Correlation of the cholesterol-to-high-density-lipoprotein Castelli risk index-1 with the choroidal and retinal nerve fiber layer thickness in patients with diabetes mellitus without retinopathy
Keywords:Castelli Index, CRI, CRI-1, Cholesterol, HDL, high-density lipoprotein, lipoprotein, diabetes mellitus, choroid, choroidal, choroidal thickness, RNFL, retinal nerve fiber layer
Purpose: To determine the choroidal thickness and retinal nerve layer (RNFL) thickness changes in patients with diabetes mellitus (DM) without retinopathy in relation to their glycated hemoglobin (HbA1c) and Castelli risk index-1 (CRI-1) levels.
Method: This study examined the right eyes of 340 subjects. CRI-1 was calculated as the total cholesterol divided by high-density lipoprotein cholesterol. Five groups of 68 eyes were defined as follows: Group 1, control group consisting of healthy subjects; Group 2, DM patients with HbA1c from 7% to 9%; Group 3, DM patients with HbA1c from 7% to 9% and CRI-1 greater than 4; Group 4, DM patients with HbA1c greater than 9.1%; and, Group 5, DM patients with HbA1c greater than 9.1% and with CRI-1 greater than 4. Optical coherence tomography (OCT) measurements were taken using enhanced depth imaging. Choroidal thickness (CT) and RNFL thickness were compared within groups.
Results: CT was found to be lower in all DM groups compared with healthy subjects. In all nasal areas, CT was significantly thinner in group 5 than group 4. RNFL loss was only seen in the inferior temporal quadrant of all DM patients compared with the control group. There was no statistically significant difference between subgroups in RNFL measurements.
Conclusion: CRI-1, which is a marker of combined dyslipidemia abnormalities, is in use to predict atherosclerotic changes in DM patients. This study determined the CRI-1 also correlates with the CT of diabetic eyes but not the RNFL, and it can be used as an additional criterion in ophthalmological follow-ups of diabetic patients.
Singh VP, Bali A, Singh N, Jaggi AS. Advanced glycation end products and diabetic complications. Korean Journal of Physiology and Pharmacology 2014; 18(1): 1-14.
Lachin JM, Genuth S, Nathan DM, et al. Effect of glycemic exposure on the risk of microvascular complications in the diabetes control and complications trial--revisited. Diabetes 2008; 57(4): 995-1001.
Masuch A, Friedrich N, Roth J, et al. Preventing misdiagnosis of diabetes in the elderly: age-dependent HbA1c reference intervals derived from two population-based study cohorts. BMC Endocrine Disorders 2019; 19(1): 20.
Bressler SB, Odia I, Maguire MG, et al. Factors Associated With Visual Acuity and Central Subfield Thickness Changes When Treating Diabetic Macular Edema With Anti-Vascular Endothelial Growth Factor Therapy: An Exploratory Analysis of the Protocol T Randomized Clinical Trial. JAMA Ophthalmology 2019; 137(4): 382-9.
Shiragami C, Shiraga F, Matsuo T, et al. Risk factors for diabetic choroidopathy in patients with diabetic retinopathy. Albrecht von Graefes Archiv fur Klinische und Experimentelle Ophthalmologie 2002; 240(6): 436-42.
Thompson IA, Durrani AK, Patel S. Optical coherence tomography angiography characteristics in diabetic patients without clinical diabetic retinopathy. Eye 2019; 33(4): 648-52.
Salazar JJ, Ramirez AI, de Hoz R, et al. Alterations in the choroid in hypercholesterolemic rabbits: reversibility after normalization of cholesterol levels. Experimental Eye Research 2007; 84(3): 412-22.
Torres R, Maia M, Noronha L, et al. Evaluation of choroid and sclera early alterations in hypercholesterolemic rabbits: histologic and histomorphometric study. Arquivos Brasileiros de Oftalmologia 2009; 72: 68-74.
Morton J, Zoungas S, Li Q, Patel AA, et al. Low HDL cholesterol and the risk of diabetic nephropathy and retinopathy: results of the ADVANCE study. Diabetes Care 2012; 35(11): 2201-6.
Rema M, Srivastava BK, Anitha B, et al. Association of serum lipids with diabetic retinopathy in urban South Indians--the Chennai Urban Rural Epidemiology Study (CURES) Eye Study-2. Diabetic Medicine 2006; 23(9): 1029-36.
Baral S, Hamal A, Shyam Bk, et al. Assessment of lipid abnormalities and cardiovascular risk indices in type 2 diabetes mellitus. Asian Journal of Medical Sciences 2019; 10: 39-44.
Criqui MH, Golomb BA. Epidemiologic aspects of lipid abnormalities. American Journal of Medicine 1998; 105(1a): 48s-57s.
Montgomery CL, Johnson HM, Johnston TP, Koulen P. Mechanisms underlying early-stage changes in visual performance and retina function after experimental induction of sustained dyslipidemia. Neurochemical Research 2018; 43(8): 1500-10.
Zhang B, Qiu Q, Yin L, et al. Measurement of retinal function with flash-electroretinography in Chinese patients with hyperlipidemia. Albrecht von Graefes Archiv fur Klinische und Experimentelle Ophthalmologie 2014; 252(9): 1385-92.
