Japanese Journal of Ophthalmology

, Volume 62, Issue 1, pp 1–23 | Cite as

Management of diabetic macular edema in Japan: a review and expert opinion

  • Hiroko Terasaki
  • Yuichiro Ogura
  • Shigehiko Kitano
  • Taiji Sakamoto
  • Toshinori Murata
  • Akito Hirakata
  • Tatsuro Ishibashi


Diabetic retinopathy is a frequent cause of visual impairment in working-age adults (≥ 30 years) and in Japan is most commonly observed in those aged 50–69 years. Diabetic macular edema (DME) is one of the main causes of vision disturbance in diabetic retinopathy, which is a clinically significant microvascular complication of diabetes. Anti-vascular endothelial growth factor (VEGF) therapy is becoming the mainstay of treatment for DME. However, to achieve sustained long-term improvement in visual acuity, conventional laser photocoagulation, vitrectomy and steroid therapy are also expected to play a role in the treatment of DME. This review summarizes the epidemiology and pathology of diabetic retinopathy and DME, evaluates the findings regarding the diagnosis and treatment of DME, and underscores the importance of systemic management of the disease in the context of the current health care situation in Japan. Finally, the unmet needs of patients with DME and prospects for research are discussed. The weight of evidence suggests that it is important to establish a multipronged treatment strategy centered on anti-VEGF therapy.


Diabetic retinopathy Diabetic macular edema Vascular endothelial growth factor Multidisciplinary treatment Expert opinion 



Medical writing and editing support was provided by Havas Worldwide Japan K.K.

Conflicts of interest

H. Terasaki, Grants (Novartis, Pfizer, Santen, Wakamoto), Consultant fee (Bayer), Honorarium (Bayer, Novartis, Pfizer, Santen, Wakamoto), Writing fee (Santen); Y. Ogura, Consultant fee (Alcon, Janssen, Wakamoto), Speaker fee (Alcon, Baush Lomb, Bayer, HOYA, Kissei, Kowa, Novartis, Santen, Sanwa, Senju, Topcon); S. Kitano, Grant (Novartis); T. Sakamoto, Grant (Alcon), Consultant fee (Senju), Honoraria (Alcon, Bayer, Novartis, Santen, Senju, Wakamoto), Travel fee for lecture (Alcon, Bayer, Novartis, Santen, Senju, Wakamoto); T. Murata, None; A. Hirakata, Grant (Santen), Honorarium (Bayer, Novartis, Santen); T. Ishibashi, Consultant fee (Alcon, Bayer, Novartis, Santen, Senju, Wakamoto).


  1. 1.
    International Diabetes Federation. IDF diabetes atlas. 7th ed. 2015. http://www.diabetesatlas.org/component/attachments/?task=download&id=116. Accessed 14 Mar 2017.
  2. 2.
    Das A, McGuire PG, Rangasamy S. Diabetic macular edema: pathophysiology and novel therapeutic targets. Ophthalmology. 2015;122:1375–94.PubMedCrossRefGoogle Scholar
  3. 3.
    Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010;376:124–36.PubMedCrossRefGoogle Scholar
  4. 4.
    Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy. N Engl J Med. 2012;366:1227–39.PubMedCrossRefGoogle Scholar
  5. 5.
    Stewart MW. Anti-VEGF therapy for diabetic macular edema. Curr Diab Rep. 2014;14:510.PubMedCrossRefGoogle Scholar
  6. 6.
    Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, et al. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011;118:615–25.PubMedCrossRefGoogle Scholar
  7. 7.
    Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119:789–801.PubMedCrossRefGoogle Scholar
  8. 8.
    Ishibashi T, Li X, Koh A, Lai TYY, Lee FL, Lee WK, et al. The REVEAL study: ranibizumab monotherapy or combined with laser versus laser monotherapy in Asian patients with diabetic macular edema. Ophthalmology. 2015;122:1402–15.PubMedCrossRefGoogle Scholar
  9. 9.
    Korobelnik JF, Do DV, Schmidt-Erfurth U, Boyer DS, Holz FG, Heier JS, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014;121:2247–54.PubMedCrossRefGoogle Scholar
  10. 10.
    Elman MJ, Aiello LP, Bressler NM, Bressler SB, The Diabetic Retinopathy Clinical Research Network, et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010;117:1064–77.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Tripathy K, Sharma YR, Chawla R, Gogia V, Singh SK, et al. Recent advances in management of diabetic macular edema. Curr Diabetes Rev. 2015;11:79–97.PubMedCrossRefGoogle Scholar
  12. 12.
    Bandello F, Cunha-Vaz J, Chong NV, Lang GE, Massin P, Mitchell P, et al. New approaches for the treatment of diabetic macular oedema: recommendations by an expert panel. Eye. 2012;26:485–93.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Mitchell P, Wong TY. Management paradigms for diabetic macular edema. Am J Ophthalmol. 2014;157:505–13.PubMedCrossRefGoogle Scholar
  14. 14.
    Bandello F, Midena E, Menchini U, Lanzetta P. Recommendations for the appropriate management of diabetic macular edema: light on DME survey and consensus document by an expert panel. Eur J Ophthalmol. 2016;26:252–61.PubMedCrossRefGoogle Scholar
  15. 15.
    Ogura Y, Shiraga F, Terasaki H, Ohji M, Ishida S, Sakamoto T, et al. Clinical practice pattern in management of diabetic macular edema in Japan: survey results of Japanese retinal specialists. Jpn J Ophthalmol. 2017;61:43–50.PubMedCrossRefGoogle Scholar
  16. 16.
    Yau JWY, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35:556–64.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Fenwick EK, Pesudovs K, Rees G, Dirani M, Kawasaki R, Wong TY, et al. The impact of diabetic retinopathy: understanding the patient’s perspective. Br J Ophthalmol. 2011;95:774–82.PubMedCrossRefGoogle Scholar
  18. 18.
