Consensus recommendations on the use of injectable poly‐l‐lactic acid in Asian patients

Injectable poly‐L‐lactic acid (PLLA) has been proven safe and effective with numerous medical applications for more than 25 years. The product has been approved in over 40 countries and is being used for soft tissue augmentation in the face and certain body parts. With the increased demand for subtle and natural‐looking aesthetic treatments in the Asia‐Pacific region, there is also a heightened need for consistent preparation and effective treatment methodologies to optimize outcomes for Asian patients.


| INTRODUC TI ON
Injectable polyl-lactic acid (PLLA) is a synthetic biocompatible, biodegradable, and absorbable biostimulatory polymer that provides soft tissue augmentation.A member of the alpha hydroxy acid family, injectable PLLA (marketed under the tradename Sculptra®, Galderma) (PLLA-SCA) is injected into the reticular dermis or subcutaneous fat to gradually stimulate collagen formation over a course of several treatments, leading to gradual volume restoration and correction/restoration of facial volume loss associated with aging. 1,2This restorative mechanism is just one of the differences of injectable PLLA from hyaluronic acid fillers.
The other practical differences are described in Table 1.
PLLA has exhibited good safety and biocompatibility, featuring an array of medical applications from vectors of sustained release of bioactive compounds to surgical fixation devices and has been used for over 20 years in the field of aesthetics. 3e use of PLLA-SCA for soft tissue augmentation to cosmetically correct wrinkles and scars was first approved in Europe in 1999.
In 2004, PLLA-SCA was approved by the U.S. Food and Drug Administration (FDA) for the treatment of facial atrophy associated with human immunodeficiency virus (HIV). 3 Today, injectable PLLA is approved for use in many countries throughout the world including the Asia-Pacific region. 4The medical aesthetic market is reportedly growing more rapidly in this region compared with other parts of the world due to the increasing affluence of the population, and the popularity of cosmetic treatments. 5lturally, there is a growing acceptance of cosmetic procedures in Asia Pacific, regardless of age.The rise in aesthetic services is driven by various factors, such as the younger population seeking beautification, the aging population seeking correction and antiaging treatments, social media pressure to maintain physical appearance, the desire to allay the physical effects of a stressful lifestyle, and economic growth. 6ile Western recommendations for PLLA injections are available, [7][8][9] there is also a need for guidance on the treatment of Asian patients because Asians have differences in structural facial anatomy (e.g., a wider face; shorter vertical height; greater infraorbital volume; flatter or more concave features along the medial maxilla; lower projections of the brow, nasal and chin projection; and fuller lips) compared with Western patients. 10Asian skin also ages more slowly compared with Caucasian skin.Furthermore, the concept of beauty may differ between the two ethnicities.Hence, there is a need to provide guidance on the use of PLLA injections on Asian patients, which is currently lacking.Overall facial harmony and rejuvenation through optimization of ethnic Asian features and/or correction of deficient structural features should be the aim of aesthetic PLLA treatments. 10veraging the increasing clinical experience and anatomical insights of aesthetic healthcare practitioners, the authors formed a consensus to provide PLLA usage guidance to meet the unique needs of patients in Asia-Pacific, and to help improve patient experience and management.This consensus was developed with the authors proposing aspects on the use of PLLA that need guidance and developed recommendations through discussion.Consensus on the recommendations were decided on by votation either during an online consensus panel meeting (held on June 28, 2022) or via e-mail voting.An agreement level of 80% or higher among the authors is needed to achieve consensus.2). 9,112.1.1 | PLLA-SCA, injectable polyl-lactic acid under the Sculptra® tradename The SCRIPT study was a 48-week, 2:1 randomized, evaluatorblinded, parallel-group study with a primary efficacy endpoint of change from baseline of nasolabial folds using the Wrinkle Assessment Scale (WAS) at Week 48.The aim of the study was to compare the safety and effectiveness profiles of Sculptra when reconstituted with 8 mL sterile water for infusion (SWFI) versus 5 mL SWFI.Both included the addition of 1 mL 2% lidocaine (immediate injection post-reconstitution).A 2-72 h of standing time was included for the control group of 5 mL reconstitution. 11e study found that (1) mean change in WAS from baseline was similar in both groups across 48 weeks; (2)   TA B L E 2 Preparation and storage of injectable PLLA-SCA.