Abadia B, Sunen I, Calvo P, et al. Choroidal thickness measured using swept-source optical coherence tomography is reduced in patients with type 2 diabetes. PloS One 2018; 13(2): e0191977.
Endo H, Kase S, Takahashi M, et al. Alteration of layer thickness in the choroid of diabetic patients. Clinical & Experimental Ophthalmology 2018; 46(8): 926-33.
Schocket LS, Brucker AJ, Niknam RM, et al. Foveolar choroidal hemodynamics in proliferative diabetic retinopathy. International Ophthalmology 2004; 25(2): 89-94.
Nagaoka T, Kitaya N, Sugawara R, et al. Alteration of choroidal circulation in the foveal region in patients with type 2 diabetes. British Journal of Ophthalmology 2004; 88(8): 1060-3.
Kase S, Endo H, Yokoi M, et al. Choroidal thickness in diabetic retinopathy in relation to long-term systemic treatments for diabetes mellitus. European Journal of Ophthalmology 2016; 26(2): 158-62.
Gupta P, Thakku SG, Sabanayagam C, et al. Characterisation of choroidal morphological and vascular features in diabetes and diabetic retinopathy. British Journal of Ophthalmology 2017; 101(8): 1038-44.
Chen Q, Tan F, Wu Y, et al. Characteristics of retinal structural and microvascular alterations in early type 2 diabetic patients. Investigative Ophthalmology & Visual Science 2018; 59(5): 2110-8.
Goldberg IJ. Diabetic dyslipidemia: causes and consequences. Journal of Clinical Endocrinology and Metabolism 2001; 86(3): 965-71.
Larsson LI, Alm A, Lithner F, et al. The association of hyperlipidemia with retinopathy in diabetic patients aged 15-50 years in the county of Umea. Acta Ophthalmologica Scandinavica 1999; 77(5): 585-91.
Toth PP, Simko RJ, Palli SR, et al. The impact of serum lipids on risk for microangiopathy in patients with type 2 diabetes mellitus. Cardiovascular Diabetology 2012; 11: 109.
Wong IY, Wong RL, Zhao P, Lai WW. Choroidal thickness in relation to hypercholesterolemia on enhanced depth imaging optical coherence tomography. Retina 2013; 33(2): 423-8.
Wong TY, Cheung N, Tay WT, et al. Prevalence and risk factors for diabetic retinopathy: the Singapore Malay Eye Study. Ophthalmology 2008; 115(11): 1869-75.
Matthews DR, Stratton IM, Aldington SJ, et al. Risks of progression of retinopathy and vision loss related to tight blood pressure control in type 2 diabetes mellitus: UKPDS 69. Archives of Ophthalmology 2004; 122(11): 1631-40.
Wu M, Chen Y, Wilson K, et al. Intraretinal leakage and oxidation of LDL in diabetic retinopathy. Investigative Ophthalmology & Visual Science 2008; 49(6): 2679-85.
Benarous R, Sasongko MB, Qureshi S, et al. Differential association of serum lipids with diabetic retinopathy and diabetic macular edema. Investigative Ophthalmology & Visual Science 2011; 52(10): 7464-9.
Sacks Frank M, Hermans Michel P, et al. Association between plasma triglycerides and high-density lipoprotein cholesterol and microvascular kidney disease and retinopathy in type 2 diabetes mellitus. Circulation 2014; 129(9): 999-1008.
Zhong Y, Yue S, Wu J, et al. Association of the serum total cholesterol to triglyceride ratio with diabetic retinopathy in Chinese patients with type 2 diabetes: a community-based study. Diabetes Therapy 2019; 10(2): 597-604.
Cao D, Yang D, Yu H, et al. Optic nerve head perfusion changes preceding peripapillary retinal nerve fibre layer thinning in preclinical diabetic retinopathy. Clinical & Experimental Ophthalmology 2019; 47(2): 219-25.
Oshitari T, Hanawa K, Adachi-Usami E. Changes of macular and RNFL thicknesses measured by Stratus OCT in patients with early stage diabetes. Eye 2009; 23(4): 884-9.
Takis A, Alonistiotis D, Panagiotidis D, et al. Comparison of the nerve fiber layer of type 2 diabetic patients without glaucoma with normal subjects of the same age and sex. Clinical Ophthalmology 2014; 8: 455-63.
Vujosevic S, Martini F, Cavarzeran F, et al. Macular and peripapillary choroidal thickness in diabetic patients. Retina 2012; 32(9): 1781-90.
Shiba C, Shiba T, Takahashi M, et al. Relationship between glycosylated hemoglobin A1c and ocular circulation by laser speckle flowgraphy in patients with/without diabetes mellitus. Albrecht von Graefes Archiv fur Klinische und Experimentelle Ophthalmologie 2016; 254(9): 1801-9.
Yucel I, Akar Y, Yucel G, et al. Effect of hypercholesterolemia on inducible nitric oxide synthase expression in a rat model of elevated intraocular pressure. Vision Research 2005; 45(9): 1107-14.
Alcala A, Jansen S, Farkouh ME, Morell M. Hypercholesterolemia is associated with visual field alterations detectable with computerized perimetry. Atherosclerosis 2007; 195(1): e167-71.
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