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Journal of Diabetes Research
Volume 2017 (2017), Article ID 2562759, 10 pages
https://doi.org/10.1155/2017/2562759
Review Article

Noninvasive Retinal Markers in Diabetic Retinopathy: Advancing from Bench towards Bedside

1Department of Ophthalmology, Odense University Hospital, Odense, Denmark
2Department of Clinical Research, University of Southern Denmark, Odense, Denmark
3Department of Neurology, Kolding Hospital, Hospital Lillebaelt, Kolding, Denmark
4Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
5Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
6Odense Patient Data Explorative Network (OPEN), Odense University Hospital and Department of Clinical Research, University of Southern Denmark, Odense, Denmark
7NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK
8Queen’s University Belfast, Belfast, UK

Correspondence should be addressed to Jakob Grauslund; kd.dysr@dnulsuarg.bokaj

Received 13 December 2016; Accepted 12 March 2017; Published 13 April 2017

Academic Editor: Andrea Scaramuzza

Copyright © 2017 Søren Leer Blindbæk et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. Klein, K. E. Lee, R. E. Gangnon, and B. E. Klein, “The 25-year incidence of visual impairment in type 1 diabetes mellitus: the Wisconsin epidemiologic study of diabetic retinopathy,” Ophthalmology, vol. 117, no. 1, pp. 63–70, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. J. Grauslund, A. Green, and A. K. Sjolie, “Blindness in a 25-year follow-up of a population-based cohort of Danish type 1 diabetic patients,” Ophthalmology, vol. 116, no. 11, pp. 2170–2174, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. 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,” New England Journal of Medicine, vol. 329, no. 14, pp. 977–986, 1993. View at Publisher · View at Google Scholar
  4. J. M. Lachin, S. Genuth, D. M. Nathan, B. Zinman, B. N. Rutledge, and D. E. R. Group, “Effect of glycemic exposure on the risk of microvascular complications in the diabetes control and complications trial—revisited,” Diabetes, vol. 57, no. 4, pp. 995–1001, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. C. D. Murray, “The physiological principle of minimum work: I. The vascular system and the cost of blood volume,” Proceedings of the National Academy of Sciences of the United States of America, vol. 12, no. 3, pp. 207–214, 1926. View at Google Scholar
  6. C. Y. Cheung, E. Lamoureux, M. K. Ikram et al., “Retinal vascular geometry in Asian persons with diabetes and retinopathy,” Journal of Diabetes Science and Technology, vol. 6, no. 3, pp. 595–605, 2012. View at Publisher · View at Google Scholar · View at Scopus
  7. B. R. Masters, “Fractal analysis of the vascular tree in the human retina,” Annual Review of Biomedical Engineering, vol. 6, pp. 427–452, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. V. F. Cosatto, G. Liew, E. Rochtchina et al., “Retinal vascular fractal dimension measurement and its influence from imaging variation: results of two segmentation methods,” Current eye Research, vol. 35, no. 9, pp. 850–856, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. T. Nagaoka and A. Yoshida, “Relationship between retinal fractal dimensions and retinal circulation in patients with type 2 diabetes mellitus,” Current eye Research, vol. 38, no. 11, pp. 1148–1152, 2013. View at Publisher · View at Google Scholar · View at Scopus
  10. R. Crosby-Nwaobi, L. Z. Heng, and S. Sivaprasad, “Retinal vascular calibre, geometry and progression of diabetic retinopathy in type 2 diabetes mellitus,” Ophthalmologica, vol. 228, no. 2, pp. 84–92, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. P. Zhu, F. Huang, F. Lin et al., “The relationship of retinal vessel diameters and fractal dimensions with blood pressure and cardiovascular risk factors,” PloS One, vol. 9, no. 9, p. e106551, 2014. View at Publisher · View at Google Scholar · View at Scopus
