Simplifying the injector's armamentarium: An international consensus regarding the use of gel science to differentiate hyaluronic acid fillers and guide treatment recommendations

The Restylane portfolio of soft tissue fillers spans a wide range of indications, due in part to their complementary manufacturing technologies [non‐animal stabilized hyaluronic acid (NASHA) and Optimal Balance Technology (OBT/XpresHAn)]. Using an array of products, injectors can achieve a holistic, natural looking effect for their patients. However, with a wide range of products it may be difficult to choose an optimal combination.


| INTRODUC TI ON
The Restylane portfolio of soft tissue fillers is broad, and this is a key differentiator that allows for unique and diversified treatment options for patients.The concept of Restylane gel technology is individualized treatment, with a portfolio of hyaluronic acid (HA) fillers from two complementary manufacturing technologies (non-animal stabilized hyaluronic acid [NASHA] and Optimal Balance Technology [OBT/XpresHAn]).This concept results in a broad range of products with distinct properties.From the two technologies, injectors can optimize their choice based on the gel's rheological properties and the patient's needs: from firm to flexible and varying degrees of integration. 1 An understanding of the rheological properties of HA-based fillers is a valuable tool for injectors, as it allows injectors to predict how a filler will react on the stress-shear curve and subsequently, aids in the selection of an appropriate filler given the indication, anatomical area, and/or patient attributes under consideration.Moreover, it can inform details of the appropriate treatment technique to employ (e.g., injection depth, injection pattern, volume).3][4][5] Therefore, to educate healthcare practitioners on how they can achieve holistic, natural-looking outcomes for their patients, there is a need to provide treatment recommendations that simplify the Restylane portfolio.A core element of this strategy is to provide differentiation of products (NASHA and OBT) and emphasize gel science [firmness (G') and flexibility (xStrain)], and another is practical guidance and medical education on use and technique.The following project was designed to meet this unmet need.

| Objectives
Simplify and align global use recommendations for NASHA versus OBT.

| Consensus group
The consensus group consisted of 14 members: Three nonvoting members who designed and executed the meeting; and 11 voting members, with international representation (Figure 1).The panelists included key opinion leaders working in the fields of dermatology (2/11; 18.00%), plastic surgery (6/11; 55.00%), and other relevant specialties [i.e., facial plastics, aesthetics, oculoplastics; 3/11 (27.00%)].These experts were chosen based on their vast experience of treating aesthetic patients, their presence on advisory boards, the frequency of their presentations at regional and international conferences, and their contribution to the literature.On average, panelists had 17 years experience working with NASHA products (range: 11-20 years), and 9 years working with OBT products (range: 5-12 years).

| Survey results
A summary of the patient profiles typically treated by the panelists is displayed in Table 1.

| Treatment recommendations
In the following sections, the top product recommendations for each anatomical region are presented, as well as common exceptions or advance techniques (listed in bullet points).

Temporal region
A large-particle HA manufactured with OBT/XpresHAn was found most suitable for treating moderate to severe volume deficits of the aesthetics, facial aging, medical education, soft tissue fillers, treatment techniques temporal region.More specifically, most respondents (8/11; 72.72%) preferred the use of Restylane Volyme (HA V ).The recommended injection device was either a 27G needle, or a 22 to 25G cannula, with the depth of injection being the subcutaneous or supraperiosteal layers.It was noted that the plane of injection depends on the degree of volume deficit.Frequently, a large deficit may require a deeper injection performed with needle, while a mild deficit may be treated more superficially with a cannula.Although not absolute, it was recommended that deeper injections (i.e., supraperiosteal) be performed with a needle, while more superficial injections (i.e., subcutaneous) be performed with a cannula.
• A minority of respondents (4/11; 36.36%) reported using Restylane Lyft (HA L ) in the temporal regions.The following reasons were given for using NASHA in the temporal regions: (i) HA L can be used to lift the corner of the eyebrows, by preferentially placing the product in the anterior-medial aspect of the temporal fossae (an outcome distinguished from the immediate, short lived (~30 min), xylocaine effect of raising the brow); (ii) HA L is dissolved easily by hyaluronidase, which may be important given the vascular anatomy of the temporal region; (iii) rheologically, HA L is the highest G' product, and therefore it is most likely to be able to lift heavy, static, tissues (i.e., deep temporal fascia) when injected deeply, below the muscle.
Of note, while one injector described diluting HA L to limit its visibility when placed superficially in the temporal region, this was acknowledged to be an advanced technique, and the consensus (100%) was to recommend that novice injectors do not inject HA L superficially in the temporal region.
• Restylane Refyne (HA R ) (3/11; 27.27%): May be suitable for mild deficits over a small surface area, where minimal volumization is required to achieve a mild to moderate aesthetic improvement.In this case, superficial injection with cannula was recommended for injecting HA R in the temporal regions.

