Eyebrow elevation using chemomodulation and myomodulation (Hyaluronic acid gel): A cohort analysis

Abstract

Purpose:

This investigation aims to assess the clinical outcomes and patient-reported satisfaction associated with non-surgical eyebrow elevation utilizing botulinum toxin (BTX) and hyaluronic acid gel (HAG) formulations with G-prime fillers.

Methods:

A retrospective analysis was conducted on a cohort of 460 subjects who underwent eyebrow elevation procedures from 2013 to 2024. The sample comprised 276 females (60%) and 184 males (40%), with a mean age of 50 years (standard deviation [SD] = 31.1 years). In the BTX group, 20 units were administered across five injection sites, including bilateral injections into the corrugator supercilii and a unilateral injection into the procerus muscle, with 0.1 mL (4 units) per site using 31-gauge needles. Pre- and 15-day post-procedure photographic evaluations were analyzed using Adobe Photoshop, and statistical analysis was performed with Microsoft Excel.

Results:

In the BTX cohort, the average increase in eyebrow height was 1.35 mm (range: 0.6–2.1 mm; SD = 1.06 mm), with a corresponding elevation from the medial limbus to the lateral brow edge averaging 1.35 mm (range: 1.0–1.7 mm; SD = 0.49 mm). The mean patient satisfaction score at 15 days post-treatment was similar for both groups: 1.73 for BTX and 1.71 for HAG, with no statistically significant difference observed (P = 0.9540).

Conclusion:

Both BTX and HAG G-prime fillers demonstrate considerable efficacy in non-surgical brow elevation, enhancing eyebrow contour, and restoring youthful facial aesthetics. These minimally invasive interventions are viable alternatives to surgical brow-lifting techniques, yielding comparable patient-reported outcomes and satisfaction levels.

Eyebrows constitute a pivotal anatomical feature in the modulation of facial expressions and contribute significantly to overall facial aesthetics, serving as a structural framework for the upper eyelid.[1] In younger individuals, the periorbital architecture is characterized by elongated ocular structures and robust, elastic dermal tissues. However, with the progressive aging process, there is a reduction in cutaneous elasticity and an involutional deflation of subcutaneous fat, culminating in the exposure of the underlying bony orbital rim.[2,3] This dynamic alteration in periorbital morphology manifests as a flattening of the lateral eyebrow contour and a diminution of the eyebrow arch, contributing to a perceived senescent appearance.[4] These age-related morphological changes often induce a desire for aesthetic rejuvenation to restore a more youthful and harmonious appearance to the face.[5,6,7,8,9]

Historically, facial volumization techniques aimed at brow rejuvenation date back to antiquity, with early uses of paraffin injections in 19^th-century Greece.[10] In more recent decades, autologous fat grafting-often combined with blepharoplasty or injectable dermal fillers-has emerged as a strategy for periorbital restoration, achieving variable results in the repletion of lost tissue volume and the re-establishment of brow contour.[11,12,13] Despite the efficacy of these procedures, traditional surgical interventions, including various brow-lifting techniques (e.g., transpalpebral, endoscopic, temporal, coronal, and direct lifts), remain fraught with inherent invasiveness, irreversibility, and the risk of suboptimal or unnatural aesthetic outcomes.[12,13,14] There is growing demand for minimally invasive options that offer natural-appearing rejuvenation with less risk and shorter recovery time.

Among the arsenal of non-surgical interventions, botulinum toxin (BTX) has garnered significant attention as a viable approach for non-invasive brow-lifting.[15,16] The intricate dynamics of brow positioning involve a balance between the medial and lateral depressor muscles-comprising the procerus, corrugator, depressor supercilii, and lateral orbicularis-orbitally directed fibers-and the frontalis muscle, functioning as the primary elevator of the brow. BTX achieves its aesthetic effect by selectively inducing chemical denervation of the depressor muscles, allowing the unopposed frontalis muscle action to elevate the brow. A growing literature has elucidated the versatility and efficacy of BTX in brow rejuvenation, with diverse approaches concerning dosage, injection sites, and technique protocols, underscoring botulinum toxin as an indispensable tool in aesthetic neuromodulation.[17,18]

In patients exhibiting volume depletion in the periorbital region, particularly those with brow descent exacerbated by such tissue loss, hyaluronic acid (HA) gels, specifically those with higher G-prime values (indicating greater viscoelastic properties), have emerged as a promising adjunct in brow restoration.[19,20] HA-based volumizing agents have been demonstrated to improve facial volume with regenerative properties conducive to tissue restoration, including wound healing and skin repair. With context to eyebrow elevation, HA fillers offer a promising modality for re-volumizing the brow complex, enhancing its lift, and restoring a youthful contour, particularly in individuals whose response to BTX may be suboptimal due to excessive volume loss or advanced tissue laxity.

