Received: 18 August 2022 | Revised: 3 November 2022 | Accepted: 29 November 2022

DOI: 10.1111/jocd.15563

ORIGINAL ARTICLE

Clinical validation of the upper face first principle—­A clinical,

prospective, interventional split-­face study

Claudia A. Hernandez MD1 | David E. Uribe Zapata MD1 | Maria Paula Bermudez MD2 |
Konstantin Frank MD3 | Nicholas Moellhoff MD3 | Michael Alfertshofer MD3 |
4 5
Robert H. Gotkin MD | Kristina Davidovic MD |
Sebastian Cotofana MD, PhD, PhD6

1
CH Dermatologia, Medellin, Medellin,
Colombia Abstract
Background: Previous clinical and anatomic investigations have identified the clinical
2
Private Practice, Bogota, Bogota,
Colombia
3
relevance of facial biomechanics. Based on this new understanding, principles for fa-
Division of Hand, Plastic and Aesthetic
Surgery, LMU University Hospital, cial aesthetic procedures were established: Lateral Face First, Deep Layers First, and
Munich, Germany Upper Face First.
4
Private Practice, New York, New York,
Objective: To test the upper face first principle by showing that an injection se-
USA
5
Center for Radiology and Magnetic quence, starting in the upper face is superior to an injection sequence starting in the
Resonance Imaging, Clinical Center of lower face.
Serbia, Belgrade, Serbia
6 Methods: This study was designed as an interventional split-­face study administering
Department of Clinical Anatomy, Mayo
Clinic College of Medicine and Science, the same amount and type of soft tissue filler for the upper, middle, and lower face
Rochester, Minnesota, USA
but in a different sequence: upper, middle, lower face versus lower, middle, and upper
Correspondence face. A total of 15 patients (5 males and 10 females) with a mean age of 39.4 years (9.6)
Sebastian Cotofana, Department of
and a mean BMI of 23.4 kg/m2 (1.7) were studied. Follow-­up at D0, D30, and D90 was
Clinical Anatomy, Mayo Clinic College of
Medicine and Science, Mayo Clinic, Stabile conducted utilizing semiquantitative scores and objective 3D imaging.
Building 9-­38, 200 First Street, Rochester
Results: Despite not reaching statistical significance, midfacial volume and jawline
55905, MN, USA.
Email: cotofana.sebastian@mayo.edu contouring were rated better at every follow-­up visit (D0, D30, D90) when treated
with the upper versus the lower face first injection algorithm. The global aesthetic
improvement scale showed statistically significantly better values for the upper face
first algorithm when compared to the lower face first algorithm at all evaluated time
points with all p < 0.001.
Conclusion: Applying the upper face first injection algorithm seems to result in
better aesthetic outcomes when directly compared to the lower face first algo-
rithm. Semiquantitative and objective outcome measurements confirm its clinical
effectiveness.

KEYWORDS
aesthetic procedure, facial anatomy, full-­face treatment, injections, soft-­tissue filler

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2022 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

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wileyonlinelibrary.com/journal/jocd J Cosmet Dermatol. 2023;22:418–425.