Forehead
Most respondents (7/11; 63.63%) preferred the use of HA R for mild volume deficits of the forehead.Due to the thinness of the skin and the superficial placement of major arteries in the forehead, the use of a needle is not recommended.Instead, supraperiosteal injection  using a 25G cannula is preferred.Furthermore, use of a needle is typically not recommended in the forehead regions as it may result in a "wavy" appearance.
• HA V (5/11; 45.45%): HA V may be more suitable than HA R for subjects with especially thick skin in the forehead region, or for those with severe volume deficits.In these cases, it was recommended that HA V is injected deep on periosteum, using a cannula.The panelists advised that this treatment should only be performed by experienced injectors, and to inject at least 15 mm above the orbital rim.Moreover, as HA V was the preferred product for the temporal fossae, it could also be used for treating the lateral forehead.This would limit the number of entry points, as well as offer an economical treatment option to patients.
• Restylane-L (HA REST ) (3/11; 27.27%): HA REST was recommended when NASHA technology was preferred to mold the product post-injection, when a limited quantity of product is desired (i.e., compared to HA V ), or as an economical solution to patients seeking to use leftover product from another treatment.

Tear troughs
Restylane Eyelight (HA E ) or HA REST were used and recommended for treating the tear troughs by 8/11 (72.72%) of the advisors.It was recommended to be injected supraperiosteally, using either a 29G needle or 25G cannula.
• Restylane Skin Boosters Vital Light (HA SBVL ) (3/11; 27.27%):A subset of advisors reported using HA SBVL in the tear trough region.The use of HA SBVL was recommended for treating fine, superficial peri-orbital wrinkles, small volume touch ups, or when used in a layering technique.For example, a layering technique could be used in patients with deep tear troughs and a tight tear trough ligament, wherein injectors first treat the patient deep with HA REST , and then HA SBVL can be injected superficially in a staged approach, during a second appointment.Of note, the use of HA SBVL in the tear troughs concerned the senior authors, as any product placed superficially may be associated with swelling; one of the most common adverse events associated with treating this area with HA.Therefore, it was recommended that the use of HA SBVL for treatment of the tear troughs only be attempted by advanced injectors.In addition, it was recommended that injection volumes remain small, and that a 30G needle or 25G cannula be used when injecting HA SBVL into the tear troughs.

Lateral zygoma
HA L was identified as the product of choice by most respondents (9/11; 81.81%) for treatment of the lateral zygoma.Recommended depths of injection included the supraperiosteal and subcutaneous layers, using either a 27G needle or 22G/25G cannula depending on the patient's skin envelope coverage and the respective treatment goals.When targeting the lateral zygoma in Asian patients, respondents suggested injecting HA L slightly superior to the lateral zygoma, to create the illusion of a longer midface region and a higher cheekbone.
• Restylane Defyne (HA D ) (5/11; 45.45%): Almost half the respondents reported using HA D in the lateral zygoma.HA D may be the preferred choice for patients without sufficient soft tissue coverage (e.g., those presenting with "bony" features), or for those that are looking for a softer more subtle effect.For instance, HA D can be used in patients with a more distinct bone structure, to blend surrounding tissues and make the bone appear less prominent.

Anteriomedial cheek
Most respondents (9/11; 81.81%) recommended HA v (HA CONTOUR in the US) as their primary choice for treating the anteromedial cheek, using a 27G/29G needle or a 22G/25G cannula.An advantage of using this OBT product for the anteromedial cheek is that it can be injected superficially or supraperiosteally.Rather than proving a lifting effect in some patients, responders recommend using small volumes of HA v to volumize the midface, soften midface concavities, and to maintain facial animation.
• HA L (6/11; 54.54%): HA L was recommended as a second choice for the treatment of the anteriomedial cheek and was the preferred choice for patients with a bony deficit and significant medial cheek recession.In these cases, it was recommended that the injection be placed into the deep fat pads, to provide a significant effect using a smaller amount of product compared to HA v .
• HA D (3/11; 27.27%):A subset of responders recommended the use of HA D in this region.One responder advocated for the use of HA D in Asian faces, for which there is often a widening of the face with less projection.In these cases, the goal of using HA D would be to create projection in the region of the medial cheeks and in turn create a narrower looking face (even in the absence of a bony deficit).Additionally, deep injections of HA D can correct the midline while superficial injections can be used to camouflage the zygomatic cutaneous ligament, even after subcision.

