Lip Enhancement and Perioral Area Correction With New Hyaluronic Acid Dermal Fillers: A Prospective Safety Study

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. 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. 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. 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 B2had 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. 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.

Hyaluronic acid (HA) fillers have become the most popular dermal fillers for esthetic nasolabial folds (NLFs) correction. Based on the cross-linking method, they can be classified as monophasic or biphasic types. The aim of this meta-analysis is to compare the efficacy and safety of monophasic HA fillers with that of biphasic HA fillers for treatment of NLFs. PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and Chinese databases were searched from inception to January 2021. Randomized controlled trials (RCTs) that compared treatment outcomes of a monophasic HA filler with a biphasic HA filler for esthetic NLF correction were selected. Twenty-two RCTs with totally 1848 subjects were included to this meta-analysis. A significantly higher improvement of NLF severity score was seen for monophasic fillers than biphasic fillers at 2 (p = 0.005), 8 (p <0.0001), 12 (p = 0.03), 16 (p = 0.005), 24 (p <0.00001), 36 (p = 0.007), and 52 week (p <0.0001) after treatment. The effect was retained regardless of ethnicity, total injection volume, and baseline NLF severity. More subjects preferred monophasic fillers over biphasic ones (≤7 months: RR = 3.45, 95% CI 1.17 to 10.11; >7 months: RR = 2.37, 95% CI 1.45 to 3.86). Rate of post-injection pain was significantly lower for monophasic fillers (RR = 0.85, 95% CI 0.78 to 0.92, p <0.0001), but no statistical difference was observed for other post-injection adverse events. Compared to biphasic HA fillers, monophasic HA fillers were associated with a greater and more durable esthetic NLFs improvement, a lower rate of post-injection pain, and were favored by more patients. 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 .

The different rheological properties of hyaluronic acid (HA) filler reflect their specific manufacturing processes and resultant physicochemical characteristics. However, there are few researches about the relationship between product differences and clinical outcome when HA fillers are used for nasolabial folds (NLFs). This study sought to compare the rheological properties, efficacy and safety of a monophasic HA filler, and a well-studied biphasic HA filler, in the treatment of NLFs. A total of 72 Korean subjects with moderate to severe NLFs were randomized to receive injections with monophasic HA or biphasic HA on the left or right side of the face. Efficacy was evaluated by the change in the Wrinkle Severity Rating Scale (WSRS) at 2, 10, 18, 26, and 52weeks. Safety was assessed on the basis of all abnormal reactions during the clinical test period. To compare the rheological characteristics of two cross-linked HA fillers, viscoelastic analysis was performed. At week 26, the mean WSRS was 2.26±0.56 for the monophasic HA side and 2.24±0.54 for the biphasic HA side. Both treatments were well tolerated. The adverse reactions were mild and transient. Monophasic HA filler had lower elasticity and higher viscosity than biphasic HA filler. Despite a number of different rheological properties, monophasic HA is noninferior to biphasic HA in the treatment of moderate to severe NLFs for 52weeks. Therefore, monophasic HA provides an alternative option for NLFs correction.

Injection of hyaluronic acid (HA) filler for nasolabial fold (NLF) correction is a popular aesthetic procedure. In relation to HA filler injections, effective pain control for patient comfort is an important concern. We compared the pain relief achieved by HA filler with 0.3% lidocaine (HAF-Lidocaine) with that achieved by HA filler without lidocaine (HAF) for NLF correction. A total of 62 subjects with visible NLFs were enrolled in this double-blind study at two university hospitals and injected with HAF-Lidocaine and HAF, randomly assigned to the each NLFs. Subjects assessed pain using the visual analog scale (VAS). Blinded independent dermatologists assessed the Wrinkle Severity Rating Scale (WSRS) and subjects assessed the Global Aesthetic Improvement Scale (GAIS) for the evaluation of effectiveness. All adverse events during the follow-up period were recorded. Immediately after treatment, 95.2% of subjects who were treated with HAF-Lidocaine reported reduced pain when compared with those who were treated with HAF and the mean VAS score difference was 38.6mm. At 15, 30, 45, and 60minutes after treatment, respectively, 67.7%, 41.9%, 32.3%, and 21.0% of subjects experienced reduced pain. Based on the mean WSRS and GAIS scores and the incidence of local injection site reactions, the clinical effectiveness and safety profile of HAF-Lidocaine were comparable to those of HAF. We conclude that HA filler containing pre-incorporated lidocaine could reduce pain in Korean patients for NLF correction, and the addition of lidocaine does not affect the effectiveness and safety of HA filler.