This study endeavors to critically assess the synergistic application of botulinum toxin and high G-prime HA fillers in the context of brow rejuvenation. Through a retrospective comparative analysis, we aim to delineate the clinical efficacy, safety profile, and aesthetic outcomes associated with this combined non-surgical approach. By evaluating these interventions, we seek to contribute to the evolving paradigm of facial rejuvenation, providing a comprehensive and evidence-based framework for the management of senescent alterations in the periorbital region.

Methods

Patient selection criteria

This clinical study was undertaken by The Esthetic Clinics® in Mumbai, Maharashtra, India, in full accordance with the bioethical standards. Informed consent was obtained from patients for permission to publish images and information in an open-access domain.

A total of 460 participants with an average age of 50 years (28 to 72 years) who had undergone eyebrow elevation with BTX or HAG G-prime filler injections were retrospectively included in the study. To keep the division uniform, participants were divided into two cohorts: 230 (50%) patients in the BTX cohort, and 230 (50%) in the HAG cohort.

Inclusion criteria

(1) Participants who had undergone eyebrow BTX or HAG G-prime injections within the last decade (2013–2024). (2) Participants followed-up for a minimum of 5 years; (3) No history of neurological disease; (4) Absence of baseline upper eyelid ptosis or clinically significant dermatochalasis. (5) Avoiding personal habits affecting the study parameters (injuring hair follicles, overusing tweezers, etc.)

Notably, all the administered injections were carried out exclusively by a singular oculoplastic surgeon.

Exclusion criteria

(1) Participants who underwent BTX before 2012; (2) Participants who were de-synced with the follow-up; (3) Participants who underwent procedures apart from BTX or HAG G-prime filler injections for eyebrow elevation. (4) Patients presenting with pre-existing eyelid ptosis or moderate-to-severe dermatochalasis, as these conditions could confound eyebrow elevation outcomes.

Rationale for cohort composition

A wide age range was included to reflect real-world patient diversity and assess the overall effectiveness of BTX and HAG across varying degrees of facial aging. While age impacts tissue elasticity and healing, combining all ages into a single cohort enabled a broad evaluation of treatment outcomes in standard clinical practice. Future studies may explore age-stratified analysis to better understand differential responses and refine treatment protocols.

Injection techniques

Muscle Anatomy and Function: The frontalis muscle serves as the sole elevator of the eyebrows, while the procerus and corrugator supercilii muscles act as depressors.[21] The procerus muscle runs vertically between the eyebrows, contributing to horizontal furrowing, whereas the corrugator supercilii muscles, positioned obliquely, are responsible for creating vertical frown lines by pulling the medial brow downward.[21] Additionally, the orbital part of the orbicularis oculi plays a role in depressing the brows, further complicating the balance of forces acting on this region.

Botulinum Toxin Injection Protocols: To achieve brow elevation, a vial containing 100 units of onabotulinumtoxin A is reconstituted with 2.5 cc of sterile saline. Utilizing 31 gauge needles and 1 mL syringes, we administer a total of 20 units of Botox across five targeted injection sites: two injections into each corrugator supercilii muscle and one injection into the procerus muscle (0.1 mL or 4 units per site). An additional injection of two units is placed below the tail of the brow to inhibit activity in the orbital part of the orbicularis oculi, thereby enhancing the lifting effect produced by the frontalis muscle.[22]

Hyaluronic acid gel (HAG) filler application: The HA G-prime filler injections are injected deep supraperiosteally through various layers, including the skin, superficial temporal fascia, innominate fascia, deep temporal fascia, and ultimately into the temporalis muscle adjacent to the bone.[10] This injection technique induces a bulging effect in the temporalis muscle, which alters its biomechanical behavior. The phenomenon known as myomodulation involves modifying muscle leverage by changing positional strain[23]; thus, injecting HA G-prime fillers into the temporalis muscle indirectly elevates the brows by enhancing muscle volume and altering its pull on surrounding structures. In the HAG group, total injected volumes were standardized across all participants to eliminate variability in filler quantity as a confounding factor.

