Importance Currently, there are no standardized outcome domains or measures in clinical trials for facial aging. Heterogeneity in outcome domains and measurement instruments across clinical trials creates difficulty in directly comparing interventions, determining superior therapies, and developing high-quality meta-analyses. Objective To develop a core outcome set (COS) of essential domains to be reported in clinical trials evaluating the efficacy of interventions for facial aging. Evidence Review PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from September 2005 to September 2015. An updated search of the same databases was performed from September 2015 to February 2026. Studies were included if (1) they were randomized clinical trial or controlled clinical trial in design, (2) they assessed the efficacy or safety of an intervention for facial aging, (3) they were published in English, and (4) they involved human participants. Complementary sources, including patient interviews, were used to capture further relevant outcomes. Two rounds of Delphi surveys, followed by consensus meetings, were used to identify outcome domains considered most important by both patient and physician stakeholders. Findings The final COS consists of 6 outcome domains: (1) overall convenience of treatment; (2) time to return to normal work and social activity; (3) overall assessment of focused area of treatment (at the point in time when treatment is expected to provide peak benefit); (4) duration of treatment effect; (5) severity of persistent local or systemic adverse events, including pigmentary change, skin texture change, delayed healing, scarring, and serious adverse events; and (6) patient satisfaction with treatment. Conclusions and Relevance The 6 outcome domains identified through a Delphi consensus are recommended for reporting in future facial aging trials to ensure that outcomes that matter most to patients and clinicians are measured and that results are comparable across interventions.
Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Cutaneous Biology: Implications for Skin Disease and Longevity
BACKGROUND Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have expanded from metabolic therapeutics to agents with broad effects on inflammation, tissue repair, cutaneous and adipose biology, and aging-related pathways. Clinicians increasingly encounter cutaneous manifestations and aesthetic sequelae with important implications for dermatologic counseling and multidisciplinary care. OBJECTIVE To review current evidence regarding GLP-1RA effects on skin biology, inflammatory dermatoses, wound healing, cutaneous adverse events, and aesthetic aging. MATERIALS AND METHODS A narrative review of clinical, translational, and mechanistic literature was performed, emphasizing psoriasis, hidradenitis suppurativa, wound repair, skin hypersensitivity reactions, autoimmune blistering disease, and facial volume loss associated with pharmacologic weight reduction. RESULTS GLP-1RAs are hypothesized to improve inflammatory skin conditions and wound repair through anti-inflammatory, immunometabolic, and proreparative pathways. Yet, their use may also be associated with injection-site reactions, hypersensitivity eruptions, rare autoimmune blistering disorders, and clinically significant facial deflation and skin laxity. Current evidence is strongest for mechanistic plausibility and observational clinical signals, whereas dermatology-specific randomized trials remain limited. CONCLUSION GLP-1RAs exert bidirectional effects on cutaneous biology. Recognition of both therapeutic opportunities and potential aesthetic or adverse sequelae is important, with patient counseling ideally occurring within a multidisciplinary framework that integrates metabolic benefits with skin health and appearance.
Intralabial Lip Compartments and Their Potential Clinical Relevance
Background: Aesthetic soft-tissue filler injections for lip enhancement are popular and performed throughout the world. When injecting lips with a cannula, as the cannula is advanced, resistance is perceived in consistent locations, potentially indicating boundaries between intralabial compartments. Objective: We aimed to investigate whether intralabial compartments exist and, if so, to describe their volumes, location, boundaries, and dimensions. Methods: This cadaveric study investigated a total of 20 human body donors (13 male, seven female) with a mean (SD) age at death of 61.9 years (23.9) and body mass index of 24.3 kg/m2 (3.7). The investigated cohort included 11 White donors, eight Asian donors, and one Black donor. Dye injections simulating minimally invasive lip treatments were conducted. Results: Independent of sex or race, six anterior and six posterior compartments in the upper and lower lip were identified, for a total of 24 lip compartments. Compartment boundaries were formed by vertically oriented septations that were found in consistent locations. The anterior compartments had volumes ranging from 0.30 to 0.39 cc; the posterior compartment volume ranged from 0.44 to 0.52 cc. The compartment volumes were larger centrally and decreased gradually toward the oral commissure. Conclusions: The volume and size of each of 24 compartments contribute to the overall appearance and shape of the lips. To achieve a natural lip shape preserving aesthetic outcome it may be preferable to administer the volumizing product using a compartment-respecting injection approach.