| E XPERT RECOMMENDATI ON S FOR PLL A TRE ATMENT IN
Step Recommendations Preparation 1. Ensure there is no powder sticking to the top of the vial or rubber stopper.
2. Use an antiseptic to clean the rubber stopper.
3. Add 5 mL of sterile water.4. Shake vigorously for approximately 1 min until a homogenous suspension is achieved.A translucent suspension with some foam on top will be obtained.5.If desired, add additional 3 mL of sterile water and shake again for a final volume of 8 mL. 11.If desired, add 1 mL of 2% lidocaine (20 mg/mL) to the solution immediately before injecting (see Final injection volume for facial treatment and Final injection volume for off-facial treatment) 100% agreement

Hydration
No need to hydrate, can be used immediately after reconstitution. 1292% agreement Storage of reconstituted PLLA Following reconstitution, the product can be used immediately or stored for up to 72 h before injection.
Refrigeration is not required. 13100% agreement Product handling Warm PLLA-SCA to body temperature to facilitate injection.Gently agitate immediately prior to injection to achieve a homogenous solution.100% agreement Final injection volume for facial treatment 9 mL, achieved by the addition of 1 mL 2% lidocaine (with or without epinephrine) immediately before injection.100% agreement Final injection volume for body treatment 9-18 mL, achieved by further dilution with additional sterile water for injection or bacteriostatic water (see Table 3) and 1 mL 2% lidocaine (with or without epinephrine) immediately before injection.85% agreement Importantly, the authors do not consider keloids as a contraindication; however, PLLA should be used with caution in these patients.
Assessments.Aside from the collection of medical data and history, some procedures can help demonstrate any objective and quantitative changes throughout PLLA treatment.Generally, patient assessment should include the following procedures 1,21,22 : • Standard photography (with considerations for background, posture, lighting, and facial expression) • Skin analysis imaging system (e.g., VISIA™, OBSERV®, Antera 3D®, among others) • Three-dimensional (3D) photo documentation • Skin pinch test 85% agreement.

| Managing expectations
Patient satisfaction can be highly subjective when it comes to aesthetic treatments.Appropriate communication between the patient and the physician is vital to achieving predictable results.
Patients need to be informed of the following treatment facets to properly manage expectations and achieve higher patient satisfaction. 9Treatment process.The gradual effects of PLLA should be explained to patients so they understand that multiple maintenance treatments will be needed for a long-lasting effect. 1,23The schedule of treatment visits and the lag time expected before visible effects of new collagen can be observed should be discussed in detail with the patient.100% agreement.
Treatment interval.For treatment intervals, 4 weeks might be too early to repeat the treatment as this is only when type 1 collagen is just beginning to be formed.Six weeks might be a more reasonable time to repeat the treatment as it takes 12-16 weeks for the formation of type 1 collagen to be completed. 992% agreement.
Amount of product and treatment costs.Physicians should explain to patients with very low facial volume or very elastotic outer skin envelope that it may take a considerable amount of product to volumize the face.The need for a surgical lift for excess skin should also be discussed with patients who have an outer skin tissue envelope. 9,17Ideally, both costs per session and the cost over the total treatment course should be discussed with the patient to ensure mutual understanding.100% agreement.
Treatment plan and aftercare.Treatment sequelae including complications and expected side effects should be discussed with the patient.Mild pain, swelling, and slight bleeding at the injection site are some of the more common short-term reactions to PLLA treatment.These expected side effects usually happen within days after the injection and can take 1-2 weeks to resolve spontaneously. 24ile the majority of the authors agree on recommending posttreatment massage, it is not compulsory.To help ensure an even distribution of the product, avoid the formation of nodules, and optimize results, the area should be massaged following each injection.Physicians can instruct the patient to perform the '5/5/5' posttreatment massage (i.e., massage the area for 5 min, five times a day, for 5 days). 1892% agreement.
Overfilling in the clinical setting.Overfilling in the first treatment session is not recommended.However, physicians can opt to overfill in later sessions when there is a marked need to fill deficiencies, but should be done with caution as it can cause marked puffiness.
Injections to the face should not exceed two vials per treatment.
Overfilling is not recommended under the instructions for use of the product. 13,2392% agreement.

