Research progress on the combination therapy of diabetic macular edema_Chinese Journal of Ocular Fundus Diseases

Authors：

Zhang Yue ^1,2 , Wang Lifang ² ,  Li Xiaorong ¹

1. Tianjin Medical University Eye Hospital, Eye Institute and School of Optometry, Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Tianjin 300384, China;
2. Hebei Ophthalmic Hospital, Hebei Institute of Traditional Chinese Medicine and Ophthalmology, Hebei Key Laboratory of Ophthalmology, Xingtai 054001, China;

Corresponding author：

Li Xiaorong, Email: xiaorli@163.com

Keywords：

Diabetic macular edema; Intravitreal injection; Anti-vascular endothelial growth factors drug; Triamcinolone acetonide; Dexamethasone intravitreal implant; Retinal photocoagulation; Vitrectomy; Review

DOI：

10.3760/cma.j.cn511434-20210803-00418

Video：

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Abstract Full text Figures/Tables Video References Cited by

Diabetic macular edema (DME) is the most threatening complication of diabetic retinopathy that affects visual function, which is characterized by intractability and recurrent attacks. Currently, the clinical routine treatments for DME mainly include intravitreal injection, grid laser photocoagulation in the macular area, subthreshold micropulse laser, periocular corticosteroid injection, and vitrectomy. Although conventional treatments are effective for some patients, persistent, refractory, and recurrent DME remains a clinical challenge that needs to be urgently addressed. In recent years, clinical studies have found that certain combination therapies are superior to monotherapy, which can not only restore the anatomical structure of the macular area and effectively reduce macular edema but also improve visual function to some extent while reducing the number of treatments and the overall cost. This makes up for the shortcomings of single treatment modalities and is highly anticipated in the clinical setting. However, the application of combination therapy in clinical practice is relatively short, and its safety and long-term effectiveness need further exploration. Currently, new drugs, new formulations, and new therapeutic targets are still under research and development to address different mechanisms of DME occurrence and development, such as anti-vascular endothelial growth factor agents designed to anchor repetitive sequence proteins with stronger inhibition of vascular leakage, multiple growth factor inhibitors, anti-inflammatory agents, and stem cell therapy. With the continuous improvement of the combination application of existing drugs and treatments and the development of new drugs and treatment technologies, personalized treatment for DME will become possible.

Citation： Zhang Yue, Wang Lifang, Li Xiaorong. Research progress on the combination therapy of diabetic macular edema. Chinese Journal of Ocular Fundus Diseases, 2023, 39(6): 505-509. doi: 10.3760/cma.j.cn511434-20210803-00418 Copy