Marking of points T1 and T2: The superior temporal ridge represents an extension of the lateral orbital wall, marking the transition of the frontal bone’s orientation. To delineate the anatomical landmarks for injection, one should draw a vertical line extending from the tail of the brow to the temporal ridge, which serves as the first reference line. The second line should be drawn to form a triangle with the first line and the base of the eyebrow, creating a triangular configuration.

The point T1 is identified as 10 mm above the eyebrow and 10 mm laterally, while point T2 is situated directly below T1. To achieve optimal aesthetic outcomes, administer 0.2 mL of high G-prime filler at each designated point (T1 and T2) until the appearance of hollowness is rectified, and there is noticeable inflation of the temporalis muscle. The selection of these injection points is critical due to the proximity to the course of the superficial temporal artery, necessitating careful consideration to avoid vascular complications during the procedure [Fig. 1].

Figure 1.

Injection landmarks and technique for eyebrow elevation. (a) Standard botulinum toxin injection sites in the glabellar and periorbital region for chemical denervation of brow depressor muscles. (b) Schematic illustration of the filler injection plane depicting passage of the needle through skin, subcutaneous tissue, temporal fascia layers, and deposition into the temporal muscle for biomechanical leverage modification. (c) Marking of anatomical points T1 and T2 along the superior temporal ridge for hyaluronic acid gel–based temporal myomodulation

Mechanism of action

The combined effect of Botox injections weakening depressor muscles and HA G-prime filler enhancing temporalis muscle volume results in a synergistic elevation of the eyebrows. By relaxing specific depressor muscles, we allow for the frontalis muscle elevation action without hindrance, thereby aiding in the elevating action.[1,10] Concurrently, temporalis myomodulation through HA G-prime filler creates an upward force that further assists in brow elevation.[10] This dual intervention not only improves aesthetic outcomes but also optimizes facial dynamics by restoring balance among facial musculature.

In conclusion, this novel technique represents a significant advancement in non-surgical brow elevation strategies, leveraging both botulinum toxin and hyaluronic acid fillers to achieve enhanced aesthetic results with minimal invasiveness and downtime. Further studies are warranted to explore long-term efficacy and patient satisfaction associated with this innovative approach.

Bruising is primarily associated with the passage of the needle through the temporal ridge.[24] To minimize the occurrence of bruising, the needle is only fully withdrawn through the skin when repositioning is necessary or for another series of passes. In case bruising or hematomas begin to form, the affected area is gently treated with pressure from a cotton tip applicator.

Placement of the needle too superficially may result in visible lumps or wheals of the HAG.[25] It is crucial, therefore, to avoid depositing large volumes of filler in a single location. To achieve smooth, feathered, three-dimensional contours, gentle and continuous pressure is applied to the syringe plunger as the needle is slowly moved through the tissues. The resulting shape is tailored to the patient’s needs, and the degree of volume applied-whether in the superior aspect of the eyebrow fat pad, the inferior aspect, feathered laterally into the temporalis muscle fossa, or added along the deep orbital rim to fill the superior sulcus-varies from patient to patient.

Data segregation and analysis

Photographs of the patients were captured both before and 15 days post-procedure. For objective assessments, Adobe Photoshop (Adobe Systems, Inc., San Jose, Calif.) was employed. Mean and standard deviation (SD) values were calculated using Microsoft Excel (Microsoft Corp., Redmond, WA, USA). Bilateral measurements of eyebrow position were conducted, utilizing the mid-pupillary horizontal plane as the reference point. The vertical distance from this plane to the upper brow margin was gauged at seven distinct points: the medial edge of the brow, the medial canthus, the medial limbus, the mid pupil, the lateral limbus, the lateral canthus, and the lateral edge of the eyebrow. To standardize measurements, a forehead tag with known dimensions (40 mm) served as a measurement scale. All measurements were undertaken in centimeters. Two independent blinded raters conducted the measurements.

