Received: 8 February 2022 | Revised: 17 May 2022 | Accepted: 14 June 2022
Heterogeneous crow's feet line patterns and customized botulinum toxin rejuvenating treatment
Maurizio Cavallini MD1 | Marco Papagni MD2 | Federica Augelli MD3 | Gabriele Ferruccio Muti MD4 | Adriano Santorelli MD5 | Mauro Raichi MD6
1Head, Operative Unit of Dermatologic and Plastic Surgery, CDI Hospital, Milan, Italy
2 Agorà — Italian Scientific Society of Aesthetic Medicine, Milan, Italy
3Operative Unit of Dermatologic and Plastic Surgery, CDI Hospital, Milan, Italy
4IDE Istituto Dermatologico Europeo, National Secretariat AICPE (Associazione Italiana Chirurghi Plastici Estetici), Milan, Italy
5Head, Plastic and Aesthetic Surgery, Health Park Clinic, Naples, Italy
6Clinical Pharmacology Consultant in Aesthetic Medicine, Sanremo, Italy
Correspondence
Dr Mauro Raichi, Via Armea 90, 18038 Sanremo, Italy. Email: mrdoc55@gmail.com
Funding information
The authors declare their study was spontaneous, born of scientific curiosity, and published literature, and they received no utility for it.
Abstract
Background: From early dynamic lines in smiling and squinting young people, crow's feet lines in the lateral canthal region evolve through prolonged tissue remodeling into mature, stable rhytids after the mid-to-late thirties, and requests for rejuvenating treatment. Because of the heterogeneous fanning behavior of crow's feet lines, individualizing neuromodulation with botulinum toxin injections might be a sound strategy to maximize aesthetic outcomes.
Aims: To investigate the prevalence of variable crow's feet line patterns at maximum contracture and while smiling and comment on the relative distribution of such patterns and the influence of aging. These considerations will be the basis and rationale for future studies that will individualize the total 24-unit dose according to the distribution of crow's feet lines.
Methods: Identifying CFL orientation at maximum frown and while smiling; assessment tool: the four-class 2015-version of Kane's classification further modified by converting the former “central fan pattern” into a new, more precisely defined “extended full-fan pattern” class.
Results: The 323 cohort subjects had a mean age of 51.5 ± 9.28 years. Although with some differences, outcomes in a central-southern real-world European Caucasian population appear similar to the distribution first studied in 2003 in a highly selected population in New England involved in double-blind clinical trials. The full-fan pattern predominated both at maximum contraction and when smiling, followed in prevalence by the upper-fan pattern at maximum contraction and the extended full-fan pattern while smiling. Age significantly influenced the crow's feet line pattern—lower-fan patterns were more frequent than other patterns in the real-world younger middle-age group (40–49 years old); full-fan and extended full-fan patterns progressively more prevalent with aging.
Conclusions: The study confirms but somewhat modifies the previous evidence about the non-homogeneous distribution of crow's feet line fanning patterns in different age groups and reinforces the case to individualize the topography of botulinum toxin injections.
KEYWORDS
Botulinum toxin, canthal rhytids, Crow's feet lines, onabotulinumtoxin A
1
BACKGROUND
As shown in a 2015 survey of women with aesthetic concerns 30–65 years old, crow's feet lines (CFLs), also known as lateral canthal lines, can severely impact the subject's aesthetic well-being: 32% and 30%, respectively, for CFLs and tear troughs.1
Adult CFLs are heterogeneous, no longer dynamic as in teenagers but manifest even in repose. 2,3 The pattern so far defined as central, limited to the lateral canthal area in younger subjects, can progress to the lower-fan one that predominates in males; it can also extend to the lateral canthal area and even to the superior malar area. The central pattern can also evolve into a full-fan pattern spreading from the superior malar area to the brow's tail. 3
However, the current worldwide botulinum toxin prescribing information does not differentiate within the heterogeneous CFL fan patterns. For onabotulinumtoxin A, the suggestion is for a total bilateral dose of 24 units in 0.6 ml, equally distributed over the lateral orbicularis oculi muscle at maximum frown with three one-fit-all injection sites per side (0.1 ml per site) and without much functional and topographic discrimination.4 However, it would only seem rational that “heterogeneous” should translate into a customized strategy.