HERNANDEZ et al.
1 | I NTRO D U C TI O N
In recent studies, the mobility of the face was investigated with ultra-
sound imaging and three-­dimensional (3D) photography.1–­3 Based on
their results, researchers coined the term facial biomechanics which
describes the physiologic movement of facial soft tissues during fa-
cial animation and facial aging.4 This new understanding of mobile,
non-­static facial anatomy has resulted in alternative treatment ap-
proaches for neuromodulators,5 soft tissue fillers6,7 and in the for-
mulation of treatment principles for minimally invasive aesthetic
procedures.4 These principles were thought to guide injectable treat-
ment to achieve superior and more natural outcomes if certain treat-
ment sequences are followed. Those principles were the following:
4
Lateral Face First, Deep Layer First, and Upper Face First.
The lateral face first principle was previously clinically validated
by Casabona et al. via an interventional split-­face study.8 The au-
thors targeted side-­symmetric injection points in the medial and
the lateral face but changed the sequence of their injections: lateral
face first versus medial face first. The results revealed that if the
lateral face first algorithm was applied, less volume was needed in
the medial face to achieve a side-­symmetric outcome. The authors
explained their findings by the layered arrangement of the facial soft
tissues which allows for a pre-­conditioning effect of the medial face
if the lateral face was treated first.
The deep layer first principle is the standard of care during daily
injectable treatments despite the fact that no study to date has pro-
vided a scientific clinical validation for its effectiveness. Interestingly,
a recent ultrasound imaging-­based study revealed that the mobility
of the deep facial fat compartments is significantly reduced when
compared to the mobility of the superficial fat compartments, most
probably due to their connection to stable and immobile deep facial
structures like nerves and ligaments.9 The superficial fat compart-
ments, on the contrary, display significant movement during facial
animation which explains the formation of apple cheeks in conjunc-
tion with the transverse facial septum.10 Injectors, therefore, favor
treating deep facial structures when trying to restructure and re-
contour the midface or when trying to provide structural support for
overlying soft tissues.
The upper face first principle refers to an injection sequence that
addresses the upper facial regions first before addressing the middle
or lower facial regions. The underlying anatomic explanation is that
administering soft tissue fillers to the upper face will provide sup-
port for the lower facial structures and induce facial repositioning
and lower facial slimming. This clinical effect was recently observed
and validated through the temporal lifting technique.11–­13
Even though repositioning and facial lifting effects following
upper facial injections have been demonstrated, there is no clinical
evidence available showing that the sequence of injectable treatment
should be performed by starting in the upper face and progressing
to the lower face. Therefore, the objective of this study is to provide
scientific evidence that following the upper-­face-­first treatment algo-
rithm results in superior aesthetic outcomes when directly compared
in a split-­face design to the lower face first injection algorithm.
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419
2 | M ATE R I A L A N D M E TH O DS
2.1 | Study participants
Patients were recruited at CH Dermatologia, Medellin, Colombia,
and treated for facial soft tissue volume loss and soft tissue repo-
sitioning. Patients were included if they met the following criteria:
no previous surgical facial procedures, no previous facial trauma, no
facial soft tissue filler injections, and no neuromodulator treatment
6 months prior to the beginning of the study Participants were in-
formed about the goals and the methodology of this study and, in
particular, about the split-­face study design. Each study participant
provided written informed consent for the use of their personal and
clinical data for research purposes prior to their study inclusion.
The study was conducted between January and May 2022 and
received institutional review board approval under the approval
number: 10AP48K58AS121/2022.
2.2 | Study design
This study was designed as a clinical, interventional split-­face study
in which one side of the face was treated differently than the con-
tralateral side. Both sides of the face were treated with the same
amount and the same type of soft tissue filler utilizing the same
injection technique. The major difference in the treatment of both
facial sides was that one side of the face (randomly assigned via coin
toss) was treated starting with the upper face whereas the contralat-
eral side was treated starting with the lower face but still utilizing
the same injection technique and injection points.
2.3 | Injection algorithm
The following, side symmetrical injection points were used to admin-
ister the identical amount of product for each facial side. The needed
volume was estimated prior to the treatment for each injection point
and side-­symmetrically injected (Figure 1).
Upper face injection point: The temporal lifting technique7,12
was performed using a dermal access point 1 cm anterior to the apex
of the tragus. From here a 22G cannula (Feeltech CO Ltd.) was ad-
vanced in a vertical orientation in the subdermal plane for the en-
tire cannula length of 50 mm. A bolus was injected slowly into the
subdermal plane without fanning or other cannula movements. An
average of 1.0 cc (0.0) per side of Restylane Lyft (Galderma) was
administered.
Middle face injection point: The dermal access point was 1 cm
caudal and 1 cm lateral to the lateral canthus. A 27G needle (Feeltech
CO Ltd.) was introduced perpendicular to the skin surface and ad-
vanced until bone contact was established. Following pre-­injection
aspiration, an average bolus of 0.51 cc (0.1) [range: 0.30–­0.70] of
Belotero Volume (Merz Pharma) was injected while maintaining con-
stant bone contact.
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420
Lower face injection point: The dermal access point for the 22G
cannula (Feeltech CO Ltd.) was located at the angle of the mandible.
The cannula was advanced strictly in the subdermal plane anteriorly
to contour the jawline and from the same dermal access vertically
(toward the zygomatic arch) to contour the ascending ramus of the
mandible. An average of 0.51 cc (0.1) (range: 0.35–­0.70) Juvederm
Voluma (Allergan) was administered.
These three injection sites were treated symmetrically on both
facial sides; on one side of the face, however, the sequence was an
upper face, middle face, lower face (Upper Face First injection al-
gorithm), whereas, on the contralateral side (of the same patient),
the injection sequence was: lower face, middle face, and upper face
(Lower Face First injection algorithm).
2.4 | Outcome measurements
Semi-­quantitative and objective outcome scoring was assessed prior
to the treatment (= at baseline, BL) immediately after the treatment
(D0), 30 days (D30), and 90 days (D90) following the initial aesthetic
injections.
2.5 | Clinical outcome scoring
Semi-­quantitative outcome assessment relied on validated midfa-
14,15
cial volume and jawline contouring scales. Both scales ranged
from 0–­4, best to worst, with both representing: 0 = none, 1 = mild,
2 = moderate, 3 = severe, and 4 = very severe. The scales were as-
sessed in person by the treating physician and by an independent
observer with aesthetic background (first assistant to the injector)
before the treatment and at each consecutive follow-­up visit.
2.6 | Facial appearance
The side-­specific facial appearance was assessed by the global
aesthetic improvement scale (GAIS) on a 5-­point Likert scale with
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HERNANDEZ et al.
F I G U R E 1 Three-­dimensional (3D)
surface scan of a female patient showing
the insertion points (indicated by a
cross) and the locations where volume
was applied (indicated by a circle/
oval). Matching colors indicate the
corresponding insertion point and location
of volume application.
0 = Much worsened, 1 = Worsened, 2 = Neutral, 3 = Improved, and
4 = Much Improved. The scale was assessed in person before the
treatment and at each consecutive follow-­up visit by the treating
physician and by the patient themselves using a mirror. The score
assessed the change of each individual facial side when compared to
before the treatment of that respective facial side; the score did not
compare side differences.
2.7 | Objective outcome scoring
Objective outcome assessment relied on 3-­d imensional (3D)
imaging as previously described. 3,16,17 In brief, standardized
full-­f ace 3D images were obtained utilizing a Vectra H2 camera
system (Canfield). The images were automatically aligned to the
baseline image and differences in volume (volume change in cc)
were calculated following the internal computational algorithm
of the Mirror software toolkit for the middle and lower facial re-
gions (Figure 2).
2.8 | Statistical analysis
Differences between facial sides in midfacial volume, jawline con-
touring, and 3D measured parameters were computed via a non-­
parametric Wilcoxon signed rank test in which both facial sides
were directly compared with each other. Semi-­quantitative outcome
scores as evaluated by the treating physician, and the observer were
averaged, and the mean value was used for further calculations. The
agreement between the ratings performed by the physician and by
the observer was determined by the inter-­class correlation coeffi-
cient (ICC) and ranged for all variables from 0.90 to 1.00; this rep-
resents excellent reliability.18 All statistical analyses were run using
SPSS Statistics 25 (IBM), and differences were considered statisti-
cally significant at a probability value of p < 0.05. Statistical testing
was performed using non-­parametric testing, but for better read-
ability, the mean value and the respective standard deviation are
provided.
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HERNANDEZ et al. 421