Background: Despite various aesthetic trends, the ideal lip proportion and lip volume remains elusive. Thus, the aim of this study was to investigate the aesthetic perception of various lip shapes to identify the most attractive lips. Methods: Fifty-nine White study participants with a mean age of 32.73 ± 9.4 years were asked to assess lips of various proportions and of various volumes. Gaze assessment and aesthetic rating of the same set of modified lip images were performed. Results: The results revealed that the lip proportion that was rated to be most attractive was the 1:1.6 ratio (upper-to-lower lip, 4.21 of a possible 5). This lip proportion, however, was not the first one to be viewed on initial image display (1.20 sec) and had the shortest duration of a stable eye fixation within the 6-second image display interval (2.18 of 6 seconds). The lip volume that received the highest aesthetic rating was the 100 percent volume (original lip size), with 4.56 of a possible 5. This lip volume, however, had the third longest interval between initial image exposure and the first stable eye fixation (0.81 second) and had the shortest duration of stable eye fixations during the 6 seconds of image display (2.22 of 6 seconds). Conclusion: The results presented could be potentially reflective of the internal cognitive processes during the involuntary and voluntary assessment of lip attractiveness.
Facial Soft Tissue Repositioning With Neuromodulators: Lessons Learned From Facial Biomechanics
Abstract Background Neuromodulators have proven efficacy in reducing facial rhytides and have also been reported to improve jawline contour and the appearance of platysmal bands. Lifting effects of the tail of the eyebrow are expected outcomes when targeting the lateral periorbital region, underscoring the versatility of neuromodulator treatments. Objectives The aim of this study was to analyze the clinical effectiveness of a novel neuromodulator-based injection algorithm with regards to its ability to reposition the middle and lower facial soft tissues. Methods Seventy-five study participants (8 males, 67 females) with a mean [standard deviation] age of 37.5 [8.5] years were injected with neuromodulators in the subdermal plane of the mandibular soft tissues following a standardized algorithm. Live rating of clinical appearance was performed, as well as volume change and skin vector displacement measured by 3-dimensional imaging at baseline, Day 14, and Day 30. Results Three-dimensional volume analysis revealed an increase in midfacial volume by 0.46 mL, and a decrease of the lower facial volume by 0.30 mL compared with baseline. Additionally, an improvement of midfacial fullness (by 0.13) and jawline contour (by 0.44) was reported on clinical rating scales at Day 30 compared with baseline. Conclusions Facial soft tissues can be repositioned during the 30-day follow-up period following a neuromodulator treatment; this was reflected through an increase in midfacial volume as well as through a decrease in lower facial volume. The novel injection algorithm presented can provide a safe and effective option for patients desiring improvement of midfacial fullness and jawline contour with neuromodulator treatment alone. Level of Evidence: 4
Validated 5 – Point photonumeric scales for the assessment of hand atrophy
AbstractObjectiveQuantifying the degree of dorsal hand atrophy is a challenging endeavor, but often necessary, in both the clinical and the research setting. The aim of this investigation was to create and consecutively validate a 5‐point photonumeric scale for assessment of dorsal hand atrophy.Material and MethodsA medical team created a novel 5‐point photonumeric scale. Twelve international raters were involved in the digital validation, while five raters performed a live validation.ResultsFor the digital validation of the Croma Hand Atrophy Assessment Scale, a total of 72 subjects (58 females, 14 males) with a mean age of 43.0 ± 14.4 years [18–73 years] were assessed. For the live validation, 88 subjects (73 females, 15 males) with a mean age of 45.0 ± 14.1 years [20–73 years] were rated. The results revealed almost perfect intra‐rater (ICC: 0.90 [95% CI: 0.88–0.92]) and inter‐rater agreements (ICC: 0.85 [95% CI: 0.81–0.89] and 0.86 [95% CI:0.82–0.89]) in the digital validation and substantial intra‐rater (ICC: 0.79 [95% CI: 0.75–0.82]) and inter‐rater agreements (ICC: 0.75 [95% CI: 0.68–0.81] and ICC: 0.67 [95% CI: 0.54–0.77]) in the live validation.ConclusionThe created scale to assess dorsal hand atrophy has been shown to provide substantial‐to‐almost perfect agreement in the digital and live validation cycles and reached comparable intra‐rater and inter‐rater agreement to already published and validated scales. It is expected that the created scale will help physicians and researchers in the assessment of hand atrophy in the clinical and research setting in the future.