The evidence of two placebo-controlled trials led to the September 2013 Food and Drug Administration (FDA) approval for onabotulinumtoxin A (Botox Cosmetic; Allergan, Inc.,). 5–7 The outcomes of those two pivot trials still inform current practice worldwide—first injection approximately 1.5–2.0 cm temporally to the lateral canthus and just temporally to the orbital rim; second and third injections 1.0–1.5 cm above and below, respectively, the first injection at an approximate 30° angle medially or, depending on the rhytid appearance, both below the first injection. 8–11
This report aims to illustrate the evidence accrued by the authors over a year of structured observations with standardized criteria about how the CFL fanning patterns distribute at maximum contracture and when smiling in a real-world ambulatory population. The report also aims to discuss the outcomes of those observations compared with previous evidence in highly selected subjects who had participated in onabotulinumtoxin A pivot studies. Identifying the most and less frequent patterns in real-world subjects will integrate the current indications for injecting botulinum toxin and will be the rational basis for future studies customizing the total 24-unit dose according to the individual CFL fan patterns.
2 | METHODS
2.1 | Study design
All investigators, acting in fixed couples (one injector, one evaluator with no exchange of roles), participated in this prospective non-interventional study, carried out between May 2020 and May
2021, and centered on assessing the CFL fanning pattern while smiling and maximum frown. Three hundred twenty-three consecutive subjects of Caucasian origin and balanced phototypes (“1”, 31.3%; “2”, 30.6%; “3”, 38.1%, data available in 160 subjects) completed the study—316 women (97.8%) and seven men (2.2%).
The participating individuals were of variable age and randomly recruited from the clients of the authors' private practices seeking aesthetic treatment for facial rejuvenation. Candidate individuals should not have received active therapies such as botulinum toxin or other injectable fillers in the previous 6 months. They should also have been free from self-perception disorders, inflammation at injection sites, albumin hypersensitivity, myasthenia gravis, or other neuromuscular diseases. Previous blepharoplasty and resurfacing, facelift or browlift procedures prevented inclusion in the study cohort; the same applied to the recent intake of agents interfering with neuromuscular transmission (e.g., aminoglycoside eye drops).
All participating subjects agreed to the anonymous elaboration and research use of their clinical data and photographic evidence by signing a written informed consent; they also agreed to the anonymous publication of study outcomes. The authors always assured the full respect of the Helsinki Declaration principles.
2.2 | CFL classes and a priori stratification
The CFLs of the cohort subjects were stratified before treatment into four classes according to the patterns dynamically exhibited by periocular rhytids following maximal orbicularis oculi contracture.
For baseline stratification, the authors used a four-class modified version of the most recent CFL fanning descriptors, described by Kane in 2015. 2,3 The authors further revised the 2015 descriptors by introducing a new “extended full-fan pattern” class ( Table 1) to describe and identify the rhytid orientations in the lateral canthal area and adjacent areas with improved precision. Figures 1 and 2 , randomly selected in the total pool of photographic documentation, illustrate some examples of the upper and lower-fan patterns; Figure 3 is an example of an extended full-fan pattern.
The investigators performed all procedures while sitting under tangential light with no previous local preparation or anesthesia other than antisepsis with a non-alcoholic solution.
2.3 | Individualized injection procedure
Table 2 summarizes the empirically individualized injection technique, partially modified compared with the recommendations of the onabotulinumtoxin A Prescribing Information and more in agreement with the preliminary dynamic assessment of CLF fanning patterns.
