Soft tissue distribution pattern of facial soft tissue fillers with different viscoelastic properties.

BACKGROUND: Soft tissue filler product distribution and tissue integration have been shown to depend on myriad factors including the injector type, injector size, and injection angle. AIM: This study aims to investigate the magnitude of product spread across fascial soft tissue layers in relation to product viscoelastic properties. PATIENTS/METHODS: A total of 168 injection procedures were conducted in two female Caucasian body donors with a mean age of 80 years (range: 79-81) and a mean body mass index of 23.6 kg/m2 (range: 21.0-26.6). The injection procedures were performed in the forehead, scalp, zygomatic arch, mandible, clavicle, and sternum. The injected materials included Belotero® Soft, Belotero® Balance, Belotero® Intense, Belotero® Volume, Radiesse® , and Radiesse® Plus. Layer-by-layer dissections were performed to investigate the vertical distribution of the injected product. RESULTS: The mean product spread was for Belotero® Soft 4.54 ± 0.91; Belotero® Balance 3.85 ± 1.19; Belotero® Intense 3.04 ± 1.34; Belotero® Volume 2.58 ± 1.27; Radiesse® 1.31 ± 0.47; and Radiesse® Plus 1.27 ± 0.45 with P < .001. Bivariate correlations between product spread and storage modulus (G') revealed an inverse relationship of moderate strength with rp  = -0.651 and P < .001. CONCLUSION: The results of the present study revealed that products that were more fluid and less viscous distributed into more superficial fascial layers than products that were less fluid and more viscous (P < .001). This relationship held true irrespective of injected location.

An In Vitro Model Assessing the Penetration of Hyaluronidase through Optic Nerve Dura for Management of Hyaluronic Acid Facial Filler Embolism.

BACKGROUND: Blindness from ophthalmic or central retinal artery embolism is one of the most devastating complications of cosmetic filler facial injections. A proposed therapy to mitigate visual loss is prompt retrobulbar injection of hyaluronidase into the retrobulbar space. Despite Zhu et al. showing a lack of evidence and very limited published literature for reversing visual loss with this intervention, it is still widely accepted as a treatment for filler-related emboli. The purpose of this study was to evaluate the penetration of hyaluronidase through optic nerve dura using an in vitro model. METHODS: At study conclusion, five 1-cm-long segments of fresh optic nerve were obtained and injected with highly crosslinked hyaluronic acid filler, then ligated on both ends in a watertight fashion. The sections were immersed in three concentrations of hyaluronidase solution for 24 hours. Histopathologic examination of the specimen was performed to assess the presence of filler. RESULTS: The optic nerve sections were 1.1 cm (range, 0.8 to 1.2 cm). Three were immersed in 20 ml of 1500 IU/ml hyaluronidase solution and two were immersed in saline as control. After 24 hours, there was a persistence of hyaluronic acid within the optic nerves. CONCLUSIONS: There is a lack of evidence for penetration of optic nerve sheath by hyaluronidase. This raises question about the effectiveness of retrobulbar injection of hyaluronidase in reversing filler-related blindness. Further studies are needed before this can be adopted as the treatment of choice. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

In Vitro Evaluation of Preinjection Aspiration for Hyaluronic Fillers as a Safety Checkpoint.

BACKGROUND: Hyaluronic acid (HA) fillers have increased in popularity. Although complications are rare, knowledge regarding their prevention and management are crucial. The utility of preinjection aspiration has become controversial. OBJECTIVE: Our study investigated the utility of preinjection aspiration as a safety checkpoint for HA fillers through comparison of physiochemical and rheological properties in an in vitro model. MATERIALS AND METHODS: Whole blood was drawn from vacutainers using syringes containing 10 commonly used HA fillers. Each HA filler was examined with the plunger pulled back at volumes of 0.2 and 0.5 cc. The time required to visualize a flash was recorded. Data were compared using physiochemical and rheological properties, pullback volumes, and needle gauges. RESULTS: Using a multivariable regression model, HA concentration, elastic modulus (G'), viscous modulus (G″), and complex modulus (G*) had significant relationships with time to flash, whereas needle gauge and pullback volume did not. However, when comparing pullback volume using an appropriate paired analysis, 0.5 cc pullback volume had a significantly decreased mean time to flash than 0.2 cc. CONCLUSION: Preinjection aspiration may have utility as a safety checkpoint for HA fillers. Practitioners may have to adjust pullback volume and waiting time to visualize the flash based on physiochemical and rheological properties.

Hyaluronic Acid After Subcutaneous Injection-An Objective Assessment.

