Two new clinical analyses examine how simultaneous, on-label 64-unit onabotulinumtoxinA treatment of the upper face delivers natural-looking, durable, and predictable outcomes across diverse patient populations and multiple treatment cycles.
As patient expectations around aesthetic injectables continue to rise, plastic surgeons face an ongoing challenge: delivering visible improvement while preserving natural expression. At the same time, demand is increasing for comprehensive upper-face rejuvenation performed efficiently and with predictable outcomes. Emerging clinical evidence around onabotulinumtoxinA is helping clarify how on-label dosing and simultaneous upper-face treatment can support these goals—providing surgeons with data-driven insight into achieving natural-looking results across diverse patient populations.
One body of evidence examining this approach comes from the Phase IV study, “High patient satisfaction with natural-looking results after onabotulinumtoxinA treatment for upper facial lines in a diverse population,” which was presented at the 2025 American Society for Dermatologic Surgery (ASDS) Annual Meeting. The study evaluates patient-reported satisfaction, perceived naturalness, and psychological impact following simultaneous, on-label 64-unit treatment of the glabella, frontalis, and crow’s feet. Vince Bertucci, MD, FRCPC, a board-certified dermatologist and owner of Bertucci Dermatology & MedSpa in Toronto, talked to Plastic Surgery Practice about what the findings reveal about dosing, injection patterns, and how plastic surgeons can address persistent concerns about a “frozen” appearance in everyday practice.
Plastic Surgery Practice: The study set out to address patients’ fear of looking “frozen.” Based on the findings, what specific aspects of the onabotulinumtoxinA injection patterns or dosing contributed most to the high rates of natural-looking results?
Vince Bertucci, MD, FRCPC: Our study directly addressed the common fear of an “unnatural” or “frozen” look by demonstrating that natural-looking outcomes can be achieved using the full on-label dosing of BOTOX® Cosmetic (onabotulinumtoxinA). The study specifically utilized the approved 64-Unit dose for upper facial lines with approved injection patterns. The key finding was that over 90% of participants reported high satisfaction with achieving a natural look, as measured by the Facial Line Satisfaction Questionnaire (FLSQ) at Day 30. This suggests that adherence to the established on-label dosing and injection patterns is effective in achieving patient-desired, natural-looking results while ensuring optimal efficacy.
PSP: Plastic surgeons often treat a diverse patient population. What did the data reveal about satisfaction and perceived natural outcomes across groups like toxin-naïve patients, men, Asian patients, and those with Fitzpatrick IV–VI skin types?
Bertucci: Our study was intentionally designed to include a diverse patient population, with enrollment objectives successfully met for toxin-naïve individuals (56%), men (29%), Asian patients (22%), and those with Fitzpatrick Skin Types IV, V, or VI (43%). The data revealed remarkably consistent results across these subgroups. Participants across all these diverse demographics reported high satisfaction with achieving a natural look and experienced improved psychological function. This indicates that the efficacy and natural aesthetic achieved with onabotulinumtoxinA 64U are not limited to a narrow patient profile, providing plastic surgeons with confidence in treating a broad range of patients.
PSP: This study used a simultaneous, on-label 64-unit upper-face treatment. For surgeons who may still segment treatments, what advantages did you see clinically or from a patient-perception standpoint in treating the glabella, frontalis, and crow’s feet together?
Bertucci: By using simultaneous treatment for the glabella, frontalis, and crow’s feet, we observed clear advantages from both a clinical and patient-perception standpoint.
From a patient-perception standpoint, this comprehensive approach led to high overall patient satisfaction with achieving a natural look and significantly improved psychological function. Patients reported feeling more confident, happy, and attractive.
Clinically, this approach demonstrates that treating the entire upper face together, using approved doses and injection patterns, can achieve improved appearance of upper facial lines while consistently producing a natural aesthetic. This holistic treatment strategy can lead to harmonized results across the upper face, overall natural outcomes and potentially streamline the treatment experience for both the patient and the provider.
PSP: The study showed meaningful improvements in psychological well-being. What changes in patients’ self-perception—confidence, attractiveness, emotional well-being—stood out most, and how should surgeons interpret this in patient counseling?
Bertucci: The study highlighted significant improvements in patients’ psychological well-being. Participants explicitly reported feeling more confident, happy, and attractive after treatment. Quantitatively, there was a significant 20.1-point improvement from baseline on the FACE-Q Psychological Function scale at Day 30, indicating that patients felt distinctly more positive about their facial appearance. Providers should interpret this as a testament to the broader impact of aesthetic treatments with onabotulinumtoxinA, as it reinforces that these interventions can offer profound psychological benefits beyond just physical changes, enhancing self-perception and emotional well-being. This understanding is crucial for patient counseling, allowing surgeons to discuss not only visible aesthetic improvements but also the positive emotional and psychological uplift patients can expect.
PSP: The study used several patient-reported outcome tools. Which metrics or patient feedback provided the clearest insight into what patients consider a natural-looking aesthetic result after neurotoxin treatment?
Bertucci: We utilized multiple patient-reported outcome tools to gain comprehensive insight. The primary endpoint, which measured responder status of ‘mostly satisfied’ or ‘very satisfied’ with achieving a natural look using the Facial Line Satisfaction Questionnaire (FLSQ) Follow-up Item 4 at Day 30, provided the clearest and most direct insight into patients’ perception of naturalness. With over 90% satisfaction reported, this metric directly quantified the success in achieving natural-looking results. Additionally, the Allergan Face Satisfaction Scale (AFSS)-Natural Appearance and the Neurotoxin Treatment Experience Assessment (NTEA) questionnaires further explored various attributes contributing to a natural outcome, supplementing the FLSQ data.