  12. A. C. Kunicki, A. J. Oliveira, M. B. Mendonca, C. T. Barbosa, and R. A. Nogueira, “Can the fractal dimension be applied for the early diagnosis of non-proliferative diabetic retinopathy?” Brazilian Journal of Medical and Biological Research, vol. 42, no. 10, pp. 930–934, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. J. Lee, B. C. Zee, and Q. Li, “Detection of neovascularization based on fractal and texture analysis with interaction effects in diabetic retinopathy,” PloS One, vol. 8, no. 12, p. e75699, 2013. View at Publisher · View at Google Scholar · View at Scopus
  14. A. Daxer, “Characterisation of the neovascularisation process in diabetic retinopathy by means of fractal geometry: diagnostic implications,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 231, no. 12, pp. 681–686, 1993. View at Publisher · View at Google Scholar · View at Scopus
  15. M. D. Knudtson, K. E. Lee, L. D. Hubbard, T. Y. Wong, R. Klein, and B. E. Klein, “Revised formulas for summarizing retinal vessel diameters,” Current eye Research, vol. 27, no. 3, pp. 143–149, 2003. View at Google Scholar
  16. T. Y. Wong, M. D. Knudtson, R. Klein, B. E. Klein, S. M. Meuer, and L. D. Hubbard, “Computer-assisted measurement of retinal vessel diameters in the Beaver Dam Eye Study: methodology, correlation between eyes, and effect of refractive errors,” Ophthalmology, vol. 111, no. 6, pp. 1183–1190, 2004. View at Publisher · View at Google Scholar · View at Scopus
  17. J. Grauslund, L. Hodgson, R. Kawasaki, A. Green, A. K. Sjolie, and T. Y. Wong, “Retinal vessel calibre and micro- and macrovascular complications in type 1 diabetes,” Diabetologia, vol. 52, no. 10, pp. 2213–2217, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. R. Klein, B. E. Klein, S. E. Moss, and T. Y. Wong, “Retinal vessel caliber and microvascular and macrovascular disease in type 2 diabetes: XXI: the Wisconsin epidemiologic study of diabetic retinopathy,” Ophthalmology, vol. 114, no. 10, pp. 1884–1892, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. J. Ding, C. Y. Cheung, M. K. Ikram et al., “Early retinal arteriolar changes and peripheral neuropathy in diabetes,” Diabetes Care, vol. 35, no. 5, pp. 1098–1104, 2012. View at Publisher · View at Google Scholar · View at Scopus
  20. C. Sabanayagam, E. S. Tai, J. Lee, S. C. Lim, and T. Y. Wong, “Retinal vessel caliber and peripheral neuropathy in diabetic participants,” Microcirculation, vol. 17, no. 4, pp. 297–302, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. M. D. Knudtson, B. E. Klein, R. Klein et al., “Variation associated with measurement of retinal vessel diameters at different points in the pulse cycle,” The British Journal of Ophthalmology, vol. 88, no. 1, pp. 57–61, 2004. View at Publisher · View at Google Scholar · View at Scopus
  22. A. S. Tsai, T. Y. Wong, R. Lavanya et al., “Differential association of retinal arteriolar and venular caliber with diabetes and retinopathy,” Diabetes Research and Clinical Practice, vol. 94, no. 2, pp. 291–298, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. R. Klein, B. E. Klein, S. E. Moss, T. Y. Wong, and A. R. Sharrett, “Retinal vascular caliber in persons with type 2 diabetes: the Wisconsin epidemiological study of diabetic retinopathy: XX,” Ophthalmology, vol. 113, no. 9, pp. 1488–1498, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. R. Klein, B. E. Klein, S. E. Moss et al., “Retinal vascular abnormalities in persons with type 1 diabetes: the Wisconsin epidemiologic study of diabetic retinopathy: XVIII,” Ophthalmology, vol. 110, no. 11, pp. 2118–2125, 2003. View at Publisher · View at Google Scholar · View at Scopus
  25. W. W. Harrison, A. Chang, M. G. Cardenas et al., “Blood pressure, vessel caliber, and retinal thickness in diabetes,” Optometry and Vision Science, vol. 89, no. 12, pp. 1715–1720, 2012. View at Publisher · View at Google Scholar · View at Scopus
  26. R. Klein, B. E. Klein, S. E. Moss et al., “The relation of retinal vessel caliber to the incidence and progression of diabetic retinopathy: XIX: the Wisconsin epidemiologic study of diabetic retinopathy,” Archives of Ophthalmology, vol. 122, no. 1, pp. 76–83, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. M. S. Roy, R. Klein, and M. N. Janal, “Retinal venular diameter as an early indicator of progression to proliferative diabetic retinopathy with and without high-risk characteristics in African Americans with type 1 diabetes mellitus,” Archives of Ophthalmology, vol. 129, no. 1, pp. 8–15, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. N. Cheung, S. L. Rogers, K. C. Donaghue, A. J. Jenkins, G. Tikellis, and T. Y. Wong, “Retinal arteriolar dilation predicts retinopathy in adolescents with type 1 diabetes,” Diabetes Care, vol. 31, no. 9, pp. 1842–1846, 2008. View at Publisher · View at Google Scholar · View at Scopus
  29. E. Alibrahim, K. C. Donaghue, S. Rogers et al., “Retinal vascular caliber and risk of retinopathy in young patients with type 1 diabetes,” Ophthalmology, vol. 113, no. 9, pp. 1499–1503, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. L. D. Hubbard, R. J. Brothers, W. N. King et al., “Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the atherosclerosis risk in communities study,” Ophthalmology, vol. 106, no. 12, pp. 2269–2280, 1999. View at Publisher · View at Google Scholar
  31. M. B. Sasongko, T. Y. Wong, T. T. Nguyen, C. Y. Cheung, J. E. Shaw, and J. J. Wang, “Retinal vascular tortuosity in persons with diabetes and diabetic retinopathy,” Diabetologia, vol. 54, no. 9, pp. 2409–2416, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. M. B. Sasongko, T. Y. Wong, T. T. Nguyen, J. E. Shaw, A. J. Jenkins, and J. J. Wang, “Novel versus traditional risk markers for diabetic retinopathy,” Diabetologia, vol. 55, no. 3, pp. 666–670, 2012. View at Publisher · View at Google Scholar · View at Scopus
  33. S. Rilven, T. L. Torp, and J. Grauslund, “Retinal oximetry in patients with ischaemic retinal diseases,” Acta Ophthalmologica, vol. 95, no. 2, pp. 119–127, 2017. View at Publisher · View at Google Scholar
  34. J. Boeckaert, E. Vandewalle, and I. Stalmans, “Oximetry: Recent insights into retinal vasopathies and glaucoma,” Bulletin de la Société Belge d'Ophtalmologie, vol. 1, no. 319, pp. 75–83, 2012. View at Google Scholar
  35. E. Stefansson, “Ocular oxygenation and the treatment of diabetic retinopathy,” Survey of Ophthalmology, vol. 51, no. 4, pp. 364–380, 2006. View at Publisher · View at Google Scholar · View at Scopus
  36. S. H. Hardarson, A. Harris, R. A. Karlsson et al., “Automatic retinal oximetry,” Investigative Ophthalmology & Visual Science, vol. 47, no. 11, pp. 5011–5016, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. S. H. Hardarson, “Retinal oximetry,” Acta Ophthalmologica, vol. 91, no. Thesis 2, pp. 1–47, 2013. View at Publisher · View at Google Scholar · View at Scopus
  38. J. M. Beach, K. J. Schwenzer, S. Srinivas, D. Kim, and J. S. Tiedeman, “Oximetry of retinal vessels by dual-wavelength imaging: calibration and influence of pigmentation,” Journal of Applied Physiology (1985), vol. 86, no. 2, pp. 748–758, 1999. View at Google Scholar
  39. C. M. Jorgensen, S. H. Hardarson, and T. Bek, “The oxygen saturation in retinal vessels from diabetic patients depends on the severity and type of vision-threatening retinopathy,” Acta Ophthalmologica, vol. 92, no. 1, pp. 34–39, 2014. View at Publisher · View at Google Scholar · View at Scopus
  40. C. Jorgensen and T. Bek, “Increasing oxygen saturation in larger retinal vessels after photocoagulation for diabetic retinopathy,” Investigative Ophthalmology & Visual Science, vol. 55, no. 8, pp. 5365–5369, 2014. View at Publisher · View at Google Scholar · View at Scopus
  41. B. Khoobehi, K. Firn, H. Thompson, M. Reinoso, and J. Beach, “Retinal arterial and venous oxygen saturation is altered in diabetic patients,” Investigative Ophthalmology & Visual Science, vol. 54, no. 10, pp. 7103–7106, 2013. View at Publisher · View at Google Scholar · View at Scopus
  42. S. H. Hardarson and E. Stefansson, “Retinal oxygen saturation is altered in diabetic retinopathy,” The British Journal of Ophthalmology, vol. 96, no. 4, pp. 560–563, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. M. Hammer, W. Vilser, T. Riemer et al., “Diabetic patients with retinopathy show increased retinal venous oxygen saturation,” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 247, no. 8, pp. 1025–1030, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. A. Green, M. Hauge, N. V. Holm, and L. L. Rasch, “Epidemiological studies of diabetes mellitus in Denmark. II. A prevalence study based on insulin prescriptions,” Diabetologia, vol. 20, no. 4, pp. 468–470, 1981. View at Google Scholar
  45. A. K. Sjolie, “Ocular complications in insulin treated diabetes mellitus. An epidemiological study,” Acta Ophthalmologica. Supplement, vol. 172, pp. 1–77, 1985. View at Google Scholar
  46. J. Grauslund, “Long-term mortality and retinopathy in type 1 diabetes,” Acta Ophthalmologica, vol. 88, no. Thesis 1, pp. 1–14, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. J. Grauslund, “Eye complications and markers of morbidity and mortality in long-term type 1 diabetes,” Acta Ophthalmologica, vol. 89, no. Thesis 1, pp. 1–19, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. G. Early Treatment Diabetic Retinopathy Study Research, “Grading diabetic retinopathy from stereoscopic color fundus photographs—an extension of the modified Airlie House classification. ETDRS report number 10,” Ophthalmology, vol. 98, Supplement 5, pp. 786–806, 1991. View at Publisher · View at Google Scholar
  49. Early Treatment Diabetic Retinopathy Study Research Group, “Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12,” Ophthalmology, vol. 98, Supplement 5, pp. 823–833, 1991. View at Publisher · View at Google Scholar
  50. M. D. Knudtson, K. E. Lee, L. D. Hubbard, T. Y. Wong, R. Klein, and B. E. Klein, “Revised formulas for summarizing retinal vessel diameters,” Current eye Research, vol. 27, no. 3, pp. 143–149, 2003. View at Google Scholar
  51. G. Liew, J. J. Wang, N. Cheung et al., “The retinal vasculature as a fractal: methodology, reliability, and relationship to blood pressure,” Ophthalmology, vol. 115, no. 11, pp. 1951–1956, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. J. Grauslund, A. Green, and A. K. Sjolie, “Prevalence and 25 year incidence of proliferative retinopathy among Danish type 1 diabetic patients,” Diabetologia, vol. 52, no. 9, pp. 1829–1835, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Grauslund, A. Green, R. Kawasaki, L. Hodgson, A. K. Sjolie, and T. Y. Wong, “Retinal vascular fractals and microvascular and macrovascular complications in type 1 diabetes,” Ophthalmology, vol. 117, no. 7, pp. 1400–1405, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. B. S. Olsen, J. Johannesen, A. K. Sjolie et al., “Metabolic control and prevalence of microvascular complications in young Danish patients with type 1 diabetes mellitus. Danish Study Group of Diabetes in Childhood,” Diabetic Medicine, vol. 16, no. 1, pp. 79–85, 1999. View at Publisher · View at Google Scholar · View at Scopus
  55. H. B. Mortensen, S. G. Hartling, and K. E. Petersen, “A nation-wide cross-sectional study of glycosylated haemoglobin in Danish children with type 1 diabetes,” Diabetic Medicine, vol. 5, no. 9, pp. 871–876, 1988. View at Publisher · View at Google Scholar
  56. H. B. Mortensen, K. Marinelli, K. Norgaard et al., “A nation-wide cross-sectional study of urinary albumin excretion rate, arterial blood pressure and blood glucose control in Danish children with type 1 diabetes mellitus. Danish Study Group of Diabetes in Childhood,” Diabetic Medicine, vol. 7, no. 10, pp. 887–897, 1990. View at Publisher · View at Google Scholar
  57. B. S. Olsen, A. Sjolie, P. Hougaard et al., “A 6-year nationwide cohort study of glycaemic control in young people with type 1 diabetes. Risk markers for the development of retinopathy, nephropathy and neuropathy. Danish Study Group of Diabetes in Childhood,” Journal of Diabetes and Its Complications, vol. 14, no. 6, pp. 295–300, 2000. View at Publisher · View at Google Scholar · View at Scopus
  58. B. S. Olsen, A. K. Sjolie, P. Hougaard et al., “The significance of the prepubertal diabetes duration for the development of retinopathy and nephropathy in patients with type 1 diabetes,” Journal of Diabetes and Its Complications, vol. 18, no. 3, pp. 160–164, 2004. View at Publisher · View at Google Scholar · View at Scopus
  59. R. Broe, M. L. Rasmussen, U. Frydkjaer-Olsen et al., “The 16-year incidence, progression and regression of diabetic retinopathy in a young population-based Danish cohort with type 1 diabetes mellitus: the Danish cohort of pediatric diabetes 1987 (DCPD1987),” Acta Diabetologica, vol. 51, no. 3, pp. 413–420, 2014. View at Publisher · View at Google Scholar · View at Scopus
  60. K. Sandahl, L. B. Nielsen, J. Svensson et al., “Increased mortality in a Danish cohort of young people with type 1 diabetes mellitus followed for 24 years,” Diabetic Medicine, vol. 34, no. 3, pp. 380–386, 2017. View at Publisher · View at Google Scholar · View at Scopus
  61. R. Broe, M. L. Rasmussen, U. Frydkjaer-Olsen et al., “Retinal vascular fractals predict long-term microvascular complications in type 1 diabetes mellitus: the Danish cohort of pediatric diabetes 1987 (DCPD1987),” Diabetologia, vol. 57, no. 10, pp. 2215–2221, 2014. View at Publisher · View at Google Scholar · View at Scopus
  62. R. Broe, “Early risk stratification in pediatric type 1 diabetes,” Acta Ophthalmologica, vol. 93, no. Thesis 1, pp. 1–19, 2015. View at Publisher · View at Google Scholar · View at Scopus
  63. R. Broe, M. L. Rasmussen, U. Frydkjaer-Olsen et al., “Retinal vessel calibers predict long-term microvascular complications in type 1 diabetes: the Danish cohort of pediatric diabetes 1987 (DCPD1987),” Diabetes, vol. 63, no. 11, pp. 3906–3914, 2014. View at Publisher · View at Google Scholar · View at Scopus
  64. M. L. Rasmussen, R. Broe, U. Frydkjaer-Olsen et al., “Retinal vascular geometry and its association to microvascular complications in patients with type 1 diabetes: the Danish cohort of pediatric diabetes 1987 (DCPD1987),” Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 255, no. 2, pp. 293–299, 2017. View at Publisher · View at Google Scholar · View at Scopus
  65. K. Lundberg, R. Kawasaki, A. K. Sjolie, T. Y. Wong, and J. Grauslund, “Localized changes in retinal vessel caliber after focal/grid laser treatment in patients with diabetic macular edema: a measure of treatment response?” Retina, vol. 33, no. 10, pp. 2089–2095, 2013. View at Publisher · View at Google Scholar · View at Scopus
  66. Early Treatment Diabetic Retinopathy Study Research Group, “Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1,” Archives of Ophthalmology, vol. 103, no. 12, pp. 1796–1806, 1985. View at Publisher · View at Google Scholar · View at Scopus
  67. 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, vol. 94, no. 7, pp. 761–774, 1987. View at Google Scholar
  68. The Early Treatment Diabetic Retinopathy Study Research Group, “Photocoagulation for diabetic macular edema: Early Treatment Diabetic Retinopathy Study report no. 4,” International Ophthalmology Clinics, vol. 27, no. 4, pp. 265–272, 1987. View at Publisher · View at Google Scholar
  69. T. L. Torp, R. Kawasaki, T. Y. Wong, T. Peto, and J. Grauslund, “Improvement in retinal venous oxygen saturation after panretinal photocoagulation is predictive of progression of proliferative diabetic retinopathy,” in The Association for Research in Vision and Ophthalmology Annual Meeting, Seattle, 2016.