1.	Singh A, Stewart JM. Pathophysiology of diabetic macular edema[J]. Int Ophthalmol Clin, 2009, 49(2): 1-11. DOI: 10.1097/IIO.0b013e31819fd164.
2.	Kim EJ, Lin WV, Rodriguez SM, et al. Treatment of diabetic macular edema[J]. Curr Diab Rep, 2019, 19(9): 68. DOI: 10.1007/s11892-019-1188-4.
3.	Wang W, Lo ACY. Diabetic retinopathy: pathophysiology and treatments[J]. Int J Mol Sci, 2018, 19(6): 1816. DOI: 10.3390/ijms19061816.
4.	Choi KS, Chung JK, Lim SH. Laser photocoagulation combined with intravitreal triamcinolone acetonide injection in proliferative diabetic retinopathy with macular edema[J]. Korean J Ophthalmol, 2007, 21(1): 11-17. DOI: 10.3341/kjo.2007.21.1.11.
5.	Heng LZ, Sivaprasad S, Crosby-Nwaobi R, et al. A prospective randomised controlled clinical trial comparing a combination of repeated intravitreal Ozurdex and macular laser therapy versus macular laser only in centre-involving diabetic macular oedema (OZLASE study)[J]. Br J Ophthalmol, 2016, 100(6): 802-807. DOI: 10.1136/bjophthalmol-2015-307136.
6.	Nakajima T, Roggia MF, Noda Y, et al. Effect of intenal limiting membrane peeling duri vitrectomy for diabetic macular edema: systematic review and meta-analysis[J]. Retina, 2015, 35(9): 1719-1725. DOI: 10.1097/IAE.0000000000000622.
7.	Jung YH, Lee Y. Efficacy of vitrectomy combined with an intraoperative dexamethasone implant in refractory diabetic macular edema[J]. Acta Diabetol, 2019, 56(6): 691-696. DOI: 10.1007/s00592-019-01305-w.
8.	Chatziralli I, Dimitriou E, Theodossiadis G, et al. Intravitreal ranibizumab alone or in combination with panretinal photocoagulation for the treatment of proliferative diabetic retinopathy with coexistent macular edema: long-term outcomes of a prospective study[J]. Acta Diabetol, 2020, 57(10): 1219-1225. DOI: 10.1007/s00592-020-01548-y.
9.	Limon U. Early effect of simultaneous intravitreal dexamethasone and bevacizumab combination treatment in patients with persistent diabetic macular edema[J]. J Fr Ophtalmol, 2021, 44(6): 849-854. DOI: 10.1016/j.jfo.2020.08.033.
10.	Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group[J]. Arch Ophthalmol, 1985, 103(12): 1796-1806. DOI: 10.1016/S0161-6420(87)33527-4.
11.	Zacks DN, Johnson MW. Combined intravitreal injection of triamcinolone acetonide and panretinal photocoagulation for concomitant diabetic macular edema and proliferative diabetic retinopathy[J]. Retina, 2005, 25(2): 135-140. DOI: 10.1097/00006982-200502000-00003.
12.	Saraiva FP, Queiroz MS, Costa PG, et al. Estudo do tratamento do edema macular difuso do diabético com triancinolona intravítrea e fotocoagulação [Use of intravitreal triamcinolone and laser photocoagulation for the treatment of diffuse diabetic macular edema][J]. Arq Bras Oftalmol, 2008, 71(4): 493-498. DOI: 10.1590/s0004-27492008000400005.
13.	Du L, Peng H, Wu Q, et al. Observation of total VEGF level in hyperglycemic mouse eyes after intravitreal injection of the novel anti-VEGF drug conbercept[J]. Mol Vis, 2015, 21: 185-193.
14.	Martin DF, Maguire MG. Treatment choice for diabetic macular edema[J]. N Engl J Med., 2015, 372(13): 1260-1261. DOI: 10.1056/NEJMe1500351.
15.	Callanan DG, Gupta S, Boyer DS, et al. Dexamethasone intravitreal implant in combination with laser photocoagulation for the treatment of diffuse diabetic macular edema[J]. Ophthalmology, 2013, 120(9): 1843-1851. DOI: 10.1016/j.ophtha.2013.02.018.