    Miyazaki M, Kubo M, Kiyohara Y, Okubo K, Nakamura H, Fujisawa K, et al. Comparison of diagnostic methods for diabetes mellitus based on prevalence of retinopathy in a Japanese population: the Hisayama study. Diabetologia. 2004;47:1411–5.PubMedCrossRefGoogle Scholar
  19. 19.
    Kawasaki R, Wang JJ, Wong TY, Kayama T, Yamashita H. Impaired glucose tolerance, but not impaired fasting glucose, is associated with retinopathy in Japanese population: the Funagata study. Diabetes Obes Metab. 2008;10:514–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Wako R, Yasukawa T, Kato A, Omori T, Ishida S, Ishibashi T, et al. Causes and prevalence of visual impairment in Japan. Nippon Ganka Gakkai Zasshi. 2014;118:495–501 (in Japanese).PubMedGoogle Scholar
  21. 21.
    Stitt AW, Lois N, Medina RJ, Adamson P, Curtis TM. Advances in our understanding of diabetic retinopathy. Clin Sci. 2013;125:1–17.PubMedCrossRefGoogle Scholar
  22. 22.
    Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994;331:1480–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Watanabe D, Suzuma K, Suzuma I, Ohashi H, Ojima T, Kurimoto M, et al. Vitreous levels of angiopoietin 2 and vascular endothelial growth factor in patients with proliferative diabetic retinopathy. Am J Ophthalmol. 2005;139:476–81.PubMedCrossRefGoogle Scholar
  24. 24.
    Kwon SH, Shin JP, Kim IT, Park DH. Aqueous levels of angiopoietin-like 4 and semaphorin 3E correlate with nonperfusion area and macular volume in diabetic retinopathy. Ophthalmology. 2015;122:968–75.PubMedCrossRefGoogle Scholar
  25. 25.
    Funatsu H, Yamashita H, Noma H, Mimura T, Yamashita T, Hori S. Increased levels of vascular endothelial growth factor and interleukin-6 in the aqueous humor of diabetics with macular edema. Am J Ophthalmol. 2002;133:70–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Funatsu H, Yamashita H, Ikeda T, Mimura T, Eguchi S, Hori S. Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology. 2003;110:1690–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Yoshimura T, Sonoda KH, Sugahara M, Mochizuki Y, Enaida H, Oshima Y, et al. Comprehensive analysis of inflammatory immune mediators in vitreoretinal diseases. PLoS One. 2009.  https://doi.org/10.1371/journal.pone.0008158.Google Scholar
  28. 28.
    Ando R, Noda K, Namba S, Saito W, Kanda A, Ishida S. Aqueous humour levels of placental growth factor in diabetic retinopathy. Acta Ophthalmol. 2014;92:e245–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Lang GE. Diabetic macular edema. Ophthalmologica. 2012;227:21–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Murata T, Nakagawa K, Khalil A, Ishibashi T, Inomata H, Sueishi K. The relation between expression of vascular endothelial growth factor and breakdown of the blood-retinal barrier in diabetic rat retinas. Lab Invest. 1996;74:819–25.PubMedGoogle Scholar
  31. 31.
    Murata T, Ishibashi T, Khalil A, Hata Y, Yoshikawa H, Inomata H. Vascular endothelial growth factor plays a role in hyperpermeability of diabetic retinal vessels. Ophthalmic Res. 1995;27:48–52.PubMedCrossRefGoogle Scholar
  32. 32.
    Tolentino MJ, McLeod DS, Taomoto M, Otsuji T, Adamis AP, Lutty GA. Pathologic features of vascular endothelial growth factor-induced retinopathy in the nonhuman primate. Am J Ophthalmol. 2002;133:373–85.PubMedCrossRefGoogle Scholar
  33. 33.
    Nguyen QD, Tatlipinar S, Shah SM, Haller JA, Quinlan E, Sung J, et al. Vascular endothelial growth factor is a critical stimulus for diabetic macular edema. Am J Ophthalmol. 2006;142:961–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Ishida S. A review 59 molecular mechanisms in and medical treatments for diabetic retinopathy. Nippon Ganka Gakkai Zasshi. 2014;118:607–18 (in Japanese).PubMedGoogle Scholar
  35. 35.
    Kanda A, Noda K, Saito W, Ishida S. Aflibercept traps galectin-1, an angiogenic factor associated with diabetic retinopathy. Sci Rep. 2015.  https://doi.org/10.1038/srep17946.Google Scholar
  36. 36.
    The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977–86.CrossRefGoogle Scholar
  37. 37.
    UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33. Lancet. 1998;352:837–53.CrossRefGoogle Scholar
  38. 38.
    The ACCORD Study Group and ACCORD Eye Study Group. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med. 2010;363:233–44.CrossRefGoogle Scholar
  39. 39.
    Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Eye Study Group and the Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Study Group. Persistent effects of intensive glycemic control on retinopathy in type 2 diabetes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) follow-on study. Diabetes Care. 2016;39:1089–100.CrossRefGoogle Scholar
  40. 40.
    The Diabetes Control and Complications Trial Research Group. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes control and complications trial. Diabetes. 1995;44:968–83.CrossRefGoogle Scholar
  41. 41.
    Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995;28:103–17.PubMedCrossRefGoogle Scholar
  42. 42.
    Kawasaki R, Tanaka S, Tanaka S, Yamamoto T, Sone H, Ohashi Y, et al. Incidence and progression of diabetic retinopathy in Japanese adults with type 2 diabetes: 8 year follow-up study of the Japan Diabetes Complications Study (JDCS). Diabetologia. 2011;54:2288–94.PubMedCrossRefGoogle Scholar
  43. 43.