Additionally, a satisfaction assessment was administered to each patient 15 days post-injection, in the form of a four-point questionnaire (1 = very satisfied, 2 = satisfied, 3 = dissatisfied, and 4 = very dissatisfied). This subjective metric was implemented to capture each patient’s perceived outcome in terms of eyebrow symmetry, aesthetic improvement, and overall experience in regard to the procedure at 15 days post-treatment follow-up.[25]

Results

This retrospective study included a cohort of 460 participants, comprising 276 (60%) females and 184 (40%) males. The average age of patients was 50 years, with SD of 31.1 years.

Prior to the administration of the injection, the apex of the brow was centered over the lateral limbus in both study cohorts. Following the injection of onabotulinumtoxin A, the brow exhibited an average height increase of 1.35 mm (0.6 to 2.1 mm; 1.06 mm SD) across all positions in the BTX cohort [Fig. 2]. The most substantial elevation occurred at the lateral limbus level, measuring 2.1 mm.

Figure 2.

Eyebrow elevation outcomes in BTX cohort.

Comparison of pre-injection (red) and post-injection (green) eyebrow heights at seven anatomical landmarks (medial brow, medial canthus, medial limbus, mid-pupil, lateral limbus, lateral canthus, and lateral brow). Post-procedure analysis demonstrated significant elevation, with the greatest increase observed at the lateral limbus (up to 2.1 mm)

In the HAG cohort [Fig. 3], the brow experienced elevation ranging from the medial limbus to the lateral brow edge with an average height increase of 1.35 mm (1 to 1.7 mm; 0.49 mm SD). There was no statistically significant change in position observed at the level of the medial brow edge and the medial canthus. The most notable elevation in the HAG cohort occurred at the lateral edge of the brow at 1.7 mm.

Figure 3.

Eyebrow elevation outcomes in HAG cohort.

Comparison of pre-injection (green) and post-injection (red) eyebrow heights at seven anatomical landmarks (medial brow, medial canthus, medial limbus, mid-pupil, lateral limbus, lateral canthus, and lateral brow). Post-procedure analysis demonstrated significant elevation, with the most pronounced increase observed at the lateral brow (up to 1.7 mm)

Upon comparing the two injection techniques, a statistically significant difference was identified in the change of eyebrow height at the levels of the medial brow, medial canthus, and lateral brow edge [Tables 1 and 2].

Table 1.

Eyebrow height difference in BTX participants (cm)

	Medial Brow (cm)	Medial Canthus (cm)	Medial Limbus (cm)	Mid Pupil (cm)	Lateral Limbus (cm)	Lateral Canthus (cm)	Lateral Brow (cm)
Pre-injection	1.518	1.706	1.92	1.983	0.971	1.961	2.008
Post-injection	1.717	1.907	2.108	2.169	1.035	2.097	2.218
Difference (Post-injection - Pre-injection)	0.205	0.201	0.188	0.186	0.21	0.136	0.065
P	<0.0001	<0.0001	<0.0001	<0.0001	<0.0012	<0.0001	<0.0121

Table 2.

Eyebrow height difference in HAG participants (cm)

	Medial Brow (cm)	Medial Canthus (cm)	Medial Limbus (cm)	Mid Pupil (cm)	Lateral Limbus (cm)	Lateral Canthus (cm)	Lateral Brow (cm)
Pre-injection	1.705	1.884	2.077	2.139	2.171	2.123	1.025
Post-injection	1.767	1.961	2.180	2.269	2.301	2.272	1.195
Difference (Post-injection−Pre-injection)	0.061	0.078	0.104	0.130	0.130	0.149	0.17
P	0.0948	0.0554	0.0110	0.0003	<0.0001	<0.0001	<0.0001

In association with the BTX cohort, maximum and minimum elevation differences were observed in the lateral limbus (2.1 mm) and the lateral brow (0.65 mm), respectively [Table 1 and Fig. 4]. Similar elevation was achieved in the medial limbus and the mid-pupil region (1.87 mm avg.).

Figure 4.

