Evolution in understanding of DME suggests new targets, treatment paradigms

While there are extensive data supporting the concept that antiVEGF agents may have a role in the treatment of diabetic macular edema (DME), emerging knowledge about DME pathogenesis is suggesting alternate therapeutic targets and new paradigms for multidrug treatment, said Lloyd P. Aiello, MD, PhD, director, Beetham Eye Institute, Joslin Diabetes Center, Boston.

"So far, antiVEGF agents have demonstrated activity in eyes with DME for reducing retinal thickness and improving visual acuity, but the responses have been variable and the benefits time-limited," Dr. Aiello said. "The incomplete inhibition of DME with the antiVEGF agents may reflect the fact that DME pathogenesis is a complex process."

Newly discovered pathways that appear to induce angiogenesis and vascular permeability independent of VEGF involve erythropoietin and carbonic anhydrase 1 and 2 among other mediators. In addition, research indicates that different pathways may be simultaneously involved, which would suggest the effectiveness of a particular therapy may reflect the extent to which the treatment-affected pathway is contributing to DME in a particular patient.

"We may need to consider that there are relative contributions of different pathways and also that these may vary between individuals and even over time within the same person," Dr. Aiello concluded. "Consequently, the efficacy of a single therapy may vary depending on what is happening in a particular patient at a particular time. Perhaps treatment paradigms should involve multidrug therapies instituted serially as we do with treatment of glaucoma."