Validated 5‐point photonumeric scales for the assessment of the jowls and chin
AbstractObjectiveThe objective of this investigation was to create and to examine the reproducibility and validity of 5‐point photonumeric assessment scales that allow objective assessment of chin retrusion and jawline sagging using a digital and a live validation.Material and methodsTwo new 5‐point photonumeric scales created to assess chin projection and jawline sagging were validated by 12 experts in a digital validation and by 5 experts in a live validation setting. Intra‐rater agreement and inter‐rater agreement were assessed.ResultsFor the digital validation, an almost perfect intra‐rater (Kappa: 0.89 [95% CI: 0.86–0.91]) and almost perfect inter‐rater agreement in both sessions (Kappa: 0.80 [95% CI: 0.74–0.86] and 0.80 [95% CI: 0.74–0.86]) was achieved for the Croma Chin Projection Assessment Scale, while intra‐rater agreement (Kappa: 0.88 [95% CI: 0.85–0.91]) was almost perfect for the Croma Jawline Sagging Assessment Scale and inter‐rater agreement being substantial in the first session (Kappa: 0.76 [95% CI: 0.71–0.81]) and almost perfect in the second session (Kappa: 0.81 [95%CI: 0.76–0.85]). For the live validation, intra‐rater agreement was almost perfect for the Croma Chin Projection Assessment Scale (Kappa: 0.82 [95%CI: 0.74–0.90]) and the Croma Jawline Sagging Assessment Scale (Kappa: 0.83 [95%CI: 0.77–0.89]), while inter‐rater agreement was substantial in both sessions for both scales.ConclusionThe created chin and jawline photonumeric grading scales are valid and reliable tools for assessing chin projection and jawline sagging. The scales will be of value for standardized chin evaluation and quantifying outcomes in clinical research and daily practice.
Validated 5‐point photonumeric scales for the assessment of the periorbital region
AbstractObjectiveThe objective of this investigation was to create and validate 5‐point photonumeric scales for the assessment of dynamic crow's feet, static crow's feet, and infraorbital hollows.Material and methodsThree novel 5‐point photonumeric scales were created by a medical team. A total of 12 raters from all over the world performed a digital validation, and a total of 5 raters a live validation of the created scale.ResultsThe statistical analysis revealed almost perfect intra‐rater and inter‐rater reliability in the digital validation of the scales for the assessment of static and dynamic crow's feet as well as infraorbital hollows. In the live validation, both crow's feet scales showed almost perfect intra‐rater reliability, while the Croma Infraorbital Hollow Assessment Scale showed substantial intra‐rater reliability. Inter‐rater reliability was substantial for all three scales in the live validation. All three scales, the Croma Dynamic Crow's Feet Assessment Scale, Croma Static Crow's Feet Assessment Scale, and Croma Infraorbital Hollow Assessment Scale, were validated digitally and in a live setting.ConclusionThe created scales to assess infraorbital hollowing, dynamic and static crow's feet have been shown to provide substantial to almost perfect agreement in the digital and live validation and can thus be considered as helpful tools in the clinical and research setting. While technical methods and appliances to assess the degrees of severity of age‐dependent features are advancing, validated scales are of great importance due to their ease of use and, as shown by the validations, reliability, and reproducibility.
Real-Time Ultrasound Imaging of the Tear Trough: Lessons Learned From Functional Anatomy
AbstractBackgroundThe tear trough is one of the most challenging facial regions for soft-tissue filler injections. A thorough understanding of the underlying facial, muscular, and vascular anatomy is crucial to perform safe and effective tear trough injectable treatments.ObjectivesThe authors sought to evaluate the location and function of the angular vein in the tear trough in 3 different facial expressions: repose, smiling, and max. orbicularis oculi contraction.MethodsTwenty study participants with a mean age of 48.3 years and mean BMI of 24.5 kg/m2 were investigated via functional ultrasound imaging. The diameter of the angular vein and the velocity and direction of venous blood flow were analyzed in repose, smiling, and during max. orbicularis oculi contraction.ResultsThe angular vein was identified in 100% of the cases to travel inside the orbicularis oculi muscle (intra-muscular course) within the tear trough, whereas the angular artery was not identified in this location. The distance between the angular vein and the inferior orbital rim was (lateral to medial): 4.6 mm, 4.5 mm, 3.9 mm, and 3.8 mm. The caudally directed blood flow was in repose 10.2 cm/s and was 7.3 cm/s at max. orbicularis oculi muscle contraction; however, no blood flow was detectable during smiling.ConclusionsThe diameter and the venous blood flow of the angular vein varied between the 3 tested facial expressions. Based on these anatomical findings, the deep injection approach to the tear trough is recommended due to the intramuscular course of the angular vein.