BACKGROUNDFull-face aesthetic treatment involving several treatment modalities may improve facial aesthetic outcome.OBJECTIVETo evaluate clinical outcomes and patient perceptions of monotherapy with either abobotulinumtoxinA (ABO) or hyaluronic acid (HA) filler followed by full-face combination treatments of ABO, HA filler, and skin-boosting HA (RSB).MATERIALS AND METHODSSubjects aged 35 to 50 years were randomized to monotherapy with 50 s.U ABO in the glabella or ≤1 mL HA filler in the nasolabial folds (NLFs)/cheeks. At Month 6 and Month 12, all subjects received combination treatment with ≤50 s.U ABO in the glabella, ≤2 mL HA filler in the NLFs/cheeks (and other facial areas as applicable), and ≤1 mL RSB (additional RSB treatment at Month 7). Assessments included global facial aesthetic appearance and improvement, first impression, perceived age, wrinkle severity, satisfaction questionnaires, and adverse events.RESULTSRepeated full-face combination treatment with ABO, HA filler, and RSB was associated with considerably higher levels of aesthetic improvement and subject satisfaction than monotherapy with ABO or HA filler. Improvement rate of glabellar lines was increasing with each treatment.CONCLUSIONRepeated combination treatment achieved greater change in global facial aesthetic appearance than monotherapy. Aesthetic improvement and subject satisfaction was high and increased with each treatment. All treatments were well tolerated.

BackgroundInjectables that behave similarly to native tissue and preserve facial expressiveness represent a new frontier in aesthetic medicine. A range of fillers made of high molecular weight hyaluronic acid (HA) chains with low crosslinking have been specifically developed to complement facial dynamics.AimsThe efficacy and safety of one of these resilient HA fillers, and its noninferiority to an effective comparator available in the US, were tested in the treatment of dynamic wrinkles.MethodsA 15‐month, prospective, multicenter, controlled, randomized, double‐blind, within‐subject (split‐face) clinical trial was conducted on 140 subjects with moderate‐to‐severe nasolabial folds (NLF). Study endpoints included improvement on a proprietary Wrinkle Severity Rating Scale (WSRS) and Global Aesthetic Improvement Scale, according to Blind Live Evaluators (BLE), subjects, and treating investigators (TI). Subject perception was evaluated with FACE‐Q and satisfaction scales.ResultsThe per‐protocol population included 88 subjects (92% women) of all Fitzpatrick phototypes, with a mean age of 57 years. WSRS improvement was significantly greater with the resilient HA than its comparator over 15 months, including at week 24 (primary endpoint), as rated by BLE and TI. Results demonstrated the noninferiority of the resilient HA filler to its comparator. Aesthetic improvement and subject satisfaction were durably high, with an overall trend toward higher scores for the resilient HA filler. Both treatments were safe and well tolerated.ConclusionThe resilient HA filler made of long chains lightly crosslinked is at least equivalent to a well‐established comparator for the correction of NLF in subjects of diverse skin phototypes.

