Abstract
Diabetic retinal complications, including macular edema (DME) and proliferative diabetic retinopathy (PDR), are the leading cause of new cases of blindness among adults aged 20–74. Chronic hyperglycemia, considered the underlying cause of diabetic retinopathy, is thought to act first through violation of the pericyte-endothelial coupling. Disruption of microvascular integrity leads to pathologic consequences including hypoxia-induced imbalance in vascular endothelial growth factor (VEGF) signaling. Several anti-VEGF medications are in clinical trials for use in arresting retinal angiogenesis arising from DME and PDR. Although a review of current clinical trials shows promising results, the lack of large prospective studies, head-to-head therapeutic comparisons, and potential long-term and systemic adverse events give cause for optimistic caution. Alternative therapies including targeting pathogenic specific angiogenesis and mural-cell-based therapeutics may offer innovative solutions for currently intractable clinical problems. This paper describes the mechanisms behind diabetic retinal complications, current research supporting anti-VEGF medications, and future therapeutic directions.
Highlights
Angiogenesis plays a critical role in the development of diabetic complications, those complications that involve the eye
This paper examines the mechanism behind diabetic retinopathy and analyzes the potential effectiveness and limitations of anti-vascular endothelial growth factor (VEGF) medications for the treatment of diabetic complications
Current clinical trial information can be found at http://www.clinicaltrials.gov/ N: Number of eyes; DME: diabetic macular edema; VA: visual Acuity; CRT: central retinal thickness; best-corrected visual acuity (BCVA): best corrected visual acuity
Summary
Angiogenesis plays a critical role in the development of diabetic complications, those complications that involve the eye. Two landmark studies in the 1990s, the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS), showed that intensive control of hyperglycemia can reduce the occurrence or progression of retinopathy, nephropathy, and neuropathy in both type one and type two diabetics [2, 3]. These findings strongly suggest that hyperglycemia is at the root of diabetic complications. Strict control of hyperglycemia to the levels outlined in these studies is extremely difficult, and diabetic complications continue to be a significant and sometimes life-ending reality in this population
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