Efficacy and Safety of Hyaluronic Acid Fillers for Midface Augmentation: A Systematic Review and Meta-Analysis
Abstract
1. Introduction
2. Materials and Methods
2.1. Protocol Registration
2.2. Data Sources and Search Strategy
2.3. Eligibility Criteria
2.4. Study Selection and Data Extraction
2.5. Risk of Bias and Certainty of Evidence
2.6. Statistical Analysis
3. Results
3.1. Search Results and Study Selection
3.2. Study Characteristics
3.3. Quality Assessment
3.4. Meta-Analysis
3.4.1. Global Aesthetic Improvement Scale (GAIS) Responder Rate
3.4.2. Mean Change in Global Aesthetic Improvement Scale (GAIS) over Time
3.4.3. Moderate to Severe Adverse Events
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study ID | Place of Study | Study Design | Trial Registration Number | Sample Size | Age (Years) | Gender (M/F) | Group 1 (Intervention) | Volume of Injection | Site of Injection | Outcomes Assessed | Conclusion | Study Follow Up |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Weiss 2016 [27] | USA | RCT | NA | 200 | 52.9 ± 7.6 mean | 17/183 | LGP-HAL | 3.8 mL | Midface (supraperiosteal to subcutaneous layer) | GAIS score, FACE-Q Score, MMVS | The treatment was safe and effective for correcting midface volume loss using LGP-HA-L | 2, 14 weeks, 12 months |
Li 2017 [22] | China | RCT | NA | 116 | 20–67 median | 6/140 | Volume | 1 mL | Deep subcutaneous/sub-periosteal (medial malar region) | Midface volume, GAIS score, patient satisfaction | Juvéderm Voluma is effective and well tolerated for midface (malar) augmentation in Chinese subjects. Significant volume increase (1.83 mL vs. 0.11 mL at 6 months, p < 0.001); high responder rates (98.2% by investigators, 93.8% by subjects); mild, localize | 1, 6 months |
Prager 2017 [25] | Germany | RCT | NA | 45 | 38–66 median | 2 Male 43 Female | CPM-26 (25 mg/mL HA) | 2 mL | Subdermal/periosteal | GAIS score | Both CPM-26 and VYC-20 were effective and well-received, with a consistent trend favoring CPM-26 based on patient-reported outcomes. | 3, 12, 18 months |
Jeong 2018 [17] | Korea | RCT | NA | 10 | 32–60 median | 0/10 | Mono-HA filler | 0.6 mL | Deep dermis | GAIS score, Moire topography, adverse events | Both novel biphasic and monophasic hyaluronic acid fillers showed similar effectiveness and safety for malar enhancement over 24 weeks, with only mild and transient injection site reactions; MRI proved useful for assessing filler distribution and volume changes | 2, 4, 8, 12, 24 weeks |
Jones 2018 [19] | USA | RCT | NA | 20 | 58.4 ± 10.4 mean | 0/20 | SP-HAL | 1 mL | Intradermal microdroplet | Cheek volume, patient satisfaction | One session of intradermal microdroplet injections of SP-HAL to the mid to lower cheek failed to show superiority over normal saline in improving skin wrinkling and elastosis; procedure was safe, with only mild, transient side effects | 7, 14, 28, 90, 180 days |
Jung 2020 [20] | Korea | RCT | NCT02721368 | 83 | 35–65 median | 19/64 | Neuvamis | 1 mL (max per side) | Not mentioned | GAIS score | Volume Lidocaine was non-inferior to VYC-20L for temporary midface volume restoration at 24 weeks; both fillers were effective, safe, and well tolerated with minimal safety concerns | 0, 4, 12, 24 weeks |
Park 2019 [24] | South Korea | RCT | NA | 9 | 30–80 median | NA | Belotero HA filler | 0.5 mL | Midface region | GAIS score, MFV scale | Monophasic fillers (B, J) demonstrated longer-lasting midface volumization than biphasic fillers (R, Y). Filler B showed excellent performance and injectability, especially in high-pressure areas, supported by objective 3D imaging data. | 2, 4, 12, 24 weeks |