Nose
Most of the respondents (9/11; 81.81%) agreed that HA L was the preferred product of choice for the nose.The rationale for choosing a suitable product for injecting into the nose included using a firmer product that would not integrate diffusely, to ensure optimal placement on bone, cartilage, or in the inter-cartilaginous space, such as into the columella.Responders primarily recommended the use of a needle for nasal injections, but the use of a cannula was found acceptable under very specific circumstances, such as when injecting into the columella.Additionally, it was noted that minimally invasive rhinoplasty using HA fillers is generally considered a more advanced technique and should not be attempted without significant clinical experience and a profound understanding of nasal anatomy.

Pyriform aperture
Almost all respondents (10/11; 90.90%) agreed that the most suitable product for the treatment of the pyriform region is HA L , because of its high G' value, targeted integration pattern, and ability to project overlying soft tissues anteriorly.To ensure optimal results, recommendations included placing the product supraperiostially using a 27G needle.Although 25G cannulas may be acceptable, it is a more technically challenging injection technique considering the length/positioning of the cannula and that the product does not exit directly at the tip of the cannula, but rather proximal to the tip.
• HA D (3/27; 27.27%): Use of HA D was reported to circumvent the potential stiffness that can arise when injecting a larger amount of HA L into the pyriform region.Using a softer and more malleable product, the filler can integrate faster into the surrounding tissues and facial expression can be maintained while providing improvements to the area.However, these advantages may come at a cost of less lifting capacity.

Nasolabial fold
The nasolabial fold was the anatomical area wherein the product choices offered the most variability among responders.Both NASHA and OBT products were recommended, however in general, OBT was preferred as the nasolabial fold is a highly mobile area.Product choice may also be dependent on which products are available in the respective countries and the severity of the nasolabial folds.
Ultimately, HA D was identified as the product of choice by most respondents (8/11; 72.72%), and especially in patients presenting with a large nasolabial fold deficit.This product was recommended to be used subcutaneously using a 27G needle or a 22G/25G cannula.Again, an appreciation of the variable vascular anatomy of this region is mandatory.
• HA R (4/11; 36.36%):For patients presenting with thin skin and/ or shallow lines, HA R may be a more suitable product compared to HA D , to achieve desired outcomes.The depth of injection for a thinner product like HA R includes the intradermal/superficial cutaneous layers.It was recommended that HA R be injected with a 29G needle or 22/25G cannula.
• HA REST (4/11; 36.36%):It was recognized that the use of HA REST for treating nasolabial folds is a traditional technique performed by some injectors, and its use has a long history of being reported in the literature.HA REST can also be used in a layering approach, wherein HA L is injected deeply and HA REST is layered above this, more superficially.It was recommended that HA REST be injected with a 27/29G needle or 22/25G cannula.Aspiration should be performed when injecting the nasolabial fold subcutaneously, although a negative aspiration does not absolutely guarantee the needle is not within a vessel.
• HA L (4/11; 36.36%):A subset of responders identified the use of HA L for this indication, suggesting that it may be optimal for men, individuals with deep nasolabial folds, and/or thick skin.Although OBT products may be more suitable for the nasolabial folds because of the amount of facial animation in this region, in the past NASHA products have been utilized successfully.Thus, advanced users may select to utilize of a firmer product in certain cases.
Recommendations to achieve an optimal visual outcome when using HA L included using very small aliquots in the superficial subcutaneous plane (being wary of the Tyndall effect), and transversing the nasolabial folds using a perpendicular injection pattern to achieve a bridging effect with the midface. 6rioral HA SBVL and HA R were both identified and recommended equally (6/11; 54.54%) as the choices for the treatment of perioral lines.
Both were recommended for use sub-dermally using either a 30G needle or a 25G cannula.Although both may be used, recommendations included the use of HA R as the primary product of choice for this indication because of its ability to target both superficial and deep fine lines, reduce anterior projection associated with filler in this area, and its increased longevity and availability compared to HA SBVL .On the other hand, HA SBVL is recommended for treatment of very superficial lines and skin hydration, and should be deposited in very small quantities in this area.It was recommended that HA SBVL be deposited in very small aliquots (0.01 mL) using the accompanying clicker system, as this will decrease the likelihood that palpable nodules form following injection.

