Diabetic macular edema (DME) remains a common cause of vision loss in patients with diabetic retinopathy. Although anti-vascular endothelial growth factor (VEGF) therapeutics have made a major impact on improving visual outcomes with DME, one-quarter or more of eyes with center-involving DME do not achieve complete resolution of the edema with anti-VEGF therapy and, even if there is good edema reduction, frequent, ongoing intravitreal injections are often necessary to control the process and obtain an optimal visual outcome over the long run. Intraocular corticosteroids can be an effective alternative in eyes with inadequate anti-VEGF response or frequent anti-VEGF need, but side effects of intraocular pressure elevation and cataract progression can add to the management burden of the condition. To address current DME unmet needs of better, more complete macular drying or greater treatment durability, there is ongoing research in targeting DME pathophysiologic pathways other than VEGF.

The following 3 articles detail some of the research progress in developing therapeutics that may help to address these unmet needs in DME. Although anti-VEGF therapy is likely to remain as first-line or foundation therapy in DME, therapeutics that target non-VEGF pathways like integrin, Rho/Rho kinase (ROCK), and plasma kallikrein may prove to be helpful add-on treatments. RP