3 | R E S U LT S
3.1 | Patient demographic data
This study analyzed a total of 15 patients (5 males and 10 females)
with a mean age of 39.4 years (9.6) (range: 30–­60) and a mean
body mass index (BMI) of 23.4 kg/m2 (1.7) (range: 19.9–­25.9). The
Fitzpatrick skin type classification was as follows: type 2 = 20.0%
(n = 3), type 3 = 46.7% (n = 7), type 4 = 26.7% (n = 4), and type
5 = 6.7% (n = 1).
At baseline (before the treatment), no statistically significant dif-
ference was observed between facial sides treated with the upper
versus lower face first algorithm for the evaluated midfacial volume
and jawline contouring scales with p > 0.05.
face first algorithm the rating was 0.67 (0.5) representing a statisti-
cally significant difference between the two treatment algorithms
with p = 0.025. At D30, the differences between the two injection
algorithms (upper vs. lower face first) were 0.30 (0.5) versus 0.33
(0.5) with p = 0.785 and at D90 were 0.13 (0.4) versus 0.27 (0.4) with
p = 0.102. (Figure 3)
For jawline contouring the values between the two injection al-
gorithms (upper vs. lower face first) were at D0 0.33 (0.6) versus 0.33
(0.6) with p = 1.00, at D30 0.13 (0.5) versus 0.20 (0.6) with p = 0.317
and were at D90 0.13 (0.6) versus 0.20 (0.4) with p = 0.317, respec-
tively. (Table 1 and Figure 4)
3.3 | Objective outcome

