Table 1. Characteristics of the included studies .
*Only outcomes present were listed in the outcomes column
**Studies combined the adverse events for both fillers
HA: hyaluronic acid; JUP: Juvederm Ultra Plus; RD: Restylane Defyne; P: Perlane; P-L: Perlane-L; BB: Belotero Balance; JU XC: Juvederm Ultra XC; NASHA: Non-Animal Stabilized Hyaluronic Acid; R: Restylane; JV XC: Juvederm Volbella XC; R-L: Restylane-L; NLF: nasolabial folds; RHA: Resilient HA; RHAR: Resilient Hyaluronic Acid Redensity; SGP-HA: small gel particle hyaluronic acid; HYC-24L: Juvéderm Ultra XC, a 24 mg/mL hyaluronic acid gel containing 0.3% (wt/wt) lidocaine; CPM-22.5: Belotero Balance, 22.5 mg/mL of hyaluronic acid
| Author | Study Design | Study Aim | Filler and units injected during initial treatment | Location on the face | Number of Treatment participants | Patient Characteristics | Outcomes* |
| Baumann, 2018 [26] | Parallel, randomized, subject and evaluator-blinded, active- controlled, intraindividual split-face comparison study | To compare the efficacy and safety of HA gel with lidocaine and HA gel without lidocaine in the treatment of moderate to severe nasolabial folds. | Juvederm Ultra Plus (JUP): 1.45mL Restylane Defyne (RD): 1.39 mL | Nasolabial Fold | n=136 (JUP) n=136 (RD) | M= 53.7 Range: 34-75 | Juvederm Ultra Plus: Swelling: n=3; Pain: n=2; Erythema: n=3 Restylane Defyne: Swelling: n=4; Pain: n=4; Erythema: n=3 |
| Beer, 2015 [27] | Randomized, no-treatment controlled, evaluator-blinded | To compare the safety and effectiveness of small particle hyaluronic acid plus lidocaine versus no treatment for lip augmentation and perioral rhytides. | Restylane: 2.179 mL | Lip and perioral | n=218 | M= 45.5 | Swelling: n=94 Pain: n=21 |
| Brandt, 2010 [28] | Randomized, double-blind, split-face study | To compare the pain relief and safety of large gel particle hyaluronic acid plus 0.3% lidocaine with that of large gel particle hyaluronic acid without lidocaine during correction of nasolabial folds and to assess filler safety in different skin types. | Perlane (P): 1.10 mL Perlane-L (P-L): 1.11 mL | Nasolabial Fold | n=60 (P) n= 60 (P-L) | M= 53.4 SD: ± 8.0 | Perlane: Swelling: n=24; Pain: n=44; Erythema: n=25; Bruising: n=23; Lumps/bumps: n=1; Itching: n=5; Skin discoloration: n=0 Perlane-L: Swelling: n=24; Pain: n=44; Erythema: n=24; Bruising: n=19; Lumps/bumps: n=1; Itching: n=9; Skin discoloration: n=1 |
| Butterwick, 2015 [29] | Randomized, controlled, Subject and evaluator blinded | Effectiveness and safety of HYC-24L and CPM-22.5 for the treatment of perioral lines | Belotero Balance (BB): 1.32 mL Juvederm Ultra XC (JU XC): 1.18 mL | Perioral | n= 136 (BB) n=136 (JU XC) | M= 58.2 SD: ± 8.4 | Belotero Balance: Swelling: n=58; Pain: n=36; Erythema: n=43; Bruising: n=62; Lumps/bumps: n=46; Firmness: n=48; Tenderness: n=45; Itching: n=9; Skin discoloration: n=18 Juvederm Ultra XC: Swelling: n=59; Pain: n=28; Erythema: n=43; Bruising: n=59; Lumps/Bumps: n=52; Firmness: n=49; Tenderness: n=49; Itching: n=15; Skin discoloration: n=12 |
| Dayan, 2015 [30] | Single-blind, randomized, no-treatment controlled study | To assess the safety and effectiveness of Juvederm Ultra XC, a 24 mg/mL hyaluronic acid gel containing 0.3% lidocaine (HYC-24L) for augmentation of the lips. | Juvederm Ultra XC: 2.13 mL | Lip and perioral | n=157 | M= 49 Range: 20-79 | Swelling: n=150; Bruising: n=147; Lumps/bumps: n=48; Firmness: n=141 |
