Tissue Fillers for the Nasolabial Fold Area: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Aesthetic Plast Surg. 2021 Oct;45(5):2300-2316. doi: 10.1007/s00266-021-02439-5. Epub 2021 Jul 13.


Tissue fillers injections remain to be one of the most commonly performed cosmetic procedures. The aim of this meta-analysis was to systematize and present available data on the aesthetic outcomes and safety of treating the nasolabial fold area with tissue fillers. We conducted a systematic review of randomized clinical trials that report outcomes concerning treatment of nasolabial fold area with tissue fillers. We searched the MEDLINE/PubMed, ScienceDirect, EMBASE, BIOSIS, SciELO, Scopus, Cochrane Controlled Register of Trials, CNKI and Web of Science databases. Primary outcomes included aesthetic improvement measured using the Wrinkle Severity Rating Scale score and Global Aesthetic Improvement Scale. Secondary outcomes were incidence rates of complications occurring after the procedure. At baseline, the pooled mean WSRS score was 3.23 (95% CI: 3.20-3.26). One month after the procedure, the pooled WSRS score had reached 1.79 (95% CI: 1.74-1.83). After six months it was 2.02 (95% CI: 1.99-2.05) and after 12 months it was 2.46 (95% CI: 2.4-2.52). One month after the procedure, the pooled GAIS score had reached 2.21 (95% CI: 2.14-2.28). After six months, it was 2.32 (95% CI: 2.26-2.37), and after 12 months, it was 1.27 (95% CI: 1.12-1.42). Overall, the pooled incidence of all complications was 0.58 (95% CI: 0.46-0.7). Most common included lumpiness (43%), tenderness (41%), swelling (34%) and bruising (29%). Tissue fillers used for nasolabial fold area treatment allow achieving a satisfying and sustainable improvement. Most common complications include tenderness, lumpiness, swelling, and bruising. LEVEL OF EVIDENCE II: "This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ."

Keywords: Dermal fillers; Hyaluronic acid; Meta-analysis; Nasolabial fold; Tissue fillers.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Cosmetic Techniques*
  • Dermal Fillers* / adverse effects
  • Humans
  • Hyaluronic Acid
  • Nasolabial Fold
  • Randomized Controlled Trials as Topic
  • Skin Aging*
  • Treatment Outcome


  • Dermal Fillers
  • Hyaluronic Acid