3.2 | Clinical outcome
Immediately after the treatment (D0), the rating of midfacial volume
(0–­4, best to worst) for the side treated with the upper face first
algorithm was 0.33 (0.5) whereas for the side treated with the lower
Utilizing 3D imaging revealed that the volume of the middle face in-
creased immediately after the treatment (D0) by 0.93 (0.4) cc for the
facial side treated with the upper face first algorithm whereas the
volume increase for the facial side treated with the lower face first
algorithm was 0.40 (0.8) cc with p = 0.053. At D30, the difference in
objectively measured volume increase following the initial aesthetic

F I G U R E 2 3D volumetric analyses
exemplified on two female patients at
D0 for the middle and lower face. Green
values indicating volume increase are
more pronounced for middle facial volume
for both injection algorithms.

F I G U R E 3 Bar graph showing the

semiquantitatively rated middle facial
volume stratified for both injection
algorithms (upper face first vs. lower
face first) at baseline (= BL, before the
treatment), at D0 (= immediately after
the treatment), at D30 (= 1 month after
the treatment), and at D90 (= 3 months
after the treatment). SD is indicated by
error bars. Probability value (= p-­value)
as calculated by Wilcoxon signed rank
test represents the statistical difference
between the two injection algorithms at
each time point.
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422 HERNANDEZ et al.

TA B L E 1 Table showing the mean scores and the respective ±1 SD of the investigated study parameters.

BL D0 D30 D90

Middle facial volume (rated) Upper face first 1.33 (0.8) 0.33 (0.5) 0.30 (0.5) 0.13 (0.4)
Lower face first 1.37 (0.8) 0.67 (0.5) 0.33 (0.5) 0.27 (0.4)
Jawline contouring (rated) Upper face first 1.27 (0.9) 0.33 (0.6) 0.13 (0.5) 0.13 (0.5)
Lower face first 1.33 (0.6) 0.33 (0.6) 0.20 (0.6) 0.20 (0.6)
GAIS Upper face first 3.93 (0.3) 4.00 (0) 4.00 (0)
Lower face first 3.23 (0.4) 3.17 (0.4) 3.23 (0.4)
Middle face volume change (3D Upper face first 0.93 (0.4) 0.97 (1.1) 0.68 (1.8)
measurements) Lower face first 0.40 (0.8) 0.46 (1.1) 0.60 (1.4)
Lower face volume change (3D Upper face first 0.37 (0.9) 0.10 (1.1) 0.12 (2.5)
measurements) Lower face first −0.13 (0.8) −0.23 (1.3) 0.26 (1.6)

Midfacial volume and jawline contouring were rated on a scale best to worst (0–­4); Global Aesthetic Improvement Scale (GAIS) was rated on a scale
of worst to best (0–­4); Middle and lower face volumes were calculated utilizing 3D imaging technology as the difference at D0 (= immediately after
the treatment), D30 (= 1 month after the treatment), and D90 (= 3 months after the treatment) when compared to baseline.

F I G U R E 4 Bar graph showing the

semiquantitatively rated lower facial
volume stratified for both injection
algorithms (upper face first vs. lower
face first) at baseline (= BL, before the
treatment), at D0 (= immediately after
the treatment), at D30 (= 1 month after
the treatment), and at D90 (= 3 months
after the treatment). Standard deviation is
indicated by error bars. Probability value
(= p-­value) as calculated by Wilcoxon
signed rank test represents the statistical
difference between the two injection
algorithms at each time point.