16.	Deschler EK, Sun JK, Silva PS. Side-effects and complications of laser treatment in diabetic retinal disease[J]. Semin Ophthalmol, 2014, 29(5-6): 290-300. DOI: 10.3109/08820538.2014.959198.
17.	罗琰君, 徐国兴. 视网膜新生血管抑制因子的研究进展[J]. 国际眼科杂志, 2017, 17(9): 1663-1666. DOI: 10.3980/j.issn.1672-5123.2017.9.14.Luo YJ, Xu GX. Research advance of retinal neovascularization inhibitory factor[J]. Int Eye Sci, 2017, 17(9): 1663-1666. DOI: 10.3980/j.issn.1672-5123.2017.9.14.
18.	Shimizu N, Oshitari T, Tatsumi T, et al. Comparisons of efficacy of intravitreal aflibercept and ranibizumab in eyes with diabetic macular edema[J/OL]. Biomed Res Int, 2017, 2017: 1747108[2017-07-03]. https://europepmc.org/article/MED/28758110. DOI: 10.1155/2017/1747108.
19.	Shah SM, Nguyen QD, Sy JP, et al. The RIDE and RISE studies of the efficacy and safety of intravitreal ranibizumab (LUCENTIS®) in clinically significant macular edema with center involvement secondary to diabetes mellitus[J]. Invest Ophthalmol Vis Sci, 2008, 49(13): 1562.
20.	Solaiman KA, Diab MM, Abo-Elenin M. Intravitreal bevacizumab and/or macular photocoagulation as a primary treatment for diffuse diabetic macular edema[J]. Retina, 2010, 30(10): 1638-1645. DOI: 10.1097/IAE.0b013e3181e1ed07.
21.	Berger A, Sheidow T, Cruess AF, et al. Efficacy/safety of ranibizumab monotherapy or with laser versus laser monotherapy in DME[J]. Can J Ophthalmol, 2015, 50(3): 209-216. DOI: 10.1016/j.jcjo.2014.12.014.
22.	Yan P, Qian C, Wang W, et al. Clinical effects and safety of treating diabetic macular edema with intravitreal injection of ranibizumab combined with retinal photocoagulation[J]. Ther Clin Risk Manag, 2016, 12: 527-533. DOI: 10.2147/TCRM.S99224.
23.	Liegl R, Langer J, Seidensticker F, et al. Comparative evaluation of combined navigated laser photocoagulation and intravitreal ranibizumab in the treatment of diabetic macular edema[J/OL]. PLoS One, 2014, 9(12): e113981[2014-12-26]. https://europepmc.org/article/MED/25541960. DOI: 10.1371/journal.pone.0113981.
24.	Herold TR, Langer J, Vounotrypidis E, et al. 3-year-data of combined navigated laser photocoagulation (Navilas) and intravitreal ranibizumab compared to ranibizumab monotherapy in DME patients[J/OL]. PLoS One, 2018, 13(8): e0202483[2018-08-23]. https://europepmc.org/article/MED/30138384. DOI: 10.1371/journal.pone.0202483.
25.	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[J]. Jpn J Ophthalmol, 2017, 61(1): 51-60. DOI: 10.1007/s10384-016-0483-8.
26.	Xu Y, Rong A, Bi Y, et al. Intravitreal conbercept injection with and without grid laser photocoagulation in the treatment of diffuse diabetic macular edema in real-life clinical practice[J/OL]. J Ophthalmol, 2016, 2016: 2143082[2016-09-29]. https://europepmc.org/article/MED/27777791. DOI: 10.1155/2016/2143082.
27.	Meng W, Li R, Xie X. Conbercept and retinal photocoagulation in the treatment of diabetic macular edema[J]. Pak J Med Sci, 2019, 35(6): 1493-1498. DOI: 10.12669/pjms.35.6.512.
28.	Soheilian M, Ramezani A, Bijanzadeh B, et al. Intravitreal bevacizumab (Avastin) injection alone or combined with triamcinolone versus macular photocoagulation as primary treatment of diabetic macular edema[J]. Retina, 2007, 27(9): 1187-1195. DOI: 10.1097/IAE.0b013e31815ec261.
