**2. Early preclinical changes of diabetic retinopathy**

Chronic hyperglycemia affects both the microvascular and neural components of the retina by increasing the oxidative stress, inflammation and hypoxia (**Figure 1**) [5]. As a type of metabolic autoregulation, the earliest changes that occur in the retinal microvasculature secondary to hyperglycemia are retinal blood vessel dilatation and blood flow changes. Pericyte apoptosis secondary to hyperglycemia is also an early event in this pathology, and because pericytes provide structural support to the retinal capillary walls, outpouching of the capillary walls occurs forming microaneurysms, the earliest clinical sign that can be overlooked in very early stages [6, 7]. Glial cell activation and

**Figure 1.**

*Early preclinical changes of diabetic retinopathy.*

neural apoptosis lead to ganglion cell death, with consequent thinning of the ganglion cell layer preclinical to the signs of diabetic retinopathy seen on fundus examination [8]. Using optical coherence tomography angiography (OCT angiography) (OCTA), the foveal avascular zone (FAZ) in both the superficial and deep capillary plexuses (SCP and DCP) was found to be larger and irregular due to perifoveal capillary loss with more tortuosity, beading and focally dilated endings of capillaries. These findings were found to be more pronounced when diabetes was associated with hypertension [8].
