A Small Trial Tests Botox Plus Collagen for Crow's-Feet

The question behind the study

Crow's-feet, the fine lines that fan out from the corner of the eye, come from two sources. Some are dynamic: they appear when the muscles around the eye contract during a smile or squint. Others are static: they stay etched in the skin even at rest, a matter of texture and volume rather than movement.

Botulinum toxin type A — the active ingredient in Botox and its relatives — relaxes the muscle, which softens the dynamic component. It does less for the static lines. That gap is the reason patients often ask whether combining a neurotoxin with a filler, in a single visit, produces a better result than the toxin alone.

A randomized controlled trial published in August 2025 in Aesthetic Plastic Surgery set out to answer that question directly.

What the researchers did

The trial was run at a single hospital affiliated with Dalian University of Technology in China. Between November 2021 and August 2022, the investigators enrolled 40 people with periorbital wrinkles and divided them at random into two groups of 20.

One group received botulinum toxin alone. The other received the same toxin plus a non-cross-linked bovine collagen filler. Standardized photographs were taken at the start and again at one week, one month, three months, and six months. Two scales did the grading: a five-grade Wrinkle Severity Rating Scale for the lines themselves, and the Global Aesthetic Improvement Scale for how satisfied each patient felt.

What the numbers showed

Both groups improved. On the broadest measure — the total effective rate — each group reached 100 percent, meaning everyone saw some benefit.

The difference appeared in the degree of improvement. The share of patients rated "markedly effective" was 90 percent in the combination group and 40 percent in the toxin-only group. Satisfaction followed the same pattern: 95 percent of the combination group reported high satisfaction, compared with 20 percent of those who received toxin alone. Both gaps were statistically significant.

Read plainly, adding the collagen filler roughly doubled the rate of clearly visible improvement and sharply raised how pleased people were with the outcome.

Why the result is easy to over-read

The headline is tidy, but the study is small and specific, and that matters.

Forty people is a modest sample. A single center in one country limits how widely the findings apply. Follow-up ran six months — long enough to see a season change, not long enough to describe how the combination behaves over a year or more, or how often it needs repeating.

The filler is also worth noting. This trial used a non-cross-linked bovine collagen product. Most medspas in the United States work with hyaluronic-acid fillers, which have different handling, longevity, and safety profiles. A result obtained with one material does not automatically transfer to another. The mechanism — adding volume and support to lines the toxin cannot reach — is plausible across products, but plausibility is not proof.

There is also the matter of blinding. When patients know they received two treatments rather than one, satisfaction scores can drift upward on expectation alone. The photographic grading offers a firmer anchor, and the wrinkle-severity gap is the more objective of the two findings.

What it means for someone weighing the choice

For a patient deciding whether to combine treatments, the trial offers a reasonable, early signal rather than a settled answer. It suggests that for crow's-feet with a static, textural component — the lines that linger when the face is at rest — a filler added to neurotoxin may do more than the toxin by itself.

That is a narrower claim than it first sounds. It does not establish which filler, how much, how often, or for whom the added cost and the added procedure are worthwhile. Combining injectables also carries the ordinary considerations of any filler: bruising, swelling, and, rarely, vascular complications that require prompt attention. None of those risks disappear because a study reported good satisfaction scores.

The honest summary is that this is one small, short randomized trial pointing in a direction that fits what clinicians already understand about how these two treatments work. Larger studies, longer follow-up, and trials using the fillers common in everyday practice would be needed before the finding could be called robust.

The wider context

Injectable safety remains an active area of research alongside efficacy. Recent work has continued to refine best practices for hyaluronic-acid filler safety, and separate presentations have explored using ultrasound to detect and treat the rare vascular blockages that fillers can cause. Those threads are a reminder that the questions around combination treatments are not only about whether they look better, but about how to deliver them safely. For now, the crow's-feet trial adds a single, carefully measured data point to a conversation that is still unfolding.