Lips
Most respondents (9/11; 81.81%) preferred and recommended the use of Restylane Kysse (HA K ) for treatment of the lips.For this indication, a 29G needle or 25G cannula was recommended and product should be deposited in the subdermal, subcutaneous and/or the submucosal layer.Using this product, the injector can create volume and projection in the lip for those who are not lacking structure or definition in this area.It was noted that product should not be placed in the muscular layer of the lip region.
• HA REST (5/11; 45.45%):While an OBT product was generally preferred for the lips since it is a highly mobile area, the use of NASHA was also recommended under specific circumstances.For example, HA REST was recommended for defining the lip boarder, without risk of product spread, in patients that require more structure rather than volume to their lips.This may be especially useful in older patients, wherein they often lack lip structure and definition.It was recommended that a 29G needle or 25G cannula is used for injecting HA REST into the lips.

Labiomental crease
The majority (8/11; 72.72%) of panelists agreed that HA D was the primary recommendation for the treatment of the labiomental crease.It was further recommended that the depth of injection be the subcutaneous layer, using either a 27G needle or 25G cannula.
Responders recommended that injectors consider an evaluation of the chin area when treating the labiomental crease, as there may be innate deficits in this lower face region as a whole.For instance, HA D would be the optimal choice for a patient that presents with hollowness in the labiomental crease yet strong bony support of the chin, and as such does not require additional projection.
• HA L (4/11; 36.36):HA L was recommended as an ideal product to use in this region, particularly for patients with a deficit in bony support (vs. a soft tissue deficit).For example, HA L may be better suited than HA D for treating a receded chin with a deep labiomental crease, where a product will not integrate into surrounding tissues and can provide more projection.Additionally, subcutaneous placement of HA L was recommended for use in individuals with thick skin.

Marionette lines
Most responders (8/11; 72.72%) recommended the use of HA D for the treatment of the marionette lines using a 27G needle or a 25G cannula.The recommended depth of injection was noted to be in the subcutaneous plane or supraperiosteally, between the ligaments at the base of the marionette lines.Depending on skin thickness and treatment goals, additional products may be considered for this indication, as described below.
• HA R (5/11; 45.45%): HA R was recommended for individuals with thin skin, minor deficits in the marionette region, and/or who are looking to maintain animated expression.Due to its low G' value, HA R can be placed more superficially and used to camouflage muscle movement in patients presenting with hypermobility in the region.
HA R should be injected with a 29G needle or 25G cannula.
• HA REST (3/11; 27.27%):In patients with thick skin and/or severe volume loss, HA REST can be used to treat the marionette lines.It was suggested that HA REST be placed in small aliquots, in a matrix-like fashion, to provide support to very deep lines.Use of HA REST for the marionette lines was also found appropriate for male patients.
The use of very superficial techniques in such folds, such as the fern technique, may be helpful. 6

Chin
The preferred product used by advisors in the chin was HA L (11/11; 100%).This was the only anatomical region wherein a 100% consensus could be reached for the preferred product choice.It was recommended that HA L be injected with a 27G needle at a supraperiosteal plane.It was noted that in general, a needle is easier to use for injections of the chin because of the difficulty in keeping the cannula within the correct plane and to follow the curvature of the chin.
However, the determination of using a needle or cannula depends on the plane of injection, where a 27G needle is preferred for deeper injections and a 25G cannula is preferred to superficial injections.HA L was found most suitable for patients presenting with a bony deficit.• HA L was most often used for rejuvenation of the male jawline, in patients with thick skin, or when a defined contour is sought.At the pre-jowl sulcus and gonial angle, HA L can also be injected at the level of the periosteum.This is a technically easier injection, but not as safe as the subcutaneous injection due to the depth of the facial artery.For this reason, the recommendation for the masses is to inject at the level of the subcutaneous layer.
• HA D was most often used in females, in patients with thin skin, or when a rounder, softer contour is preferred.HA D is also flexible enough to mold around the mandibular ligament, to lift it without adding volume.
Note: Exemplary cases demonstrating the use of the consensus recommendations are depicted in Figures 2 and 3.

