Modern diagnostic and treatment aspects of diabetic macular edema

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Diabetic macular oedema (DMO) is the leading cause of vision loss and disability in working-age people with diabetes mellitus.
This literature review describes pathogenetic mechanisms, concepts, diagnostic techniques and capabilities of novel laser technologies in the treatment of DMO. In recent years, the role of cytokines and growth factors in retinal neurodegeneration has been actively investigated. Modern diagnostic techniques for the treatment of diabetic macular oedema, in addition to conventional techniques, include optical coherence tomography, autofluorescence and microperimetry. These techniques allow the visualization of retinal structures and its functional condition, and they can be used to detect DMO at early stages and to provide the most effective treatment. The evolution of laser technology resulted in the formation of new approaches to DMO treatment. Subthreshold micropulse laser (SML) treatment, in conjunction with conventional photocoagulation, has pronounced therapeutic effects. SML shows high selectivity towards retinal pigment epithelium while avoiding neurosensory retina injury. Owing to the chronic nature of DMO and pathogenetic mechanisms recently discovered, further elaboration of the SML technique appears to be a very promising treatment.

About the authors

Alexander Viktorovich Doga

S. Fyodorov Eye Microsurgery Federal State Institution, Moscow


Russian Federation

MD, PhD, Professor, Deputy-director of S. Fyodorov Eye Microsurgery Scientific Centre

Galina Fedorovna Kachalina

S. Fyodorov Eye Microsurgery Federal State Institution, Moscow


Russian Federation

MD, PhD, Head of Retinal Laser Surgery Department

Elena Konstantinovna Pedanova

S. Fyodorov Eye Microsurgery Federal State Institution, Moscow


Russian Federation

MD, PhD, Research assistant, Department of Retinal Laser Surgery

Dmitriy Anatol'evich Buryakov

S. Fyodorov Eye Microsurgery Federal State Institution, Moscow

Author for correspondence.