<b>Hintergrund: </b>Behandlungen mit Hyaluronsäure (HA) zählen zu den am häufigsten eingesetzten minimal-invasiven Verfahren zur Augmentation von Falten und Volumendefiziten. Es gibt jedoch eine große Anzahl an verschiedenen Produkten, die wesentliche Unterschiede in der Art der Herstellung und der damit verbundenen Eigenschaften aufweisen. <b>Zielsetzung:</b> Ziel der Studie war die intraindividuelle In-vivo-Evaluierung der Effekte eines monophasischen HA-Fillers mit Cohesive Polydensified Matrix (CPM^®) mit denen eines biphasischen, nicht-animalischen, stabilisierten HA-Fillers (NASHA^®) auf die Patientenwahrnehmung. <b>Methoden:</b> In den randomisierten, doppelblinden Halbseitenvergleich wurden 20 Patienten im Alter von 35 bis 65 Jahren mit einer symmetrischen Ausprägung der Nasolabialfalten (WSRS für NLF Grad 3 – 4) eingeschlossen. Die Patienten wurden einmalig mit einem monophasischen CPMHA-Filler und einem biphasischen NASHA-Filler zu gleichen Injektionsvolumina behandelt; touch-ups waren nicht erlaubt. Mittels validierter Scores wurde 2, 24 und 48 Wochen nach Studienbeginn die Faltentiefe und die ästhetische Verbesserung durch den Prüfarzt ermittelt (WSRS, GAIS) und anhand verblindeter Fotos die Faltentiefe durch einen Independent Rater beurteilt (Merz-Scale). Zudem wurde eine Patientenselbstbeurteilung erhoben (Injektionsempfinden, WSRS, GAIS, Patientenzufriedenheit). <b>Ergebnisse: </b>Die Daten von 20 Patienten (52 ± 5,6 Jahre) dokumentierten eine signifikant geringere Schmerzempfindung bei Injektion des monophasischen HA-Präparates (p ≤ 0,011). Eine signifikant verbesserte Patientenzufriedenheit zeigte sich mit beiden HA-Produkten bis zu 48 Wochen, jedoch ergaben sich signifikante Unterschiede zugunsten des monophasischen CPMHA-Fillers nach 24 und 48 Wochen (p = 0,002, p = 0,005). Eine signifikant bessere Bewertung der Faltentiefe (WSRS) und ästhetischen Verbesserung (GAIS) durch die Patienten zeigte sich 2 Wochen nach Injektion des monophasischen CPMHA-Produktes (p ≤ 0,012, p ≤ 0,011), während nach 24 und 48 Wochen ähnlich signifikante Ergebnisse auftraten. Die Beurteilung der ästhetischen Verbesserung der NLF durch den Prüfarzt dokumentierte nach 2 Wochen signifikant bessere Effekte des monophasischen HA-Produktes (p ≤ 0,025), während nach 24 und 48 Wochen ähnlich signifikante Ergebnisse auftraten. Die vom Independent Rater mittels Merz-Scale gescorte Ausprägung der NLF zeigte nach 2 und 24 Wochen eine ähnlich signifikante Reduzierung der NLF mit beiden Prüfprodukten, während sich nach 48 Wochen nur die CPMHA-injizierte NLF signifikant verminderte (p = 0,034). Das WSRS-Prüfarzt-Rating ergab eine signifikant verringerte Faltentiefe mit beiden HA-Fillern bis zu 48 Wochen. <b>Schlussfolgerung:</b> Die einmalige Injektion eines mono- und biphasischen HA-Fillers im randomisierten, doppelblinden Halbseitenvergleich dokumentierte signifikante Verbesserungen mit beiden Präparaten bei allen einbezogenen Parametern bis zu 48 Wochen. Es zeigten sich jedoch signifikante Unterschiede bzgl. Injektionsempfinden, Faltentiefe, ästhetischer Verbesserung und Patientenzufriedenheit, die darauf hinweisen, dass die Behandlung mit dem monophasischen CPMHA-Filler besser toleriert wird.

Background: A previous 6-month study using a more highly concentrated novel hyaluronic acid (HA) filler, PP-501-B, found nasolabial fold (NLF) improvements with increased tolerability.Objective: We investigated the long-term efficacy, durability and safety of PP-501-B in the correction of NLFs.Methods: Subjects completing the initial six-month study were enrolled in this 24-month, randomized, multicenter, double-blind, split-face, extension study. The injection areas and treatment procedures were identical to those of the initial study: each subject was injected with PP-501-B in one NLF and with Restylane Perlane (Q-med) in the contralateral NLF. We reassessed wrinkle improvement using the five-point Wrinkle Severity Rating Scale (WSRS) and changes in the Global Aesthetic Improvement Scale at 12, 18 and 24 months after the initial treatment.Results: Of the 81 patients enrolled, 72 completed the study. The WSRS score significantly decreased from baseline throughout the follow-up period after retreatment with both fillers. There was no significant difference in the WSRS scores between the two fillers at 24 months. Both fillers were well tolerated with no severe complications or adverse reactions.Conclusion: The new HA filler PP-501-B is safe and effective in the long term for the correction of moderate-to-severe NLFs, even after a second treatment.

