Current Treatments for Diabetic Macular Edema

Abstract

Diabetic retinopathy is a major retinal disorder and a leading cause of blindness. Diabetic macular edema (DME) is an ocular complication in patients with diabetes, and it can impair vision significantly. DME is a disorder of the neurovascular system, and it causes obstructions of the retinal capillaries, damage of the blood vessels, and hyperpermeability due to the expression and action of vascular endothelial growth factor (VEGF). These changes result in hemorrhages and leakages of the serous components of blood that result in failures of the neurovascular units (NVUs). Persistent edema of the retina around the macula causes damage to the neural cells that constitute the NVUs resulting in diabetic neuropathy of the retina and a reduction in vision quality. The macular edema and NVU disorders can be monitored by optical coherence tomography (OCT). Neuronal cell death and axonal degeneration are irreversible, and their development can result in permanent visual loss. Treating the edema before these changes are detected in the OCT images is necessary for neuroprotection and maintenance of good vision. This review describes the effective treatments for the macular edema that are therefore neuroprotective.

Keywords: anti-vascular endothelial growth factor; diabetic macular edema; diabetic neuropathy; diabetic retinopathy; retinal neurovascular unit.

Figure 1

Molecular structure of anti-VEGF agents [33,34,35]. (a) Ranibizumab is the Fab fragment of a humanized monoclonal antibody against VEGF. (b) Aflibercept is a recombinant protein composed of Fc fragment of human IgG, human VEGFR-1 and VEGFR-2. (c) Bevacizumab is a recombinant humanized monoclonal IgG antibody that has two antigen-binding domains. (d) Faricimab is an anti-VEGF/anti-Ang-2 humanized bispecific monoclonal antibody. (e) Brolucizumab is a humanized anti-VEGF monoclonal antibody with a single-chain F_V fragment that inhibits all isoforms of VEGF-A binding to the VEGF receptors. V_L: light chain variable domain, V_H: heavy chain variable domain, Fab: fragment antigen binding, VEGFR: vascular endothelial growth factor receptor, IgG: immunoglobulin G, Fc: fragment crystallizable, VEGF: vascular endothelial growth factor, Ang-2: angiopoietin-2.