treatment was for the two injection algorithms (upper vs. lower face
first) 0.97 (1.1) cc versus 0.46 (1.1) cc with p = 0.078 whereas at
D90 the volume increase was 0.68 (1.8) cc versus 0.60 (1.4) cc with
p = 0.570, respectively (Table 1 and Figure 5).
The objectively measured lower facial volume increase for the
two injection algorithms (upper vs. lower face first) was at D0 0.38
(0.9) cc versus −0.13 (0.8) cc with p = 0.044; at D30, 0.10 (1.1) cc
versus −0.23 (1.3) cc with p = 0.307 and at D90, 0.12 (2.5) cc versus
0.25 (1.6) cc with p = 0.712 (Table 1 and Figure 6).
To investigate whether visible facial asymmetries resulted from
the split-­face study design, the GAIS score, as evaluated by the pa-
tient, was compared between the left and the right side of the face,
independent of the performed injection algorithm (upper versus.
lower face first). The results revealed that the patients rated their
facial sides (right versus left facial side) at D0 with 3.68 (0.5) versus
3.50 (0.5) and p = 0.296, at D30 with 3.77 (0.4) versus 3.41 (0.5) and
p = 0.057, and at D90 with 3.68 (0.5) versus 3.50 (0.5) and p = 0.358,
respectively.

3.4 | Global aesthetic improvement 4 | DISCUSSION

The global aesthetic improvement scale (0–­4; worst to best), when
assessed by the treating physician and by the patient, showed sig-
nificantly better values for the upper face first algorithm when com-
pared to the lower face first algorithm at all evaluated time points:
D0: 3.93 (0.3) versus 3.23 (0.4) with p < 0.001; D30 4.0 (0.0) versus
3.17 (0.4) with p < 0.001; and D90 4.0 (0.0) versus 3.23 (0.4) with
p < 0.001 (Table 1 and Figure 7).
This interventional split-­f ace study was designed to test whether
the upper face first algorithm provides superior aesthetic out-
comes when compared to the lower face first injection algorithm.
To test this hypothesis, a side-­s ymmetric injection technique was
performed which administered the same amount and the same
type of soft tissue filler product at each of the injection sites lo-
cated in the upper, middle, and lower face. This was achieved via a
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HERNANDEZ et al. 423

F I G U R E 5 Bar graph showing the

objectively measured (via 3D imaging)
middle facial volume stratified for both
injection algorithms (upper face first vs.
lower face first) at baseline (= BL, before
the treatment), at D0 (= immediately after
the treatment), at D30 (= 1 month after
the treatment), and at D90 (= 3 months
after the treatment). Standard deviation is
indicated by error bars. Probability value
(= p-­value) as calculated by Wilcoxon
signed rank test represents the statistical
difference between the two injection
algorithms at each time point.

F I G U R E 6 Bar graph showing the objectively measured (via 3D imaging) lower facial volume stratified for both injection algorithms
(upper face first vs. lower face first) at baseline (= BL, before the treatment), at D0 (= immediately after the treatment), at D30 (= 1 month
after the treatment), and at D90 (= 3 months after the treatment). Standard deviation is indicated by error bars. Probability value (= p-­value)
as calculated by Wilcoxon signed rank test represents the statistical difference between the two injection algorithms at each time point.

