劉大川, 吳航, 楊惠青. 玻璃體手術治療彌漫性非牽引性糖尿病性黃斑水腫的臨床效果. 中華眼科雜志, 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. 中華醫學會內分泌學分會. 中國成人 2 型糖尿病 HbA1c 控制目標的專家共識. 中華內分泌代謝雜志, 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. 羅向霞, 陳浩, 段俊國. 血脂代謝異常與糖尿病視網膜病變的關系探討. 眼科新進展, 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. 劉愛玲, 閆俊茹, 李成龍. 血脂、血壓對早期糖尿病視網膜病變進展的影響. 臨床眼科雜志, 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. 王玉潔, 周慧超, 孫蘭芳, 等. 糖尿病合并高尿酸血癥與糖尿病視網膜病變相關性研究. 中國醫藥科學, 2012, 2(6): 16-17.

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抗血管內皮生長因子時代糖尿病視網膜病變的治療演變

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