Ten-Year and Beyond Follow-up After Treatment With Highly Purified Liquid-Injectable Silicone for HIV-Associated Facial Lipoatrophy: A Report of 164 Patients.

BACKGROUND: Highly purified liquid-injectable silicone (LIS) has been established as a permanent agent for off-label correction of HIV-associated facial lipoatrophy (HIV-FLA). However, controversy exists about long-term safety. OBJECTIVE: To establish the safety and efficacy at 10 years or greater of LIS for HIV-FLA. METHODS: Patients from 3 practices with 10-year or greater in-person office follow-up were analyzed to determine the number of LIS treatments and total volume required to achieve optimal correction. The nature of any treated adverse events was noted. RESULTS: One hundred sixty-four patients had 10-year or greater in-office follow-up. All subjects maintained long-term correction with an average of 9 treatments, average of 1.56 mL per treatment, and an average total of 14.1 mL. Two patients had severe adverse events manifesting as temporary facial edema. Four patients experienced mild-to-moderate excess fibroplasia presenting as perceived overcorrection, and 6 patients had nondisfiguring subcutaneous firmness. All adverse events were successfully treatable, mostly with intralesional 5-fluorouracil and triamcinolone. CONCLUSION: Liquid-injectable silicone is an effective long-term treatment option for HIV-FLA. When injected in small quantities with the microdroplet serial puncture technique at monthly or greater intervals, optimal correction appears durable for more than 10 years. Adverse events consisted mostly of excess fibroplasia and were treatable.

Management of Patient Experience With ATX-101 (Deoxycholic Acid Injection) for Reduction of Submental Fat.

BACKGROUND: ATX-101 (deoxycholic acid injection; Kythera Biopharmaceuticals, Inc., Westlake Village, CA [an affiliate of Allergan plc, Dublin, Ireland]) was recently approved for submental fat (SMF) reduction in the United States (Kybella) and Canada (Belkyra). The pivotal trials supporting these approvals revealed that ATX-101 is associated with common injection-site treatment reactions consistent with its mechanism of action and administration procedure. OBJECTIVE: The purpose of this study was to evaluate 4 patient experience management paradigms targeting the common injection-site adverse events of pain, swelling/edema, and bruising after a single treatment session with ATX-101. METHODS: In this double-blind, parallel-group, exploratory Phase 3b study (ClinicalTrials.gov identifier: NCT02007434), subjects with moderate to severe SMF were randomized 4:1 within each paradigm to receive ATX-101 2 mg/cm or placebo. In Paradigm 1, subjects received a cold pack application to the treatment area. In Paradigm 2, in addition to cold pack application, subjects were treated with topical lidocaine and injectable lidocaine containing epinephrine. In Paradigm 3, in addition to the interventions of Paradigm 2, subjects received loratadine and ibuprofen. Subjects in Paradigm 4 received the same interventions in Paradigm 3, plus application of a chin strap. RESULTS: Eighty-three subjects were treated. In ATX-101-treated subjects, peak pain occurred within 1 to 5 minutes of treatment, with median values at these time points ranging from 21.4 to 35.7 mm on a 100-mm pain visual analog scale ("mild"). Pain ratings reduced substantially by 15 minutes; at 4 hours after injection, pain was characterized as mild tenderness or mild achiness. Compared with cold alone, treatment with topical and injectable lidocaine reduced median peak pain by 17%. Addition of ibuprofen and loratadine resulted in a total reduction in pain by 40%. Peak swelling/edema in ATX-101-treated subjects was "modest," with mean values ≤1.7 (on a 0-5 scale) across all paradigms. Swelling/edema was not substantially mitigated by the interventions, including ibuprofen, loratidine, and the use of a chin strap. Bruising associated with ATX-101 treatment was confined to the treatment area, with mean values between 1.0 and 1.4 on a 0-to-5 scale. Bruising was modestly reduced by injectable lidocaine with epinephrine. CONCLUSION: Results from this study support the safety of ATX-101 for SMF reduction, and demonstrate that pain and bruising associated with ATX-101 treatment can be mitigated by a series of simple measures.