Background: Since lips have a significant role in facial aesthetic perception, lip augmentation is an increasingly popular aesthetic procedure. Objective: To evaluate aesthetic improvement and facial dynamics with hyaluronic acid (HA) fillers in the lips and perioral region at 8 weeks after the last treatment compared to pre-treatment. Methods and Materials: In this open-label study, all subjects received HARK in the lips, and an additional group also received HARR and/or HARD in nasolabial folds (NLFs) and marionette lines (MLs). Assessments included aesthetic improvement, naturalness of facial expressions, perception of age, and lip texture. Results: Nineteen subjects received HARK only; 40 received HARK and HARR and/or HARD. The primary objective was met. All subjects experienced aesthetic improvement in lip fullness at week 8. The investigators also reported aesthetic improvement in all subjects. For the majority of subjects, aesthetic improvement was associated with maintenance of natural and youthful facial expressions, and improved lip texture. Most treatment-emergent adverse events were mild; none were serious. Conclusion: HARK is a well-tolerated and effective treatment for enhancing lip fullness, maintaining naturalness and youthfulness of facial expressions, and smoothing lip texture, whether used alone or in combination with HARR/ HARD in the NLFs and/or MLs. J Drugs Dermatol. 20(4): 402-408. doi:10.36849/JDD.2021.5525More on lip augmentation.

Hyaluronic acid (HA) fillers are FDA approved for improving the appearance of the nasolabial folds. Previous reports on the use of HA for this treatment have focused on injections directly into the location of the desired correction. To our knowledge, a study has not been done evaluating the efficacy of injecting a low volume of HA into the adjacent area of volume loss to correct both volume loss and adjacent lines. The objective of this study was to compare the effectiveness and safety of three HA injection protocols including deep dermal cheek injection, mid- to deep dermal local nasolabial fold injection, and both injections for the correction of nasolabial folds. This was a split-face, randomized study evaluating the use of three injection techniques - (i) deep bolus injection into the mid- to lateral cheek, (ii) local mid- to deep dermal injection into the nasolabial fold, and (iii) both deep injection into the mid- to lateral cheek and local mid- to deep dermal injection into the nasolabial fold - for the treatment of moderate to severe nasolabial folds. Wrinkle severity and Global Aesthetic Improvement Scales were measured before and 4-6weeks after treatment as assessed by a blinded investigator. Patient and physician observations showed improvement both globally and in wrinkle severity score with each technique used with no statistical difference between techniques. Patients showed a slight preference for injection to both the mid- to lateral cheek and nasolabial fold, which was associated with the greatest amount of filler product administered. No serious adverse events were reported. Injection of a dermal filler, at low volumes, into either the nasolabial fold or mid- to lateral cheek results in similar improvement to the correction of the nasolabial folds.

Soft-tissue augmentation with hyaluronic acid (HA) fillers has become one of the most popular cosmetic procedures performed. HA fillers represent safe and commonly used fillers. Several different HA fillers are available. The differences lie in the manufacturing process, allowing for tailored uses. A small-particle HA with lidocaine (SP-HAL; Restylane Silk; Galderma, Uppsala, Sweden) was approved by the US Food and Drug Administration in June 2014 but has been available for many years in Canada as Restylane Fine Lines and in Europe as Restylane Vital. Relevant articles were reviewed relating to the composition, effectiveness, and safety of SP-HAL. We also discuss the author's extensive clinical experience in the use of this product in Canada. SP-HAL has demonstrated proven benefits for lip fullness, augmentation, and treatment of perioral rhytides. Although off-label in the United States, SP-HAL is also well suited for the treatment of superficial fine lines, including periorbital, forehead, marionette, and smile lines. In addition, it has also been used in the tear trough region. A novel application for SP-HAL includes use as a skinbooster with intradermal micropuncture. In this technique, small aliquots of product are injected so as to gradually rejuvenate the skin in areas such as the face and hands. Side effects of SP-HAL were generally transient and mild. The most common side effects were swelling, tenderness, bruising, pain, and redness. SP-HAL is an effective and safe HA filler with varied clinical uses.

Since lips have a significant role in facial aesthetic perception, lip augmentation is an increasingly popular aesthetic procedure. To evaluate aesthetic improvement and facial dynamics with hyaluronic acid (HA) fillers in the lips and perioral region at 8 weeks after the last treatment compared to pre-treatment. In this open-label study, all subjects received HARK in the lips, and an additional group also received HARR and/or HARD in nasolabial folds (NLFs) and marionette lines (MLs). Assessments included aesthetic improvement, naturalness of facial expressions, perception of age, and lip texture. Nineteen subjects received HARK only; 40 received HARK and HARR and/or HARD. The primary objective was met. All subjects experienced aesthetic improvement in lip fullness at week 8. The investigators also reported aesthetic improvement in all subjects. For the majority of subjects, aesthetic improvement was associated with maintenance of natural and youthful facial expressions, and improved lip texture. Most treatment-emergent adverse events were mild; none were serious. HARK is a well-tolerated and effective treatment for enhancing lip fullness, maintaining naturalness and youthfulness of facial expressions, and smoothing lip texture, whether used alone or in combination with HARR/ HARD in the NLFs and/or MLs. J Drugs Dermatol. 20(4): 402-408. doi:10.36849/JDD.2021.5525.