| Dayan, 2020 [31] | Prospective, randomized, within-patient controlled study, evaluator- blinded | To evaluate the safety and effectiveness of Vollure for correction of moderate to severe nasolabial folds over 18 months and after repeat treatment. | Juvederm Vollure XC: 1.7 mL | Nasolabial Fold | n=123 | M= 54.0 Range: 33-83 | Swelling: n=105; Pain: n=88; Erythema: n=90; Bruising: n=69; Lumps/bumps: n=100; Firmness: n= 108; Tenderness: n=103; Itching: n=38; Skin discoloration: n=33 |
| Dover, 2009 [32] | Blinded, prospective, randomized subject and evaluator | To report the efficacy, durability, and safety data of a large particle NASHA filler and a small particle NASHA filler. | Perlane (P): 2.3 mL Restylane (R): 2.4 mL | Nasolabial Fold | n=141 (P) n=142 (R) | 53.7 ± 9.0 54.4 ± 8.1 | Perlane: Swelling: n=9; Pain: n=1; Erythema: n=4; Bruising: n=36; Lumps/bumps: n=3; Tenderness: n=5; Itching: n=0; Skin discoloration: n=0 Restylane: Swelling: n=5; Pain: n=1; Erythema: n=2; Bruising: n=41; Lumps/bumps: n=3; Tenderness: n=7; Itching: n=1; Skin discoloration: n=1 |
| Few, 2015 [33] | Single-blind, randomized controlled study | The effectiveness of Juvederm Voluma XC was examined from the patient perspective. | Juvederm Voluma XC: 5.09 mL | Midface | n=235 | M= 56 Range: 35-65 | Swelling: n=200; Pain: n=155; Erythema: n=154; Bruising: n=181; Lumps/bumps: n=189; Firmness: n=192; Tenderness: n=215; Itching: n=90; Skin discoloration: n=96 |
| Geronemus, 2017 [34] | Prospective, randomized, controlled, evaluator blinded | To evaluate the safety and effectiveness of VYC-15L for lip and perioral enhancement versus a nonaminal stabiliaed HA with lidocaine. | Juvederm Volbella XC (JV XC): 2.6 mL Restylane-L (R-L): 2.6 mL | Lips | n=168 (JV- XC) n=56 (R-L) | Juvederm Volbella XC: M: 53 Range: 22-78 Restylane-L: M= 55 Range: 23-75 | Juvederm Volbella XC: Swelling: n=159; Pain: n=19; Bruising: n=30; Lumps/bumps: n=153; Firmness: n=153 Restylane-L: Swelling: n=54; Pain: n=11; Bruising: n=10; Lumps/bumps: n= 50; Firmness: n= 52 |
| Glogau, 2012 [35] | Randomized, no treatment controlled, evaluator blinded study | To assess the effectiveness and safety of small gel particle hyaluronic acid for lip augmentation. | Restylane: 1.2 mL | Lips | n=135 | 47.8 ± 10.5 | Swelling: n=42; Pain: n=15; Erythema: n=3; Lumps/bumps: n=5; Tenderness: n=4; |
| Jones, 2013 [36] | Evaluator-blind, randomized controlled study | To study the safety and effectiveness of a new 20 mg/mL HA gel specifically formulated and optimized for mid-face volumizing. | Juvederm Voluma XC: 5.07 mL | Midface | n=235 | M= 55.0 Range: 35-65 | Swelling: n=201; Firmness: n=193; Lumps/bumps: n=191; Tenderness: n=216 |
| Kaufman, 2019 [37] | Prospective, multicenter, controlled, randomized, double-blind, within subject (split-face) clinical trial | The efficacy and safety of one of these resilient HA fillers, and its noninferiority to an effective comparator available in the US, were testing in the treatment of dynamic wrinkles. | Restylane Lyft: 1.42 mL RHA4: 1.54 mL | Nasolabial Fold | n=120 | 57.4 ± 10.0 | ** Swelling: n=27; Firmness: n=49; Lumps/bumps: n=55; Tenderness: n=21 |