Development and Validation of a Photonumeric Scale for Assessment of Chin Retrusion.

BACKGROUND: A validated scale is needed for objective and reproducible comparisons of chin appearance before and after chin augmentation in practice and clinical studies. OBJECTIVE: To describe the development and validation of the 5-point photonumeric Allergan Chin Retrusion Scale. METHODS: The Allergan Chin Retrusion Scale was developed to include an assessment guide, verbal descriptors, morphed images, and real subject images for each scale grade. The clinical significance of a 1-point score difference was evaluated in a review of multiple image pairs representing varying differences in severity. Interrater and intrarater reliability was evaluated in a live-subject validation study (N = 298) completed during 2 sessions occurring 3 weeks apart. RESULTS: A difference of ≥1 point on the scale was shown to reflect a clinically meaningful difference (mean [95% confidence interval] absolute score difference, 1.07 [0.94-1.20] for clinically different image pairs and 0.51 [0.39-0.63] for not clinically different pairs). Intrarater agreement between the 2 live-subject validation sessions was substantial (mean weighted kappa = 0.79). Interrater agreement was substantial during the second rating session (0.68, primary end point). CONCLUSION: The Allergan Chin Retrusion Scale is a validated and reliable scale for physician rating of severity of chin retrusion.

Consensus Recommendations for Combined Aesthetic Interventions in the Face Using Botulinum Toxin, Fillers, and Energy-Based Devices.

BACKGROUND: The aging process is a complex interplay of intrinsic and extrinsic factors across multiple layers of the face. Accordingly, combining aesthetic interventions targeting different manifestations of aging often leads to better results than single modalities alone. However, no guidelines for a pan-facial approach using multiple interventions have been published to date. OBJECTIVE: To develop consensus recommendations for the optimal combination and ideal sequence of botulinum toxin (BoNT), hyaluronic acid, calcium hydroxylapatite, and microfocused ultrasound with visualization (MFU-V) in persons of all Fitzpatrick skin types. METHODS AND MATERIALS: Fifteen specialists convened under the guidance of a certified moderator. Consensus was defined as approval from 75% to 94% of all participants, whereas agreement of ≥95% denoted a strong consensus. RESULTS: Optimal aesthetic treatment of the face begins with a thorough patient assessment and an individualized treatment plan. Spacing consecutive treatments 1 to 2 weeks apart allows for resolution of side effects and/or to assess results. For same-day treatments, BoNT and fillers may be performed together in either sequence, whereas MFU-V is recommended before injectable agents. CONCLUSION: Expert consensus supports a combination approach using multiple modalities in specific sequence for the safe and effective treatment of the aging face.

A systematic review of filler agents for aesthetic treatment of HIV facial lipoatrophy (FLA).

HIV facial lipoatrophy (FLA) is characterized by facial volume loss. HIV FLA affects the facial contours of the cheeks, temples, and orbits, and is associated with social stigma. Although new highly active antiretroviral therapy medications are associated with less severe FLA, the prevalence of HIV FLA among treated individuals exceeds 50%. The goal of our systematic review is to examine published clinical studies involving the use of filler agents for aesthetic treatment of HIV FLA and to provide evidence-based recommendations based on published efficacy and safety data. A systematic review of the published literature was performed on July 1, 2015, on filler agents for aesthetic treatment of HIV FLA. Based on published studies, poly-L-lactic acid is the only filler agent with grade of recommendation: B. Other reviewed filler agents received grade of recommendation: C or D. Poly-L-lactic acid may be best for treatment over temples and cheeks, whereas calcium hydroxylapatite, with a Food and Drug Administration indication of subdermal implantation, may be best used deeply over bone for focal enhancement. Additional long-term randomized controlled trials are necessary to elucidate the advantages and disadvantages of fillers that have different biophysical properties, in conjunction with cost-effectiveness analysis, for treatment of HIV FLA.

A Pilot Study on the Treatment of Posterior Cheek Enlargement in HIV+ Patients With Botulinum Toxin A.

