Grant M Comer1, Thomas A Ciulla. 1. Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Abstract
PURPOSE OF REVIEW: Diabetic retinopathy (DR) is a potentially visually devastating complication of chronic hyperglycemia and other associated systemic abnormalities. Numerous large, prospective, randomized clinical trials have delineated the current standard prevention and treatment protocols including intensive glycemic and blood pressure control and laser photocoagulation for neovascularization and clinically significant macular edema. However, despite standard intervention, vision loss from DR still occurs at an alarming rate. Thus, more recently, researchers have directed their efforts towards better understanding the microscopic changes occurring in DR to develop more effective pharmacologic prevention and treatment strategies. RECENT FINDINGS: Phase II and III clinical studies involving antivascular endothelial growth factor (VEGF) and protein kinase C (PKC) inhibitors for the management of diabetic macular edema are underway. Researchers recently found elevated pigment endothelium-derived factor (PEDF) associated with active neovascularization, a finding that counteracts prior claims of endogenous anti-angiogenic properties. Other clinical trials are underway to evaluate the efficacy of octreotide, celecoxib, and candesartan on DR. Small clinical studies have suggested beneficial treatment effects for triamcinolone acetonide, interferon alpha-2a, and supplemental oxygen; however, other studies involving losartan, vitamins C and E, and atorvastatin failed to show any benefit. SUMMARY: Over the past decade, numerous animal models have led to a more thorough understanding of the early microvascular alterations and later neovascularization and edema observed in DR. These discoveries and subsequent human clinical studies involving direct and indirect growth factor modulation, extracellular matrix alteration, vitreolysis, and alternative DR pathways including dyslipidemia, hypoxia, and sorbitol are reviewed in this manuscript.
PURPOSE OF REVIEW: Diabetic retinopathy (DR) is a potentially visually devastating complication of chronic hyperglycemia and other associated systemic abnormalities. Numerous large, prospective, randomized clinical trials have delineated the current standard prevention and treatment protocols including intensive glycemic and blood pressure control and laser photocoagulation for neovascularization and clinically significant macular edema. However, despite standard intervention, vision loss from DR still occurs at an alarming rate. Thus, more recently, researchers have directed their efforts towards better understanding the microscopic changes occurring in DR to develop more effective pharmacologic prevention and treatment strategies. RECENT FINDINGS: Phase II and III clinical studies involving antivascular endothelial growth factor (VEGF) and protein kinase C (PKC) inhibitors for the management of diabetic macular edema are underway. Researchers recently found elevated pigment endothelium-derived factor (PEDF) associated with active neovascularization, a finding that counteracts prior claims of endogenous anti-angiogenic properties. Other clinical trials are underway to evaluate the efficacy of octreotide, celecoxib, and candesartan on DR. Small clinical studies have suggested beneficial treatment effects for triamcinolone acetonide, interferon alpha-2a, and supplemental oxygen; however, other studies involving losartan, vitamins C and E, and atorvastatin failed to show any benefit. SUMMARY: Over the past decade, numerous animal models have led to a more thorough understanding of the early microvascular alterations and later neovascularization and edema observed in DR. These discoveries and subsequent human clinical studies involving direct and indirect growth factor modulation, extracellular matrix alteration, vitreolysis, and alternative DR pathways including dyslipidemia, hypoxia, and sorbitol are reviewed in this manuscript.
Authors: Shubha Varma; Brajesh K Lal; Ruifang Zheng; Jerome W Breslin; Satoshi Saito; Peter J Pappas; Robert W Hobson; Walter N Durán Journal: Am J Physiol Heart Circ Physiol Date: 2005-06-17 Impact factor: 4.733
Authors: Roberto Bassi; Alessio Trevisani; Sara Tezza; Moufida Ben Nasr; Francesca Gatti; Andrea Vergani; Antonio Farina; Paolo Fiorina Journal: Exp Diabetes Res Date: 2012-03-29