Sir,
Chowdhury et al,1 have timely reviewed this important topic. We have also comprehensively reviewed association studies (cross-sectional and prospective) and intervention studies carried out over the last 50 years2 relating to dyslipidaemia and diabetic retinopathy (DR). Overall, as has been pointed out by Chowdhury et al,1 positive associations of any grade of DR with levels of total cholesterol and triglycerides were observed. In addition, association of DR with low levels of high-density lipoprotein cholesterol (HDL-C) was also shown.3 Further, there is a possible association of DR with insulin resistance and its components such as procoagulant factors.3
As emphasised by Chowdhury et al,1 hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have shown beneficial effects on DR in a few trials. The review, however, does not contain a recent study carried out by our group, since it was published after acceptance of the manuscript of Chowdhury et al.1 We conducted a double-blind placebo-controlled randomized trial comparing 50 patients with Type II diabetes with hypercholesterolaemia, treated with either simvastatin or placebo.4 All patients had good glycaemic and blood pressure control and had DR characterized by nonclinically significant macular oedema. Interestingly, visual acuity worsened in seven patients in the placebo group, but none in the simvastatin group (P=0.009). Fundus fluorescein angiography and colour fundus photograph improved in one patient on simvastatin therapy, while seven patients showed worsening in the placebo group (P=0.009). Such data, albeit in a small number of patients, are supported by a considerable body of evidence showing benefits of HMG-CoA reductase inhibitors in diabetic nephropathy, another microvascular complication of diabetes mellitus.5
According to the current guidelines, all patients of Type II diabetes with hypercholesterolaemia should be treated with the lipid-lowering therapy; hence, possible treatment-related benefit for DR would be extended to all such patients. However, there remains a vast margin for research on this issue. For example, benefits of lipid-lowering therapy on DR could be explored on patients with normal lipid levels, hypertriglyceridemia alone, and low levels of HDL-C alone. Furthermore, therapy(ies) could be attempted which improve(s) several lipid parameters simultaneously. Finally, the role of lowering elevated lipoprotein(a) levels and ameliorating procoagulant factors remains to be investigated.
The precise mechanism(s) whereby dyslipidaemia may cause or exacerbate DR remain(s) speculative. Besides damage to endothelial cells and pericytes by oxidized low-density lipoprotein cholesterol6 as emphasized by Chowdhury et al,1 the following mechanisms may be operative; elevation of blood viscosity and alteration in the fibrinolytic system,7 incorporation of triglycerides in the cellular membrane causing retinal leakage,8 and basal linear deposits in Bruch's membrane.9 Further, HMG-CoA reductase inhibitors are now known to have beneficial effects on the vascular tissues other than those because of their lipid-lowering properties. In case of DR, their antioxidant properties might protect the outer retina from the oxidative damage. Prevention of apoptosis of the retinal endothelial cells by these drugs may be an additional mechanism that may preserve vascular integrity.10
Unfortunately, unlike macrovascular disease, medical treatment of microvascular disease in diabetes, particularly DR, remains in the nascent stage. Given the rapid global increase in the incidence and prevalence of diabetes and morbidities because of diabetic microvascular disease, this research area deserves more attention.
References
Chowdhury TA, Hopkins D, Dodson PM, Vafidis GC . The role of serum lipids in exudative diabetic maculopathy: is there a place for lipid lowering therapy? Eye 2002; 16: 689–693.
Misra A, Kumar S, Vikram NK, Kumar A . The role of lipids in the development of diabetic microvascular complications: implications for therapy. Am J Cardiovasc Drugs 2003 (in press).
Kordonouri O, Danne T, Hopfenmuller W, Enders I, Hovener G, Weber B . Lipid profiles and blood pressure: are they risk factors for the development of early background retinopathy and incipient nephropathy in children with insulin-dependent diabetes mellitus? Acta Paediatr 1996; 85: 43–48.
Sen K, Misra A, Kumar A, Pandey RM . Simvastatin retards progression of retinopathy in diabetic patients with hypercholesterolemia. Diabetes Res Clin Pract 2002; 56: 1–11.
Fried LF, Forrest KY, Ellis D, Chang Y, Silvers N, Orchard TJ . Lipid modulation in insulin-dependent diabetes mellitus: effect on microvascular outcomes. J Diabetes Complications 2001; 15: 113–119.
Kawamura M, Heinecke JW, Chait A . Pathophysiological concentrations of glucose promote oxidative modification of low density lipoprotein by a superoxide-dependent pathway. J Clin Invest 1994; 94: 771–778.
Freyberger H, Schifferdecker E, Schatz H . Regression of hard exudates in diabetic background retinopathy in therapy with etofibrate antilipemic agent. Med Klin 1994; 89: 594–597.
Ebeling P, Koivisto VA . Occurrence and interrelationships of complications in insulin-dependent diabetes in Finland. Acta Diabetol 1997; 34: 33–38.
Dithmar S, Curcio CA, Le NA, Brown S, Grossniklaus HE . Ultrastructural changes in Bruch's membrane of apolipoprotein E-deficient mice. Invest Ophthalmol Vis Sci 2000; 41: 2035.
Kureishi Y, Luo Z, Shiojima I, Bialik A, Fulton D, Lefer DJ et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and, promotes angiogenesis in normocholesterolemic animals. Nat Med 2000; 6: 1004–1010.
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Misra, A., Vikram, N. & Kumar, A. Diabetic maculopathy and lipid-lowering therapy. Eye 18, 107–108 (2004). https://doi.org/10.1038/sj.eye.6700530
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DOI: https://doi.org/10.1038/sj.eye.6700530