Introduction
Methods
Search Strategy
Eligibility Assessment
Extraction Strategy
Outcomes of Interest
Quality Assessment
Statistical Analysis
Results
Acquiring the Studies
Characteristics of the Included Studies
Author | Publication year | Study design | Location | Multicenter versus single center | Follow-up length | Age* | No patients | Filler | Presented outcomes |
---|---|---|---|---|---|---|---|---|---|
Ahn | 2012 | Double blind | South Korea | multicenter | 14 weeks | 46.68 | 40 | Mesoglow/IAL System | WSRS/GAIS/Complications |
Baumann | 2018 | Evaluator blind | USA | multicenter | 48 weeks | 53.7 | 162 | Restylane Defyne/Juvederm Ultra Plus | Complications |
Beer | 2007 | Evaluator blind | USA | single center | 6 months | 53±12 | 15 | HA/hylan B plus | WSRS/GAIS |
Brandt | 2010 | Double blind | USA | multicenter | 2 weeks | 53.4±8 | 60 | Perlane—LGP/Perlane –L—LGP with 0.3% lidocaine hydrochloride | Complications |
Buntrock | 2013 | Double blind | Germany | single center | 48 weeks | 52±5.6 | 20 | CPMHA/biphasic HA filler (NASHA) | WSRS |
Carruthers | 2005 | Double blind | Canada | multicenter | 12 months | 51,9 (34–83) | 150 | Restylane Perlane/Hylaform | Complications |
Choi | 2015 | Double blind | South Korea | multicenter | 24 weeks | 52.48 ± 8.23 | 66 | PP-501-A-Lidocaine/Restylane Lidocaine | WSRS/GAIS/Complications |
Dover | 2009 | Double blind | USA | multicenter | 24 weeks | 54.05 | 283 | NASHA | Complications |
Fagien | 2018 | Evaluator blind | USA | multicenter | 48 weeks | 53.9±8.22 | 170 | Juvederm Ultra/Restylane Refyne with lidocaine 3% | Complications |
Fino | 2019 | Double blind | Italy | single center | 6 months | 50.4±8.3 | 65 | Ial System Duo/Belotero Basic/Balance | Complications |
Galadari | 2015 | Double blind | United Arab Emirates | single center | 12 months | 46 | 40 | polycaprolactone (PCL)/NASHA | WSRS |
Gold | 2018 | Double blind | USA | multicenter | 24 weeks | 55.4±10.1 | 163 | Revanesse Versa/Restylane | Complications |
Grimes | 2009 | Double blind | USA | multicenter | 25 weeks | 50 (32–75) | 53 | Juvederm Ultra, Juvederm Ultra Plus, Juvederm 30, Hylaform, Hylaform Plus, Captique | Complications |
Heden | 2010 | Double blind | Sweden | multicenter | 12 months | 54 | 42 | NASHA | Complications |
Hong | 2018 | Patient/evaluator-blinded | South Korea | single center | 48 weeks | 48.3±7.36 | 91 | DHF-001, Restylane SubQ | WSRS/ |
Hu | 2017 | Evaluator blind | China | single center | 12 months | (30–65) | 57 | HA (Nature, Beijing Aimeike Bio-tech Co.), autologous fat injection | WSRS/GAIS/Complications |