| Treatment recommendations for younger patients
Patient selection and managing expectations.Younger patients may have questions about PLLA, such as the suitability of PLLA injections for younger people and the process of collagen synthesis.
The physician should address these concerns by educating the patient on how increased collagen production can provide gradual, natural-looking smoothness and softness, and a long-lasting treatment effect.
Indications.Facial PLLA treatment can address problems related to aging, structural deficits, and more.Treatments may include the replacement of volume deficit (temporal areas, medial and lateral cheek, buccal areas) and improvement in skin textures (decrease laxity and increase elasticity).Corrections of facial asymmetry and structural deficits can also be achieved with PLLA treatments.For example, while Westerners prefer more emphasis on the cheekbones, Asians generally want to correct the hollowness of the lateral and anteromedial cheek while minimizing the prominence of the lateral cheekbone.For some Asians, PLLA can be used to correct a concave forehead to show a more convex profile.
Injection techniques.The following are recommendations for facial PLLA treatment in younger Asian patients: • Follow the recommended handling, storage, and preparation of injectable PLLA (Table 1).
• Due to less volume loss in younger patients, they would require more focused injections in specific areas (compared to older patients, who would need diffused injections in more areas).
• The proper plane of injection is medium to deep (subdermal to subcutaneous) (in contrast to older patients who would require injection in multiple planes).
• For the temporal area, consider the use of a needle using bolus injections.For the midface, a cannula should be used for threading and fanning techniques.

92% agreement.
Treatment plan.Discuss with the patient that the treatment plan will most likely include 3 +/− 1 sessions, using one to two vials per session with 4-to 6-week intervals, using three to six vials in total.92% agreement.

| Treatment recommendations for patients aged 40s to 50s
Indications.The most common priority areas in this age group among Asians are tear trough/malar volume loss (rated by physicians) and nasolabial folds (rated by patients). 10PLLA is uniquely suited to address volume loss in the malar region as well as the temples.To help achieve comprehensive rejuvenation, a combination treatment of PLLA and hyaluronic acid (HA) fillers may be used on the face and neck. 25jection techniques.The following are recommendations for facial PLLA treatment in Asian patients aged 40s to 50s: • Follow the recommended handling, storage, and preparation of injectable PLLA (Table 1).
• PLLA can be used effectively by injecting it into the temporal fat pads.The fat pad (found between the superficial and deep

| Treatment recommendations for patients age 60s
Indications.For patients aged 60 and above, numerous indications are usually present including sagging skin and jowls.A decrease in collagen, loss of fat, epidermal thinning, and changes to the bony aspects of the face all contribute to this complex aging process. 26jection techniques.The following are recommendations for facial PLLA treatment in patients who are in their 60s: • Follow the recommended handling, storage, and preparation of injectable PLLA (Table 1).
• The treatment of patients in their 60s requires treatment in several areas.
• A multilayer approach for volume lifting, "re-inflation" of tissues, and "rebuilding the tent poles" that support facial structures (i.e., restore the bony structure, deep fat tissue, subdermal support) should be utilized.This approach is recommended as it results in a more natural look.
• Physicians should take note of these considerations in technique when treating the subdermal layer, deep fat layer, and supraperiosteal layer: • Superficial injections alone can result in "doughy" features.
• Too much injection volume can inhibit muscle action.
• Injecting directly inside the periosteal membrane might result in hard nodules.
Treatment plan.Generally, more areas are treated and more vials are used for patients in their 60s.To support the multilayer approach for a more natural look, treatments should be regular to combat the continuous aging process rather than to correct aging effects over a short duration.Physicians should provide instructions on what the patient should expect after treatment (e.g., mild pain at the site, swelling, tenderness, or slight bleeding).Post-treatment massage techniques ('5/5/5' massage) can also be recommended.100% agreement.