29.	Faghihi H, Roohipoor R, Mohammadi SF, et al. Intravitreal bevacizumab versus combined bevacizumab-triamcinolone versus macular laser photocoagulation in diabetic macular edema[J]. Eur J Ophthalmol, 2008, 18(6): 941-948. DOI: 10.1177/112067210801800614.
30.	Soheilian M, Ramezani A, Obudi A, et al. Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema[J]. Ophthalmology, 2009, 116(6): 1142-1150. DOI: 10.1016/j.ophtha.2009.01.011.
31.	Jin E, Luo L, Bai Y, et al. Comparative effectiveness of intravitreal bevacizumab with or without triamcinolone acetonide for treatment of diabetic macular edema[J]. Ann Pharmacother, 2015, 49(4): 387-397. DOI: 10.1177/1060028014568006.
32.	Riazi-Esfahani M, Riazi-Esfahani H, Ahmadraji A, et al. Intravitreal bevacizumab alone or combined with 1 mg triamcinolone in diabetic macular edema: a randomized clinical trial[J]. Int Ophthalmol, 2018, 38(2): 585-598. DOI: 10.1007/s10792-017-0496-4.
33.	Neto HO, Regatieri CV, Nobrega MJ, et al. Multicenter, randomized clinical trial to assess the effectiveness of intravitreal injections of bevacizumab, triamcinolone, or their combination in the treatment of diabetic macular edema ophthalmic surg lasers imaging retina[J]. Ophthalmic Surg Lasers Imaging Retina, 2017, 48(9): 734-740. DOI: 10.3928/23258160-20170829-08.
34.	Shimura M, Yasuda K, Minezaki T, et al. Reduction in the frequency of intravitreal bevacizumab administrations achieved by posterior subtenon injection of triamcinolone acetonide in patients with diffuse diabetic macular edema[J]. Jpn J Ophthalmol, 2016, 60(5): 401-407. DOI: 10.1007/s10384-016-0458-9.
35.	Maturi RK, Glassman AR, Liu D, et al. Diabetic retinopathy clinical research network. effect of adding dexamethasone to continued ranibizumab treatment in patients with persistent diabetic macular edema: a DRCR network phase 2 randomized clinical trial[J]. JAMA Ophthalmol, 2018, 136(1): 29-38. DOI: 10.1001/jamaophthalmol.2017.4914.
36.	Maturi RK, Bleau L, Saunders J, et al. A 12-month, single-masked, randomized controlled study of eyes with persistent diabetic macular edema after multiple anti-VEGF injections to assess the sfficacy of the dexamethasone-delayed delivery systwm as an adjunct to bevacizumab compared with continued bevacizumab monotherapy[J]. Retina, 2015, 35(8): 1604-1614. DOI: 10.1097/IAE.0000000000000533.
37.	Kim JH, Kang SW, Ha HS, et al. Vitrectomy combined with intravitreal triamcinolone acetonide injection and macular laser photocoagulation for nontractional diabetic macular edema[J]. Korean J Ophthalmol, 2013, 27(3): 186-193. DOI: 10.3341/kjo.2013.27.3.186.
38.	Kim YT, Kang SW, Kim SJ, et al. Combination of vitrectomy, IVTA, and laser photocoagulation for diabetic macular edema unresponsive to prior treatments; 3-year results[J]. Graefe’s Arch Clin Exp Ophthalmol, 2012, 250(5): 679-684. DOI: 10.1007/s00417-011-1888-1.
39.	Mehta H, Gillies M, Fraser-Bell S. Perspective on the role of Ozurdex (dexamethasone intravitreal implant) in the management of diabetic macular oedema[J]. Ther Adv Chronic Dis, 2015, 6(5): 234-245. DOI: 10.1177/2040622315590319.
40.	Bansal P, Gupta V, Gupta A, et al. Efficacy of Ozurdex implant in recalcitrant diabetic macular edema-a single-center experience[J]. Int Ophthalmol, 2016, 36(2): 207-216. DOI: 10.1007/s10792-015-0103-5.
