Opthea Limited commenced a Phase 1b/2a trial evaluating the safety and efficacy of OPT-302 in patients with center-involved diabetic macular edema (DME). Following submission of the study protocol to the Food and Drug Administration (FDA), and ethics approval by the central Institutional Review Board, clinical trial sites have been activated and are recruiting patients in the US. This marks the expansion of the clinical development program for OPT-302 into a second ocular indication and targets a severe complication of diabetes. Characterized by retinal thickening from leaky blood vessels, DME is the leading cause of blindness in diabetics and is estimated to affect over 2 million people globally. Existing standard of care treatments for DME are limited and include inhibitors of VEGF-A, steroids and laser therapy. Despite these treatments, many patients remain refractory and have a sub-optimal response to therapy with persistent fluid and impaired vision. OPT-302 blocks VEGF-C and VEGF-D, which cause vessels to grow and leak. Used in combination with a VEGF-A inhibitor, OPT-302 has the potential to improve clinical outcomes in DME patients. This multi-centre clinical trial to be conducted in the US and Australia is a two-part design consisting of a Phase 1b dose escalation of OPT-302 (0.3, 1 and 2 mg) used in combination with the VEGF-A inhibitor Eylea (aflibercept, 2 mg), followed by a Phase 2a randomised, controlled dose expansion with treatment allocated in a 2:1 ratio to either OPT-302 with Eylea, or Eylea monotherapy. The trial will enrol 117 patients with persistent central involved diabetic macular edema despite prior anti-VEGF-A therapy with each patient dosed on a monthly basis for 3 months via intravitreal (ocular) injection. The primary objectives are to evaluate the safety/tolerability and efficacy of OPT-302 by determination of the clinical response rate as defined by the proportion of patients receiving combination OPT-302 and Eylea achieving a 5 letter gain in visual acuity (VA) compared to baseline at week 12. In addition, a number of secondary measures will be investigated, including changes in mean VA, diabetic retinopathy severity score, and anatomical parameters such as central subfield thickness (CST) and macular volume from baseline to week 12.