Hyun | 2014 | Evaluator blind | South Korea | multicenter | 24 weeks | 51.9±6.9 | 58 | Restylane, Aesthefill | WSRS/Complications |
Joo | 2016 | Double blind | South Korea | multicenter | 24 weeks | 47.62±7.64 | 60 | Neuramis, Perlane-L | WSRS/GAIS |
Kim | 2016 | Evaluator blind | South Korea | multicenter | 24 months | 49.6±11.8 | 13 | HA-G-monophasic, HA-P-biphasic | GAIS/Complications |
Lee | 2014 | Double blind | South Korea | multicenter | 12 months | 42.2 | 57 | Terafill, Koken | WSRS/GAIS |
Levy | 2009 | Single blind | Switzerland | multicenter | 53 | 126 | Juvederm Ultra 3, Restylane Perlane | Complications | |
Lindqvist | 2005 | Single blind | Sweden/Norway | multicenter | 12 months | 49.4 | 68 | Perlane, Zyplast | Complications |
Lupo | 2007 | Double blind | USA | multicenter | 24 weeks | 49 | 87 | Juvederm Ultra +, Zyplast | WSRS |
Marmur | 2010 | Single blind | USA | single center | 1 month | 50 | CaHA+lidocaine, CaHA | Complications | |
Moers-Carpi | 2007 | Evaluator blind | Germany/Spain | multicenter | 12 months | 50.5 (34–67) | 60 | CaHA, NASHA | Complications |
Monheit | 2018 | Double blind | USA | multicenter | 6 months | 54 (33–83) | 123 | VYC-17.5L (HA+lidocaine) | Complications |
Monheit | 2010 | Patient/evaluator-blinded | USA | multicenter | 36 weeks | 52.7±9.3 | 140 | DGE, NASHA | Complications |
Monheit | 2010 | Single blind | USA | single center | 2 weeks | 45 (29–68) | 45 | Prevelle SILK, Captique | Complications |
Moon | 2014 | Evaluator blind | South Korea | multicenter | 6 months | 47.2 (21–66) | 57 | Porcine collagen, Bovine collagen | WSRS/Complications |
Narins | 2007 | Evaluator blind | USA | multicenter | 6 months | 56 | 149 | Dermicol-P35, NASHA | Complications |
Narins | 2010 | Evaluator blind | USA | multicenter | 24 weeks | 52.4 (25.7–75.7) | 118 | CPMHA. bovine collagen | GAIS |
Nast | 2011 | Double blind | Germany | single center | 4 weeks | 54.8±8.8 | 60 | HA-biphasic, HA-monophasic | WSRS |
Onesti | 2009 | Double blind | Italy | single center | 6 months | 50.2 | 74 | Captique, Puragen | Complications |
Pak | 2015 | Double blind | South Korea | multicenter | 6 months | 69 | Neuraminis, Restylane | WSRS/Complications | |
Park | 2011 | Evaluator blind | South Korea | single center | 4 months | 48.4±5 | 12 | Teosyal, HA (Titan) + Infrared | WSRS/GAIS/Complications |
Park | 2015 | Double blind | South Korea | multicenter | 6 months | 45.76±7.77 | 98 | PP-501-B, Restylane Perlane PER | WSRS/GAIS/Complications |
Prager | 2010 | Patient/evaluator-blinded | Germany | single center | 1 month | 45.8 | 20 | Belotero, Restylane | Complications |