Huh 2020 [16] | Korea | RCT | NCT02119780 | 68 | 20–65 median | NA | YVOC (22 mg/mL HA) | 4.0 mL (each side) | Anteromedial malar | GAIS score, MFV score | The HA fillers injected for the anteromedial malar augmentation maintained the volume well for up to 52 weeks. Additionally, both YVOC and RESS show similar effectiveness and safety profiles | 2, 14, 28, 52 weeks |
Nikolis 2020 [23] | Canada | RCT | NA | 30 | 30–75 median | 0/30 | Restylane Lyft (HAL) | 2× per session | Not mentioned | MFVDS score, GAIS score, patient satisfaction | The use of a treatment algorithm may improve outcomes for patients seeking injectable treatments for midfacial volume loss and contour deficiencies | 2, 8, 16 weeks |
Jones 2021 [18] | USA (New York) | RCT | NA | 210 | 24–80 median | 24/176 | HARC | 6.0 mL (each side) | Subperiosteal/subcutaneous (midface) | GAIS score, FACE-Q Score | HARC was well tolerated and non-inferior to Control for correction of midface fullness at 12 weeks after last injection. Aesthetic improvement and subject satisfaction were high and lasted through week 48 | 12, 24, 36 weeks |
Kerscher 2017 [21] | Germany | RCT | NA | 45 | 18–63 median | 1 Male 44 Female | CPM-26 | 2 mL | Not mentioned | Photographic assessment, GAIS scores | CPM-26 was non-inferior to VYC-20 based on MAS ratings at M3 and demonstrated a favorable safety and effectiveness profile for midfacial volume enhancement with results lasting up to M18. | 1, 8, 12, 18 months |
Yi 2023 [28] | Korea | RCT | NA | 92 | 46.5 ± 8.72 mean | 4 Male 98 Female | Giselleligne (multilayered HA) | NA | Midface Region | MFVDS score, GAIS score, operator satisfaction | This study showed that HAVOL is effective and well tolerated for midface treatment in a Chinese population | 1, 4, 8, 12, 24 weeks |
Siperstein 2022 [29] | US | RCT | NA | 15 | 42.1 mean | 4 Male 11 Female | VYC-17.5 L (a hyaluronic acid filler) | 1 mL per side | Midface region | GAIS score, MMVS score, subject satisfaction, effectiveness and safety of HAVOL in the treatment of midface volume deficit and/or midface contour deficiency | Giselleligne is a safer, more user-friendly, and more effective alternative to existing products for improving the midfacial volume. | 1, 3, 6, 9, and 12 months post-injection |
Ren 2024 [26] | China | RCT | NCT03289052 | 148 | 41.3 ± 10.1 mean | 12/136 | HA_VOL (Restylane® Volyme) group | 8 mL (Total) | Midface region | GAIS score, MMVS score, subject satisfaction, effectiveness and safety of HAVOL in the treatment of midface volume deficit and/or midface contour deficiency | Giselleligne is a safer, more user-friendly, and more effective alternative to existing products for improving the midfacial volume. | 1, 3, 6, 9, and 12 months post-injection |
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Safia, A.; Abd Elhadi, U.; Merchavy, S.; Batheesh, R.; Bathish, N. Efficacy and Safety of Hyaluronic Acid Fillers for Midface Augmentation: A Systematic Review and Meta-Analysis. Medicina 2025, 61, 1823. https://doi.org/10.3390/medicina61101823
Safia A, Abd Elhadi U, Merchavy S, Batheesh R, Bathish N. Efficacy and Safety of Hyaluronic Acid Fillers for Midface Augmentation: A Systematic Review and Meta-Analysis. Medicina. 2025; 61(10):1823. https://doi.org/10.3390/medicina61101823
Chicago/Turabian StyleSafia, Alaa, Uday Abd Elhadi, Shlomo Merchavy, Ramzy Batheesh, and Naji Bathish. 2025. "Efficacy and Safety of Hyaluronic Acid Fillers for Midface Augmentation: A Systematic Review and Meta-Analysis" Medicina 61, no. 10: 1823. https://doi.org/10.3390/medicina61101823
APA StyleSafia, A., Abd Elhadi, U., Merchavy, S., Batheesh, R., & Bathish, N. (2025). Efficacy and Safety of Hyaluronic Acid Fillers for Midface Augmentation: A Systematic Review and Meta-Analysis. Medicina, 61(10), 1823. https://doi.org/10.3390/medicina61101823