Russian Federation

MD, PhD-student, Department of Retinal Laser Surgery


  1. IDF Diabetes Atlas. 6-th edition. 2013. Available from:
  2. Lipatov DV, Aleksandrova VK, Atarshchikov DS, Bessmertnaya EG, Kon IL, Kuz'min AG, et al. Current report from Russian Diabetic Retinopathy Register. Diabetes mellitus 2014; (1):4-7. Available from: doi: 10.14341/DM201414-7.
  3. Klein R, Klein BEK, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology 1984;91(12):1464-1474. Available from: PubMed PMID: 6521986. doi: 10.1016/S0161-6420(84)34102-1.
  4. Bresnick GH. Diabetic Maculopathy. Ophthalmology 1983;90(11):1301-1317. Available from: PubMed PMID: 6664669. doi: 10.1016/S0161-6420(83)34388-8.
  5. Balashevich LI, Izmajlov AS. Diabeticheskaja oftal'mopatija. Saint-Peterburg: Human; 2012.
  6. Rangasamy S, McGuire PG, Das A. Diabetic retinopathy and inflammation: Novel therapeutic targets. Middle East Afr J Ophthalmol 2012;19(1):52-4103. Available from: doi: 10.4103/0974-9233.92116.
  7. Simo R, Carrasco E, Garcia-Ramirez M, Hernandez C. Angiogenic and Antiangiogenic Factors in Proliferative Diabetic Retinopathy. Curr Diabetes Rev 2006;2(1):71-98. Available from: PubMed PMID: 18220619. doi: 10.2174/157339906775473671.
  8. Joussen AM, Smyth N, Niessen C. Pathophysiology of diabetic macular edema. Dev Ophthalmol 2007;39:1-12. Available from: PubMed PMID: 17245075. doi: 10.1159/000098495.
  9. Hamann S. Molecular mechanisms of water transport in the eye. International Review of Cytology 2002;215:395-431. doi: 10.1016/S0074-7696(02)15016-9.
  10. Bok D. The retinal pigment epithelium: a versatile partner in vision. Journal of Cell Science 1993;17:189-195. Available from: doi: 10.1242/jcs.1993.Supplement_17.27.
  11. Strauss O. The Retinal Pigment Epithelium in Visual Function. Physiological Reviews 2005;85(3):845-881. Available from: doi: 10.1152/physrev.00021.2004.
  12. Vujosevic S, Midena E. Retinal Layers Changes in Human Preclinical and Early Clinical Diabetic Retinopathy Support Early Retinal Neuronal and Müller Cells Alterations. Journal of Diabetes Research 2013;2013:905058. Available from: PubMed PMID: 23841106. doi: 10.1155/2013/905058.
  13. Newman E, Reichenbach A. The Müller cell: a functional element of the retina. Trends in Neurosciences 1996;19(8):307-312. Available from: PubMed PMID: 8843598. doi: 10.1016/0166-2236(96)10040-0.
  14. Bringmann A, Reichenbach A, Wiedemann P. Pathomechanisms of CystoidMacular Edema. Ophthalmic Res 2004;36(5):241-249. Available from: PubMed PMID: 15583429. doi: 10.1159/000081203.
  15. Tout S, Chan-Ling T, Holländer H, Stone J. The role of müller cells in the formation of the blood-retinal barrier. Neuroscience 1993;55(1):291-301. Available from: PubMed PMID: 8350991. doi: 10.1016/0306-4522(93)90473-S.
  16. Ola M, Nawaz M, Khan H, Alhomida A. Neurodegeneration and Neuroprotection in Diabetic Retinopathy. IJMS 2013;14(2):2559-2572. Available from: doi: 10.3390/ijms14022559.
  17. Jain A, Varshney N, Smith C. The Evolving Treatment Options for Diabetic Macular Edema. Int J Inflam 2013;2013:689276. doi: 10.1155/2013/689276.
  18. Villarroel M, Ciudin A, Hernández C, Simó R. Neurodegeneration: An early event of diabetic retinopathy. WJD 2010;1(2):57-64. Available from: doi: 10.4239/wjd.v1.i2.57.
  19. Barber AJ, Gardner TW, Abcouwer SF. The Significance of Vascular and Neural Apoptosis to the Pathology of Diabetic Retinopathy. Investigative Ophthalmology and Visual Science 2011;52(2):1156-1163. Available from: PubMed PMID: 21357409. doi: 10.1167/iovs.10-6293.
  20. Okada K, Yamamoto S, Mizunoya S, Hoshino A, Arai M, Takatsuna Y. Correlation of retinal sensitivity measured with fundus-related microperimetry to visual acuity and retinal thickness in eyes with diabetic macular edema. Eye 2005;20(7):805-809. Available from: PubMed PMID: 16021181. doi: 10.1038/sj.eye.6702014.
  21. Yang X, Zou H, Xu X. [Correlation of retinal sensitivity, visual acuity and central macular thickness in different types of diabetic macular edema]. Zhonghua Yan Ke Za Zhi 2013;49(12):1081-1088. Available from: PubMed PMID: 24499694.
  22. Vujosevic S. Diabetic Macular Edema: Correlation between Microperimetry and Optical Coherence Tomography Findings. Investigative Ophthalmology & Visual Science 2006;47(7):3044-3051. Available from: PubMed PMID: 16799051. doi: 10.1167/iovs.05-1141.
  23. Control D. 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(14):977-986. Available from: doi: 10.1056/NEJM199309303291401.
  24. Diabetes Control and Complication 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(8):968-983. Available from: doi: 10.2337/diabetes.44.8.968.
