Efficacy and safety of two hyaluronic acid fillers with different injection depths for the correction of moderate-to-severe nasolabial folds: A 52-week, prospective, randomized, double-blinded study in a Chinese population

J Cosmet Dermatol. 2022 Mar;21(3):940-948. doi: 10.1111/jocd.14744. Epub 2022 Jan 12.


Background: Hyaluronic acid (HA) fillers are known to be effective for the correction of facial wrinkles and folds, but there is no clinical study that compares the efficacy of small-to-medium-particle HA fillers and large-particle HA fillers for the correction of nasolabial folds (NLFs). Moreover, injection depth also plays an important role in the correction of NLFs as well as improvement of facial aesthetics.

Objectives: To assess the efficacy, safety, and durability of a small-to-medium-particle HA filler, Restylane, and a large-particle HA filler, Yishumei, as well as the effect of injection depth in the correction of moderate-to-severe NLFs and facial aesthetics in a Chinese population.

Methods: This 52-week, prospective, randomized, double-blind study enrolled 100 participants with moderate-to-severe NLFs. The participants were randomized to receive either Restylane (Group A) or Yishumei (Group B). Group A and Group B were further randomly divided into a superficial injection group (Group A1 & B1) and a deep injection group (Group A2&B2) according to injection depth. Improvement in the Wrinkle Severity Rating Scale (WSRS) score and Global Aesthetic Improvement Scale (GAIS) and participants' satisfaction were evaluated as endpoints. All adverse events were monitored throughout the study.

Results: The treatments were well tolerated by all the participants. All four groups showed a reduction in their mean WSRS scores and GAIS scores by week 12. At week 24, the WSRS and GAIS scores did not change in Group A1 and A2, while participants in Group B1 and Group B2 had higher WSRS and GAIS scores than those in the previous weeks. By week 52, the WSRS scores in all the groups returned to almost baseline levels. The mean FACE-Q scores increased compared with the baseline scores in all groups through week 24. Most participants were satisfied with their treatment, and no meaningful differences were found between the fillers in terms of participant satisfaction. The most common adverse events were swelling, redness, and tenderness at the injection site, but they resolved spontaneously without treatment.

Conclusion: The two HA fillers had good therapeutic effect on NLFs in the early stage of treatment, but Restylane had a more prolonged effect. Moreover, compared with the superficial injection, the deep injection provided slight midface lifting and improved facial aesthetics.

Keywords: Restylane; WSRS score; Yishumei; hyaluronic acid; nasolabial folds.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • China
  • Cosmetic Techniques* / adverse effects
  • Dermal Fillers* / adverse effects
  • Double-Blind Method
  • Humans
  • Hyaluronic Acid / adverse effects
  • Nasolabial Fold
  • Prospective Studies
  • Skin Aging*
  • Treatment Outcome


  • Dermal Fillers
  • Hyaluronic Acid