In addition to having a younger and more attractive appearance after facial aesthetic treatment, patients desire natural-looking and long-lasting results. To evaluate perceived naturalness of dynamic facial expressions after treatment with hyaluronic acid fillers in nasolabial folds (NLFs) and lower face wrinkles and folds. Subjects requiring treatment of moderate-to-severe NLFs and at least one other lower face indication were treated with hyaluronic acid fillers. Assessments included perceived naturalness, attractiveness and age, NLF severity, aesthetic improvement, satisfaction, and safety. Sixty-three subjects were enrolled. Six months after treatment, naturalness of facial expression was maintained or enhanced for ≥98% of subjects, attractiveness was enhanced for ≥61% of subjects, and ≥34% of subjects looked younger, as assessed by investigators and an independent evaluator. Wrinkle severity had improved at least 1 grade for ≥54% of subjects at Month 12. Aesthetic improvement was reported for ≥92% of subjects 12months after treatment. Satisfaction with treatment outcome was high. Local tolerability events and adverse events were mainly mild or moderate and resolved spontaneously. Hyaluronic acid treatment in NLFs and lower face was well tolerated and achieved natural-looking results, long-lasting aesthetic improvement, and high satisfaction with treatment outcome.

Nasolabial folds (NLFs) are a common cosmetic concern that makes people look older. Hyaluronic acid (HA)-based fillers are increasingly popular for minimally invasive facial wrinkle and fold correction. This study aimed to evaluate the efficacy and safety of a new monophasic HA filler, CUREA®, for NLF correction compared to the widely used Juvederm®. A 24-week, prospective, single-center, double-blind, randomized, split-face, non-inferiority controlled trial was conducted. Seventy-four participants with moderate-to-severe NLFs were enrolled and treated with CUREA® on one side of the face or Juvederm® on the other. Evaluation included NLF improvement as determined using the Wrinkle Severity Rating Scale (WSRS), participant satisfaction, and adverse events. At 24 weeks, CUREA® significantly improved WSRS scores from 3.16 ± 0.84 at baseline to 2.59 ± 0.87 at week 24 (P <0.001). CUREA® demonstrated efficacy for NLF correction within the predefined non-inferiority margin compared to Juvederm®. The safety profiles and participant satisfaction for CUREA® were similar to those for Juvederm®. Only mild, transient local reactions were observed, and participants were satisfied with the clinical improvement of both fillers throughout the 24-week follow up. CUREA® is comparable to Juvederm® in NLF correction and safety profiles, and its efficacy lasts up to 24 weeks.

Autologous cultured fibroblast injections for soft tissue augmentation are a potential alternative to other filler materials. No studies have compared autologous fibroblast injections and hyaluronic acid (HA) fillers for treating nasolabial folds (NLFs). To compare the efficacies and safeties of autologous cultured fibroblast injections and HA fillers for treating NLFs. This prospective, evaluator-blinded, pilot study enrolled 60 Thai female adult patients diagnosed with moderate to severe NLFs. They were randomized to receive either 3 treatments of autologous fibroblasts at 2-week intervals or 1 treatment with HA fillers. The primary outcome was the clinical improvement of the NLFs graded by 2 blinded dermatologists immediately after injection and at 1-, 3-, 6-, and 12-month follow-ups. Objective measurement of the NLF volume was evaluated. Patient self-assessment scores, pain scores, and adverse reactions were recorded. Of the 60 patients, 55 (91.7%) completed the study protocol. The NLF volumes improved significantly in the autologous fibroblast group at all follow-ups relative to baseline (P = 0.000, 0.004, 0.000, 0.000, and 0.003). The patients in the autologous fibroblast group rated more noticeable NLF improvements than those in the HA filler group (3-month follow-up, 58.41% vs. 54.67%; 6-month follow-up, 52.50% vs. 46%; 12-month follow-up, 44.55% vs. 31.33%). No serious adverse reactions were recorded. Autologous fibroblast injections are safe and effective for treating NLFs. These injections also promise sustained growth of living cells, possibly leading to a greater persistence than shown by other fillers.