    Hirose A, Furushima D, Yamaguchi N, Kitano S, Uchigata Y. Prediction of retinopathy at 20 years after onset in younger-onset type 1 diabetes using mean metabolic memory-free HbA1c values: the importance of using HbA1c data of total, not partial, diabetes duration. Diabetes Care. 2013;36:3812–4.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Varma R, Bressler NM, Doan QV, Gleeson M, Danese M, Bower JK, et al. Prevalence of and risk factors for diabetic macular edema in the United States. JAMA Ophthalmol. 2014;132:1334–40.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317:703–13.PubMedCentralCrossRefGoogle Scholar
  46. 46.
    Xie X, Atkins E, Lv J, Bennett A, Neal B, Ninomiya T, et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet. 2016;387:435–43.PubMedCrossRefGoogle Scholar
  47. 47.
    Do DV, Wang X, Vedula SS, Marrone M, Sleilati G, Hawkins BS, et al. Blood pressure control for diabetic retinopathy. Cochrane Database Syst Rev. 2015.  https://doi.org/10.1002/14651858.CD006127.pub2.Google Scholar
  48. 48.
    Keech AC, Mitchell P, Summanen PA, O’Day J, Davis TM, Moffitt MS, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet. 2007;370:1687–97.PubMedCrossRefGoogle Scholar
  49. 49.
    Klein BE, Myers CE, Howard KP, Klein R. Serum lipids and proliferative diabetic retinopathy and macular edema in persons with long-term type 1 diabetes mellitus: the Wisconsin Epidemiologic Study of Diabetic Retinopathy. JAMA Ophthalmol. 2015;133:503–10.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Das R, Kerr R, Chakravarthy U, Hogg RE. Dyslipidemia and diabetic macular edema: a systematic review and meta-analysis. Ophthalmology. 2015;122:1820–7.PubMedCrossRefGoogle Scholar
  51. 51.
    Kameda Y, Kumakawa M, Endo N, Iwamoto Y, Kitano S. Association of systemic health and functional outcomes with changes in hard exudates associated with clinically significant macular oedema over the natural course of the disease. Br J Ophthalmol. 2010;94:725–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Shaya FT, Aljawadi M. Diabetic retinopathy. Clin Ophthalmol. 2007;1:259–65.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Harris Nwanyanwu K, Talwar N, Gardner TW, Wrobel JS, Herman WH, Stein JD. Predicting development of proliferative diabetic retinopathy. Diabetes Care. 2013;36:1562–8.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Singh RP, Habbu K, Ehlers JP, Lansang MC, Hill L, Stoilov I. The impact of systemic factors on clinical response to ranibizumab for diabetic macular edema. Ophthalmology. 2016;123:1581–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Sophie R, Lu N, Campochiaro PA. Predictors of functional and anatomic outcomes in patients with diabetic macular edema treated with ranibizumab. Ophthalmology. 2015;122:1395–401.PubMedCrossRefGoogle Scholar
  56. 56.
    Song YS, Nagaoka T, Omae T, Yokota H, Takahashi A, Yoshida A. Systemic risk factors in bilateral proliferative diabetic retinopathy requiring vitrectomy. Retina. 2016;36:1309–13.PubMedCrossRefGoogle Scholar
  57. 57.
    Ciardella AP. Partial resolution of diabetic macular oedema after systemic treatment with furosemide. Br J Ophthalmol. 2004;88:1224–5.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    The Royal College of Ophthalmologists. Diabetic Retinopathy Guidelines. 2012. https://www.rcophth.ac.uk/wp-content/uploads/2014/12/2013-SCI-301-FINAL-DR-GUIDELINES-DEC-2012-updated-July-2013.pdf. Accessed 14 Mar 2017.
  59. 59.
    Ghanchi F, The Diabetic Retinopathy Guidelines Working Group. The Royal College of Ophthalmologists’ clinical guidelines for diabetic retinopathy: a summary. Eye. 2013;27:285–7.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Wu L, Fernandez-Loaiza P, Sauma J, Hernandez-Bogantes E, Masis M. Classification of diabetic retinopathy and diabetic macular edema. World J Diabetes. 2013;4:290–4.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol. 1985;103:1796–806.CrossRefGoogle Scholar
  62. 62.
    Hirano T, Iesato Y, Toriyama Y, Imai A, Murata T. Detection of fovea-threatening diabetic macular edema by optical coherence tomography to maintain good vision by prophylactic treatment. Ophthalmic Res. 2014;52:65–73.PubMedCrossRefGoogle Scholar
  63. 63.
    Otani T, Kishi S, Maruyama Y. Patterns of diabetic macular edema with optical coherence tomography. Am J Ophthalmol. 1999;127:688–93.PubMedCrossRefGoogle Scholar
  64. 64.
    Diabetic Retinopathy Clinical Research Network. Diurnal variation in retinal thickening measurement by OCT in center-involved diabetic macular edema. Arch Ophthalmol. 2006;124:1701–7.PubMedCentralCrossRefGoogle Scholar
  65. 65.
    Browning DJ, Glassman AR, Aiello LP, Bressler NM, Bressler SB, Danis RP, et al. Optical coherence tomography measurements and analysis methods in optical coherence tomography studies of diabetic macular edema. Ophthalmology. 2008;115:1366–71.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Bolz M, Schmidt-Erfurth U, Deak G, Mylonas G, Kriechbaum K, Scholda C. Optical coherence tomographic hyperreflective foci: a morphologic sign of lipid extravasation in diabetic macular edema. Ophthalmology. 2009;116:914–20.PubMedCrossRefGoogle Scholar
  67. 67.
    Uji A, Murakami T, Nishijima K, Akagi T, Horii T, Arakawa N, et al. Association between hyperreflective foci in the outer retina, status of photoreceptor layer, and visual acuity in diabetic macular edema. Am J Ophthalmol. 2012;153:710–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Kang JW, Chung H, Chan Kim H. Correlation of optical coherence tomographic hyperreflective foci with visual outcomes in different patterns of diabetic macular edema. Retina. 2016;36:1630–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Murakami T, Uji A, Ogino K, Unoki N, Yoshitake S, Dodo Y, et al. Macular morphologic findings on optical coherence tomography after microincision vitrectomy for proliferative diabetic retinopathy. Jpn J Ophthalmol. 2015;59:236–43.PubMedCrossRefGoogle Scholar
  70. 70.