TABLE 5 Distribution of CFL fanning patterns by age groups over the lateral canthal and nearby skin areas at maximum contraction (modified Kane's descriptors). Data correctly registered for 321 subjects out of 323 in the prospective cohort (two missing data)
Distribution of CFL patterns by age groups at maximum contraction
TABLE 6 Distribution of CFL fanning patterns by age groups over the lateral canthal and nearby skin areas while smiling (modified Kane's descriptors). Data correctly registered for 320 subjects out of 323 in the prospective cohort (three missing data)
Distribution of CFL patterns by age groups while smiling
4 | DISCUSSION
The orbicularis oculi muscle originates from the nasal segment of the frontal bone, the frontal process of the maxilla, the medial palpebral ligament, and the lacrimal bone. It is the main target of botulinum toxin neuromodulation. The occipitofrontalis, corrugator supercilii, and depressor supercilii muscles, and the skin and subcutaneous tissue of the eyebrow surround the orbital part of the orbicularis oculi muscle, the primary target of neuromodulation. Medially and inferiorly, the orbital part blends with the levator labii superioris, levator nasolabialis, and zygomaticus minor muscles and even the temporal aspect of the epicranial aponeurosis, while the supraorbital vein and the zygomaticofacial nerve pierce it.12 The palpebral branches of the infraorbital nerve also pierce the muscle but do not cause technical problems to the operator because they run deeply.12
Some care is paramount in some individuals with the lower-fan pattern because the facial artery runs more in-depth between the zygomatic major muscle and the buccinator muscle. The zygomatic major muscle extends diagonally from the zygomaticotemporal suture area, laterally to the origin of the zygomaticus minor muscle, until fusing with the modiolus and the muscles of the upper lip.12
In teenagers, dynamic lines already radiate outward from the lateral canthus during smiling or squinting due to the repeated contraction of mimic muscles, notably the orbicularis oculi muscle. 2 In the mid-to-late thirties, non-dynamic rhytids become manifest, with incidence and severity variably influenced by heavy smoking, subcutaneous fat, chronic sun exposure, increased solar elastosis, perifollicular fibrosis, and thinner epidermis. Histology reveals the aging and deterioration of the elastic tissue network from that early age. 2
CFL effacement benefits from several treatment strategies, including surgical procedures to weaken the orbicularis oculi muscle,13 chemical peels,14 collagen injections to fill fine rhytids and botulinum
toxin injections since the early 1990s.15 More recent options include laser resurfacing and surgical procedures such as brow lifts that do not weaken the lateral canthal musculature. 2
The use of botulinum toxin to alleviate dynamic rhytids has expanded since onabotulinumtoxin A approval in the USA in 1993.10 The one-size-fits-all approach codified in the still current onabotulinumtoxin A Prescribing Information persisted over the years. However, a contradiction became apparent a decade later: crow's feet rhytids are far from homogeneous, with the CFL presentation following patterns analogous to the non-homogeneous smile patterns already long known in the 1990s. 2 As shown by the favorable outcomes in the two pivotal trials, the procedures described in the current botulinum toxin prescribing information are probably appropriate for most subjects with moderate or severe dynamic CFLs. 3 Yet, the periorbital areas are also those most frequently fraught with adverse botulinum toxin sequelae.16
In 2003, Kane identified four main CFL patterns: a “full-fan pattern” (prevalence, 47%) with lateral canthal rhytids extending from the lower lateral brow across the upper eyelid, through the lateral canthus, and across the lower eyelid/upper cheek junction; a “lowerfan pattern” with the crinkling of the lower lid/upper cheek area alone (prevalence, 25%); an “upper-fan pattern” severely affecting the upper lid skin down to the lateral canthus (prevalence, 18%); a “central-fan pattern” or lateral canthus pattern, with rhytids affecting only the skin areas surrounding the lateral canthus (prevalence, 10%). 2 Kane found stability of the individual fan patterns over time and only a six-per cent prevalence of fanning asymmetry. 2 He also demonstrated a relationship between the CFL fan pattern and CFL severity, age, and gender: more common full-fan and lower-fan patterns in severe versus moderate CFL while frowning maximally, full fan increasing with age, and a lower-fan pattern was more frequent in the male gender than in women. 3 Subjective aesthetic dissatisfaction
was also variable, with full-fan individuals reaching a zenith of dissatisfaction at maximum smile compared with other CFL patterns. 3
Nineteen years later, the CFL outcomes in a real-world ambulatory Caucasian population of central-southern Europe confirmed with some differences the CFL patterns described by Kane in a selected New England population of subjects enrolled in pivot clinical trials. Overall, the full-fan pattern appeared again as the most frequent, but the lower-fan was less prevalent than previously reported. Full-fan and upper-fan (51.7% and 23.1%, respectively,) were the most common CFL patterns at maximum contracture; patterns were similar while simply smiling. Possibly a bit surprisingly, there was no significant increase in “lower-fan pattern” prevalence when smiling. Age confirmed its influence on the distribution of CFL fan patterns. Somewhat differently from what happened in the selected patients from onabotulinumtoxin
A pivot studies (full-fan pattern increasing with age), 2,3 the full-fan pattern was the most prevalent in the two central middle-age groups. However, prevalence decreased somewhat in older subjects while the prevalence of the extended full-fan pattern increased markedly.