41.	Mello Filho P, Andrade G, Maia A, et al. effectiveness and safety of intravitreal dexamethasone implant (Ozurdex) in patients with diabetic macular edema: a real-world experience[J]. Ophthalmologica, 2019, 241(1): 9-16. DOI: 10.1159/000492132.
42.	Lee DH, Kim YJ, Yoon YH. Minimally invasive microincision vitrectomy surgery with an intraoperative dexamethasone implant for refractory diabetic macular edema[J]. Ophthalmologica, 2016, 235(3): 150-156. DOI: 10.1159/000443751.
43.	Chin HS, Park TS, Moon YS, et al. Difference in clearance of intravitreal triamcinolone acetonide between vitrectomized and nonvitrectomized eyes[J]. Retina, 2005, 25(5): 556-560. DOI: 10.1097/00006982-200507000-00002.
44.	Kim KT, Jang JW, Kang SW, et al. Vitrectomy combined with intraoperative dexamethasone implant for the management of refractory diabetic macular edema[J]. Korean J Ophthalmol, 2019, 33(3): 249-258. DOI: 10.3341/kjo.2018.0100.
45.	Kogo J, Shiono A, Sasaki H, et al. Foveal microstructure analysis in eyes with diabetic macular edema treated with vitrectomy[J]. Adv Ther, 2017, 34(9): 2139-2149. DOI: 10.1007/s12325-017-0598-4.
46.	Rinaldi M, dell'Omo R, Morescalchi F, et al. ILM peeling in nontractional diabetic macular edema: review and metanalysis[J]. Int Ophthalmol, 2018, 38(6): 2709-2714. DOI: 10.1007/s10792-017-0761-6.
47.	Toshima S, Morizane Y, Kimura S, et al. Planned foveal detachment technique for the resolution of diabetic macular edema resistant to anti-vascular endothelial growth factor therapy[J]. Retina, 2019, 39(1): S162-168. DOI: 10.1097/IAE.0000000000001771.
48.	Abdel Hadi AM. Evaluation of vitrectomy with planned foveal detachment as surgical treatment for refractory diabetic macular edema with or without vitreomacular interface abnormality[J/OL]. J Ophthalmol, 2018, 2018: 9246384[2018-05-07]. https://europepmc.org/article/MED/29854429. DOI: 10.1155/2018/9246384.
49.	Morizane Y, Kimura S, Hosokawa M, et al. Planned foveal detachment technique for the resolution of diffuse diabetic macular edema[J]. Jpn J Ophthalmol, 2015, 59(5): 279-287. DOI: 10.1007/s10384-015-0390-4.
50.	Mieno H, Marunaka Y, Inaba T, et al. pH balance and lactic acid increase in the vitreous body of diabetes mellitus patients[J/OL]. Exp Eye Res, 2019, 188: 107789[2019-09-03]. https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(19)30365-3. DOI: 10.1016/j.exer.2019.107789.
51.	王佳琳, 赵露, 尤冉, 等. 视网膜下注射平衡盐溶液治疗难治性糖尿病黄斑水肿一例[J]. 中华眼底病杂志, 2018, 34(4): 396-397. DOI: 10.3760/cma.j.issn.1005-1015.2018.04.019.Wang JL, Zhao L, You R, et al. Subretinal injection of balanced salt solution in the treatment of refractory diabetic macular edema: a case report[J]. Chin J Ocul Fundus Dis, 2018, 34(4): 396-397. DOI: 10.3760/cma.j.issn.1005-1015.2018.04.019.
52.	Ghanbari H, Kianersi F, Sonbolestan SA, et al. Intravitreal diclofenac plus bevacizumab versus bevacizumab alone in treatment-naive diabetic macular edema: a randomized double-blind clinical trial[J]. Int Ophthalmol, 2017, 37(4): 867-874. DOI: 10.1007/s10792-016-0335-z.
53.	Mirshahi A, Tadayoni R, Mohsenzadeh N, et al. Efficacy of adjuvant topical timolol-dorzolamide with intravitreal bevacizumab injection in diabetic macular edema: a contralateral eye study[J]. J Curr Ophthalmol, 2019, 31(2): 168-171. DOI: 10.1016/j.joco.2019.01.008.