    Silva PS, Dela Cruz AJ, Ledesma MG, van Hemert J, Radwan A, Cavallerano JD, et al. Diabetic retinopathy severity and peripheral lesions are associated with nonperfusion on ultrawide field angiography. Ophthalmology. 2015;122:2465–72.PubMedCrossRefGoogle Scholar
  71. 71.
    Oliver SC, Schwartz SD. Peripheral vessel leakage (PVL): a new angiographic finding in diabetic retinopathy identified with ultra wide-field fluorescein angiography. Semin Ophthalmol. 2010;25:27–33.PubMedCrossRefGoogle Scholar
  72. 72.
    Wessel MM, Nair N, Aaker GD, Ehrlich JR, D’Amico DJ, Kiss S. Peripheral retinal ischaemia, as evaluated by ultra-widefield fluorescein angiography, is associated with diabetic macular oedema. Br J Ophthalmol. 2012;96:694–8.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Patel RD, Messner LV, Teitelbaum B, Michel KA, Hariprasad SM. Characterization of ischemic index using ultra-widefield fluorescein angiography in patients with focal and diffuse recalcitrant diabetic macular edema. Am J Ophthalmol. 2013;155:1038–44.PubMedCrossRefGoogle Scholar
  74. 74.
    Hasegawa N, Nozaki M, Takase N, Yoshida M, Ogura Y. New insights into microaneurysms in the deep capillary plexus detected by optical coherence tomography angiography in diabetic macular edema. Invest Ophthalmol Vis Sci. 2016;57:348–55.CrossRefGoogle Scholar
  75. 75.
    Spaide RF, Klancnik JM Jr, Cooney MJ. Retinal vascular layers imaged by fluorescein angiography and optical coherence tomography angiography. JAMA Ophthalmol. 2015;133:45–50.PubMedCrossRefGoogle Scholar
  76. 76.
    Zhang M, Wang J, Pechauer AD, Hwang TS, Gao SS, Liu L, et al. Advanced image processing for optical coherence tomographic angiography of macular diseases. Biomed Opt Express. 2015;6:4661–75.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Kim AY, Chu Z, Shahidzadeh A, Wang RK, Puliafito CA, Kashani AH. Quantifying microvascular density and morphology in diabetic retinopathy using spectral-domain optical coherence tomography angiography. Invest Ophthalmol Vis Sci. 2016;57:OCT362–70.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Diabetic Retinopathy Clinical Research Network. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015;372:1193–203.CrossRefGoogle Scholar
  79. 79.
    Virgili G, Menchini F, Casazza G, Hogg R, Das RR, Wang X, et al. Optical coherence tomography (OCT) for detection of macular oedema in patients with diabetic retinopathy. Cochrane Database Syst Rev. 2015.  https://doi.org/10.1002/14651858.CD008081.pub3.Google Scholar
  80. 80.
    Shimura M, Yasuda K, Nakazawa T, Hirano Y, Sakamoto T, Ogura Y, et al. Visual outcome after intravitreal triamcinolone acetonide depends on optical coherence tomographic patterns in patients with diffuse diabetic macular edema. Retina. 2011;31:748–54.PubMedCrossRefGoogle Scholar
  81. 81.
    Shimura M, Yasuda K, Yasuda M, Nakazawa T. Visual outcome after intravitreal bevacizumab depends on the optical coherence tomographic patterns of patients with diffuse diabetic macular edema. Retina. 2013;33:740–7.PubMedCrossRefGoogle Scholar
  82. 82.
    Lewis H, Abrams GW, Blumenkranz MS, Campo RV. Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. Ophthalmology. 1992;99:753–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Tachi N, Ogino N. Vitrectomy for diffuse macular edema in cases of diabetic retinopathy. Am J Ophthalmol. 1996;122:258–60.PubMedCrossRefGoogle Scholar
  84. 84.
    Jonas JB, Söfker A. Intraocular injection of crystalline cortisone as adjunctive treatment of diabetic macular edema. Am J Ophthalmol. 2001;132:425–7.PubMedCrossRefGoogle Scholar
  85. 85.
    Genetic Engineering and Biotechnology News. EC clears Novartis’ Lucentis for diabetic macular edema. http://www.genengnews.com/gen-news-highlights/ec-clears-novartis-lucentis-for-diabetic-macular-edema/81244487/. Accessed 14 Mar 2017.
  86. 86.
    Genentech. FDA approves Lucentis® (ranibizumab injection) for treatment of diabetic macular edema (DME). http://www.gene.com/media/press-releases/14127/2012-08-10/fda-approves-lucentis-ranibizumab-inject. Accessed 14 Mar 2017.
  87. 87.
    Globe Newswire. Novartis International AG: Novartis shows continued commitment in Japan with Lucentis® approval in fourth Japanese indication, diabetic macular edema. http://inpublic.globenewswire.com/2014/02/21/Novartis+shows+continued+commitment+in+Japan+with+Lucentis+approval+in+fourth+Japanese+indication+diabetic+macular+edema+HUG1763674.html;jsessionid=9j7LTG0DcKRmMzL3M9jlpy1vpS3LtDgk60GpXYQVlYPFmc0mf61l!-1082031361. Accessed 14 Mar 2017.
  88. 88.
    Regeneron. EYLEA® (aflibercept) injection receives EU approval for the treatment of diabetic macular edema (DME). http://investor.regeneron.com/releaseDetail.cfm?releaseid=865393. Accessed 14 Mar 2017.
  89. 89.
    Regeneron. EYLEA® (aflibercept) injection receives FDA approval for the treatment of diabetic macular edema (DME). http://investor.regeneron.com/releaseDetail.cfm?releaseid=862822. Accessed 14 Mar 2017.
  90. 90.