Prager | 2012 | Patient/evaluator-blinded | Germany | single center | 12 months | 45.8 | 20 | Belotero, Restylane | Complications |
Rhee | 2014 | Evaluator blind | South Korea | multicenter | 6 months | 68 | Elravie, Restylane | WSRS | |
Rzany | 2011 | Evaluator blind | France/Germany | multicenter | 6 months | 50.6±10.1 | 81 | Emervel Classic, Restylane | Complications |
Rzany | 2017 | Patient/evaluator-blinded | France/Germany | multicenter | 18 months | 50.8 | 81 | Emervel Classic, Restylane | Complications |
Schachter | 2016 | Double blind | Canada | multicenter | 1 month | 48.84±9.43 | 102 | CaHA (Radiesse) + lidocaine, CaHA (Radiesse) | Complications |
Sharma | 2011 | No blinding | UK | single center | 9 months | 17 | Juvederm Ultra 3, Uma Jeunesse | Complications | |
Sharma | 2018 | Single blind | UK | single center | 9 months | 40.5±11.02 | 73 | Uma Jeunesse Classic, Uma Jeunesse Ultra | Complications |
Smith | 2007 | Evaluator blind | USA | multicenter | 6 months | 54.7 | 117 | CaHA (Radiesse), human-based collagen (Cosmoplast) | Complications |
Suh | 2017 | Double blind | South Korea | multicenter | 24 weeks | 46.02±7.21 | 60 | Dermalax implant plus, Restylane Sub-Q | Complications |
Taylor | 2010 | Patient/evaluator-blinded | USA | multicenter | 24 weeks | 150 | Restylane, Perlane | WSRS/GAIS | |
Weiss | 2010 | Double blind | USA | multicenter | 2 weeks | 52.1±6.6 | 60 | Restylane + lidocaine, Restylane | Complications |
Wu | 2016 | Double blind | China | multicenter | 15 months | 44.7 (24–61) | 88 | Restylane, BioHyalux | Complications |
Wu | 2016 | Double blind | China | multicenter | 6 months | 39 (26–58) | 109 | Restylane, Juvederm Ultra | Complications |
Zhou | 2016 | Double blind | China | single center | 24 weeks | 47.85 | 50 | Matrifill, Restylane | WSRS |
Improvement of the Nasolabial Fold Area—A Meta-Analysis of Reported WSRS Scores
Overall | HA combined | Monophasic HA | Biphasic HA | Collagen | PLA | PCL | Mesoglow | IAL-systems | Autologous fat | |
---|---|---|---|---|---|---|---|---|---|---|
Baseline | 3.23 [3.20–3.26] | 3.26 [3.21–3.3] | 3.23 [3.16–3.30] | 3.27 [3.22–3.32] | 2.91 [2.84–2.99] | 3.47 [3.28–3.66] | 3.2 [3.07–3.33] | 3.2 [3.07–3.33] | 3.5 [3.31–3.69] | |
I2 | 93% | 95% | 94% | 95% | 0% | NA | NA | NA | NA | |
No of studies | 15 | 10 | 6 | 8 | 3 | 1 | 0 | 1 | 1 | 1 |
1st week | 2.91 [2.82–2.99] | 2.91 [2.82–2.99] | 2.85 [2.73–2.98] | 2.96 [2.84–3.08] | ||||||
I2 | 99% | 99% | 100% | 100% | ||||||
No of studies | 2 | 2 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