BACKGROUND: Hyaluronic acid (HA) fillers are the preferred injectable products for aesthetic correction of skin depressions and restoration of facial volume. OBJECTIVE: To investigate the subcutaneous distribution of 3, biophysically distinct, CE-marked and FDA-approved HA fillers. MATERIALS AND METHODS: BELB, JUVV, and RESL were injected ex vivo in porcine and human skin. Immediately after injection, the skin samples were snap-frozen, cross-sectioned, and visualized using stereomicroscopy and full-field optical coherence tomography. Images were compared with histological sections after hematoxylin and eosin staining. RESULTS: Hyaluronic acid fillers were distributed as homogeneous bolus in the ex vivo skin. The injection bulks were found to preserve the fibrous trabecular network, shift the fat lobules, and displace the adjacent adipocyte layers independently of the formulation injected. CONCLUSION: For the first time, the subcutaneous injection of 3 HA fillers with markedly different biophysical properties was systematically investigated by complementary visualization techniques. Despite their different properties, no difference in distribution was found after subcutaneous injection. The global preservation of the hypodermis structure observed was consistent with the good tolerability seen in clinical practice after implantation of the HA fillers in the subcutaneous skin layer.

Hyaluronic acid gel based on CPM® technology with and without lidocaine: Is there a difference?

BACKGROUND: In 2011, a cohesive polydensified matrix (CPM® ) hyaluronic acid (HA) gel filler was approved by the USA Food and Drug Administration. In 2014, lidocaine was added to the gel during its manufacturing process. OBJECTIVES: To compare the behavior and rheological properties of a CPM® HA gel with and without lidocaine. METHODS: In our office, we performed simple tests to document the cohesiveness and resistance to traction force of both gels. In two different laboratories, the rheological properties of both gels were measured. We used comparative data of the gel without lidocaine collected from over 6 years. We also observed the gels' behavior when injected into the superficial and mid-reticular dermis, comparing their distribution using both ultrasonography and histology. RESULTS: Over more than 10 years, we observed no difference between both gels, even if clinically we felt a difference in the gels' viscosity upon injection. Their behaviors during injection were similar. Using more sophisticated tests measuring the gels' rheological properties with different techniques, namely sheer sweeps, a difference was, however, noted between the two gels. CONCLUSIONS: Adding lidocaine to CPM® HA gel renders it more viscous. Whether this means a difference in the clinical results, however, would require a comparative clinical study over an extended time period.

Durability, Behavior, and Tolerability of 5 Hyaluronidase Products.

BACKGROUND: Hyaluronic acid (HA) dermal fillers are commonly used in cosmetic dermatology. Due to differences in their physical characteristics, HA fillers demonstrate different sensitivity to degradation by hyaluronidase (Hase) because of HA concentration and differences in cross-linking. Similarly, there are differences in the activity of Hase products depending on source and concentration. OBJECTIVE: The primary objective was to demonstrate the differences in potency and activity of 5 Hase products when used to degrade 5 different HA products using a human in vivo model. MATERIALS AND METHODS: The study subject was a healthy, consenting adult woman scheduled to undergo abdominoplasty. Skin to be excised was injected with 0.1 to 0.2 mL of each filler (10 injections each) leaving a visible lump. Immediately afterward, the HA lumps were injected with 4 IU of each Hase product every 2 minutes until the HA lumps were no longer visible or palpable. This procedure was repeated after 30 days. Injected tissues were excised after abdominoplasty for histological analysis. RESULTS: The 5 Hase products displayed a wide range of doses and times required to completely degrade the 5 HA products ranging from <2 to >16 minutes. CONCLUSION: Cosmetic practitioners should familiarize themselves with differences in HA and Hase products.

The Kinetics of Reversible Hyaluronic Acid Filler Injection Treated With Hyaluronidase.

BACKGROUND: Hyaluronidase is an enzyme capable of dissolution of hyaluronic acid (HA). There is a lack of evidence-based research defining time- and concentration-dependent reversal of HA filler using hyaluronidase. OBJECTIVE: To explore the efficacy of different concentrations of hyaluronidase in digesting commercially available HA-based reversible fillers-Belotero Balance (BEL), Juvederm Ultra XC (JUVXC), Juvederm Ultra Plus (JUVX+), Juvederm Voluma XC (JUVV), Restylane-L (RESL), Restylane Silk (RESS), and Perlane/Restylane Lyft (RESLYFT). MATERIALS AND METHODS: This was a blinded randomized study involving 15 participants. Participants received HA filler injection into their back, followed by no secondary injection, or injection with normal saline, 20 or 40 units of hyaluronidase. Using a 5-point palpation scale, the degradation of HA filler was monitored over 14 days. RESULTS: In the authors' study, there is a significant decrease in HA filler degradation using 20 and 40 units of hyaluronidase compared with no secondary injection or normal saline. There is no significant difference in HA filler dissolution when comparing 20 to 40 units of hyaluronidase. CONCLUSION: Lower concentrations of hyaluronidase may be just as effective as higher concentrations to degrade HA filler in situations where the reversal of cutaneous augmentation with HA filler arises.