    Regeneron. Regeneron announces EYLEA® (aflibercept) injection approved for the treatment of diabetic macular edema (DME) in Japan. http://investor.regeneron.com/releaseDetail.cfm?releaseid=883500. Accessed 14 Mar 2017.
  91. 91.
    Presta LG, Chen H, O’Connor SJ, Chisholm V, Meng YG, Krummen L, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997;57:4593–9.PubMedGoogle Scholar
  92. 92.
    Ferrara N, Damico L, Shams N, Lowman H, Kim R. Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina. 2006;26:859–70.PubMedCrossRefGoogle Scholar
  93. 93.
    Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA. 2002;99:11393–8.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Papadopoulos N, Martin J, Ruan Q, Rafique A, Rosconi MP, Shi E, et al. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis. 2012;15:171–85.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Stewart MW. Pharmacokinetics, pharmacodynamics and pre-clinical characteristics of ophthalmic drugs that bind VEGF. Expert Rev Clin Pharmacol. 2014;7:167–80.PubMedCrossRefGoogle Scholar
  96. 96.
    Prünte C, Fajnkuchen F, Mahmood S, Ricci F, Hatz K, Studnička J, et al. Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: the RETAIN study. Br J Ophthalmol. 2016;100:787–95.PubMedCrossRefGoogle Scholar
  97. 97.
    Diabetic Retinopathy Clinical Research Network. Treatment for central-involved diabetic macular edema in eyes with very good visual acuity. Version 3.0 (April 18, 2014). http://publicfiles.jaeb.org/Treatment_CIDME_Eyes_Good_Vision_V3.pdf. Accessed 14 Mar 2017.
  98. 98.
    Ip MS, Domalpally A, Sun JK, Ehrlich JS. Long-term effects of therapy with ranibizumab on diabetic retinopathy severity and baseline risk factors for worsening retinopathy. Ophthalmology. 2015;122:367–74.PubMedCrossRefGoogle Scholar
  99. 99.
    Brown DM, Schmidt-Erfurth U, Do DV, Holz FG, Boyer DS, Midena E, et al. Intravitreal aflibercept for diabetic macular edema: 100-week results from the VISTA and VIVID studies. Ophthalmology. 2015;122:2044–52.PubMedCrossRefGoogle Scholar
  100. 100.
    Schmidt-Erfurth U, Lang GE, Holz FG, Schlingemann RO, Lanzetta P, Massin P, et al. Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study. Ophthalmology. 2014;121:1045–53.PubMedCrossRefGoogle Scholar
  101. 101.
    Elman MJ, Ayala A, Bressler NM, Browning D, Flaxel CJ, Glassman AR, et al. Intravitreal Ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: 5-year randomized trial results. Ophthalmology. 2015;122:375–81.PubMedCrossRefGoogle Scholar
  102. 102.
    Bressler SB, Glassman AR, Almukhtar T, Bressler NM, Ferris FL, Googe JM Jr, et al. Five-year outcomes of ranibizumab with prompt or deferred laser versus laser or triamcinolone plus deferred ranibizumab for diabetic macular edema. Am J Ophthalmol. 2016;164:57–68.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Ashraf M, Souka A, Adelman R. Predicting outcomes to anti-vascular endothelial growth factor (VEGF) therapy in diabetic macular oedema: a review of the literature. Br J Ophthalmol. 2016;100:1596–604.PubMedCrossRefGoogle Scholar
  104. 104.
    Korobelnik JF, Kleijnen J, Lang SH, Birnie R, Leadley RM, Misso K, et al. Systematic review and mixed treatment comparison of intravitreal aflibercept with other therapies for diabetic macular edema (DME). BMC Ophthalmol. 2015.  https://doi.org/10.1186/s12886-015-0035-x.PubMedPubMedCentralGoogle Scholar
  105. 105.
    Avery RL, Gordon GM. Systemic safety of prolonged monthly anti-vascular endothelial growth factor therapy for diabetic macular edema: a systematic review and meta-analysis. JAMA Ophthalmol. 2016;134:21–9.PubMedCrossRefGoogle Scholar
  106. 106.
    Wells JA, Glassman AR, Ayala AR, Jampol LM, Bressler NM, Bressler SB, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial. Ophthalmology. 2016;123:1351–9.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Heier JS, Bressler NM, Avery RL, Bakri SJ, Boyer DS, Brown DM, et al. Comparison of aflibercept, bevacizumab, and ranibizumab for treatment of diabetic macular edema: extrapolation of data to clinical practice. JAMA Ophthalmol. 2016;134:95–9.PubMedCrossRefGoogle Scholar
  108. 108.
    Do DV, Schmidt-Erfurth U, Gonzalez VH, Gordon CM, Tolentino M, Berliner AJ, et al. The DA VINCI Study: phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema. Ophthalmology. 2011;118:1819–26.PubMedCrossRefGoogle Scholar
  109. 109.
    Dugel PU, Layton A, Varma R. Diabetic macular edema diagnosis and treatment in the real world: an analysis of medicare claims data (2008 to 2010). Ophthalmic Surg Lasers Imaging Retina. 2016;47:258–67.PubMedCrossRefGoogle Scholar
  110. 110.
    Bressler SB, Ayala AR, Bressler NM, Melia M, Qin H, Ferris FL III, et al. Persistent macular thickening after ranibizumab treatment for diabetic macular edema with vision impairment. JAMA Ophthalmol. 2016;134:278–85.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Rahimy E, Shahlaee A, Khan MA, Ying GS, Maguire JI, Ho AC, et al. Conversion to aflibercept after prior anti-VEGF therapy for persistent diabetic macular edema. Am J Ophthalmol. 2016;164:118–27.PubMedCrossRefGoogle Scholar
  112. 112.
    Ogura Y, Sakamoto T, Yoshimura N, Ishibashi T. Phase 2/3 clinical trial of WP-0508 (MaQaid® intravitreal injection) for diabetic macular edema. Atarashii Ganka (J Eye). 2014;31:1876–84.Google Scholar
  113. 113.