BACKGROUND: Posterior cheek enlargement in human immunodeficiency virus (HIV)+ individuals can lead to significant cosmetic disfigurement. Both parotid gland and masseter muscle overlie the mandibular ramus, contributing to lower facial contour. However, posterior cheek enlargement has not been well characterized anatomically. There are also limited treatment options. Botulinum toxin is a highly efficacious minimally invasive option for improving the shape of the lower face. OBJECTIVE: A pilot study was undertaken to better characterize posterior cheek enlargement in HIV+ patients and explore treatment with botulinum toxin A. MATERIALS AND METHODS: Five HIV+ patients with posterior cheek enlargement were treated with botulinum toxin A. Clinical, photographic, and radiological evaluations allowed the precise calculation of any change in volumes resulting from botulinum toxin A. RESULTS: All 5 patients had a good response with a mean decrease of 21.4% and 11.2% in the volumes of the masseter muscle and parotid gland, respectively. The effect was long lasting even at 6 months after injection and well tolerated. CONCLUSION: Botulinum toxin A may be a less invasive treatment of posterior cheek enlargement in HIV+ patients, with advantages of a good result that is long lasting with good tolerability and minimal risk.

HIV-associated facial lipoatrophy treated with injectable silicone oil: a pilot study.

BACKGROUND: Facial lipoatrophy (FLA) is associated with HIV infection and is part of the lipodystrophy syndrome. Temporary filler treatments do not meet the need of the patient, as there is a lack of permanence, and excessive cost. OBJECTIVE: We sought to evaluate the safety and efficacy of a highly purified medical-grade 1000-cst liquid injectable silicone in the treatment of HIV-associated FLA using the serial microdroplet injection technique. METHODS: Twenty patients with HIV-associated lipoatrophy were treated with liquid injectable silicone with a maximum of 6 treatment sessions (2.0 mL each session maximum). Patients were evaluated at 9-, 12-, and 18-month follow-up sessions. Safety, efficacy, injection volumes, and patient satisfaction were evaluated. RESULTS: No persistent adverse effects were reported throughout the study. Most of the patients achieved complete correction of their HIV-associated FLA after 6 treatments and maintained this correction to the 18-month follow-up. LIMITATIONS: This is a noncomparative, nonblinded study. Study patient population size is small. CONCLUSION: Given our small sample size of 20 patients, our results suggest that, if administered correctly, liquid injectable silicone is potentially a safe, effective, and natural-feeling treatment option for HIV-associated FLA. Larger studies may be needed to confirm safety, efficacy, and permanence.

Current status of surgery in dermatology.

An article titled "Current issues in dermatologic office-based surgery" was published in the JAAD in October 1999 (volume 41, issue 4, pp. 624-634). The article was developed by the Joint American Academy of Dermatology/American Society for Dermatologic Surgery Liaison Committee. A number of subjects were addressed in the article including surgical training program requirements for dermatology residents and selected advances in dermatologic surgery that had been pioneered by dermatologists. The article concluded with sections on credentialing, privileging, and accreditation of office-based surgical facilities. Much has changed since 1999, including more stringent requirements for surgical training during dermatology residency, and the establishment of 57 accredited Procedural Dermatology Fellowship Training Programs. All of these changes have been overseen and approved by the Residency Review Committee for Dermatology and the Accreditation Committee for Graduate Medical Education. The fertile academic environment of academic training programs with interaction between established dermatologic surgeons and fellows, as well as the inquisitive nature of many of our colleagues, has led to the numerous major advances in dermatologic surgery, which are described herein.

Anatomic guidelines for augmentation of the cheek and infraorbital hollow.