Clinical outcome of eyebrow elevation following intervention. Representative case demonstrating pre-treatment appearance (left) and post-treatment outcome at 2-week follow-up (right). Notable improvement is observed in eyebrow height and contour, highlighting the efficacy of minimally invasive chemomodulation and myomodulation techniques.

In association with the HAG cohort, maximum and minimum differences were observed in the lateral brow (1.7 mm) and the medial brow (0.61 mm), respectively [Table 2].

A total of 446 patients (97%) reported a high satisfaction rate in eyebrow elevation using both BTX and HAG extension. Among the 460 patients included in the study, 14 were excluded from the satisfaction analysis due to incomplete post-procedure follow-up or non-submission of patient satisfaction questionnaires within the specified 15-day evaluation period. As a result, satisfaction data were analyzed for 446 patients. These exclusions were necessary to maintain data integrity and ensure that only complete, comparable responses were included in the patient-reported outcome measures. The mean patient satisfaction score at 15 days was 1.73 and 1.71 for the BTX and HAG cohorts, respectively (P = 0.9540). Although the P value for the satisfaction score is not statistically significant, it holds a critical clinical relevance. The comparable satisfaction ratings suggest that both treatments are similarly effective from the patient’s perspective in achieving desirable aesthetic outcomes. Given the distinct mechanisms, durations of action, and clinical applications of BTX and HAG, the ability to achieve equivalent satisfaction supports the individualized selection of either treatment based on patient needs, anatomical considerations, and practitioner expertise. This reinforces the utility of both agents as viable non-surgical options for eyebrow elevation in aesthetic practice. In both groups, no patient reported any eyelid ptosis, eyebrow asymmetries, or ocular movement anomalies.

Discussion

The upper orbital space plays a crucial role in delineating the three-dimensional contours that contribute to periorbital aesthetics.[26] During youth, the fullness of the dermis, subcutaneous fat pads, and deep fat pads collaboratively generate a three-dimensional plumpness that defines the aesthetic characteristics of a youthful eyelid.[2,3,26] As the aging process unfolds, a reduction in volume within the dermis and various fat pads can lead to a sagging appearance. This can result in the inelastic skin being drawn into the eyelid space, giving rise to the perception of eyebrow drooping.[27] While gravitation may play a role in lateral eyebrow descent with age, its impact is generally considered less significant than the deflationary effects in contributing to the overall aged appearance.[28]

The average age of the participants in this study was 50 years, with SD of 31.1 years, which coincided with Kokoska et al.,[29] reporting an average participant age of 50.5 years. BTX was delivered across five targeted injection sites: two injections into each corrugator supercilii muscle and one injection into the procerus muscle. The concept of myomodulation was targeted with an attempt to cause the muscle under the eyebrow region to bulge and alter its lever pull.[28,30]

The optimal rejuvenation of the aging upper orbit requires a comprehensive approach that considers the loss of volume and rehabilitative strategies focusing predominantly on elevating the eyebrow. The eyebrow’s smooth, full, three-dimensional shape, shaped by subcutaneous and deep fat pads, defines its character.[31] This contor envelops the orbital rim, extending variably into the eyelid space. By projecting the skin forward, the three-dimensional volume effectively lifts the eyelid skin out of the orbital space, akin to how a fully inflated balloon stretches and smoothens its rubber surface.

Previous reports have consistently asserted that injecting BTX into the brow depressors typically leads to unopposed elevation of the eyebrow due to the action of the brow elevators.[32] Nonetheless, our investigation reveals that simultaneous injection of the medial eyebrow depressors and the lateral orbicularis induces an enhanced lateral eyebrow elevation, peaking at the lateral edge of the eyebrow, without affecting the medial eyebrow. Our hypothesis suggest that injecting the medial eyebrow depressors results in the diffusion of BTX into the frontalis, causing a partial inactivation of its medial fibers. This partial paralysis, in turn, triggers an augmented resting tone in the remaining frontalis fibers, resulting in a significant elevation of the lateral eyebrow. Notably, similar findings were previously documented observing to lateral eyebrow elevation within 2 weeks post-injecting 20 to 40 units of onabotulinumtoxinA into the glabella alone.[17]

The results of this study revealed two key factors impacting eyebrow shape and elevation in the context of BTX for brow-lifting. Firstly, a subcutaneous injection is observed to depict lower efficacy since it is considered unsafe for vessels and the adherence of soft tissues is strong to the skin. Additionally, since the filler trace could disappear quickly, injecting the BTX/HAG G-prime fillers into the brow edge (the sliding space) is not considered efficient.

