*4.6.1 Corticosteroids*

Corticosteroids inhibit leukostasis, adhesion, transmigration of leukocytes and downregulate the expression of prostaglandins, cytokines, and growth factors, especially VEGF [179]. They also alter the composition of the basal endothelial membrane by changing the local ratio of laminin isoforms, suppressing basement membrane dissolution, and strengthening tight junctions to limit permeability and leakage [180]. Long-term steroid use may have a neuroprotective effect on the retina [181].

Corticosteroids are now usually second-line therapy. Some of the indications for intravitreal steroids in DME include non-response to anti-VEGF, non-compliant patients, pregnancy, history of recent arterial thromboembolic events (ATEs), patients with hard exudates (HE) at the center of the fovea, pseudophakic patients (there is no risk of cataract) and vitrectomized eyes [182]. In vitrectomized eyes, corticosteroid intravitreal implants release drugs at a constant rate and provide predictable pharmacokinetics [183, 184].

In clinical trials that studied the use of intravitreal steroids in treating DME, pseudophakic eyes were shown to have better visual acuity (VA) outcomes than phakic eyes [185, 186]. The DRCRnet, protocol U concluded that pseudophakic patients with persistent DME showed better VA outcomes with combination treatment of Ranibizumab and Dexamethasone intravitreal (DEX) implant compared with Ranibizumab alone [187].