BACKGROUND: Mid-face reflation requires a sophisticated knowledge of bony and soft tissue anatomy. OBJECTIVE: To blend knowledge of the relevant anatomy with clinical experience to generate procedural guidelines for reproducible volumization of the midface. METHODS AND MATERIALS: A demonstration of cadaver head dissection was followed by injection of colored hyaluronic acid and calcium hydroxylapatite fillers into cadaver heads in the anatomy laboratory. The injected cadaver heads were then dissected to assess the anatomical position of the injected fillers. Live patient injections followed using the anatomic learning. RESULTS: Best practice guidelines for midface and infraorbital hollow injections were discussed. CONCLUSIONS: Aesthetic augmentation of the midface requires knowledge of the properties of each filler and of the underlying anatomy, as well as an understanding and documentation of the subject's aesthetic concerns.

Validated assessment scales for the lower face.

BACKGROUND: Aging in the lower face leads to lines, wrinkles, depression of the corners of the mouth, and changes in lip volume and lip shape, with increased sagging of the skin of the jawline. Refined, easy-to-use, validated, objective standards assessing the severity of these changes are required in clinical research and practice. OBJECTIVE: To establish the reliability of eight lower face scales assessing nasolabial folds, marionette lines, upper and lower lip fullness, lip wrinkles (at rest and dynamic), the oral commissure and jawline, aesthetic areas, and the lower face unit. METHODS AND MATERIALS: Four 5-point rating scales were developed to objectively assess upper and lower lip wrinkles, oral commissures, and the jawline. Twelve experts rated identical lower face photographs of 50 subjects in two separate rating cycles using eight 5-point scales. Inter- and intrarater reliability of responses was assessed. RESULTS: Interrater reliability was substantial or almost perfect for all lower face scales, aesthetic areas, and the lower face unit. Intrarater reliability was high for all scales, areas and the lower face unit. CONCLUSION: Our rating scales are reliable tools for valid and reproducible assessment of the aging process in lower face areas.

Facial Soft-Tissue Fillers: Assessing the State of the Science conference---Proceedings report.

The American Academy of Dermatology and the American Society of Plastic Surgeons, with the support of other sister societies, conducted the Facial Soft-Tissue Fillers: Assessing the State of the Science conference in December of 2009. The American Academy of Dermatology and the American Society of Plastic Surgeons established a panel of leading experts in the field of soft-tissue fillers-from researchers to clinicians-and other stakeholders for the conference to examine and discuss issues of patient safety, efficacy, and effectiveness in relation to the approved and off-label use of soft-tissue fillers, and other factors, including the training and level of experience of individuals administering fillers. This report summarizes the deliberations and key points made by the panel and presenters to the panel, and includes a summary of the panel's near-term and longer term recommendations for next steps to help guide future efforts to address the safety, efficacy, and effectiveness of facial soft-tissue fillers. This report represents the panel's assessment of the medical knowledge available on facial soft-tissue fillers at the time of the conference.

Facial Soft-Tissue Fillers conference: Assessing the State of the Science.

The American Academy of Dermatology and the American Society of Plastic Surgeons, with the support of other sister societies, conducted the Facial Soft-Tissue Fillers: Assessing the State of the Science conference in December of 2009. The American Academy of Dermatology and the American Society of Plastic Surgeons established a panel of leading experts in the field of soft-tissue fillers-from researchers to clinicians-and other stakeholders for the conference to examine and discuss issues of patient safety, efficacy, and effectiveness in relation to the approved and off-label use of soft-tissue fillers, and other factors, including the training and level of experience of individuals administering fillers. This report represents the systematic literature review that examines comprehensively the available evidence and gaps in the evidence related to soft-tissue fillers, to inform and support the work of the state-of-the-science conference panel. This evidence-based medicine review will serve as the foundation for future evidence-based medicine reports in this growing field.

Multicenter, randomized, parallel-group study of onabotulinumtoxinA and hyaluronic acid dermal fillers (24-mg/ml smooth, cohesive gel) alone and in combination for lower facial rejuvenation: satisfaction and patient-reported outcomes.