PSP: How did the safety profile observed in this real-world, phase IV population compare with the established safety expectations for onabotulinumtoxinA in upper facial lines?
Bertucci: The safety profile observed in this real-world, Phase IV study population was entirely consistent with the established safety profile for BOTOX® Cosmetic (onabotulinumtoxinA) in upper facial lines. No new or unexpected safety concerns were identified in this diverse patient group, which included toxin-naïve individuals, men, Asian patients, and those with Fitzpatrick Skin Types IV-VI. This consistency further reinforces the well-known and predictable safety of on-label onabotulinumtoxinA 64U treatment for upper facial lines across a broad patient demographic, providing continued confidence for plastic surgeons in its use.
While patient perception and satisfaction speak to real-world success, a second analysis—also presented at the 2025 ASDS Annual Meeting—examines how the same 64-unit upper-face approach performs across multiple treatment cycles, including durability, onset of effect, and region-specific response. That work is detailed in the post hoc analysis, “Efficacy of OnabotulinumtoxinA 64U for Simultaneous Treatment of Forehead, Glabellar, and Lateral Canthal Lines: Post Hoc Analysis Insights From 3 Treatment Cycles.” Rosalyn George, MD, a board-certified dermatologist and founder of Wilmington Dermatology Center in North Carolina, shared with Plastic Surgery Practice how these data support a standardized, single-session upper-face protocol and what they mean for long-term treatment planning and patient counseling.
Plastic Surgery Practice: What clinical rationale supports using 64 units to treat the forehead, glabella, and crow’s feet simultaneously, and how might this influence real-world treatment planning for plastic surgeons?
Rosalyn George, MD: The clinical rationale for the 64 unit (U) dose (20 U FHL, 20 U GL, 24 U LCL) for simultaneous upper facial lines (UFL) treatment is rooted in the widespread use of onabotulinumtoxinA for these areas and a clear patient desire for comprehensive upper-face rejuvenation. This specific combined dosage demonstrated significant improvements in dynamic lines at maximum contraction and lines at rest across all three treatment cycles. For plastic surgeons, this provides a validated, standardized, and efficient “single-session” approach to addressing the entire upper face, streamlining treatment protocols and addressing interconnected aesthetic concerns for optimal patient outcomes.
PSP: Responder rates remained consistently high across all three treatment cycles. What do you think contributes to this durability, and how should surgeons interpret it when discussing repeat treatment expectations with patients?
George: The consistently high responder rates across all three treatment cycles suggest a highly durable and reproducible efficacy for onabotulinumtoxinA 64U. This sustained performance likely stems from the effective and long-lasting results at the established dosage and injection pattern. For surgeons, this consistency is a significant advantage: it allows them to confidently set patient expectations for similar positive outcomes with subsequent treatments, ensuring long-term satisfaction and facilitating predictable, scheduled maintenance plans. This data builds trust in the reliability of the treatment over time.
PSP: The study showed meaningful improvement in lines at rest. How should surgeons think about this outcome in the context of skin quality and early aging prevention?
George: The meaningful improvement in lines at rest is a key finding. For surgeons, this broadens the perception of onabotulinumtoxinA’s benefits beyond just muscle relaxation for dynamic wrinkles. It suggests that treatment with 64U onabotulinumtoxinA can contribute to an overall enhancement of skin texture and appearance. In the context of early aging prevention, the ability to improve lines at rest offers a more holistic and proactive approach to facial rejuvenation, helping patients maintain a smoother, more youthful complexion over time by improving intrinsic skin appearance, not just muscle-related movements.
PSP: With onset of effect reported as early as Day 1 and a median onset at Day 2, how might this rapid onset shape patient expectations?
George: The rapid onset of effect, observed as early as Day 1 with a median onset at Day 2 for UFL, is a highly desirable characteristic that significantly enhances patient satisfaction. This quick visible response allows surgeons to effectively manage patient expectations by assuring them that they will experience noticeable results very soon after treatment. This offers immediate gratification and provides practical benefits, especially for patients looking for rapid aesthetic improvement.
PSP: Were there any notable response differences between the forehead, glabellar, and lateral canthal areas, and how should those differences guide treatment customization?
George: While all areas showed strong efficacy, there were slight, but notable, differences in responder rates at maximum contraction. At Day 14 of cycle 1, the forehead lines (FHL) had the highest response at 95.2%, followed by glabellar lines (GL) at 83.9%, and lateral canthal lines (LCL) at 70.8%. These percentages, while all high compared to placebo, indicate subtle variations in the magnitude of peak improvement across regions. Surgeons can consider these nuances to guide treatment customization and, more importantly, to precisely manage patient expectations about the specific degree of improvement in each treated area, even when using a standardized UFL protocol.
PSP: The study included both a placebo-controlled cycle and open-label cycles. What should clinicians understand about the consistency and reliability of results across these phases?
George: The study’s design, incorporating both a double-blinded, placebo-controlled cycle and subsequent open-label cycles, provides a comprehensive understanding of onabotulinumtoxinA 64U. The initial placebo-controlled cycle is fundamental for definitively proving the efficacy of the treatment, establishing that observed improvements are directly attributable to onabotulinumtoxinA rather than other factors. The open-label cycles then extend this validation by evaluating the treatment’s long-term safety, sustained efficacy, and consistency over multiple administrations in a more real-world context, confirming its practical utility and predictability for repeated use. PSP
Opening photo: ID 20635570 © Konstantin Iuganov | Dreamstime.com. Headshots courtesy of Allergan Aesthetics.