2 weeks | 1.78 [1.72–1.85] | 1.91 [1.83–2] | 1.83 [1.7–1.95] | 1.98 [1.87–2.09] | 1.55 [1.43–1.66] | |||||
I2 | 89% | 88% | 94% | 76% | NA | |||||
No of studies | 5 | 4 | 3 | 3 | 1 | 0 | 0 | 0 | 0 | 0 |
1 month | 1.79 [1.74–1.83] | 2.04 [1.98–2.1] | 2.46 [2.31–2.6] | 1.95 [1.88–2.02] | 1.65 [1.52–1.77] | 3.55 [3.4–3.71] | 0.72 [0.6–0.85] | 0.79 [0.66–0.92] | 1.57 [1.39–1.76] | |
I2 | 99% | 98% | 0% | 98% | NA | NA | 90% | 74% | NA | |
No of studies | 7 | 4 | 2 | 3 | 1 | 0 | 1 | 1 | 1 | 1 |
2 months | 1.64 [1.6–1.68] | 1.83 [1.79–1.87] | 1.82 [1.77–1.87] | 1.82 [1.77–1.87] | 0.33 [0.18–0.48] | 0.28 [0.12–0.44] | ||||
I2 | 98% | 88% | 91% | 84% | NA | NA | ||||
No of studies | 8 | 7 | 4 | 6 | 0 | 0 | 0 | 1 | 1 | 0 |
3 months | 2.03 [1.97–2.1] | 2.13 [2.03–2.22] | 1.62 [1.45–1.79] | 2.35 [2.24–2.46] | 1.9 [1.79–2] | 2.54 [2.33–2.75] | 1.61 [1.4–1.82] | |||
I2 | 93% | 96% | NA | 93% | 0% | NA | NA | |||
No of studies | 6 | 3 | 1 | 3 | 2 | 0 | 1 | 0 | 0 | 1 |
4 months | 1.68 [1.65–1.72] | 1.97 [1.93–2.01] | 1.89 [1.83–1.95] | 1.97 [1.93–2.02] | 0.18 [0.06–0.3] | 0.2 [0.06–0.34] | ||||
I2 | 99% | 95% | 90% | 96% | NA | NA | ||||
No of studies | 9 | 8 | 4 | 7 | 0 | 0 | 0 | 1 | 1 | 0 |
5 months | 1.59 [1.42–1.76] | 2 [1.72–2.28] | 2 [1.72–2.28] | 1.37 [1.16–1.58] | ||||||
I2 | 92% | NA | NA | NA | ||||||
No of studies | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
6 months | 2.02 [1.99–2.05] | 2.08 [2.04–2.11] | 2.13 [2.08–2.19] | 2.05 [2.01–2.09] | 1.9 [1.83–1.98] | 1.88 [1.68–2.08] | 1.96 [1.67–2.25] | |||
I2 | 94% | 0% | 94% | 94% | 97% | NA | NA | |||
No of studies | 15 | 12 | 7 | 10 | 3 | 0 | 1 | 0 | 0 | 1 |
9 months | 2.25 [2.18–2.31] | 2.29 [2.2–2.38] | 2.29 [2.2–2.38] | 2.28 [2.16–2.39] | 2 [1.83–2.17] | 2.32 [1.95–2.69] | ||||
I2 | 40% | 0% | 0% | 0% | NA | NA | ||||
No of studies | 4 | 2 | 0 | 2 | 1 | 1 | 0 | 0 | 1 | |
12 months | 2.46 [2.4–2.52] | 2.46 [2.38–2.54] | 2.7 [2.43–2.97] | 2.44 [2.36–2.52] | 2.52 [2.4–2.63] | 2.16 [1.96–2.36] | 2.79 [2.48–3.1] | |||
I2 | 84% | 88% | NA | 90% | 0% | NA | NA | |||
No of studies | 5 | 3 | 1 | 3 | 1 | 0 | 1 | 0 | 0 | 1 |
Improvement of the Nasolabial Fold Area: A Meta-Analysis of Reported GAIS Scores
Overall | HA combined | Monophasic HA | Biphasic HA | Collagen | Mesoglow | IAL-systems | Autologous fat | |
---|---|---|---|---|---|---|---|---|
2 weeks | 3.21 [3.11–3.32] | 3.21 [3.11–3.32] | 3.28 [3.13–3.43] | 3.15 [3.01–3.3] | ||||
I2 | 71% | 71% | 74% | 76% | ||||
No of studies | 3 | 3 | 2 | 2 | 0 | 0 | 0 | 0 |
1 month | 2.21 [2.14–2.28] | 2.86 [2.55–3.17] | 2.9 [2.53–3.28] | 2.77 [2.21–3.34] | 2.08 [1.97–2.19] | 2.03 [1.93–2.14] | 3 [2.8–3.2] | |