BACKGROUND: Patient-reported outcomes (PROs) are important assessment benchmarks after aesthetic procedures. Systematic studies of PROs have not been conducted in the lower face. OBJECTIVE: To study satisfaction and other PROs after treatment of the lower face with onabotulinumtoxinA and a 24-mg/mL smooth, cohesive hyaluronic acid (HA) gel filler, alone or in combination. METHODS: Ninety female participants aged 35 to 55 were randomized to one of three groups: 24-mg/mL cohesive gel alone (n=30), onabotulinumtoxinA alone (n=30), or the combination (n=30). Effectiveness outcomes were investigator- and participant-rated satisfaction and the participant Self-Perception of Age (SPA) and participant-rated Look and Feel of the Lips and Mouth (LAF) questionnaires. Participants maintained a 14-day diary to record severity of treatment site responses. RESULTS: All treatments resulted in significant improvements from baseline at all end points and on all PRO measures. For all measures and most time points, the 24-mg/mL cohesive gel treatment groups experienced greater improvements than onabotulinumtoxinA alone. Participant-rated severity of treatment-related reactions was mainly mild and transient. CONCLUSION: OnabotulinumtoxinA and 24-mg/mL cohesive HA gel treatments, used alone or in combination for lower face rejuvenation, resulted in significant improvement in investigator- and participant-reported outcomes.

Multicenter, randomized, parallel-group study of the safety and effectiveness of onabotulinumtoxinA and hyaluronic acid dermal fillers (24-mg/ml smooth, cohesive gel) alone and in combination for lower facial rejuvenation.

BACKGROUND: Combination treatment with toxins and fillers is the standard regimen in facial rejuvenation. Systematic studies of botulinum toxin alone and in combination with hyaluronic acid (HA) have not, however, been conducted in the lower face. OBJECTIVE: To evaluate safety and effectiveness and compare combination treatment with onabotulinumtoxinA and a 24-mg/mL smooth, cohesive HA gel filler with either treatment alone for rejuvenation of the perioral area and lower face in female subjects. METHODS: Ninety female participants aged 35 to 55 were randomized to one of three groups: 24-mg/mL cohesive gel alone (n=30), onabotulinumtoxinA alone (n=30), or the combination (n=30). Effectiveness outcomes included perioral, lip fullness, and oral commissure assessments and scores on the Cosmetic Improvement and Global Aesthetic Improvement Scales. Adverse events were monitored throughout. RESULTS: For all end points and most time points, subjects treated with onabotulinumtoxinA plus the 24-mg/mL cohesive gel had greater improvement from baseline than subjects treated with onabotulinumtoxinA or the 24-mg/mL cohesive gel filler alone. CONCLUSION: Based on a range of end points, onabotulinumtoxinA and 24-mg/mL cohesive HA gel treatments are effective and safe when either alone or in combination to rejuvenate the lower face. Combination therapy is superior to either modality used alone.

Evaluation of injectable calcium hydroxylapatite for the treatment of facial lipoatrophy associated with human immunodeficiency virus.

OBJECTIVE: To evaluate the safety and effectiveness of soft tissue augmentation with calcium hydroxylapatite (CaHA) microspheres in an aqueous gel in patients with facial lipoatrophy (FLA) secondary to human immunodeficiency virus (HIV) disease. METHODS: This 12-month open-label, prospective study enrolled 30 subjects (29 men and 1 woman) with HIV-associated FLA. After the initial treatment phase (up to 2 injections, 30 days apart), patients were followed up at 3, 6, and 12 months. Patients were offered touch-up injections at 6 and 12 months. Measurements included confirmed changes in the Global Aesthetic Improvement Scale and in cheek thickness. RESULTS: Average initial treatment volume was 9.5 mL per patient (both sides); total volumes per patient after 12 months averaged 16.1 mL. At all time points, all patients were rated as improved or better and responded affirmatively to satisfaction questions. Cheek thickness measurements increased substantially over baseline (p<.001). Most commonly reported adverse events were edema (93%), ecchymosis (83%), and erythema (77%). CONCLUSIONS: CaHA is an appropriate and well-tolerated treatment for patients with HIV-associated FLA. With an excellent safety profile, CaHA provides immediate correction of FLA and appears to provide lasting improvement in appearance.

