Sir,

We would like to address several challenges arising from the article by Ashraf et al1 regarding the alternative roles for aflibercept (Eylea, Regeneron Pharmaceuticals, Tarrytown, NY, USA) in the management of eyes with non-naive diabetic macular edema (DME).

1. We do not agree the authors’assertion that switching to aflibercept may be a valid option for patients being treated with alternate anti-vascular endothelial growth factor (VEGF) agents. The presumed pharmacologic advantages of aflibercept over bevacizumab (Avastin, Genentech, South San Francisco, CA, USA) or ranibizumab (Lucentis, Genentech) (for example, a higher binding affinity for VEGF-A and activity against VEGF-B, and placental-derived growth factor) were not confirmed by the poor results of the latest publications. Thus, Wood et al2 reported persistent macular edema in 50% of the eyes and a loss in visual acuity (1 line) in 21.4% of the eyes after aflibercept injection. Rahimy et al3 displayed incomplete resolution of the DME (significant decrease of foveal thickness to 348.7 μm, a value that was more than the cutoff for the upper level of normal foveal thickness4), increase in the number of eyes with epiretinal membranes from 18 to 20, and of those with vitreomacular traction from 2 to 4 after switching to aflibercept.

2. VEGF is one contributor to macular edema in patients with diabetic retinopathy. Besides, a panoply of proinflammatory and proangiogenic cytokines, chemokines, and growth factors may be associated with pathophysiology of DME. They are maximally expressed in the ischemic lesions of the long-standing DME and exacerbate the deterioration primarily caused by VEGF in the initially damaged macular ganglion cell complex.

3. The specific anti-VEGF drugs represent the frontline therapy for the treatment of DME, but only the VEGF inhibition may not be sufficient to decrease inflammatory response. Therefore, addition of a non-specific anti-VEGF substance, that is, a corticosteroid injection, is mandatory.

Altogether, regardless of the intravitreal pharmacotherapy chosen, namely, specific (bevacizumab/ranibizumab/aflibercept) or nonspecific (corticosteroid implant) anti-VEGF agents, the efficacy of the treatment depends primarily on the promptness of the therapy after DME onset. Both groups of anti-VEGF substances provide similar rates of vision improvement, but with superior anatomic outcomes and fewer injections in the corticosteroid implant-treated eyes. However, more patients receiving the corticosteroid implant lose vision mainly due to cataract.5