Diabetic macular edema: new concepts in patho-physiology and treatment

Xinyuan Zhang, Huan Zeng, Shian Bao, Ningli Wang, Mark C Gillies, Xinyuan Zhang, Huan Zeng, Shian Bao, Ningli Wang, Mark C Gillies

Abstract

Diabetic macular edema (DME), a serious eye complication caused primarily by hyperglycemia, is one of the major causes of blindness. DME, which is characterized by cystic retinal thickening or lipid deposition, is prone to relapse after successful treatment. DME is a complex pathological process caused by multiple factors, including breakdown of the inner and outer blood-retinal barriers, oxidative stress, and elevated levels of vascular endothelial growth factor which have been demonstrated in both preclinical and clinical studies. Starling's law theory explains many of the features of DME. Early detection and treatment of DME can prevent vision loss. Current effective interventions for DME include treatment of systemic risk factors, such as elevated blood glucose, blood pressure and dyslipidemia. Ophthalmic treatments include laser photocoagulation, surgery and intraocular pharmacotherapy. New drugs, which are given by intraocular injection, have emerged in recent years to become first line treatment for DME that affects the central macula with loss of vision. Laser photocoagulation is still the gold standard of treatment for DME which does not involve the central macular. This review outlines these new treatments with particular emphasis on the optimal timing of how they are given.

Keywords: Apoptosis; Diabetic retinopathy; Microvasculopathy; Neuronal degenerative diseases; Therapeutic strategy.

Figures

Figure 1
Figure 1
The inner blood retinal barrier and tight junction proteins. Three integral proteins form tight junction complexes: occludin, claudins and junctional adhesion molecules (JAMs) & endothelial cell-selective adhesion molecule (ESAM). Tricellulin is a recently discovered tightjunction protein that contributes to the structure and function of tricellular contacts of neighboring cells in many epithelial tissues Occludin and claudins are trans-membrane proteins, predicted to have four trans-membrane and two extra-cellular domains, which are the major structural components of tight junction strands. There are also a group of proteins named membrane-associated guanylate kinase homologs that are positioned on the cytoplasmic surface of junctional contacts. Zonula occludens (ZO) belongs to the MAGUKs family and is thought to interact with occlude.
Figure 2
Figure 2
Retinal neurovascular unit. The retinal neurovascular unit contains the retinal blood retinal barrier, pericyte, glial cells (astrocytes and Muller cells), neurons.
Figure 3
Figure 3
Hyperglycemia and its metabolic pathways. Four distinct glucose metabolic pathways are activated by hyperglycemia: Diacylglycerol (DAG)–protein kinase C (PKC), advanced glycation endproducts/ receptor for advanced glycation end-products, Polyol (sorbitol) and Hexosamine pathways. Activation of the metabolic pathways leads microvascular dysfunction, neuronal apoptosis, glial reactivity and component deposition.
Figure 4
Figure 4
Treatment strategies for diabetic macular edema. Strict blood glucose, lipid and blood pressure control is critical for prevention and treatment of DME. According to the recommendations of the American Diabetes Association, HbA1C should be controlled at 6.5-7% and blood pressure should be below 130/85 mmHg, with total lipids lower than 100 mg/dL. Local treatments for eyes with DME include laser photocoagulation, vitrectomy surgery, and intravitreal injection of drugs (glucocorticoid hormone, anti-VEGF agents and PKC inhibitors).

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Source: PubMed

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