appearance. Subjects were required to sign informed consent for participation in the study.
Key exclusion criteria included previous facial surgery or permanent implant in area to be treated; permanent filler or fat injection in the facial area; treatment with non-HA fillers in the last 24 months; treatment with HA fillers in the facial area within 12 months before treatment; and revitalization treatment with neurotoxin, laser or light, mesotherapy, chemical peeling, or dermabrasion in the facial area within six months before treatment. Exclusion criteria also included hypersensitivity to any ingredient of the study product or to anesthesia, history of severe allergies, active skin disease, inflammation, or other related conditions in the treatment area.
Treatment Procedure
Subjects were treated with HAR and/or HARL in 2–4 of predefined areas; upper cheeks, nasolabial folds, temples, nose, and chin, including at least one of the mandatory areas, upper cheeks and nasolabial folds. The aim of the treatment was to achieve a clinically meaningful improvement in facial appearance using 3–5 mL study products. The investigator could choose what study product(s) to use in different facial indications, in accordance with the Instructions for Use, and was free to use both products in one subject. However, only one study product and a maximum of 2 mL could be used in each treatment area. A second treatment was performed after 12 months in the same treatment areas and with the same product(s) as used at the first treatment (maximum volume 3 mL). Touch-up of 1 mL was allowed 1 month after both treatments. Subjects were followed for 24 months after initial treatment, including an optional third treatment at the end of the study (Figure 1).
Outcome Assessments
Photographs were taken at all study visits to the clinic to document treatment effect. Standardized 2D/3D photographs were taken at each visit from different angles with the LifeVizâ„¢ II camera system (QuantifiCare, France).
The primary objective of the study was to evaluate perceived improvement of facial aesthetic appearance 6 months after first treatment compared to baseline, as assessed by subjects themselves using the Global Aesthetic Improvement Scale (GAIS; rating Very much improved/Much improved/Improved/ No change/Worse).
Secondary objectives included improvement of facial aesthetic appearance using GAIS, assessed by subjects (1, 3, 9, and 12 months after first treatment; 1, 3, 6, 9, and 12 months after second treatment), investigators (1, 3, 6, 9, and 12 months after first and second treatment), and three blinded evaluators with no information on study treatments (6 and 12 months after first and second treatment). GAIS ratings by subjects and investigators were performed by use of 2D-photographs, live assessment and mirror. Blinded evaluators performed the GAIS ratings retrospectively using 3D-photographs.
Subject satisfaction with facial appearance and treatment was evaluated using questionnaires at baseline, and 1, 3, 6, 9, and 12 months after first and second treatment.
A survey was completed by blinded evaluators to evaluate first impression of various measures of success (social skills, academic performance, attractiveness, dating success, occupational success, financial success, relationship success, and athletic success). Scoring from 1–10 was made for each measure and was based on retrospective review of photographs displayed on a computer screen, taken at baseline and 3 months after first and second treatment.
Upper cheek fullness and nasolabial fold wrinkle severity was assessed by investigators using validated aesthetic scales8,9 at baseline, and 1, 3, 6, 9, and 12 months after first and second treatment, and by blinded evaluators (baseline, and 6 and 12 months after first and second treatment), both using 2D photographs.
Safety assessments included recording of pre-defined expected post-treatment symptoms (ie, bruising, redness, pain, tenderness, itching, and swelling) using a subject diary during 14 days after first and second treatment. Any symptom still ongoing at day 15 was reported as an adverse event. Evaluations of adverse events were made throughout the study.
Subjects who were treated in the chin according to protocol and who were photographed before and after treatment were
