Diabetic retinopathy (DR) is one of the leading causes of
blindness in the working population worldwide. Vascular leakage, angiogenesis and neuronal degeneration are key features of DR. Current effective interventions for DR include treatment of systemic risk factors such as elevated
blood glucose, blood pressure and
dyslipidemia. Ocular treatments include
vascular endothelial growth factor A (
VEGF-A) inhibitors,
laser photocoagulation and surgery. While anti-
VEGF therapy has become as first-line treatment for diabetic
macular edema (DME) that causes
reduced vision, intravitreal
glucocorticoids also have been shown to be efficacious in this situation. It has been reported that all the major
pathological processes of DR are susceptible to
glucocorticoid treatment. The effects of
glucocorticoids on vascular leakage and angiogenesis may be mediated through their well established anti-inflammatory role. Alternatively,
glucocorticoids may affect other mechanisms known to be activated in DR. Potential mechanisms for the anti-inflammatory effects of
glucocorticoids include blockage of
cytokine production and inhibition of leukocyte adhesion induced by
VEGF-A.
Glucocorticoids decrease the expression of
VEGF-A directly, and increase the production, or decrease phosphorylation, of tight junction-associated
proteins.
Glucocorticoids have also been shown to be neuroprotective, in contrast to
VEGF-A inhibitors which animal studies suggest may be neurotoxic. This review outlines the
biological properties of synthetic
glucocorticoids, with particular emphasis on the potential beneficial effect of combining
glucocorticoids with anti-
VEGF treatment for DME and DR.