    Business Wire. Allergan announces OZURDEX® (dexamethasone 700 mcg intravitreal implant in applicator) now approved in the European Union for the treatment of diabetic macular edema. http://www.businesswire.com/news/home/20140902005319/en/Allergan-Announces-OZURDEX%C2%AE-dexamethasone-700-mcg-intravitreal. Accessed 14 Mar 2017.
  114. 114.
    pSivida corp. Diabetic Macular Edema/ILUVIEN®. http://www.psivida.com/products-iluvien.html. Accessed 14 Mar 2017.
  115. 115.
    Sakamoto T, Hida T, Tano Y, Negi A, Takeuchi S, Ishibashi T, et al. Survey of triamcinolone acetonide for ocular diseases in Japan. Nippon Ganka Gakkai Zasshi. 2007;111:936–45 (in Japanese).PubMedGoogle Scholar
  116. 116.
    Serizawa S, Ohkoshi K, Minowa Y, Takahashi O. Prognosis of patients with diabetic macular edema before Japanese approval of anti-vascular endothelial growth factor. Jpn J Ophthalmol. 2015;59:244–51.PubMedCrossRefGoogle Scholar
  117. 117.
    Shimura M, Yasuda K, Minezaki T, Noma H. Reduction in the frequency of intravitreal bevacizumab administrations achieved by posterior subtenon injection of triamcinolone acetonide in patients with diffuse diabetic macular edema. Jpn J Ophthalmol. 2016;60:401–7.PubMedCrossRefGoogle Scholar
  118. 118.
    Campochiaro PA, Hafiz G, Mir TA, Scott AW, Zimmer-Galler I, Shah SM, et al. Pro-permeability factors in diabetic macular edema; the Diabetic Macular Edema Treated with Ozurdex Trial. Am J Ophthalmol. 2016;168:13–23.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Arimura N, Otsuka H, Yamakiri K, Sonoda Y, Nakao S, Noda Y, et al. Vitreous mediators after intravitreal bevacizumab or triamcinolone acetonide in eyes with proliferative diabetic retinopathy. Ophthalmology. 2009;116:921–6.PubMedCrossRefGoogle Scholar
  120. 120.
    Elman MJ, Bressler NM, Qin H, Beck RW, Ferris FL 3rd, Friedman SM, et al. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2011;118:609–14.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    VanderBeek BL, Bonaffini SG, Ma L. The association between intravitreal steroids and post-injection endophthalmitis rates. Ophthalmology. 2015;122:2311–5.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Bressler SB, Qin H, Melia M, Bressler NM, Beck RW, Chan CK, et al. Exploratory analysis of the effect of intravitreal ranibizumab or triamcinolone on worsening of diabetic retinopathy in a randomized clinical trial. JAMA Ophthalmol. 2013;131:1033–40.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Oshitari T, Kitamura Y, Nonomura S, Arai M, Takatsuna Y, Sato E, et al. Risk factors for refractory diabetic macular oedema after sub-Tenon’s capsule triamcinolone acetonide injection. J Ophthalmol. 2015.  https://doi.org/10.1155/2015/195737.PubMedPubMedCentralGoogle Scholar
  124. 124.
    Early Treatment Diabetic Retinopathy Study research group. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 2. Ophthalmology. 1987;94:761–74.CrossRefGoogle Scholar
  125. 125.
    Diabetic Retinopathy Clinical Research Network. Comparison of modified-ETDRS and mild macular grid laser photocoagulation strategies for diabetic macular edema. Arch Ophthalmol. 2007;125:469–80.PubMedCentralCrossRefGoogle Scholar
  126. 126.
    Stefánsson E. The therapeutic effects of retinal laser treatment and vitrectomy. A theory based on oxygen and vascular physiology. Acta Ophthalmol Scand. 2001;79:435–40.PubMedCrossRefGoogle Scholar
  127. 127.
    Park YG, Kim EY, Roh YJ. Laser-based strategies to treat diabetic macular edema: history and new promising therapies. J Ophthalmol. 2014.  https://doi.org/10.1155/2014/769213.Google Scholar
  128. 128.
    Varley MP, Frank E, Purnell EW. Subretinal neovascularization after focal argon laser for diabetic macular edema. Ophthalmology. 1988;95:567–73.PubMedCrossRefGoogle Scholar
  129. 129.
    Schatz H, Madeira D, McDonald HR, Johnson RN. Progressive enlargement of laser scars following grid laser photocoagulation for diffuse diabetic macular edema. Arch Ophthalmol. 1991;109:1549–51.PubMedCrossRefGoogle Scholar
  130. 130.
    Luttrull JK, Dorin G. Subthreshold diode micropulse laser photocoagulation (SDM) as invisible retinal phototherapy for diabetic macular edema: a review. Curr Diabetes Rev. 2012;8:274–84.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Lock JH, Fong KC. An update on retinal laser therapy. Clin Exp Optom. 2011;94:43–51.PubMedCrossRefGoogle Scholar
  132. 132.
    Hirano T, Iesato Y, Imai A, Toriyama Y, Kikushima W, Murata T. Effect of laser wavelength on delivering appropriate laser burns through the opaque lens using a pattern scan laser. Ophthalmic Res. 2014;51:204–9.PubMedCrossRefGoogle Scholar
  133. 133.
    Inagaki K, Ohkoshi K, Ohde S, Deshpande GA, Ebihara N, Murakami A. Comparative efficacy of pure yellow (577-nm) and 810-nm subthreshold micropulse laser photocoagulation combined with yellow (561-577-nm) direct photocoagulation for diabetic macular edema. Jpn J Ophthalmol. 2015;59:21–8.PubMedCrossRefGoogle Scholar
  134. 134.
    Hirano T, Toriyama Y, Iesato Y, Imai A, Hirabayashi K, Nagaoka T, 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. 2016;61:51–60.PubMedCrossRefGoogle Scholar
  135. 135.