1. Singh A, Stewart JM. Pathophysiology of diabetic macular edema[J]. Int Ophthalmol Clin, 2009, 49(2): 1-11. DOI: 10.1097/IIO.0b013e31819fd164.
2. Kim EJ, Lin WV, Rodriguez SM, et al. Treatment of diabetic macular edema[J]. Curr Diab Rep, 2019, 19(9): 68. DOI: 10.1007/s11892-019-1188-4.
3. Wang W, Lo ACY. Diabetic retinopathy: pathophysiology and treatments[J]. Int J Mol Sci, 2018, 19(6): 1816. DOI: 10.3390/ijms19061816.
4. Choi KS, Chung JK, Lim SH. Laser photocoagulation combined with intravitreal triamcinolone acetonide injection in proliferative diabetic retinopathy with macular edema[J]. Korean J Ophthalmol, 2007, 21(1): 11-17. DOI: 10.3341/kjo.2007.21.1.11.
5. Heng LZ, Sivaprasad S, Crosby-Nwaobi R, et al. A prospective randomised controlled clinical trial comparing a combination of repeated intravitreal Ozurdex and macular laser therapy versus macular laser only in centre-involving diabetic macular oedema (OZLASE study)[J]. Br J Ophthalmol, 2016, 100(6): 802-807. DOI: 10.1136/bjophthalmol-2015-307136.
6. Nakajima T, Roggia MF, Noda Y, et al. Effect of intenal limiting membrane peeling duri vitrectomy for diabetic macular edema: systematic review and meta-analysis[J]. Retina, 2015, 35(9): 1719-1725. DOI: 10.1097/IAE.0000000000000622.
7. Jung YH, Lee Y. Efficacy of vitrectomy combined with an intraoperative dexamethasone implant in refractory diabetic macular edema[J]. Acta Diabetol, 2019, 56(6): 691-696. DOI: 10.1007/s00592-019-01305-w.
8. Chatziralli I, Dimitriou E, Theodossiadis G, et al. Intravitreal ranibizumab alone or in combination with panretinal photocoagulation for the treatment of proliferative diabetic retinopathy with coexistent macular edema: long-term outcomes of a prospective study[J]. Acta Diabetol, 2020, 57(10): 1219-1225. DOI: 10.1007/s00592-020-01548-y.
9. Limon U. Early effect of simultaneous intravitreal dexamethasone and bevacizumab combination treatment in patients with persistent diabetic macular edema[J]. J Fr Ophtalmol, 2021, 44(6): 849-854. DOI: 10.1016/j.jfo.2020.08.033.
10. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group[J]. Arch Ophthalmol, 1985, 103(12): 1796-1806. DOI: 10.1016/S0161-6420(87)33527-4.
11. Zacks DN, Johnson MW. Combined intravitreal injection of triamcinolone acetonide and panretinal photocoagulation for concomitant diabetic macular edema and proliferative diabetic retinopathy[J]. Retina, 2005, 25(2): 135-140. DOI: 10.1097/00006982-200502000-00003.
12. Saraiva FP, Queiroz MS, Costa PG, et al. Estudo do tratamento do edema macular difuso do diabético com triancinolona intravítrea e fotocoagulação [Use of intravitreal triamcinolone and laser photocoagulation for the treatment of diffuse diabetic macular edema][J]. Arq Bras Oftalmol, 2008, 71(4): 493-498. DOI: 10.1590/s0004-27492008000400005.
13. Du L, Peng H, Wu Q, et al. Observation of total VEGF level in hyperglycemic mouse eyes after intravitreal injection of the novel anti-VEGF drug conbercept[J]. Mol Vis, 2015, 21: 185-193.
14. Martin DF, Maguire MG. Treatment choice for diabetic macular edema[J]. N Engl J Med., 2015, 372(13): 1260-1261. DOI: 10.1056/NEJMe1500351.
15. Callanan DG, Gupta S, Boyer DS, et al. Dexamethasone intravitreal implant in combination with laser photocoagulation for the treatment of diffuse diabetic macular edema[J]. Ophthalmology, 2013, 120(9): 1843-1851. DOI: 10.1016/j.ophtha.2013.02.018.
16. Deschler EK, Sun JK, Silva PS. Side-effects and complications of laser treatment in diabetic retinal disease[J]. Semin Ophthalmol, 2014, 29(5-6): 290-300. DOI: 10.3109/08820538.2014.959198.
17. 罗琰君, 徐国兴. 视网膜新生血管抑制因子的研究进展[J]. 国际眼科杂志, 2017, 17(9): 1663-1666. DOI: 10.3980/j.issn.1672-5123.2017.9.14.Luo YJ, Xu GX. Research advance of retinal neovascularization inhibitory factor[J]. Int Eye Sci, 2017, 17(9): 1663-1666. DOI: 10.3980/j.issn.1672-5123.2017.9.14.
18. Shimizu N, Oshitari T, Tatsumi T, et al. Comparisons of efficacy of intravitreal aflibercept and ranibizumab in eyes with diabetic macular edema[J/OL]. Biomed Res Int, 2017, 2017: 1747108[2017-07-03]. https://europepmc.org/article/MED/28758110. DOI: 10.1155/2017/1747108.
19. Shah SM, Nguyen QD, Sy JP, et al. The RIDE and RISE studies of the efficacy and safety of intravitreal ranibizumab (LUCENTIS®) in clinically significant macular edema with center involvement secondary to diabetes mellitus[J]. Invest Ophthalmol Vis Sci, 2008, 49(13): 1562.