| DISCUSS ION
There was variability among the treatment techniques proposed by this international group, with total (100%) agreement for any one recommendation being rare.This diversity of opinion may reflect geographical (e.g., types of products available on the local market), cultural (e.g., what is taught to, or considered by, injectors as "routine" practice), or ethnic/social differences (e.g., varying treatment goals) present in each respective practice.Considering the variability of opinion present in this expert group, it becomes easier to understand why some injectors find the Restylane portfolio complex to use, especially for injectors without the same level of experience and familiarity with using the portfolio as the panelists.For this reason, the present proposal sought to simplify use of the portfolio, by bringing together a global group of experts to unify and align product use recommendations.A consensus regarding the top product choice for each facial region was reached (Figure 4; Table 2).In addition, common exceptions and more advanced techniques were described.In this way, this paper benefits readers from various level of experience in different ways.For the novice injector, the top product choice can usually be selected for the "average" patient, defined as a middle-aged female with normal skin thickness and who displays signs of aging.For more advanced injectors, they can learn new tips and tricks by considering alternative product choices or treatment techniques.
While there have been several consensus statements regarding the use of HA for facial rejuvenation published in the literature to date, they present with several limitations which are absent in the present analyses.0][11] Another significant limitation of other consensuses is that they were developed by local groups (e.g., North Americans, Brazilians, Asians), and do not take into consideration the impact of geographical differences in practice. 12,13This is problematic as novice injectors are attending various training sessions (e.g., conference presentations, cadaveric  7 HA-V is marketed as "Restylane Contour" in the United States.G primes for HA-SBV and HA-SBVL have not been previosuly reported in the literature, as i) G prime is not a relevant measure for these products as they do not have filler indications (i.e., volumizing, lifting), and ii) G prime for HA-SBVL is not possible to measure because the gel is too aqueous.
Abbreviations: NASHA, non-animal stabilized hyaluronic acid; OBT, Optimal Balance Technology (marketed as "XpresHAn" in the United States).a Based on consensus recommendations for the top product choice for each facial region.

2 | ME THODS 2 . 1 |
ProceduresTwo pre-meeting, online surveys were deployed to each voting member, with the goal of collecting information on their demographics, clientele, and treatment strategies.This information was summarized, presented to the group for review, and used to formulate an in-depth discussion aimed at aligning global treatment recommendations during a consensus meeting (July 2023).

TA B L E 1
Clinical populations treated by the panelists (N = 11).

• HA D ( 5 /
11; 45.45%): HA D was recommended for use in patients with a soft tissue deficit, as it has the highest G' of the OBT family.HA D can be injected into the subcutaneous layer, and even used in a layering technique, in combination with deeply placed HA L .In this technique, HA L would lift the tissue while HA D would project tissues.JawlinePanelists reported that HA L (10/11; 90.90%) and HA D (7/11; 63.63%) were the most suitable products for the jawline area.It was recommended that both products be injected with a 25G cannula into the subcutaneous layer.It was noted that jawline treatments are often accompanied by supplemental correction of the chin, and panelists advised that injectors be conscientious of the volumes used in mobile areas, as large quantities of filler in such regions can lead to poor aesthetic outcomes.It was also advised to avoid injecting deep, near the ramus and carotid artery.

F I G U R E 2
A 34-year-old female before (left) and after (right) bilateral treatment of the tear troughs (0.25 mL per side of HA REST ), anterior-medial cheek (0.5 mL per side of HA V ), chin (1 mL of HA L ), and jawline (0.5 mL per side of HA D ).Photos courtesy of Frank Rosengaus, MD.

F I G U R E 3 F I G U R E 4
A 30-year-old female before (left) and after (right) bilateral treatment of the tear troughs (0.25 mL per side of HA REST ), lateral zygoma (0.25 mL per side of HA D ), and bridge of the nose (0.3 mL of HA L ).Photos courtesy of Frank Rosengaus, MD.Consensus recommendations for the top product choice for each facial region.TA B L E 2 Rheological properties of hyaluronic acid fillers manufactured with NASHA and OBT technology.In general, NASHA-based fillers demonstrate the highest G primes (gel strength/firmness), while OBT-based products demonstrate the highest xStrains (flexibility).Nasolabial folds, marionette lines, labiomental crease Note: G prime and xStrain data originally reported by Ohrlund et al., 2023.