LAUSR

PURPOSE To compare intravitreal nesvacumab (anti-angiopoietin 2) plus aflibercept with intravitreal aflibercept injection (IAI) in diabetic macular edema (DME). METHODS Eyes (n=302) were randomized (1:2:3) to nesvacumab 3 mg+aflibercept 2 mg (LD combo), nesvacumab 6 mg+aflibercept 2 mg (HD combo), or IAI 2 mg at baseline, weeks 4 and 8. LD combo continued every 8 weeks (q8w). HD combo was re-randomized at week 12 to q8w or every 12 weeks (q12w); IAI to q8w, q12w or HD combo q8w through week 32. RESULTS Week 12 BCVA gains for LD and HD combos vs. IAI were 6.8, 8.5, and 8.8 letters; week 36 changes were similar. CST reductions at week 12 were -169.4, -184.0, and -174.6 µm (nominal P=0.0183, HD combo vs. IAI); week 36 reductions for LD combo and HD combo q8w and q12w versus IAI were -210.4, -223.4 and -193.7 versus -61.9 µm (nominal P<0.05). At week 12, 13.3% and 21.3% vs. 15.2% had ≥2-step DRSS improvement (LD and HD combos vs. IAI) and 59.6% and 66.3% vs. 53.7% had complete foveal center fluid resolution. Safety was comparable across groups. CONCLUSION Nesvacumab+aflibercept demonstrated no additional visual benefit over IAI. Anatomic improvements with HD combo may warrant further investigation.