Radiographic and computed tomographic studies of calcium hydroxylapatite for treatment of HIV-associated facial lipoatrophy and correction of nasolabial folds.

OBJECTIVES: This study sought to assess the radiographic appearance produced by calcium hydroxylapatite soft tissue filler (CaHA; Radiesse, BioForm Medical Inc.) following augmentation to correct the nasolabial folds or facial wasting associated with human immunodeficiency virus lipoatrophy. METHODS: A total of 58 patients, with either lipoatrophy or pronounced nasolabial folds, were treated with CaHA. Radiographic (X-ray) and computed tomographic (CT) imaging studies were conducted pre- and posttreatment in most patients; the images were sent to an independent laboratory to be analyzed by two evaluators who were board-certified radiologists and blinded to study purpose, product, and patient condition. RESULTS: While results for X-ray evaluation showed inconsistencies in visualization of CaHA, CT scans showed consistent visualization in nearly all cases in patients who were imaged immediately after treatment. In addition, the results indicated no obscuration of underlying structures by CaHA and no evidence of CaHA migration. CONCLUSIONS: Earlier clinical trials established CaHA as a safe and effective soft tissue filler. This CaHA study shows no overt radiographic safety concerns. CaHA is unlikely to be confused with conventional abnormal and adverse radiographic findings. The product is not always visible on X-ray. Although usually visible on CT scans, its appearance is distinct from surrounding bony structures and does not interfere with normal analysis. In addition, the product does not obscure underlying structures on CT scans.

Hyaluronic acid gel in skin rejuvenation.

Hyaluronans have become the most popular agents used for soft tissue augmentation in the entire facial area. They are biodegradeable, nonpermanent and have a remarkable safety profile. Their natural biocompatibility means that no pretreatment skin test is necessary. The soft pliable enhancement of natural tissue turgor and contour makes them very acceptable in the lips and perioral and periocular regions. The more viscous agents are very helpful in the treatment of facial lipoatrophy particularly in the region of the cheeks and chin.

Introduction to Fillers.

BACKGROUND: Over the last few years, injectable soft-tissue fillers have become an integral part of cosmetic therapy, with a wide array of products designed to fill lines and folds and revolumize the face. METHODS: This review describes cosmetic fillers currently approved by the Food and Drug Administration and discusses new agents under investigation for use in the United States. RESULTS: Because of product refinements over the last few years-greater ease of use and longevity, the flexibility of multiple formulations within one line of products, and the ability to reverse poor clinical outcomes-practitioners have gravitated toward the use of biodegradable agents that stimulate neocollagenesis for sustained aesthetic improvements lasting up to a year or more with minimal side effects. Permanent implants provide long-lasting results but are associated with greater potential risk of complications and require the skilled hand of the experienced injector. CONCLUSIONS: A variety of biodegradable and nonbiodegradable filling agents are available or under investigation in the United States. Choice of product depends on injector preference and the area to be filled. Although permanent agents offer significant clinical benefits, modern biodegradable fillers are durable and often reversible in the event of adverse effects.

Blindness caused by cosmetic filler injection: a review of cause and therapy.

Vascular occlusion causing blindness is a rare yet greatly feared complication of the use of facial aesthetic fillers. The authors performed a review of the aesthetic literature to ascertain the reported cases of blindness and the literature reporting variations in the vascular anatomy of the human face. The authors suggest a small but potentially helpful addition to the accepted management of the acute case. Cases of blindness, mostly irreversible, from aesthetic filler injections have been reported from Asia, Europe, and North America. Autologous fat appears to be the most frequent filler causing blindness. Some cases of partial visual recovery have been reported with hyaluronic acid and calcium hydroxylapatite fillers. The sudden profusion of new medical and nonmedical aesthetic filler injectors raises a new cause for alarm about patient safety. The published reports in the medical literature are made by experienced aesthetic surgeons and thus the actual incidence may be even higher. Also, newer injectors may not be aware of the variations in the pattern of facial vascular arborization. The authors present a summary of the relevant literature to date and a suggested helpful addition to the protocols for urgent management.