| Monheit, 2018 [38] | Prospective, multicenter, randomized, within-subject controlled study, double-blind | To evaluate the safety and effectiveness of VYC-17.5L for correction of moderate to severe nasolabial folds (NLF) compared with a control HA dermal filler. | Juvederm Vollure XC: 1.4 mL | Nasolabial Fold | n=122 | M= 54 Range: 33-83 | Swelling: n=105; Pain: n=88; Erythema: n=90; Bruising: n= 69; Lumps/bumps: n=100; Firmness: n=108; Tenderness: n=103; Itching: n=38; Skin discoloration: n=33 |
| Monheit.2020 [39] | Prospective, multicenter, active- controlled, randomized, double-blinded, within-subject (split-face) trial | The efficacy, durability, and safety of 2 of these RHA fillers and their noninferiority to an effective HA comparator available in the US, were tested in the treatment of dynamic facial wrinkles. | RHA2/Juvderm: 1.54 mL RHA3/Juvederm: 1.52 mL | Nasolabial Fold | n=148 | 55.4 ± 11.0 | ** Swelling: n=16; Lumps/bumps: n=35; Firmness: n=40; Tenderness: n=18 |
| Rivkin, 2019 [40] | Prospective, multicenter, controlled study, evaluator-blind | To evaluate safety and effectiveness of repeat treatment with VYC-15L administered 1 year after treatment for lip and perioral enhancement. | Juvederm Volbella XC: 0.95 mL | Lips and perioral | n=120 | M= 53 Range: 22-78 | Swelling: n=112; Pain: n=92; Erythema: n=90; Bruising: n=98; Lumps/bumps: n=102; Firmness: n=102; Tenderness: n=108; Itching: n=33; Skin discoloration: n=41 |
| Sundaram, 2022 [41] | Randomized, evaluator- blind, no treatment control, multicenter, prospective clinical trial | To demonstrate superiority of RHAR over no-treatment control for correction of moderate to severe dynamic perioral rhytides. | Resilient Hyaluronic Acid Redensity: 2.0 mL | Lips and perioral | n=199 | 61.6 ± 7.2 | Swelling: n=146; Pain: n=54; Erythema: n=131; Bruising: n=154; Lumps/bumps: n=115; Firmness: n=115; Tenderness: n=105; Itching: n=31; Skin discoloration: n=94 |
| Taylor, 2009 [42] | Prospective, randomized, split-face, patient blinded, and evaluator blinded, comparative, multicenter study | To compare the safety and efficacy of two variable particle NASHA fillers in the correction of nasolabial folds in patients with Fitzpatrick skin types IV, V and VI. | Restylane (R): 3mL Perlane (P): 3mL | Nasolabial Fold | n=150 (R) n=150 (P) | Range: 18 - 75 | Restylane: Swelling: n=4; Pain: n=3; Erythema: n=16; Bruising: n=10; Lump/bumps: n=1; Tenderness: n=4; Itching: n=3; Skin discoloration: n=10 Perlane: Swelling: n=4; Pain: n=3; Erythema: n=16; Bruising: n=12; Lump/bumps: n=0; Tenderness: n=4; Itching: n=1; Skin discoloration: n=8 |
| Weiss, 2010 [43] | Randomized, double-blind, split face study | To compare the pain relief and safety of small gel particle HA plus 0.3% lidocaine hydrochloride with that of SGP-HA without lidocaine during correction of nasolabial folds and to assess filler safety in different skin types. | Restylane (R): 1.23 mL Restylane-L (R-L): 1.24 mL | Nasolabial Fold | n=60 (R) n=60 (R-L) | 52.1 ± 6.6 | Restylane: Swelling: n=22; Pain: n=44; Erythema: n=27; Bruising: n=19; Lumps/bumps: n=2; Itching: n=4 Restylane-L: Swelling: n=24; Pain: n=40; Erythema: n=28; Bruising: n= 23; Lumps/bumps: n=1; Itching: n=6 |
| Weiss, 2016 [44] | Evaluator-blind, randomized trial | To evaluate whether large gel particle hyaluronic acid with lidocaine is more effective in the treatment of midface deficiencies than no treatment. | Restylane: 6.23 mL | Midface | n=199 | M= 52.6 | Swelling: n=15; Pain: n=17; Bruising: n=36 |