Purpose: To determine whether changes in retinal vascular calibre and geometry are associated with progression of diabetic retinopathy in type 2 diabetes (T2D). Procedures: The retinal vascular calibre and geometry of 30 subjects with more than 20 years of diagnosed T2D with no retinopathy (NR) were compared to 30 subjects that progressed to proliferative diabetic retinopathy (PDR). The images of PDR subjects included in this study were those obtained before the onset of retinopathy. The diameter of retinal arterioles (CRAE), retinal venules (CRVE), tortuosity of retinal vessels, junctional exponent deviation (JEa) and fractal dimension (Df) were measured using Singapore I Vessel Assessment (SIVA 3.0) software and compared using Mann-Whitney U test. Results: The median CRAE and the median CRVE were significantly wider in PDR subjects compared to NR subjects (p = 0.014 and 0.016), respectively. Curvature tortuosity of the retinal arteries and veins and Df were significantly decreased in the PDR subjects compared to NR subjects (p = 0.015, 0.016 and 0.03, respectively). The JEa was significantly increased in PDR subjects (p = 0.01). Conclusions: Retinal vessel calibre and geometry of the retinal vasculature may be important risk factors for the progression to PDR. More longitudinal prospective studies will be needed to further explore the findings of this study.

World Health Organisation: Prevalence of diabetes worldwide. 2011. http://www.who.int/diabetes/facts/world_figures/en/.
International Diabetes Federation: Diabetes facts. 2011. http://www.idf.org.
Minassian D, Reidy A: Future sight loss UK 2: an epidemiological and economic model for sight loss in the decade 2010–2020. 2009.
UK Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854–865.
Ismail-Beigi F, Craven T, Banerji MA, Basile J, Calles J, Cohen RM, Cuddihy R, Cushman WC, Genuth S, Grimm RH Jr, Hamilton BP, Hoogwerf B, Karl D, Katz L, Krikorian A, O’Connor P, Pop-Busui R, Schubart U, Simmons D, Taylor H, Thomas A, Weiss D, Hramiak I: Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet 2010;376:419–430.
Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, Forder P, Pillai A, Davis T, Glasziou P, Drury P, Kesäniemi YA, Sullivan D, Hunt D, Colman P, d’Emden M, Whiting M, Ehnholm C, Laakso M: Effects of long-term fenofibrate therapy on cardiovascular events in 9,795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005;366:1849–1861.
Hesse L: Fractal dimension in diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 1994;232:447–448.
Avakian A, Kalina RE, Sage EH, Rambhia AH, Elliott KE, Chuang EL, Clark JI, Hwang JN, Parsons-Wingerter P: Fractal analysis of region-based vascular change in the normal and non-proliferative diabetic retina. Curr Eye Res 2002;24:274–280.
Cheung N, Rogers SL, Donaghue KC, Jenkins AJ, Tikellis G, Wong TY: Retinal arteriolar dilation predicts retinopathy in adolescents with type 1 diabetes. Diabetes Care 2008;31:1842–1846.
Cheung CY, Tay WT, Mitchell P, Wang JJ, Hsu W, Lee ML, Lau QP, Zhu AL, Klein R, Saw SM, Wong TY: Quantitative and qualitative retinal microvascular characteristics and blood pressure. J Hypertens 2011;29:1380–1391.
Roy MS, Klein R, Janal MN: 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. Arch Ophthalmol 2011;129:8–15.
Kunicki AC, Oliveira AJ, Mendonca MB, Barbosa CT, Nogueira RA: Can the fractal dimension be applied for the early diagnosis of non-proliferative diabetic retinopathy? Braz J Med Biol Res 2009;42:930–934.
Rogers SL, Tikellis G, Cheung N, Tapp R, Shaw J, Zimmet PZ, Mitchell P, Wang JJ, Wong TY: Retinal arteriolar caliber predicts incident retinopathy: the Australian Diabetes, Obesity and Lifestyle (AusDiab) study. Diabetes Care 2008;31:761–763.
Wong TY, Klein R, Sharrett AR, Nieto FJ, Boland LL, Couper DJ, Mosley TH, Klein BE, Hubbard LD, Szklo M: Retinal microvascular abnormalities and cognitive impairment in middle-aged persons: the Atherosclerosis Risk in Communities Study. Stroke 2002;33:1487–1492.
Liew G, Mitchell P, Rochtchina E, Wong TY, Hsu W, Lee ML, Wainwright A, Wang JJ: Fractal analysis of retinal microvasculature and coronary heart disease mortality. Eur Heart J 2011;32:422–429.
Sun C, Liew G, Wang JJ, Mitchell P, Saw SM, Aung T, Tai ES, Wong TY: Retinal vascular caliber, blood pressure, and cardiovascular risk factors in an Asian population: the Singapore Malay Eye Study. Invest Ophthalmol Vis Sci 2008;49:1784–1790.
Grauslund J, Green A, Kawasaki R, Hodgson L, Sjolie AK, Wong TY: Retinal vascular fractals and microvascular and macrovascular complications in type 1 diabetes. Ophthalmology 2010;117:1400–1405.
Cheung N, Liew G, Lindley RI, Liu EY, Wang JJ, Hand P, Baker M, Mitchell P, Wong TY: Retinal fractals and acute lacunar stroke. Ann Neurol 2010;68:107–111.
Sng CC, Sabanayagam C, Lamoureux EL, Liu E, Lim SC, Hamzah H, Lee J, Tai ES, Wong TY: Fractal analysis of the retinal vasculature and chronic kidney disease. Nephrol Dial Transplant 2010;25:2252–2258.
Cheung N, Donaghue KC, Liew G, Rogers SL, Wang JJ, Lim SW, Jenkins AJ, Hsu W, Li Lee M, Wong TY: Quantitative assessment of early diabetic retinopathy using fractal analysis. Diabetes Care 2009;32:106–110.
ETDRS: Grading diabetic retinopathy from stereoscopic color fundus photographs – an extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1991;98:786–806.
Wong TY, Knudtson MD, Klein R, Klein BE, Meuer SM, Hubbard LD: Computer-assisted measurement of retinal vessel diameters in the Beaver Dam Eye Study: methodology, correlation between eyes, and effect of refractive errors. Ophthalmology 2004;111:1183–1190.
Knudtson MD, Lee KE, Hubbard LD, Wong TY, Klein R, Klein BE: Revised formulas for summarizing retinal vessel diameters. Curr Eye Res 2003;27:143–149.
Murray CD: The physiological principle of minimum work applied to the angle of branching of arteries. J Gen Physiol 1926;9:835–841.
Hughes AD, Wong TY, Witt N, Evans R, Thom SA, Klein BE, Chaturvedi N, Klein R: Determinants of retinal microvascular architecture in normal subjects. Microcirculation 2009;16:159–166.
Tillin T, Evans RM, Witt NW, Sharp PS, McKeigue PM, Chaturvedi N, Hughes AD: Ethnic differences in retinal microvascular structure. Diabetologia 2008;51:1719–1722.
Griffith TM, Edwards DH, Davies RL, Harrison TJ, Evans KT: EDRF coordinates the behaviour of vascular resistance vessels. Nature 1987;329:442–445.
Stanton AV, Wasan B, Cerutti A, Ford S, Marsh R, Sever PP, Thom SA, Hughes AD: Vascular network changes in the retina with age and hypertension. J Hypertens 1995;13:1724–1728.
Mainster MA: The fractal properties of retinal vessels: embryological and clinical implications. Eye (Lond) 1990;4:235–241.
Daxer A: The fractal geometry of proliferative diabetic retinopathy: implications for the diagnosis and the process of retinal vasculogenesis. Curr Eye Res 1993;12:1103–1109.
Landini G, Murray PI, Misson GP: Local connected fractal dimensions and lacunarity analyses of 60 degrees fluorescein angiograms. Invest Ophthalmol Vis Sci 1995;36:2749–2755.
Cheng SC, Huang YM: A novel approach to diagnose diabetes based on the fractal characteristics of retinal images. IEEE Trans Inf Technol Biomed 2003;7:163–170.
SPSS Inc: SPSS for Windows rel. 17.0.0. 2008.
Skovborg F, Nielsen AV, Lauritzen E, Hartkopp O: Diameters of the retinal vessels in diabetic and normal subjects. Diabetes 1969;18:292–298.
ETDRS: Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1991;98:823–833.
Klein R, Klein BE, Moss SE, Wong TY, Hubbard L, Cruickshanks KJ, Palta M: The relation of retinal vessel caliber to the incidence and progression of diabetic retinopathy: XIX: the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Arch Ophthalmol 2004;122:76–83.
Remky A, Arend O, Beausencourt E, Elsner AE, Bertram B: Retinal vessels before and after photocoagulation in diabetic retinopathy: determining the diameter using digitized color fundus slides. Klin Monbl Augenheilkd 1996;209:79–83.
Gottfredsdóttir MS, Stefánsson E, Jónasson F, Gíslason I: Retinal vasoconstriction after laser treatment for diabetic macular edema. Am J Ophthalmol 1993;115:64–67.
Wilson CA, Stefánsson E, Klombers L, Hubbard LD, Kaufman SC, Ferris FL 3rd: Optic disk neovascularization and retinal vessel diameter in diabetic retinopathy. Am J Ophthalmol 1988;106:131–134.
Saldivar E, Cabrales P, Tsai AG, Intaglietta M: Microcirculatory changes during chronic adaptation to hypoxia. Am J Physiol Heart Circ Physiol 2003;285:H2064–H2071.
Arden GB, Gündüz MK, Kurtenbach A, Völker M, Zrenner E, Gündüz SB, Kamis U, Oztürk BT, Okudan S: A preliminary trial to determine whether prevention of dark adaptation affects the course of early diabetic retinopathy. Eye (Lond) 2010;24:1149–1155.
Klein R, Klein BE, Knudtson MD, Wong TY, Tsai MY: Are inflammatory factors related to retinal vessel caliber? The Beaver Dam Eye Study. Arch Ophthalmol 2006;124:87–94.
Islam FM, Nguyen TT, Wang JJ, Tai ES, Shankar A, Saw SM, Aung T, Lim SC, Mitchell P, Wong TY: Quantitative retinal vascular calibre changes in diabetes and retinopathy: the Singapore Malay Eye Study. Eye (Lond) 2009;23:1719–1724.
Kifley A, Wang JJ, Cugati S, Wong TY, Mitchell P: Retinal vascular caliber, diabetes, and retinopathy. Am J Ophthalmol 2007;143:1024–1026.
Cheung N, Wang JJ, Klein R, Couper DJ, Sharrett AR, Wong TY: Diabetic retinopathy and the risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. Diabetes Care 2007;30:1742–1746.
Quigley MG: Prognosis and retinal vessel features. Ophthalmology 2007;114:1796–1797, author reply 1797.
Gardiner TA, Archer DB, Curtis TM, Stitt AW: Arteriolar involvement in the microvascular lesions of diabetic retinopathy: implications for pathogenesis. Microcirculation 2007;14:25–38.
Frank RN: Diabetic retinopathy. N Engl J Med 2004;350:48–58.
Cheung CY, Zheng Y, Hsu W, Lee ML, Lau QP, Mitchell P, Wang JJ, Klein R, Wong TY: Retinal vascular tortuosity, blood pressure, and cardiovascular risk factors. Ophthalmology 2011;118:812–818.
Yamakawa K, Bhutto IA, Lu Z, Watanabe Y, Amemiya T: Retinal vascular changes in rats with inherited hypercholesterolemia – corrosion cast demonstration. Curr Eye Res 2001;22:258–265.
Witt N, Wong TY, Hughes AD, Chaturvedi N, Klein BE, Evans R, McNamara M, Thom SA, Klein R: Abnormalities of retinal microvascular structure and risk of mortality from ischemic heart disease and stroke. Hypertension 2006;47:975–981.
Tomita Y, Kubis N, Calando Y, Tran Dinh A, Meric P, Seylaz J, Pinard E: Long-term in vivo investigation of mouse cerebral microcirculation by fluorescence confocal microscopy in the area of focal ischemia. J Cereb Blood Flow Metab 2005;25:858–867.
Liew G, Wang JJ, Cheung N, Zhang YP, Hsu W, Lee ML, Mitchell P, Tikellis G, Taylor B, Wong TY: The retinal vasculature as a fractal: methodology, reliability, and relationship to blood pressure. Ophthalmology 2008;115:1951–1956.
Chen J, Smith LE: Retinopathy of prematurity. Angiogenesis 2007;10:133–140.
Chen Y, Li XX, Yin H, Gilbert C, Liang JH, Jiang YR, Zhao MW: Risk factors for retinopathy of prematurity in six neonatal intensive care units in Beijing, China. Br J Ophthalmol 2008;92:326–330.
Hardarson SH, Stefánsson E: Oxygen saturation in branch retinal vein occlusion. Acta Ophthalmol 2011, E-pub ahead of print.
Blondal R, Sturludottir MK, Hardarson SH, Halldorsson GH, Stefánsson E: Reliability of vessel diameter measurements with a retinal oximeter. Graefes Arch Clin Exp Ophthalmol 2011;249:1311–1317.
Antonetti DA, Barber AJ, Bronson SK, Freeman WM, Gardner TW, Jefferson LS, Kester M, Kimball SR, Krady JK, LaNoue KF, Norbury CC, Quinn PG, Sandirasegarane L, Simpson IA: Diabetic retinopathy: seeing beyond glucose-induced microvascular disease. Diabetes 2006;55:2401–2411.
Barber AJ, Gardner TW, Abcouwer SF: The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy. Invest Ophthalmol Vis Sci 2011;52:1156–1163.
Mahal S, Strain WD, Martinez-Perez ME, Thom SA, Chaturvedi N, Hughes AD: Comparison of the retinal microvasculature in European and African-Caribbean people with diabetes. Clin Sci (Lond) 2009;117:229–236.
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