| Other considerations
The following are general considerations for Asian patients undergoing facial PLLA treatment: • For heavy faces, physicians should look for areas of volume loss and PLLA may be injected into those areas to add more support and lifting.Heavy faces allow for more specific injections, especially in the upper half of the face, which pulls up the lower face.
This approach generally produces the more desired inverted triangle facial shape.PLLA can also be injected posteriorly to the hairline and also intradermally to improve skin laxity.85% agreement.
• The authors have noted that their patients who are athletes seem to experience a shorter duration of effect with PLLA.However, athletes can still benefit from PLLA as they generally have less superficial and deep subcutaneous fat.85% agreement.
• Smokers have perioral creases, which can be treated with injectable PLLA.A single study found that smokers have less giant cell formation, which lowers collagen production. 27However, other authors did not find any substantial difference in the effects of PLLA among smokers.85% agreement.
• HIV-infected patients may have wasting, which would also benefit from PLLA. 28100% agreement.

| Body treatment with PLLA
Indications.PLLA has long been used for facial indications and these indications have expanded over the years to include off-face areas, such as the neck and chest, abdomen, arms, hands, thighs, knees, and buttocks. 9,29,302][33] For the neck, only the lateral aspects need to be treated.85% agreement.
Injection techniques.The following are recommendations for PLLA body treatment in patients in Asia-Pacific: • Follow the recommended handling, storage, and preparation of injectable PLLA (Table 1).
• Table 3 shows the recommendations for PLLA body treatment in Asian patients.
• Physicians can also use one to two vials with a dilution of 16 mL for an A4-sized area.
• The use of 22-25G cannulas or 25-26G needles is also recommended for body indications.

| Managing adverse events
While the majority of the authors recommend PLLA treatment injection because of its abundant safety data and lower complication rate, the best practice is to maintain vigilance for the common side effects of PLLA to ensure predictable results and increased patient satisfaction.The following are the most common side effects associated with PLLA injections 1,9 : • Pain in post-injection site.
• Localized redness, bruising, swelling, and tenderness-mostly mild to moderate and self-limiting.
5][36][37] Long-term studies are also underway to more comprehensively evaluate the safety of these higher reconstitution volumes. 38e authors noted that AEs experienced in their clinical practice were rare (<10%).100% agreement.
The following are recommended techniques to help alleviate nodules 39 : • An 80% improvement was noted when nodules were treated with normal saline solution after two to three sessions.
• For non-inflammatory nodules, intralesional normal saline injection with lidocaine may be used.Intralesional triamcinolone can be used for inflammatory granulomas.
TA B L E 3 Summary of PLLA off-face usage for body rejuvenation.