I2 | 94% | 0% | 0% | NA | 88% | 86% | NA | |
No of studies | 4 | 2 | 2 | 1 | 0 | 1 | 1 | 1 |
2 months | 2.47 [2.43–2.52] | 2.65 [2.58–2.71] | 2.63 [2.51–2.74] | 2.66 [2.58–2.74] | 1.75 [1.6–1.9] | 1.75 [1.61–1.89] | ||
I2 | 97% | 74% | 0% | 87% | NA | NA | ||
No of studies | 5 | 4 | 2 | 3 | 0 | 1 | 1 | 0 |
3 months | 2.32 [2.21–2.44] | 2.01 [1.68–2.33] | 2.01 [1.68–2.33] | 2.37 [2.25–2.5] | ||||
I2 | 90% | 96% | 96% | 0% | ||||
No of studies | 2 | 2 | 0 | 1 | 1 | 0 | 0 | 0 |
4 months | 2.24 [2.2–2.29] | 2.34 [2.28–2.4] | 2.51 [2.39–2.63] | 2.27 [2.2–2.35] | 1.4 [1.23–1.57] | 1.4 [1.25–1.56] | ||
I2 | 98% | 98% | 50% | 98% | NA | NA | ||
No of studies | 6 | 5 | 2 | 4 | 0 | 1 | 1 | 0 |
5 months | 2.78 [2.6–2.96] | |||||||
I2 | NA | |||||||
No of studies | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
6 months | 2.32 [2.26–2.37] | 2.35 [2.29–2.42] | 2.36 [2.22–2.5] | 2.35 [2.28–2.43] | 2.08 [1.93–2.24] | |||
I2 | 93% | 95% | NA | 96% | 0% | |||
No of studies | 5 | 4 | 1 | 4 | 1 | 0 | 0 | 0 |
9 months | 1.68 [1.52–1.83] | 1.68 [1.52–1.83] | ||||||
I2 | 0% | 0% | ||||||
No of studies | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
12 months | 1.27 [1.12–1.42] | 1.27 [1.12–1.42] | ||||||
I2 | 0% | 0% | ||||||
No of studies | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Complications After Treatment of the Nasolabial Fold Area
Overall | HA combined | Monophasic HA | Biphasic HA | Collagen | PLA | PCL | Mesoglow | IAL-systems | Autologous fat | |
---|---|---|---|---|---|---|---|---|---|---|
All complications | 0.58 [0.46–0.7] | 0.59 [0.46–0.72] | 0.59 [0.36–0.8] | 0.6 [0.43–0.76] | 0.4 [0.12–0.7] | 0.82 [0.69–0.93] | 0.88 [0.72–0.99] | |||
I2 | 98% | 98% | 98% | 98% | 94% | NA | 77% | |||
No of studies | 19 | 17 | 11 | 14 | 2 | 0 | 0 | 1 | 2 | 0 |
Redness | 0.26 [0.19–0.33] | 0.23 [0.16–0.3] | 0.26 [0.14–0.39] | 0.2 [0.13–0.29] | 0.25 [0.02–0.53] | 0.5 [0.34–0.66] | 0.43 [0.27–0.58] | 0.29 [0.13–0.47] | ||
I2 | 97% | 96% | 97% | 96% | 97% | NA | NA | NA | ||
No of studies | 28 | 22 | 13 | 19 | 4 | 0 | 0 | 1 | 1 | 1 |
Bruising | 0.29 [0.23–0.35] | 0.28 [0.22–0.36] | 0.29 [0.19–0.4] | 0.28 [0.19–0.38] | 0.16 [0–0.80] | 0.18 [0.07–0.31] | 0.27 [0.18–0.36] | 0.33 [0.16–0.51] | ||
I2 | 95% | 95% | 93% | 95% | 99% | NA | 0% | NA | ||
No of studies | 22 | 14 | 11 | 13 | 2 | 0 | 0 | 1 | 2 | 1 |
Swelling | 0.34 [0.26–0.44] | 0.32 [0.23–0.42] | 0.41 [0.25–0.57] | 0.27 [0.16–0.39] | 0.14 [0–0.38] | 0.67 [0.52–0.81] | 0.65 [0.49–0.79] | 0.4 [0.22–0.58] | ||
I2 | 98% | 98% | 97% | 98% | 97% | NA | NA | NA | ||