Comparison of Intra-arterial and Subcutaneous Testicular Hyaluronidase Injection Treatments and the Vascular Complications of Hyaluronic Acid Filler.

BACKGROUND: Hyaluronidase is a key preventative treatment against vascular complications of hyaluronic acid (HA) filler injection, but the degradation profile of HA to hyaluronidase is limited, and the comparison between intra-arterial and subcutaneous injections of hyaluronidase has not been studied. OBJECTIVE: To evaluate HA degradation to hyaluronidase and compare different treatments between intra-arterial and subcutaneous testicular hyaluronidase injections. MATERIALS AND METHODS: The authors observed HA degradation to hyaluronidase in vitro via microscopic examination and particle analysis. Rabbit ears were used for the in vivo study. There were 2 control groups receiving ligation or HA-induced embolism in the arteries, respectively, and 2 intervention groups receiving hyaluronidase treatments in different regions. The laser Doppler blood perfusion monitoring measurements were made at defined time points, and biopsies were taken on Day 2. RESULTS: Nearly, all of the HAs degraded in vitro at the 1-hour time point. Subcutaneous hyaluronidase treatment showed better recovery of blood perfusion. Histology showed severe inflammation in the embolism group and mild inflammation in the intervention groups. CONCLUSION: A complete enzymatic degradation of HA filler to hyaluronidase needs a certain time, and subcutaneous hyaluronidase treatment may be the better option.

Physiochemical properties and application of hyaluronic acid: a systematic review.

BACKGROUND: Hyaluronic acid is a widely available, biocompatible, polysaccharide with distinguishing physiochemical properties which inspire its application throughout several fields of medicine. OBJECTIVE: We aim to investigate the application of hyaluronic acid and its effectiveness throughout several fields of medicine, including several therapies administered and prescribed by general health practitioners. METHODS: We conducted a systematic review on randomized controlled trials about the physiochemical properties of hyaluronic acid and its application through primary care. Studies included in this review were peer reviewed and met our inclusion criteria. FINDINGS: Factors were clustered into the following: uses throughout several fields of medicine, physiochemical properties, bioavailability, tolerance, effectiveness, and adverse effects. Therapies with hyaluronic acid provided long-lasting, pain relieving, moisturizing, lubricating, and dermal filling effect. Tissue hydration, elasticity, and durability improved. CONCLUSIONS: Adjunct therapy with hyaluronic acid provides longer-lasting therapeutic effect when compared to the use of glucocorticosteroids and NSAIDs in osteoarthritic chronic diseases, is well-established in ophthalmology due to its lubricating properties for the corneal endothelium, and improves tissue hydration and cellular resistance to mechanical damage in aesthetic dermatology, and has marginal adverse effects. Several trials indicated its role in tumor markers, liver diseases, and in pharmaceuticals, but further research would be necessary to draw conclusive results in those fields.

Hyaluronic Acid Filler in HIV-Associated Facial Lipoatrophy: Evaluation of Tissue Distribution and Morphology with MRI.

OBJECTIVE: This prospective observational study evaluated magnetic resonance imaging (MRI) findings of hyaluronic acid (HA) injections used for the correction of HIV-associated facial lipoatrophy. METHODS: Ten consecutive males underwent subdermal HA injection (mean 1.3 ± 0.6 ml per side) and MRI examinations prior to and then 1, 6 and 12 months after injection. Two radiologists blinded to the clinical data assessed morphologic and quantitative changes. RESULTS: MRI revealed HA deposition in the subdermal and deep fat compartments. A significant HA volume increase was observed 1 month after injection (mean increase 331%, p < 0.0001) as compared to the injected amount. No volume reduction occurred at 12 months (p = 0.9961). The measured bound water content did not change (p > 0.9991), whereas skin thickness and tissue vascularization increased during the first 6 months (p = 0.01). CONCLUSION: Our data show that the cosmetic results of HA injections are caused by water binding in the deep facial fat and by a transient increase in vascularization and skin thickness.