Published in the Journal of Cosmetic Dermatology on August 1, 2025, this randomized, double-blind, split-face RCT took 25 women (mean age 48.8) and gave everyone bilateral onabotulinumtoxinA, 36U total, for crow's feet. One month later, one randomized side got VYC-12 (Skinvive) 0.5 mL and the other a sham injection. Follow-up ran 6 months with EMG, the Merz wrinkle scale, and FACE-Q.

The control that matters: EMG muscle-activity reduction was equal on both sides (p=.86). The HA booster added nothing to the paralysis, which is exactly what you want to confirm before crediting it for anything. What it did add showed up in the skin. Crow's feet at rest favored the BTX-plus-HA side at 3 months (p=.04), and at contraction the combination side was superior at both 3 months (p=.007) and 6 months (p=.001). FACE-Q satisfaction was higher for the combination side at 3 and 6 months (p=.001), with no adverse events in either arm.

The takeaway is about sequencing, not stacking for its own sake. An HA skin-quality booster layered on a neuromodulator will not deepen muscle relaxation, but it measurably improves the static and contracted periorbital lines that toxin alone cannot erase, and it holds patient satisfaction out to 6 months. Practical order of operations: treat with toxin first, then layer the HA microdroplet booster about 4 weeks later to address residual etched lines and overall skin quality.

Source: Journal of Cosmetic Dermatology — https://pmc.ncbi.nlm.nih.gov/articles/PMC12355333/