    Takamura Y, Tomomatsu T, Matsumura T, Arimura S, Gozawa M, Takihara Y, et al. The effect of photocoagulation in ischemic areas to prevent recurrence of diabetic macular edema after intravitreal bevacizumab injection. Invest Ophthalmol Vis Sci. 2014;55:4741–6.PubMedCrossRefGoogle Scholar
  136. 136.
    Diabetic Retinopathy Clinical Research Network. 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;31:1009–27.PubMedCentralCrossRefGoogle Scholar
  137. 137.
    Writing Committee for the Diabetic Retinopathy Clinical Research. Network. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA. 2015;314:2137–46.CrossRefGoogle Scholar
  138. 138.
    Yamamoto T, Akabane N, Takeuchi S. Vitrectomy for diabetic macular edema: the role of posterior vitreous detachment and epimacular membrane. Am J Ophthalmol. 2001;132:369–77.PubMedCrossRefGoogle Scholar
  139. 139.
    Yamamoto S, Yamamoto T, Ogata K, Hoshino A, Sato E, Mizunoya S. Morphological and functional changes of the macula after vitrectomy and creation of posterior vitreous detachment in eyes with diabetic macular edema. Doc Ophthalmol. 2004;109:249–53.PubMedCrossRefGoogle Scholar
  140. 140.
    Terasaki H, Kojima T, Niwa H, Piao CH, Ueno S, Kondo M, et al. Changes in focal macular electroretinograms and foveal thickness after vitrectomy for diabetic macular edema. Invest Ophthalmol Vis Sci. 2003;44:4465–72.PubMedCrossRefGoogle Scholar
  141. 141.
    Stefánsson E, Landers MB 3rd, Wolbarsht ML. Increased retinal oxygen supply following pan-retinal photocoagulation and vitrectomy and lensectomy. Trans Am Ophthalmol Soc. 1981;79:307–34.PubMedPubMedCentralGoogle Scholar
  142. 142.
    Stefánsson E. Physiology of vitreous surgery. Graefes Arch Clin Exp Ophthalmol. 2009;247:147–63.PubMedCrossRefGoogle Scholar
  143. 143.
    Yamakoshi T, Kachi S, Sugita J, Asami T, Ishikawa K, Ito Y, et al. Triamcinolone-assisted removal of internal limiting membrane enhances the effect of vitrectomy for diabetic macular edema. Ophthalmic Res. 2009;41:203–9.PubMedCrossRefGoogle Scholar
  144. 144.
    Kumagai K, Furukawa M, Ogino N, Larson E, Iwaki M, Tachi N. Long-term follow-up of vitrectomy for diffuse nontractional diabetic macular edema. Retina. 2009;29:464–72.PubMedCrossRefGoogle Scholar
  145. 145.
    Abe S, Yamamoto T, Kashiwagi Y, Kirii E, Goto S, Yamashita H. Three-dimensional imaging of the inner limiting membrane folding on the vitreomacular interface in diabetic macular edema. Jpn J Ophthalmol. 2013;57:553–62.PubMedCrossRefGoogle Scholar
  146. 146.
    Diabetic Retinopathy Clinical Research Network. Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. Ophthalmology. 2010;117:1087–93.PubMedCentralCrossRefGoogle Scholar
  147. 147.
    Bonnin S, Sandali O, Bonnel S, Monin C, El Sanharawi M. Vitrectomy with internal limiting membrane peeling for tractional and nontractional diabetic macular edema: long-term results of a comparative study. Retina. 2015;35:921–8.PubMedCrossRefGoogle Scholar
  148. 148.
    Kumagai K, Hangai M, Ogino N, Larson E. Effect of internal limiting membrane peeling on long-term visual outcomes for diabetic macular edema. Retina. 2015;35:1422–8.PubMedCrossRefGoogle Scholar
  149. 149.
    Nakajima T, Roggia MF, Noda Y, Ueta T. Effect of internal limiting membrane peeling during vitrectomy for diabetic macular edema: systematic review and meta-analysis. Retina. 2015;35:1719–25.PubMedCrossRefGoogle Scholar
  150. 150.
    Kojima T, Terasaki H, Nomura H, Suzuki T, Mori M, Ito Y, et al. Vitrectomy for diabetic macular edema: effect of glycemic control (HbA(1c)), renal function (creatinine) and other local factors. Ophthalmic Res. 2003;35:192–8.PubMedCrossRefGoogle Scholar
  151. 151.
    Shimonagano Y, Makiuchi R, Miyazaki M, Doi N, Uemura A, Sakamoto T. Results of visual acuity and foveal thickness in diabetic macular edema after vitrectomy. Jpn J Ophthalmol. 2007;1:204–9.CrossRefGoogle Scholar
  152. 152.
    Nakamura S, Ogino N, Kumagai K, Furukawa M, Atsumi K, Demizu S, et al. The influence of hard exudates on the results of vitrectomy for macular edema due to diabetic retinopathy. Nippon Ganka Gakkai Zasshi. 2003;107:519–25 (In Japanese).PubMedGoogle Scholar
  153. 153.
    Yamamoto T, Hitani K, Tsukahara I, Yamamoto S, Kawasaki R, Yamashita H, et al. Early postoperative retinal thickness changes and complications after vitrectomy for diabetic macular edema. Am J Ophthalmol. 2003;135:14–9.PubMedCrossRefGoogle Scholar
  154. 154.
    Murakami T, Yoshimura N. Structural changes in individual retinal layers in diabetic macular edema. J Diabetes Res. 2013.  https://doi.org/10.1155/2013/920713.PubMedPubMedCentralGoogle Scholar
  155. 155.
    Sakamoto A, Nishijima K, Kita M, Oh H, Tsujikawa A, Yoshimura N. Association between foveal photoreceptor status and visual acuity after resolution of diabetic macular edema by pars plana vitrectomy. Graefes Arch Clin Exp Ophthalmol. 2009;247:1325–30.PubMedCrossRefGoogle Scholar
  156. 156.