  25. Stratton IM, Kohner EM, Aldington SJ, Turner RC, Holman RR, Manley SE, et al. UKPDS 50: Risk factors for incidence and progression of retinopathy in Type II diabetes over 6 years from diagnosis. Diabetologia 2001;44(2):156-163. Available from: PubMed PMID: 11270671. doi: 10.1007/s001250051594.
  26. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. The Lancet 2005;366(9500):1849-1861. Available from: doi: 10.1016/S0140-6736(05)67667-2.
  27. Sizova MV. Plasmapheresis in treatment of diabetic macular edema [dissertation]. Moscow; 2011.
  28. Meyer-Schwickerath GRE, Schott K. Diabetic Retinopathy and Photocoagulation. American Journal of Ophthalmology 1968;66(4):597-603. Available from: doi: 10.1016/0002-9394(68)91279-8.
  29. Schatz H, Patz A. Cystoid Maculopathy in Diabetics. Archives of Ophthalmology 1976;94(5):761-768. Available from: doi: 10.1001/archopht.1976.03910030369004.
  30. Early Treatment Diabetic Retinopathy Study Research Group . Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study (ETDRS) report No 1. Arch. Ophthalmol 1985;103(12):1796-1806. doi: 10.1001/archopht.1985.01050120030015.
  31. Early Treatment Diabetic Retinopathy Study Research Group . Treatment Techniques and Clinical Guidelines for Photocoagulation of Diabetic Macular Edema. Ophthalmology 1987;94(7):761-774. Available from: PubMed PMID: 3658348. doi: 10.1016/S0161-6420(87)33527-4.
  32. Krasnov MM, Saprykin PI, Doronin PP, Nikol'skaja GM, Akopjan VS. Electron microscopic study of tissues of the fundus with laser photocoagulation. Vestnik oftal'mologii 1973;89(2):13-15.
  33. Deufrains A, Ditce U, Brandt HP, Vitver V. Light coagulation in the treatment of diabetic retinopathy. Vestnik oftal'mologii 1980;96(2):28-31.
  34. 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(11):1549-1001. Available from: PubMed PMID: 1755735. doi: 10.1001/archopht.1991.01080110085041.
  35. Lovestam-Adrian M, Agardh E. Photocoagulation of diabetic macular oedema; complications and visual outcome. Acta Ophthalmol Scand 2000;78(6):667-671. Available from: doi: 10.1034/j.1600-0420.2000.078006667.x.
  36. Khodzhaev NS, Chernykh VV, Romenskaya IV, Kuntysheva KE, Trunov AN. Influence lazerokoagulyatsii retinal clinical and laboratory parameters in patients diabetic macular edema. Vestnik NGU 2011;9(4):48-53.
  37. Itaya M, Sakurai E, Nozaki M, Yamada K, Yamasaki S, Asai K, et al. Upregulation of VEGF in Murine Retina via Monocyte Recruitment after Retinal Scatter Laser Photocoagulation. Investigative Ophthalmology & Visual Science 2007;48(12):5677-5683. Available from: PubMed PMID: 18055819. doi: 10.1167/iovs.07-0156.
  38. Er H, Doganay S, Turkoz Y, Cekmen M, Daglioglu MC, Gunduz A, et al. The levels of cytokines and nitric oxide in rabbit vitreous humor after retinal laser photocoagulation. Ophthalmic Surg Lasers 2000;31(6):479-483. Available from: PubMed PMID: 11095125.
  39. Ogata N, Ando A, Uyama M, Matsumura M. Expression of cytokines and transcription factors in photocoagulated human retinal pigment epithelial cells. Graefe's Arch Clin Exp Ophthalmol 2001;239(2):87-95. Available from: doi: 10.1007/s004170000235.
  40. Lanzetta P, Dorin G, Pirracchio A, Bandello F. Theoretical bases of non-ophthalmoscopically visible endpoint photocoagulation. Semin Ophthalmol 2001;16(1):8-11. Available from: PubMed PMID: 15487692. doi: 10.1076/soph.
  41. Roider J, Brinkmann R, Wirbelauer C, Laqua H, Birngruber R. Subthreshold (retinal pigment epithelium) photocoagulation in macular diseases: a pilot study. British Journal of Ophthalmology 2000;84(1):40-47. Available from: PubMed PMID: 10611098. doi: 10.1136/bjo.84.1.40.
  42. Bandello F, Polito A, Del Borrello M, Zemella N, Isola M. "Light" versus "classic" laser treatment for clinically significant diabetic macular oedema. British Journal of Ophthalmology 2005;89(7):864-870. Available from: PubMed PMID: 15965168. doi: 10.1136/bjo.2004.051060.
  43. Kachalina GF, Pavlova ES. Subthreshold Argon Coagulation of the Retina in the Treatment of Focal Diabetic Maculopathy. Ophthalmosurgery 2004;(3):43-46.
  44. Roider J, Michaud NA, Flotte TJ, Birngruber R. Response of the Retinal Pigment Epithelium to Selective Photocoagulation. Arch Ophthalmol 1992;110(12):1786-1792. Available from: PubMed PMID: 1463423. doi: 10.1001/archopht.1992.01080240126045.
  45. Lavinsky D, Sramek C, Wang J, Huie P, Dalal R, Mandel Y, et al. Subvisible retinal laser therapy: titration algorithm and tissue response. Retina 2014;34(1):87-97. Available from: PubMed PMID: 23873164. doi: 10.1097/IAE.0b013e3182993edc.