| PLLA combined with other facial rejuvenation procedures
Injectable PLLA can be used with other facial rejuvenation procedures because of its biocompatible and biodegradable microparticles.PLLA, CaHA, and HA are commonly used in combination with one another, with neurotoxins, and with energy devices. 9,40,41ile there are marked differences between PLLA and HA (Table 1), these differences complement each other when used in combination therapy.Importantly, the combination of PLLA and HA may be used in precision treatment to individualize treatment results depending on the patient's needs and desired effects.
Indications for use.HA is more suitable for hyperdynamic areas and/or thin skin (e.g., the forehead, under the eye, nose, lip, or chin) than PLLA, which may have a risk of nodules.In contrast, PLLA-SCA would be more appropriate for the jaw line or lateral cheek, and for the treatment of broader areas to improve fine wrinkles and sagging (e.g., ages 30s to 50s).Both PLLA and HA may be used for the anteromedial cheek and the nasolabial fold.PLLA with energy-based devices (EBDs).Typically, energy devices may be used first before proceeding with PLLA treatment, especially if both treatments will be done on the same day. 40,41However, it can be in any order if the treatments are done on different days.
The majority of the authors (>80%) use EBDs with PLLA in the same session.
The two kinds of EBDs used with PLLA treatment are the following: • Radiofrequency (RF) EBD.If the facial volume is satisfactory, monopolar RF treatment may be done every 6-12 months for the maintenance of skin elasticity, improving fine wrinkles, and sagging.However, if the volume is not satisfactory, the additional treatment with one to two vials of PLLA every year is recommended.The injection of PLLA first stimulates fibroblast formation, which may result in better effects from RF when performed 1 month after.
• High-intensity focused ultrasound (HIFU) EBD.HIFU can be used together with PLLA but not with RF.Microfocused ultrasound targets various planes and may be done before or after PLLA injection.However, PLLA treatment is recommended first to reduce the need for energy devices.This approach may also be used to minimize pain for patients with thin facial skin.
PLLA with oral supplements.None of the authors recommend oral supplements due to concerns about their efficacy.

| SUMMARY
The safety and efficacy profile of PLLA has remained reliable globally This was followed in 2009 by an approval for cosmetic treatments in immunocompetent patients for correction of shallow to deep nasolabial fold contour deficiencies and other facial wrinkles in which deep dermal grid pattern injection technique is appropriate.PLLA-SCA also received approvals in Australia in 2008, Taiwan and Korea in 2010, Singapore in 2011, Hong Kong and Malaysia in 2017, and the Philippines in 2019.

A S IAN PATIENTS 2 . 1 |
PLLA-SCA preparation, reconstitution, dilution, and storage Advancements in clinical insight and experience have led the way to changes in techniques in proper PLLA preparation and storage.Before these new clinical techniques are discussed, it is important to note first the recommended PLLA-SCA product preparation (Table 20 100% agreement.Attitudes toward treatment.Physicians should also include personality as an important consideration as some patients may feel dissatisfied despite the good effects of treatment.85% agreement.Contraindications.The product information of PLLA-SCA lists the following as contraindications to its use: (1) history of hypersensitivity to any of the constituents to the product; (2) severe allergies manifested by a history of anaphylaxis or history or presence of multiple severe allergies; (3) active disease, such as inflammation (skin eruption such as cysts, pimples, rashes or hives), infection or tumors, in or near the intended treatment site, until the underlying process has been controlled; and (4) for PLLA-SCA with lidocaine, a history of hypersensitivity to lidocaine or other amide-type local anesthetics.13 Physician and patient communication.Clear communication between the physician and the patient is key to developing realistic treatment goals.Patient communication can be facilitated through various means like the presentation of visual aids, counseling, and the concise discussion of a personalized PLLA treatment program.100%agreement.Visual comparisons or data.Visual comparisons or graphs from clinical studies can help educate the patient about the treatment process in a visual way for easier understanding and greater retention.Photographs help in showing the long-term benefits, so ensure that pretreatment photographs using standardized lighting are well taken.Photographs of the skin pinch test as well as dynamic videos can help patients visualize and appreciate the treatment results.21,22100% agreement.Realistic treatment goals.Physicians can counsel the patient about realistic treatment goals and how there are different responses for different patients.Patients should be educated about aging-associated volume loss and how responses to the treatment depend on each unique patient profile. 9100% agreement.
Physicians should provide instructions on what the patient should expect after treatment (e.g., mild pain at the site, swelling, tenderness, or slight bleeding).The physician should instruct the patient to avoid the use of cosmetics on the needle entry sites on the day of treatment.After the treatment, the patient's usual daily skincare regime can be continued and cosmetics can be used in case of bruising on Day 2. As mentioned earlier, post-treatment massage techniques such as the '5/5/5' massage can help distribute PLLA more evenly.
temporal fascia) is an extension of the buccal fat pad.Hence, treatment of the temporal fat pad may cause lifting of the midface.85% agreement.Treatment plan.Physicians should provide instructions on what the patient should expect after treatment (e.g., mild pain at the site, swelling, tenderness, or slight bleeding).Post-treatment massage techniques, such as the '5/5/5' technique, can be performed to aid PLLA distribution.For maintenance, PLLA can be repeated when effects are declining.The duration of treatment effect should be explained to patients as aging also persists, which contributes to the declining effects.Yearly follow-ups can be done but the physician should decide on the need for additional PLLA treatment on a caseby-case basis.92% agreement.
Physicians should provide instructions on what the patient should expect after treatment (e.g., mild pain at the site, swelling, tenderness, or slight bleeding).Post-treatment massage techniques, such as the '5/5/5' techniques, are recommended.85% agreement.