No of studies | 28 | 22 | 12 | 19 | 4 | 0 | 0 | 1 | 1 | 1 |
Pruritus | 0.17 [0.11–0.22] | 0.17 [0.11–0.24] | 0.22 [0.13–0.32] | 0.13 [0.06–0.22] | 0.07 [0–0.2] | 0.43 [0.27–0.58] | 0.35 [0.21–0.51] | |||
I2 | 96% | 96% | 94% | 97% | 92% | NA | NA | |||
No of studies | 22 | 18 | 11 | 15 | 3 | 0 | 0 | 1 | 1 | 0 |
Skin induration | 0.11 [0.02–0.27] | 0.14 [0–0.37] | 0.27 [0–0.84] | 0.06 [0–0.17] | 0.07 [0.02–0.15] | |||||
I2 | 97% | 98% | 98% | 93% | 78% | |||||
No of studies | 7 | 6 | 3 | 4 | 3 | 0 | 0 | 0 | 0 | 0 |
Tenderness | 0.41 [0.21–0.63] | 0.39 [0.17–0.64] | 0.66 [0.23–1] | 0.32 [0.1–0.57] | 0.55 [0.39–0.7] | 0.53 [0.37–0.68] | x [x] | |||
I2 | 98% | 99% | 98% | 98% | NA | NA | x% | |||
No of studies | 7 | 6 | 2 | 5 | 0 | 0 | 0 | 1 | 1 | x |
Skin discoloration | 0.07 [0.03–0.11] | 0.08 [0.03–0.13] | 0.14 [0.06–0.24] | 0.02 [0–0.05] | 0.01 [0–0.04] | 0.05 [0–0.15] | ||||
I2 | 92% | 93% | 93% | 80% | 0% | NA | ||||
No of studies | 12 | 10 | 7 | 5 | 1 | 1 | 0 | 0 | 0 | 0 |
Pain | 0.28 [0.2–0.38] | 0.31 [0.2–0.41] | 0.4 [0.23–0.58] | 0.23 [0.12–0.36] | 0.07 [0–0.19] | 0.57 [0.42–0.73] | 0.75 [0.27–1] | 0.19 [0.06–0.35] | ||
I2 | 98% | 98% | 98% | 98% | 89% | NA | 95% | NA | ||
No of studies | 27 | 21 | 13 | 16 | 3 | 0 | 0 | 1 | 2 | 1 |
Nodulus | 0.05 [0.01–0.1] | 0.06 [0.01–0.15] | 0.24 [0.0–0.63] | 0.02 [0.01–0.03] | 0.02 [0.01–0.05] | 0.05 [0–0.15] | 0.11 [0.02–0.25] | |||
I2 | 96% | 97% | 99% | 35% | 0% | NA | NA | |||
No of studies | 15 | 9 | 4 | 8 | 2 | 1 | 0 | 0 | 0 | 1 |
Hematoma | 0.09 [0–0.23] | 0.14 [0–0.23] | 0.14 [0–0.39] | 0.14 [0–0.52] | 0.01 [0–0.02] | |||||
I2 | 97% | 96% | 95% | 97% | NA | |||||
No of studies | 6 | 0 | 4 | 4 | 1 | 0 | 0 | 0 | 0 | 0 |
Infection | 0.01 [0–0.03] | 0.03 [0–0.10] | 0.09 [0.01–0.19] | 0.01 [0–0.02] | ||||||
I2 | 48% | 1% | 0% | NA | ||||||
No of studies | 4 | 0 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 0 |
Vascular adverse events | 0.01 [0–0.02] | 0.01 [0–0.02] | 0.01 [0.0–0.02] | 0.01 [0–0.03] | ||||||
I2 | 0% | 0% | NA | 0% | ||||||
No of studies | 3 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
Migration | 0.08 [0.01–0.17] | 0.08 [0.01–0.17] | ||||||||
I2 | 69% | 69% | ||||||||
No of studies | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Numbness | 0.13 [0.01–0.35] | 0.13 [0.01–0.35] | ||||||||
I2 | 92% | 92% | ||||||||
No of studies | 3 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Lumpiness | 0.43 [0.13–0.76] | 0.43 [0.13–0.76] | 0.34 [0.04–0.72] | 0.82 [0.74–0.89] | ||||||
I2 | 97% | 97% | 97% | NA | ||||||
No of studies | 4 | 4 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |