Changes in retinal geometric parameters predict risk and progression of diabetic retinopathy (DR). We have shown that vitamin D deficiency (VDD) is associated with DR. We hypothesized that VDD mediates changes in retinal geometric parameters. Retinal vascular geometric parameters were assessed using a semiautomated computer program in photographs from young people with type 1 diabetes (T1D) and summarized as central retinal arteriolar and venular equivalents (CRAE, CRVE), fractal dimension, length-diameter ratio, branching angle and curvature tortuosity. Parameters were compared between those with and without DR and VDD (25-hydroxyvitamin D concentration ≤ 50？nmol/L). Retinal vascular geometric parameters were also compared across quartiles of vitamin D levels. Median CRVE was higher in patients with DR compared with those without (median (IQR) CRVE 247.3？μm (31.3) versus 238.8？μm (23.5), ). Fractal dimension was marginally greater in patients without VDD (1.49 (0.06) versus 1.47 (0.07) ). There was no difference in CRAE, CRVE, length-diameter ratio, branching angle, and curvature tortuosity between those with and without VDD and across quartiles of 25OHD. In conclusion, DR is associated with higher CRVE in young people with T1D; however, VDD is not associated with changes in retinal vascular geometric measures, suggesting an earlier role in the time course of DR pathogenesis. 1. Introduction Despite improvements in treatment, diabetic retinopathy (DR) remains a significant complication of type 1 diabetes (T1D). Identification of early treatable predictors of DR, may allow more aggressive management of those at high risk. There is increasing evidence that vitamin D deficiency (VDD) may play a role in pathogenesis of DR. In adults with type 2 diabetes, lower 25-hydroxyvitamin D (25OHD) levels have been associated with proliferative DR [1, 2]. We have shown that VDD is associated with a twofold increased risk of DR (OR 2.12, 95% CI 1.03–4.33) independent of diabetes duration and HbA1c [3]. Changes in retinal microvascular geometry can be used to predict DR prior to the development of microaneurysms or hemorrhage [4, 5]. These retinal measurements include retinal arteriolar and venular calibers, vessel tortuosity, length-diameter ratio, branching angles, and fractal dimension. In the Wisconsin Epidemiology Study of Diabetic Retinopathy (WESDR), an increase in retinal venular caliber of 10？μm was associated with higher 6-year incidence of DR, progression of DR, and incidence of proliferative DR [6]. Longitudinal studies from our group have demonstrated that
References
[1]
H. Aksoy, F. Ak？ay, N. Kurtul, O. Baykal, and B. Avci, “Serum 1,25 dihydroxy vitamin D (1,25(OH)2D3), 25 hydroxy vitamin D (25(OH)D) and parathormone levels in diabetic retinopathy,” Clinical Biochemistry, vol. 33, no. 1, pp. 47–51, 2000.
[2]
A. Suzuki, M. Kotake, Y. Ono et al., “Hypovitaminosis D in type 2 diabetes mellitus: association with microvascular complications and type of treatment,” Endocrine Journal, vol. 53, no. 4, pp. 503–510, 2006.
[3]
H. Kaur, K. C. Donaghue, A. K. Chan et al., “Vitamin D deficiency is associated with retinopathy in children and adolescents with type 1 diabetes,” Diabetes Care, vol. 34, no. 6, pp. 1400–1402, 2011.
[4]
T. Y. Wong, “Retinal vessel diameter as a clinical predictor of diabetic retinopathy progression: time to take out the measuring tape,” Archives of Ophthalmology, vol. 129, no. 1, pp. 95–96, 2011.
[5]
M. K. Ikram, C. Y. Cheung, M. Lorenzi, et al., “Retinal vascular caliber as a biomarker for diabetes microvascular complications,” Diabetes Care, vol. 36, no. 3, pp. 750–759, 2013.
[6]
R. Klein, C. E. Myers, K. E. Lee, R. Gangnon, and B. E. K. Klein, “Changes in retinal vessel diameter and incidence and progression of diabetic retinopathy,” Archives of Ophthalmology, vol. 130, no. 6, pp. 749–755, 2012.
[7]
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.
[8]
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.
[9]
P. Benitez-Aguirre, M. E. Craig, M. B. Sasongko et al., “Retinal vascular geometry predicts incident retinopathy in young people with type 1 diabetes: a prospective cohort study from adolescence,” Diabetes Care, vol. 34, no. 7, pp. 1622–1627, 2011.
[10]
M. B. Sasongko, T. Y. Wong, K. C. Donaghue et al., “Retinal arteriolar tortuosity is associated with retinopathy and early kidney dysfunction in type 1 diabetes,” American Journal of Ophthalmology, vol. 153, no. 1, pp. 176.e1–183.e1, 2012.
[11]
N. Cheung, K. C. Donaghue, G. Liew et al., “Quantitative assessment of early diabetic retinopathy using fractal analysis,” Diabetes Care, vol. 32, no. 1, pp. 106–110, 2009.
[12]
D. M. Albert, E. A. Scheef, S. Wang et al., “Calcitriol is a potent inhibitor of retinal neovascularization,” Investigative Ophthalmology & Visual Science, vol. 48, no. 5, pp. 2327–2334, 2007.
[13]
Y.-F. Yiu, Y.-H. Chan, K.-H. Yiu et al., “Vitamin D deficiency is associated with depletion of circulating endothelial progenitor cells and endothelial dysfunction in patients with type 2 diabetes,” Journal of Clinical Endocrinology and Metabolism, vol. 96, no. 5, pp. E830–E835, 2011.
[14]
Statistics ABO, “SocioEconomic Indexes for Areas,” http://www.abs.gov.au/.
[15]
M. B. Sasongko, J. J. Wang, K. C. Donaghue et al., “Alterations in retinal microvascular geometry in young type 1 diabetes,” Diabetes Care, vol. 33, no. 6, pp. 1331–1336, 2010.
[16]
W. L. Shueh, N. Cheung, J. J. Wang et al., “Retinal vascular fractal dimension and risk of early diabetic retinopathy: a prospective study of children and adolescents with type 1 diabetes,” Diabetes Care, vol. 32, no. 11, pp. 2081–2083, 2009.
[17]
T. Y. Wong, M. D. Knudtson, R. Klein, B. E. K. 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.
[18]
C. Munns, M. R. Zacharin, C. P. Rodda et al., “Prevention and treatment of infant and childhood vitamin D deficiency in Australia and New Zealand: a consensus statement,” Medical Journal of Australia, vol. 185, no. 5, pp. 268–272, 2006.
[19]
S. L. Rogers, G. Tikellis, N. Cheung et al., “Retinal arteriolar caliber predicts incident retinopathy,” Diabetes Care, vol. 31, no. 4, pp. 761–763, 2008.
[20]
M. F. Holick, “The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action,” Molecular Aspects of Medicine, vol. 29, no. 6, pp. 361–368, 2008.
[21]
C. McGreevy and D. Williams, “New insights about vitamin D and cardiovascular disease: a narrative review,” Annals of Internal Medicine, vol. 155, no. 12, pp. 820–826, 2011.
[22]
J. Vojtková, M. Ciljaková, L. Vojarová, K. Janíková, Z. Michnová, and V. Sagiová, “Hypovitaminosis D in children with type 1 diabetes mellitus and its influence on biochemical and densitometric parameters,” Acta Medica, vol. 55, no. 1, pp. 18–22, 2011.
[23]
M. F. Holick, N. C. Binkley, H. A. Bischoff-Ferrari et al., “Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited,” Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 4, pp. 1153–1158, 2012.
[24]
M. F. Holick, “Vitamin D deficiency,” The New England Journal of Medicine, vol. 357, no. 3, pp. 266–281, 2007.
[25]
E. Downie, M. E. Craig, S. Hing, J. Cusumano, A. K. F. Chan, and K. C. Donaghue, “Continued reduction in the prevalence of retinopathy in adolescents with type 1 diabetes: role of insulin therapy and glycemic control,” Diabetes care, vol. 34, no. 11, pp. 2368–2373, 2011.
