Fenofibrate and diabetic retinopathy
2008; Elsevier BV; Volume: 371; Issue: 9614 Linguagem: Inglês
10.1016/s0140-6736(08)60332-3
ISSN1474-547X
AutoresGerald Liew, Mark C. Gillies, Jie Jin Wang,
Tópico(s)Retinopathy of Prematurity Studies
ResumoWe were intrigued that the benefits reported in the FIELD study (Nov 17, p 1687)1Keech A Mitchell P Summanen P et al.for the FIELD study investigatorsEffect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial.Lancet. 2007; 370: 1687-1697Summary Full Text Full Text PDF PubMed Scopus (834) Google Scholar were independent of the a-priori postulated biological mechanism. A C Keech and colleagues hypothesised that fenofibrate would reduce retinopathy progression in patients with type 2 diabetes by lowering blood lipids. However, although fenofibrate reduced first laser therapy by 30%, this effect was not mediated by improved lipid, glycaemic, or blood pressure profiles. Keech and colleagues are unsure of the underlying mechanism of action.These unexplained findings underscore our limited understanding of the pathogenesis of diabetic retinopathy. Diabetes duration, hyperglycaemia, and hypertension undoubtedly have key roles; yet intensive control of glucose and blood pressure in clinical trials has achieved only limited success in preventing retinopathy. Further, retinopathy lesions can develop in the absence of diabetes, hypertension, and dyslipidaemia,2Klein R Klein BE Moss SE Wang Q Hypertension and retinopathy, arteriolar narrowing, and arteriovenous nicking in a population.Arch Ophthalmol. 1994; 112: 92-98Crossref PubMed Scopus (169) Google Scholar where their presence is not benign and can confer increased cardiovascular risk.3Wong TY Klein R Couper DJ et al.Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study.Lancet. 2001; 358: 1134-1140Summary Full Text Full Text PDF PubMed Scopus (679) Google Scholar These observations highlight that other processes must be involved in the pathogenesis of retinopathy.The FIELD findings are clearly important therapeutically, but the trial's lasting contribution might be to provoke further research into underlying mechanisms of action of fenofibrate (eg, improving endothelial function, reducing local inflammatory processes), which could lead to new treatments.Keech and colleagues state that “statins have proven unsuccessful in preventing diabetic retinopathy”, which seems premature, since the statement seems to be based on a single case-control study. The two randomised trials that examined this issue found statins beneficial and attributed this to improved lipid profiles;4Sen K Misra A Kumar A Pandey RM Simvastatin retards progression of retinopathy in diabetic patients with hypercholesterolemia.Diabetes Res Clin Pract. 2002; 56: 1-11Summary Full Text Full Text PDF PubMed Google Scholar, 5Gupta A Gupta V Thapar S Bhansali A Lipid-lowering drug atorvastatin as an adjunct in the management of diabetic macular edema.Am J Ophthalmol. 2004; 137: 675-682Summary Full Text Full Text PDF PubMed Scopus (163) Google Scholar another, ACCORD-EYE, is in progress. ACCORD-EYE compares simvastatin and fenofibrate, and will help clarify the roles of lipid lowering (and fenofibrate) in retinopathy.MG is principal investigator of two clinical trials examining whether intravitreal triamcinolone improves diabetic macular oedema. Both trials are funded by the Australian National Health and Medical Research Council. JJW and GL declare that they have no conflict of interest. We were intrigued that the benefits reported in the FIELD study (Nov 17, p 1687)1Keech A Mitchell P Summanen P et al.for the FIELD study investigatorsEffect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial.Lancet. 2007; 370: 1687-1697Summary Full Text Full Text PDF PubMed Scopus (834) Google Scholar were independent of the a-priori postulated biological mechanism. A C Keech and colleagues hypothesised that fenofibrate would reduce retinopathy progression in patients with type 2 diabetes by lowering blood lipids. However, although fenofibrate reduced first laser therapy by 30%, this effect was not mediated by improved lipid, glycaemic, or blood pressure profiles. Keech and colleagues are unsure of the underlying mechanism of action. These unexplained findings underscore our limited understanding of the pathogenesis of diabetic retinopathy. Diabetes duration, hyperglycaemia, and hypertension undoubtedly have key roles; yet intensive control of glucose and blood pressure in clinical trials has achieved only limited success in preventing retinopathy. Further, retinopathy lesions can develop in the absence of diabetes, hypertension, and dyslipidaemia,2Klein R Klein BE Moss SE Wang Q Hypertension and retinopathy, arteriolar narrowing, and arteriovenous nicking in a population.Arch Ophthalmol. 1994; 112: 92-98Crossref PubMed Scopus (169) Google Scholar where their presence is not benign and can confer increased cardiovascular risk.3Wong TY Klein R Couper DJ et al.Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study.Lancet. 2001; 358: 1134-1140Summary Full Text Full Text PDF PubMed Scopus (679) Google Scholar These observations highlight that other processes must be involved in the pathogenesis of retinopathy. The FIELD findings are clearly important therapeutically, but the trial's lasting contribution might be to provoke further research into underlying mechanisms of action of fenofibrate (eg, improving endothelial function, reducing local inflammatory processes), which could lead to new treatments. Keech and colleagues state that “statins have proven unsuccessful in preventing diabetic retinopathy”, which seems premature, since the statement seems to be based on a single case-control study. The two randomised trials that examined this issue found statins beneficial and attributed this to improved lipid profiles;4Sen K Misra A Kumar A Pandey RM Simvastatin retards progression of retinopathy in diabetic patients with hypercholesterolemia.Diabetes Res Clin Pract. 2002; 56: 1-11Summary Full Text Full Text PDF PubMed Google Scholar, 5Gupta A Gupta V Thapar S Bhansali A Lipid-lowering drug atorvastatin as an adjunct in the management of diabetic macular edema.Am J Ophthalmol. 2004; 137: 675-682Summary Full Text Full Text PDF PubMed Scopus (163) Google Scholar another, ACCORD-EYE, is in progress. ACCORD-EYE compares simvastatin and fenofibrate, and will help clarify the roles of lipid lowering (and fenofibrate) in retinopathy. MG is principal investigator of two clinical trials examining whether intravitreal triamcinolone improves diabetic macular oedema. Both trials are funded by the Australian National Health and Medical Research Council. JJW and GL declare that they have no conflict of interest. Fenofibrate and diabetic retinopathy – Authors' replyWe accept Gerald Liew and colleagues' suggestion that statins might yet also prove to have a role in retinopathy prevention, although the studies they reference are preliminary and need confirmation. In the randomised controlled CARDS trial, atorvastatin did not significantly reduce the rate of laser requirement for retinopathy compared with placebo (hazard ratio 0·87, 95% CI 0·65–1·17, p=0·36).1 The ACCORD-EYE study will mainly provide evidence on the role of fenofibrate added to a statin, not on the statin itself. Full-Text PDF
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