20. Solaiman KA, Diab MM, Abo-Elenin M. Intravitreal bevacizumab and/or macular photocoagulation as a primary treatment for diffuse diabetic macular edema[J]. Retina, 2010, 30(10): 1638-1645. DOI: 10.1097/IAE.0b013e3181e1ed07.
21. Berger A, Sheidow T, Cruess AF, et al. Efficacy/safety of ranibizumab monotherapy or with laser versus laser monotherapy in DME[J]. Can J Ophthalmol, 2015, 50(3): 209-216. DOI: 10.1016/j.jcjo.2014.12.014.
22. Yan P, Qian C, Wang W, et al. Clinical effects and safety of treating diabetic macular edema with intravitreal injection of ranibizumab combined with retinal photocoagulation[J]. Ther Clin Risk Manag, 2016, 12: 527-533. DOI: 10.2147/TCRM.S99224.
23. Liegl R, Langer J, Seidensticker F, et al. Comparative evaluation of combined navigated laser photocoagulation and intravitreal ranibizumab in the treatment of diabetic macular edema[J/OL]. PLoS One, 2014, 9(12): e113981[2014-12-26]. https://europepmc.org/article/MED/25541960. DOI: 10.1371/journal.pone.0113981.
24. Herold TR, Langer J, Vounotrypidis E, et al. 3-year-data of combined navigated laser photocoagulation (Navilas) and intravitreal ranibizumab compared to ranibizumab monotherapy in DME patients[J/OL]. PLoS One, 2018, 13(8): e0202483[2018-08-23]. https://europepmc.org/article/MED/30138384. DOI: 10.1371/journal.pone.0202483.
25. 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[J]. Jpn J Ophthalmol, 2017, 61(1): 51-60. DOI: 10.1007/s10384-016-0483-8.
26. Xu Y, Rong A, Bi Y, et al. Intravitreal conbercept injection with and without grid laser photocoagulation in the treatment of diffuse diabetic macular edema in real-life clinical practice[J/OL]. J Ophthalmol, 2016, 2016: 2143082[2016-09-29]. https://europepmc.org/article/MED/27777791. DOI: 10.1155/2016/2143082.
27. Meng W, Li R, Xie X. Conbercept and retinal photocoagulation in the treatment of diabetic macular edema[J]. Pak J Med Sci, 2019, 35(6): 1493-1498. DOI: 10.12669/pjms.35.6.512.
28. Soheilian M, Ramezani A, Bijanzadeh B, et al. Intravitreal bevacizumab (Avastin) injection alone or combined with triamcinolone versus macular photocoagulation as primary treatment of diabetic macular edema[J]. Retina, 2007, 27(9): 1187-1195. DOI: 10.1097/IAE.0b013e31815ec261.
29. Faghihi H, Roohipoor R, Mohammadi SF, et al. Intravitreal bevacizumab versus combined bevacizumab-triamcinolone versus macular laser photocoagulation in diabetic macular edema[J]. Eur J Ophthalmol, 2008, 18(6): 941-948. DOI: 10.1177/112067210801800614.
30. Soheilian M, Ramezani A, Obudi A, et al. Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema[J]. Ophthalmology, 2009, 116(6): 1142-1150. DOI: 10.1016/j.ophtha.2009.01.011.
31. Jin E, Luo L, Bai Y, et al. Comparative effectiveness of intravitreal bevacizumab with or without triamcinolone acetonide for treatment of diabetic macular edema[J]. Ann Pharmacother, 2015, 49(4): 387-397. DOI: 10.1177/1060028014568006.
32. Riazi-Esfahani M, Riazi-Esfahani H, Ahmadraji A, et al. Intravitreal bevacizumab alone or combined with 1 mg triamcinolone in diabetic macular edema: a randomized clinical trial[J]. Int Ophthalmol, 2018, 38(2): 585-598. DOI: 10.1007/s10792-017-0496-4.
33. Neto HO, Regatieri CV, Nobrega MJ, et al. Multicenter, randomized clinical trial to assess the effectiveness of intravitreal injections of bevacizumab, triamcinolone, or their combination in the treatment of diabetic macular edema ophthalmic surg lasers imaging retina[J]. Ophthalmic Surg Lasers Imaging Retina, 2017, 48(9): 734-740. DOI: 10.3928/23258160-20170829-08.
34. Shimura M, Yasuda K, Minezaki T, et al. Reduction in the frequency of intravitreal bevacizumab administrations achieved by posterior subtenon injection of triamcinolone acetonide in patients with diffuse diabetic macular edema[J]. Jpn J Ophthalmol, 2016, 60(5): 401-407. DOI: 10.1007/s10384-016-0458-9.
35. Maturi RK, Glassman AR, Liu D, et al. Diabetic retinopathy clinical research network. effect of adding dexamethasone to continued ranibizumab treatment in patients with persistent diabetic macular edema: a DRCR network phase 2 randomized clinical trial[J]. JAMA Ophthalmol, 2018, 136(1): 29-38. DOI: 10.1001/jamaophthalmol.2017.4914.
36. Maturi RK, Bleau L, Saunders J, et al. A 12-month, single-masked, randomized controlled study of eyes with persistent diabetic macular edema after multiple anti-VEGF injections to assess the sfficacy of the dexamethasone-delayed delivery systwm as an adjunct to bevacizumab compared with continued bevacizumab monotherapy[J]. Retina, 2015, 35(8): 1604-1614. DOI: 10.1097/IAE.0000000000000533.