  46. Gao X, Xing D. Molecular mechanisms of cell proliferation induced by low power laser irradiation. J Biomed Sci 2009;16:4. Available from: doi: 10.1186/1423-0127-16-4.
  47. Fedoruk NA, Fedorov AA, Bolshunov AV. Pathomorphological and histochemical manifestations of interaction of laser irradiation with tissues of a chorioretinal complex. Vestnik oftal'mologii 2009;-(3):61-64.
  48. Vujosevic S, Bottega E, Casciano M, Pilotto E, Convento E, Midena E. Microperimetry and fundus autofluorescence in diabetic macular edema: subthreshold micropulse diode laser versus modified early treatment diabetic retinopathy study laser photocoagulation. Retina 2010;30(6):908-916. Available from: PubMed PMID: 20168272. doi: 10.1097/IAE.0b013e3181c96986.
  49. Nakamura Y, Mitamura Y, Ogata K, Arai M, Takatsuna Y, Yamamoto S. Functional and morphological changes of macula after subthreshold micropulse diode laser photocoagulation for diabetic macular oedema. Eye 2009;24(5):784-788. Available from: PubMed PMID: 19680274. doi: 10.1038/eye.2009.207.
  50. Inagaki K, Ohkoshi K, Ohde S. Spectral-domain optical coherence tomography imaging of retinal changes after conventional multicolor laser, subthreshold micropulse diode laser, or pattern scanning laser therapy in Japanese with macular edema. Retina 2012;32(8):1592-1600. Available from: PubMed PMID: 22466485. doi: 10.1097/IAE.0b013e3182445386.
  51. Luttrull JK, Sinclair SH. Safety of transfoveal subthreshold diode micropulse laser for fovea-involving diabetic macular edema in eyes with good visual acuity. Retina 2014;34(10):2010-2020. Available from: PubMed PMID: 24837050. doi: 10.1097/IAE.0000000000000177.
  52. Kotsur TV, Izmaylov AS. Analysis of laser coagulation efficiency in macula and microphotocoagulation of high density in diabetic maculopathy treatment. Vestnik Orenburgskogo gosudarstvennogo universiteta 2013;4(153):150-152.
  53. Sivaprasad S, Sandhu R, Tandon A, Sayed-Ahmed K, McHugh DA. Subthreshold micropulse diode laser photocoagulation for clinically significant diabetic macular oedema: a three-year follow up. Clin Exp Ophthalmol 2007;35(7):640-644. Available from: doi: 10.1111/j.1442-9071.2007.01566.x.
  54. Lavinsky D, Cardillo JA, Melo LAS, Dare A, Farah ME, Belfort R. Randomized Clinical Trial Evaluating mETDRS versus Normal or High-Density Micropulse Photocoagulation for Diabetic Macular Edema. Investigative Ophthalmology & Visual Science 2011;52(7):4314-4323. Available from: PubMed PMID: 21345996. doi: 10.1167/iovs.10-6828.
  55. Figueira J, Khan J, Nunes S, Sivaprasad S, Rosa A, de Abreu JF, et al. Prospective randomised controlled trial comparing sub-threshold micropulse diode laser photocoagulation and conventional green laser for clinically significant diabetic macular oedema. British Journal of Ophthalmology 2008;93(10):1341-1344. Available from: PubMed PMID: 19054831. doi: 10.1136/bjo.2008.146712.
  56. Neroyev VV, IYu M. Wide-range subthreshold micropulse infrared exposure in the treatment of diabetic macular edema. Zdravookhranenie Rossiyskoy Federatsii 2010;-(5):41-43.
  57. Balashevich LI, Chizh LV, Gatsu MV. Sposob modifitsirovannoy subporogovoy panmakulyarnoy mikrofotokoagulyatsii setchatki pri diabeticheskom makulyarnom oteke. Patent RF № 2308920, prioritet ot 04.10.2005.
  58. Roider J, Liew SHM, Klatt C, Elsner H, Poerksen E, Hillenkamp J, et al. Selective retina therapy (SRT) for clinically significant diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 2010;248(9):1263-1272. Available from: PubMed PMID: 20393742. doi: 10.1007/s00417-010-1356-3.
  59. Yu AK, Merrill KD, Truong SN, Forward KM, Morse LS, Telander DG. The Comparative Histologic Effects of Subthreshold 532- and 810-nm Diode Micropulse Laser on the Retina. Investigative Ophthalmology & Visual Science 2013;54(3):2216-2224. Available from: PubMed PMID: 23439599. doi: 10.1167/iovs.12-11382.
  60. Pelosini L, Hamilton R, Mohamed M, Hamilton AMP, Marshall J. Retina rejuvenation therapy for diabetic macular edema: a pilot study. Retina 2013;33(3):548-558. Available from: PubMed PMID: 23023529. doi: 10.1097/IAE.0b013e3182670fea.
  61. Scott AW, Bressler NM. Update on the diabetic retinopathy clinical research network. Retina today 2008;3(5):49-52. Available from:
  62. Elman MJ, Qin H, Aiello LP, Beck RW, Bressler NM, Ferris FL, et al. Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt versus Deferred Laser Treatment. Ophthalmology 2012;119(11):2312-2318. Available from: doi: 10.1016/j.ophtha.2012.08.022.

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