Overall, compared with the previous evidence by Kane, 2,3 there were differences for the upper-fan (somewhat more frequent, especially at maximum contraction) and the full-fan pattern, more frequent by about a third.
Whether those relatively minor variations mirror differences in ethnicity or some other reason is unclear. For instance, Kane's individuals included a small number of Asian subjects and belonged to a preselected cohort suitable for clinical trial evaluations. Conversely, real-world individuals attending the authors' private offices composed the cohort herein investigated—in the authors' opinion, a fundamental difference from Kane's original contributions. Moreover, the long-term purposes of the study were different from Kane's. Although both studies appear descriptive and quite similar, the authors' main intention was to emphasize the crucial need to study (by default) the orbicularis oculi muscle dynamics and CLF fan pattern. In the authors' perception, the dynamic study of the CLF fan pattern relying on formal categorizing procedures should become standard before botulinum toxin injections.
A comparative study will investigate if incorporating a systematic dynamic analysis of crow's feet line patterns followed by individualized botulinum toxin injections benefits aesthetic outcomes compared with the conventional fixed-point strategy. The second purpose of this preliminary investigation is to lay solid foundations and establish a documented rationale for the foreseen comparative study, complete with a full statistical analysis that is only preliminary. A preliminary session of collective self-training prevented the most likely bias—differences among authors in classifying CFLs. Not investigating the role of CFL severity on the distribution of CFL patterns might be considered another weak point of the study.
5 | CONCLUSIONS
This one-year investigation in 323 subjects with crow's feet lines comes from the work of a pool of Italian aesthetic medicine and
surgery specialists who have been using botulinum toxin for up to 20 years—about a 100 person-years of observations, treatments, and shared experience. About 20 years after Kane's landmark study in 2003, this report confirms the non-homogeneous distribution of crow's feet line patterns in a central-southern European (northern Italy) Caucasian population and reinforces the case to individualize the botulinum toxin injection programs in the periocular zone. We found that the somewhat rigid injection patterns stemming from the onabotulinumtoxin A pivot studies (three points, four units per point) could benefit from individualizing the injection points in the orbicularis oculi area. This concept may be especially true if the dynamic assessment before treatment reveals an upper-fan pattern (the lower injection possibly forsaken) or a lower-fan pattern (opposite injection strategy). In the case of a full-fan pattern or an extended full-fan pattern, the treatment strategy may contemplate increasing injections up to three more external points.
A comparative study will investigate if incorporating a systematic dynamic study of crow's feet line fanning patterns followed by individualized botulinum toxin injections benefits aesthetic outcomes compared with the conventional fixed-point strategy. The second purpose of this preliminary investigation is to lay a solid foundation and establish a documented rationale for this forthcoming comparative study.
AUTHORS' CONTRIBUTION
All authors sought and got informed consent from the subjects enrolled in the study. All authors are accountable for the manuscript's clinical and editorial accuracy and integrity submitted to the Journal of Cosmetic Dermatology, including all comments on outcomes. The authors confirm they adhered to the ethical policies of the journal, as noted on the journal's author guidelines page.
CONFLICTS OF INTEREST
The authors declare they have no conflict of interest inappropriately influencing the representation or interpretation of their research outcomes.
DATA AVAILABILITY STATEMENT
The datasets generated and analyzed in the study are not publicly available. However, according to the current regulations, the corresponding author currently archives all datasets with full details of participating subjects. After conversion in an anonymous form, the corresponding author can make all datasets available on reasonable request.
ETHICS STATEMENT
The participating subjects voluntarily sought to undergo routinary ambulatory aesthetic medicine procedures involving botulinum toxin injections for crow's feet lines. The study was purely observational in a subset of those subjects that regularly attended the authors' private practices, and it did not involve additional invasive procedures. However, preliminarily the aims of the observational study were detailed to all individuals, and an agreement was obtained. These
considerations allowed waiving the requirement for any approval by an Ethical Committee.
PHOTOGRAPH CONSENT STATEMENT
All photographs and iconographic material, unrecognizable, and submitted with the patients' agreement, belong to the authors.
ORCID
Adriano Santorelli https://orcid.org/0000-0003-0500-461X
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How to cite this article: Cavallini M, Papagni M, Augelli F, Muti GF, Santorelli A, Raichi M. Heterogeneous crow's feet line patterns and customized botulinum toxin rejuvenating treatment. J Cosmet Dermatol. 2022;21:4294-4300. doi: 10.1111/jocd.15172