41
For the anteromedial cheek, HA filler is injected into the suborbicularis oculi fat layer (deep) while PLLA is injected into the subcutaneous and subdermal layers.For the nasolabial fold, HA filler is injected into the supraperiosteal layer while PLLA is injected into the subcutaneous layer.Injecting PLLA along the lateral face and fillers medially is also recommended.100% agreement.Practical injection considerations.A mixture of 1:100 000 epilidocaine and a 22-25G microcannula is used for PLLA, with a retrograding injection technique to minimize bruising and tissue injury.A thicker gauge prevents the clogging of the cannula.However, a 25G to 26G needle may be used on the temporal and alar recesses.100% agreement.Combining PLLA with other fillers or botulinum toxins.Combination treatment can reduce AEs as it reduces the amount needed for each individual treatment.All (100%) authors inject toxins in the same session as PLLA.All (100%) of the authors also inject HA fillers with PLLA in the same session.However, the fillers are injected into areas other than the PLLA-treated area.

for more than 20
years.Various factors influence the fast-moving, aesthetic outlook in the Asia Pacific region, and the reported Asian commonality of preference for natural-appearing enhancements makes injectable PLLA a unique treatment option for this population.While facial volumization is the main objective in patients seeking nonsurgical treatments, the strategy varies for younger and older patients.Younger Asians opt for injectable PLLAs to improve structural features with subtle and natural-looking results, whereas older patients choose PLLA treatments to lessen the signs of aging due to volume loss and sagging skin.Off-face uses of PLLA are increasingly being utilized in Asian clinics, bringing new techniques to the table and ushering in continuous improvements in treatment methodologies.

Table 2
was updated based on the results of the Sculptra Contemporary Reconstitution and Injection Procedure Trial (SCRIPT) study.

A SS E SS MENT AND S ELEC TI ON
19d the influence of social medial.10Ingeneral,lessPLLAvolume(aswithother types of fillers) is required in younger patients to achieve the desired results. 17greement.Patient's habits.Patients' habits can directly or indirectly affect the outcome of PLLA treatments.Smokers typically have poor skin quality characterized by premature aging, early skin wrinkling, and skin dryness due to reduced skin microcirculation.18Improperdiet,especiallyinadequateprotein intake, can also result in poor skin quality and effect collagen production.19100%agreement.Period of treatment results.Physicians should assess whether the patient needs immediate or gradual results.A patient seeking immediate gratification might not be a good candidate for PLLA treatments as visible results are typically observed after the third monthly treatment.Patients who seek a rejuvenated appearance with long-lasting outcome may be more suitable candidates.A survey about treatment desires reported that 75% of women preferred gradual results that last for 2 years over immediate results lasting for 12 months.
Patients can be reassured if the nodules are non-visible, whereas physicians should watch and wait or treat with oral corticosteroids if the nodules are visible.Steroid injections may stimulate the nodules.Cannulas are recommended for use in the administration of PLLA.Pain, swelling, and bruising in the treatment area following the use of cannulas are considered mild AEs and should be expected.A recent study demonstrated the safety of using a cannula in PLLA injections.A single-center, retrospective chart review of 27 patients who were treated with PLLA in the face and/or neck regions found that the incidence rates of AEs remained low if appropriate PLLA preparation and treatment techniques were followed.The study