37. Kim JH, Kang SW, Ha HS, et al. Vitrectomy combined with intravitreal triamcinolone acetonide injection and macular laser photocoagulation for nontractional diabetic macular edema[J]. Korean J Ophthalmol, 2013, 27(3): 186-193. DOI: 10.3341/kjo.2013.27.3.186.
38. Kim YT, Kang SW, Kim SJ, et al. Combination of vitrectomy, IVTA, and laser photocoagulation for diabetic macular edema unresponsive to prior treatments; 3-year results[J]. Graefe’s Arch Clin Exp Ophthalmol, 2012, 250(5): 679-684. DOI: 10.1007/s00417-011-1888-1.
39. Mehta H, Gillies M, Fraser-Bell S. Perspective on the role of Ozurdex (dexamethasone intravitreal implant) in the management of diabetic macular oedema[J]. Ther Adv Chronic Dis, 2015, 6(5): 234-245. DOI: 10.1177/2040622315590319.
40. Bansal P, Gupta V, Gupta A, et al. Efficacy of Ozurdex implant in recalcitrant diabetic macular edema-a single-center experience[J]. Int Ophthalmol, 2016, 36(2): 207-216. DOI: 10.1007/s10792-015-0103-5.
41. Mello Filho P, Andrade G, Maia A, et al. effectiveness and safety of intravitreal dexamethasone implant (Ozurdex) in patients with diabetic macular edema: a real-world experience[J]. Ophthalmologica, 2019, 241(1): 9-16. DOI: 10.1159/000492132.
42. Lee DH, Kim YJ, Yoon YH. Minimally invasive microincision vitrectomy surgery with an intraoperative dexamethasone implant for refractory diabetic macular edema[J]. Ophthalmologica, 2016, 235(3): 150-156. DOI: 10.1159/000443751.
43. Chin HS, Park TS, Moon YS, et al. Difference in clearance of intravitreal triamcinolone acetonide between vitrectomized and nonvitrectomized eyes[J]. Retina, 2005, 25(5): 556-560. DOI: 10.1097/00006982-200507000-00002.
44. Kim KT, Jang JW, Kang SW, et al. Vitrectomy combined with intraoperative dexamethasone implant for the management of refractory diabetic macular edema[J]. Korean J Ophthalmol, 2019, 33(3): 249-258. DOI: 10.3341/kjo.2018.0100.
45. Kogo J, Shiono A, Sasaki H, et al. Foveal microstructure analysis in eyes with diabetic macular edema treated with vitrectomy[J]. Adv Ther, 2017, 34(9): 2139-2149. DOI: 10.1007/s12325-017-0598-4.
46. Rinaldi M, dell'Omo R, Morescalchi F, et al. ILM peeling in nontractional diabetic macular edema: review and metanalysis[J]. Int Ophthalmol, 2018, 38(6): 2709-2714. DOI: 10.1007/s10792-017-0761-6.
47. Toshima S, Morizane Y, Kimura S, et al. Planned foveal detachment technique for the resolution of diabetic macular edema resistant to anti-vascular endothelial growth factor therapy[J]. Retina, 2019, 39(1): S162-168. DOI: 10.1097/IAE.0000000000001771.
48. Abdel Hadi AM. Evaluation of vitrectomy with planned foveal detachment as surgical treatment for refractory diabetic macular edema with or without vitreomacular interface abnormality[J/OL]. J Ophthalmol, 2018, 2018: 9246384[2018-05-07]. https://europepmc.org/article/MED/29854429. DOI: 10.1155/2018/9246384.
49. Morizane Y, Kimura S, Hosokawa M, et al. Planned foveal detachment technique for the resolution of diffuse diabetic macular edema[J]. Jpn J Ophthalmol, 2015, 59(5): 279-287. DOI: 10.1007/s10384-015-0390-4.
50. Mieno H, Marunaka Y, Inaba T, et al. pH balance and lactic acid increase in the vitreous body of diabetes mellitus patients[J/OL]. Exp Eye Res, 2019, 188: 107789[2019-09-03]. https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(19)30365-3. DOI: 10.1016/j.exer.2019.107789.
51. 王佳琳, 赵露, 尤冉, 等. 视网膜下注射平衡盐溶液治疗难治性糖尿病黄斑水肿一例[J]. 中华眼底病杂志, 2018, 34(4): 396-397. DOI: 10.3760/cma.j.issn.1005-1015.2018.04.019.Wang JL, Zhao L, You R, et al. Subretinal injection of balanced salt solution in the treatment of refractory diabetic macular edema: a case report[J]. Chin J Ocul Fundus Dis, 2018, 34(4): 396-397. DOI: 10.3760/cma.j.issn.1005-1015.2018.04.019.
52. Ghanbari H, Kianersi F, Sonbolestan SA, et al. Intravitreal diclofenac plus bevacizumab versus bevacizumab alone in treatment-naive diabetic macular edema: a randomized double-blind clinical trial[J]. Int Ophthalmol, 2017, 37(4): 867-874. DOI: 10.1007/s10792-016-0335-z.
53. Mirshahi A, Tadayoni R, Mohsenzadeh N, et al. Efficacy of adjuvant topical timolol-dorzolamide with intravitreal bevacizumab injection in diabetic macular edema: a contralateral eye study[J]. J Curr Ophthalmol, 2019, 31(2): 168-171. DOI: 10.1016/j.joco.2019.01.008.

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