Various recommendations exist regarding filler injection positioning. Griepentrog et al.[32] demonstrated that injecting in the pre-periosteal plane requires less volume yet achieves a robust result. Lambros et al.[33] suggest injecting into the sub-orbicularis and subcutaneous fat, while Cohen et al.[34] advocate for injection into the subcutaneous plane. The retro-orbicularis oculi fat extends from the eyebrow region, draping over the superior orbital rim to the upper eyelid, contributing to a smooth contour over the superior orbital rim. Injecting into the plane of the retro-orbicularis oculi fat proves effective in creating smooth, appropriate contours.[35] The eyebrow hairs emerge from the three-dimensional structure of the eyebrow fat pad, varying significantly in thickness, geographic distribution, and shape. Despite their impact on appearance, including a vast industry focused on shaping, coloring, thinning, removing, or tattooing hair to influence their distribution, it is recommended to avoid being overly distracted by the distribution of eyebrow hairs when assessing the three-dimensional shape of the eyebrow.

However, one of the main limitations that could persist in this approach encompasses the measurement error; although the photographic assessment was performed by experienced reviewers, it is critical to consider that the manual assessment of the pre-and post-procedure images may introduce a degree of inter-variability and human measurement error. To mitigate this, a standardized measurement protocol was followed, and multiple assessments were averaged when discrepancies were noted.

Another limitation is that although the study required a minimum 5-year follow-up for inclusion to ensure comprehensive patient tracking and documentation procedure, the clinical and patient-related outcomes are limited to a 15-day follow-up post-procedure. Hence, the primary findings of the study only reflect the short-term efficacy and satisfaction. Long-term outcomes—such as duration of effect, need for retreatment, and delayed adverse events—were not within the scope of this evaluation and represent an important area for future investigation.

We obtained favorable outcomes using both BTX and HAG G-prime fillers, with no lasting adverse reactions. Temporary side effects ranged from pain, bruising, and swelling to edema. Given that both approaches yielded high and comparable satisfaction rates without any complications, the healthcare providers should choose the most appropriate technique tailored to the patient’s specific requirements.

Conclusion

The aging process, causing a reduction in skin elasticity and tissue deflation, often leads to changes in the eyebrow’s structure and appearance. The study employed detailed injection protocols for both BTX and HAG, ensuring precise placement and dosage distribution. Objective assessments, including bilateral measurements and satisfaction surveys, were conducted. The results indicated a statistically significant elevation in eyebrow height for both groups, with the BTX group showing a more pronounced lateral eyebrow lift. The overall satisfaction rate was high (97%), with no reported adverse reactions, highlighting the safety and efficacy of both methods. In conclusion, the modest elevation achieved through various brow-lifting techniques—specifically, Botox injections yielding an elevation of 1–3 mm, direct surgical brow lifts resulting in 0.6–2.1 mm, indirect surgical brow lifts achieving 1.5 to 2.0 mm, and temporal surgical brow lifts producing 1.8–1.9 mm—raises critical questions regarding the efficacy of these interventions when only minimal improvements are attained. The ephemeral nature of results from Botox monotherapy, which typically lasts between 6 weeks and a maximum of 3 months, further underscores the necessity for more durable alternatives.

In contrast, the innovative integration of high HAG G-prime fillers with Botox not only alleviates the action of the depressor muscles but also significantly prolongs the aesthetic outcomes, sustaining effects for up to 2 years. This synergistic approach effectively utilizes Botox to relax the depressors of the brow while employing high G-prime fillers for temporal myomodulation, resulting in aesthetic outcomes that are favorably comparable to those achieved through both direct and indirect surgical brow lifts and advocating for a paradigm shift in brow enhancement strategies, favoring less invasive methodologies that deliver sustained and favorable results while minimizing patient morbidity and enhancing overall satisfaction.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest:

There are no conflicts of interest.

Funding Statement

Nil.