Pharmacotherapy for diabetic retinopathy.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Comer
Grant M
GM
Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Ciulla
Thomas A
TA
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D002986:Clinical Trials as Topic; D003930:Diabetic Retinopathy / Q000188:drug therapy*; D005109:Extracellular Matrix / Q000187:drug effects; D006131:Growth Inhibitors / Q000627:therapeutic use; D006801:Humans
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D006131:Growth Inhibitors