Disentangling the association between retinal non-perfusion and anti-VEGF agents in diabetic retinopathy

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM) and the leading cause of blindness in patients with DM. In the pathogenesis of DR, chronic hyperglycemia leads to biochemical and structural alterations in retinal blood vessels' wall, resulting in hyperpermeability and non-perfusion. Since vascular endothelial growth factor (VEGF) has been found to play a significant role in the pathogenesis of DR, this review sheds light on the effect of intravitreal anti-VEGF agents on retinal non-perfusion in patients with DR. Based on the existing literature, anti-VEGF agents have been shown to improve DR severity, although they cannot reverse retinal ischemia. The results of the published studies are controversial and differ based on the location of retinal non-perfusion, as well as the imaging modality used to assess retinal non-perfusion. In cases of macular non-perfusion, most of studies showed no change in both fundus fluorescein angiography (FFA) and optical coherence tomography (OCTA) in patients with DR treated with intravitreal anti-VEGF agents, while few studies reported worsening of non-perfusion with enlargement of foveal avascular zone (FAZ). Regarding peripheral ischemia, studies using wide-field-FFA demonstrated an improvement or stability in non-perfusion areas after anti-VEGF treatment. However, the use of wide-field-OCTA revealed no signs of re-perfusion of retinal vessels post anti-VEGF treatment. Further prospective studies with long follow-up and large sample size are still needed to draw solid conclusions.