    Murakami T, Nishijima K, Akagi T, Uji A, Horii T, Ueda-Arakawa N, et al. Segmentational analysis of retinal thickness after vitrectomy in diabetic macular edema. Invest Ophthalmol Vis Sci. 2012;53:6668–74.PubMedCrossRefGoogle Scholar
  157. 157.
    Kim J, Kang SW, Shin DH, Kim SJ, Cho GE. Macular ischemia and outcome of vitrectomy for diabetic macular edema. Jpn J Ophthalmol. 2015;59:295–304.PubMedCrossRefGoogle Scholar
  158. 158.
    Adelman R, Parnes A, Michalewska Z, Parolini B, Boscher C, Ducournau D. Strategy for the management of diabetic macular edema: the European vitreo-retinal society macular edema study. Biomed Res Int. 2015.  https://doi.org/10.1155/2015/352487.Google Scholar
  159. 159.
    Yamada Y, Suzuma K, Kumagami T, Fujikawa A, Kitaoka T. Systemic factors influence the prognosis of diabetic macular edema after pars plana vitrectomy with internal limiting membrane peeling. Ophthalmologica. 2013;229:142–6.PubMedCrossRefGoogle Scholar
  160. 160.
    Yoshida S, Kubo Y, Kobayashi Y, Zhou Y, Nakama T, Yamaguchi M, et al. Increased vitreous concentrations of MCP-1 and IL-6 after vitrectomy in patients with proliferative diabetic retinopathy: possible association with postoperative macular oedema. Br J Ophthalmol. 2015;99:960–6.PubMedCrossRefGoogle Scholar
  161. 161.
    Sawa M, Ohji M, Kusaka S, Sakaguchi H, Gomi F, Saito Y, et al. Nonvitrectomizing vitreous surgery for epiretinal membrane long-term follow-up. Ophthalmology. 2005;112:1402–8.PubMedCrossRefGoogle Scholar
  162. 162.
    Niwa Y, Kakinoki M, Sawada T, Wang X, Ohji M. Ranibizumab and Aflibercept: intraocular pharmacokinetics and their effects on aqueous VEGF level in Vitrectomized and Nonvitrectomized macaque eyes. Invest Ophthalmol Vis Sci. 2015;56:6501–5.PubMedCrossRefGoogle Scholar
  163. 163.
    Yanyali A, Aytug B, Horozoglu F, Nohutcu AF. Bevacizumab (Avastin) for diabetic macular edema in previously vitrectomized eyes. Am J Ophthalmol. 2007;144:124–6.PubMedCrossRefGoogle Scholar
  164. 164.
    Bressler SB, Melia M, Glassman AR, Almukhtar T, Jampol LM, Shami M, et al. Ranibizumab plus prompt or deferred laser for diabetic macular edema in eyes with vitrectomy before anti-vascular endothelial growth factor therapy. Retina. 2015;35:2516–28.PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    Okamoto Y, Okamoto F, Hiraoka T, Oshika T. Vision-related quality of life and visual function following intravitreal bevacizumab injection for persistent diabetic macular edema after vitrectomy. Jpn J Ophthalmol. 2014;58:369–74.PubMedCrossRefGoogle Scholar
  166. 166.
    Koyanagi Y, Yoshida S, Kobayashi Y, Kubo Y, Yamaguchi M, Nakama T, et al. Comparison of the effectiveness of intravitreal ranibizumab for diabetic macular edema in vitrectomized and nonvitrectomized eyes. Ophthalmologica. 2016;236:67–73.PubMedCrossRefGoogle Scholar
  167. 167.
    MaQaid® [package insert in Japanese]. WAKAMOTO PHARMACEUTICAL CO., LTD. Tokyo. http://www.wakamoto-pharm.co.jp/mpc/medic/pdf/0000000021_1.pdf Accessed Mar 14, 2017.
  168. 168.
    Flaxel CJ, Edwards AR, Aiello LP, Arrigg PG, Beck RW, Bressler NM, et al. Factors associated with visual acuity outcomes after vitrectomy for diabetic macular edema: diabetic retinopathy clinical research network. Retina. 2010;30:1488–95.PubMedCrossRefGoogle Scholar
  169. 169.
    Hartley KL, Smiddy WE, Flynn HW Jr, Murray TG. Pars plana vitrectomy with internal limiting membrane peeling for diabetic macular edema. Retina. 2008;28:410–9.PubMedCrossRefGoogle Scholar
  170. 170.
    Morizane Y, Kimura S, Hosokawa M, Shiode Y, Hirano M, Doi S, et al. Planned foveal detachment technique for the resolution of diffuse diabetic macular edema. Jpn J Ophthalmol. 2015;59:279–87.PubMedCrossRefGoogle Scholar
  171. 171.
    Apte RS. What is chronic or persistent diabetic macular edema and how should it be treated? JAMA Ophthalmol. 2016;134:285–6.PubMedCrossRefGoogle Scholar

Copyright information

© Japanese Ophthalmological Society 2017

Authors and Affiliations

  • Hiroko Terasaki
    • 1
  • Yuichiro Ogura
    • 2
  • Shigehiko Kitano
    • 3
  • Taiji Sakamoto
    • 4
  • Toshinori Murata
    • 5
  • Akito Hirakata
    • 6
  • Tatsuro Ishibashi
    • 7
  1. 1.Department of OphthalmologyNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Department of Ophthalmology and Visual ScienceNagoya City University Graduate School of Medical SciencesNagoyaJapan
  3. 3.Department of Diabetic Ophthalmology, Diabetes CenterTokyo Women’s Medical UniversityTokyoJapan
  4. 4.Department of OphthalmologyKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
  5. 5.Department of OphthalmologyShinshu University School of MedicineMatsumotoJapan
  6. 6.Department of OphthalmologyKyorin University School of MedicineTokyoJapan
  7. 7.Kyushu University HospitalFukuokaJapan

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