Diabetic Macular Edema Pathophysiology: Vasogenic versus Inflammatory

Abstract

Diabetic macular edema (DME) can cause blindness in diabetic patients suffering from diabetic retinopathy (DR). DM parameters controls (glycemia, arterial tension, and lipids) are the gold standard for preventing DR and DME. Although the vascular endothelial growth factor (VEGF) is known to play a role in the development of DME, the pathological processes leading to the onset of this disease are highly complex and the exact sequence in which they occur is still not completely understood. Angiogenesis and inflammation have been shown to be involved in the pathogenesis of this disease. However, it still remains to be clarified whether angiogenesis following VEGF overexpression is a cause or a consequence of inflammation. This paper provides a review of the data currently available, focusing on VEGF, angiogenesis, and inflammation. Our analysis suggests that angiogenesis and inflammation act interdependently during the development of DME. Knowledge of DME etiology seems to be important in treatments with anti-VEGF or anti-inflammatory drugs. Current diagnostic techniques do not permit us to differentiate between both etiologies. In the future, diagnosing the physiopathology of each patient with DME will help us to select the most effective drug.

Figure 1

Optical coherence tomography of the macular area, description of different layers: RPE/Bruch's complex: retinal pigment epithelium and Bruch's layer; ELM: external limiting membrane; ellipsoid zone: inner segments/outer segments of photoreceptors (ellipsoid layer); ONL: outer nuclear layer (photoreceptors); OPL: outer plexiform layer; INL: inner nuclear layer (bipolar cell); IPL: inner plexiform layer; GCL: ganglion cell layer; NFL: nerve fiber layer.

Figure 2

The different pathways in the development of diabetic macular edema.

Figure 3

Evolution of a patient with diabetic macular edema, from 2012 to 2015. The patient did not respond to anti-VEGF but to steroids. Perhaps, the hyperreflective retinal spots, seen in the first tomography in the outer plexiform layer temporal to the fovea, can be a predictive sign of a positive response to steroids.

Figure 4

Absence of ellipsoid (ellipsoid zone) layer and external limiting membrane (ELM).

Figure 5

Cystoid diabetic macular edema with hyperreflective retinal spots.

Figure 6

Normal fluorescein angiography showing the avascular foveal area and the perifoveal capillary network.

Figure 7

Fluorescein angiography of a patient with proliferative diabetic retinopathy. New vessels are visible in the optic disc and temporal (superior and inferior) arcades, and macular cysts and microaneurysms can be observed.

Figure 8

Fluorescein angiography of a patient with severe diabetic retinopathy and macular ischemia. We observe the rupture of avascular zone by ischemia and also hyperfluorescence area in macula at temporal side.

Figure 9

OCT angiography of a patient. (a) Superficial plexus, (b) inner plexus, and (c) optical coherence tomography.