  70. A. S. Vergmann, T. L. Torp, L. K. Lundberg, T. Peto, and J. Grauslund, “Retinal vessel caliber as a potential marker of treatment outcome in patients with proliferative diabetic retinopathy,” in EURETINA, Copenhagen, 2016.
  71. C. Y. Cheung, M. K. Ikram, R. Klein, and T. Y. Wong, “The clinical implications of recent studies on the structure and function of the retinal microvasculature in diabetes,” Diabetologia, vol. 58, no. 5, pp. 871–885, 2015. View at Publisher · View at Google Scholar · View at Scopus
  72. Early Treatment Diabetic Retinopathy Study Research Group, “Early photocoagulation for diabetic retinopathy. ETDRS report number 9,” Ophthalmology, vol. 98, Supplement 5, pp. 766–785, 1991. View at Google Scholar
  73. R. Rajendram, S. Fraser-Bell, A. Kaines et al., “A 2-year prospective randomized controlled trial of intravitreal bevacizumab or laser therapy (BOLT) in the management of diabetic macular edema: 24-month data: report 3,” Archives of Ophthalmology, vol. 130, no. 8, pp. 972–979, 2012. View at Publisher · View at Google Scholar · View at Scopus
  74. M. J. Elman, L. P. Aiello, R. W. Beck et al., “Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema,” Ophthalmology, vol. 117, no. 6, pp. 1064–1077, 2010. View at Publisher · View at Google Scholar · View at Scopus
  75. D. V. Do, Q. D. Nguyen, D. Boyer et al., “One-year outcomes of the da Vinci study of VEGF trap-eye in eyes with diabetic macular edema,” Ophthalmology, vol. 119, no. 8, pp. 1658–1665, 2012. View at Publisher · View at Google Scholar · View at Scopus
  76. G. Barteselli, I. Kozak, S. El-Emam, J. Chhablani, M. A. Cortes, and W. R. Freeman, “12-month results of the standardised combination therapy for diabetic macular oedema: intravitreal bevacizumab and navigated retinal photocoagulation,” The British Journal of Ophthalmology, vol. 98, no. 8, pp. 1036–1041, 2014. View at Publisher · View at Google Scholar · View at Scopus
  77. R. Liegl, J. Langer, F. Seidensticker et al., “Comparative evaluation of combined navigated laser photocoagulation and intravitreal ranibizumab in the treatment of diabetic macular edema,” PloS One, vol. 9, no. 12, article e113981, 2014. View at Publisher · View at Google Scholar · View at Scopus
  78. S. Blindbaek, “Aflibercept and navigated versus convensional laser in diabetic macular edema (ADDENDUM),” http://ClinicalTrials.gov
  79. E. Agardh and P. Tababat-Khani, “Adopting 3-year screening intervals for sight-threatening retinal vascular lesions in type 2 diabetic subjects without retinopathy,” Diabetes Care, vol. 34, no. 6, pp. 1318–1319, 2011. View at Publisher · View at Google Scholar · View at Scopus
  80. T. Aspelund, O. Thornorisdottir, E. Olafsdottir et al., “Individual risk assessment and information technology to optimise screening frequency for diabetic retinopathy,” Diabetologia, vol. 54, no. 10, pp. 2525–2532, 2011. View at Publisher · View at Google Scholar · View at Scopus
  81. G. Dimitrova, E. Chihara, H. Takahashi, H. Amano, and K. Okazaki, “Quantitative retinal optical coherence tomography angiography in patients with diabetes without diabetic retinopathy,” Investigative Ophthalmology & Visual Science, vol. 58, no. 1, pp. 190–196, 2017. View at Publisher · View at Google Scholar
  82. D. S. Ting, G. S. Tan, R. Agrawal et al., “Optical coherence tomographic angiography in type 2 diabetes and diabetic retinopathy,” JAMA Ophthalmology, 2017. View at Publisher · View at Google Scholar