thorough pre-­injection patient assessment in which it was deter-
mined, a priori, how much product is needed for each of the three
targeted facial injection regions. Once the amount of product
was decided and documented, each of the three injection points
was treated with that pre-­d etermined amount; the administered
amounts were identical for both facial sides. However, the treat-
ment sequence for one facial side was upper, middle, and lower
face (upper face first injection algorithm), whereas the contralat-
eral treatment sequence was lower, middle, and upper face (lower
face injection algorithm).
The results revealed that the rating for midfacial volume, which
was evaluated by the treating physician and by an observer with aes-
thetic background, displayed greater scores for the facial side treated
with the upper face first algorithm when compared to the contralat-
eral side treated with the lower face first algorithm: D0 0.33 versus
0.67, D30 0.30 versus 0.33, and at D90 0.13 versus 0.27. The same
trend was observed for the rating of jawline contouring in which the
upper face first algorithm resulted in better outcome scores when
compared to the lower face first algorithm. For both scores, the sta-
tistical significance failed to reach the significance level of p ≤ 0.05.
This can be potentially explained by the minute changes induced
by the small amounts of administered soft tissue filler which were
1.0 cc for the upper face injection, 0.51 cc for the middle face, and
0.51 cc for the lower face injections. The small amounts of injected
filler can induce only a certain magnitude of change which might
have not been sufficiently large to display a statistically significant
difference. However, despite not reaching the set significance level,
a trend toward better outcomes for the upper-­face first algorithm
is detectable and can be used as an indication of its clinical validity.
Another reason why the significance levels were not reached could
be due to the small sample size (n = 15). A larger sample size would
have potentially allowed for greater stability of the values for each
algorithm to be able to discriminate between true change or coinci-
dence. Here, it must be noted that this study was self-­funded and did
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424
not receive financial support from the aesthetic industry. Therefore,
the products utilized, the analyses performed, and the preparation
of this publication are the sole product of the authors of this study;
this also includes that the data presented is not influenced by any
third party, and results can be considered unbiased.
Critical evaluation of the semi-­quantitatively assessed outcome
scores could suggest that the ratings for midfacial volume and jaw-
line contouring are biased toward one of the two injection algo-
rithms with a higher score being attributed by the injector to favor
the outcome. Therefore, the interclass correlation coefficient (ICC)
was calculated as a measure of agreement between the treating phy-
sician and a non-­injecting observer with an aesthetic background.
The calculations revealed an excellent agreement with ICC ≥ 0.90
between the two raters which supports the validity of the results
obtained.
To provide additional comparative calculations the change in vol-
ume compared to the baseline was calculated by using 3-­dimensional
imaging and surface volume calculations. This validated method-
ology aligns the obtained follow-­up images of each follow-­up visit
to the baseline image and the difference in the surface volume
are computed. The results of the mid-­facial analyses revealed that
the volume increase of the midface (after the average injection of
0.51 cc) was 0.93 cc for the upper face first algorithm, whereas the
volume increase for the lower face first algorithm was 0.40 cc. The
observation that a higher volume was measured than injected can be
explained by the fact that the temple was treated first with the tem-
poral lifting technique; this technique was shown previously to be
able to reposition the midfacial soft tissues.12 Repositioning the mid-
facial soft tissues allows for a greater projection following soft tissue
filler volume injection in comparison to the filler injection without
previous soft tissue repositioning. This would explain why the objec-
tively measured volume increase was 0.91 cc, but the injected vol-
ume was 0.51 cc, respectively. The lower face first algorithm started
with volume application in the lower face which most likely resulted
in the fact that the facial soft tissues were not repositioned but ei-
ther remained in their original position or were pulled caudally (in-
stead of cranially). The injection of 0.51 cc soft tissue filler resulted
in an objectively measured volume increase of only 0.40 cc which
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HERNANDEZ et al.
F I G U R E 7 Bar graph showing the
Global Aesthetic Improvement Scale
(GAIS) stratified for both injection
algorithms (upper face first versus. lower
face first) at baseline (= BL, before the
treatment), at D0 (= immediately after
the treatment), at D30 (= 1 month after
the treatment), and at D90 (= 3 months
after the treatment). Standard deviation is
indicated by error bars. Probability value
(= p-­value) as calculated by Wilcoxon
signed rank test represents the statistical
difference between the two injection
algorithms at each time point.
represents a reduced effectiveness compared to the contralateral
side treated with the upper face first algorithm. This reduced effec-
tiveness is most likely the result of the “pure” volume application
without previous repositioning. Repositioning facial soft tissue first
allows for a rearrangement of retinacula cutis and other facial lig-
aments which can translate the volumizing effect more effectively
toward the skin surface. Volumizing alone will still provide an aes-
thetic effect that is clinically beneficial. However, this effect can be
enhanced by repositioning procedures first; this is most likely the
explanatory mechanism behind the results observed in this study.
Focusing on the lower face, it was detected that the volume
increase compared to baseline was 0.37 cc for the upper face first
algorithm, whereas, for the lower face first algorithm, a volume de-
crease was detected by 0.13 cc despite an average volume of 0.51 cc
was injected. This surprising effect can be explained when assuming
that volume application without prior stabilization or repositioning
of the facial soft tissues resulted in a repositioning of the soft tissues
in a more caudal position. This shift of the lower facial soft tissues
toward the neck can be measured on the skin surface as volume de-
creases which was still detectable at 1 month following the treat-
ment with 0.23 cc.
The greatest difference between the two performed injection
algorithms was observed immediately after the aesthetic treatment
at D0. However, this effect was less prominent at D30 and D90 fol-
low-­up. A potential explanation for this observation could be the
integration of administered filler material into the facial soft tissues
with its consecutive loss of effect. Once the rheologic properties
of the product are broken down, both repositioning and volumizing
effects settle; this can be observed for all values at D90. However,
the curve of the rated and the measured effects are congruent in
their timeline and show their dependence on the utilized material.
It can be speculated that with different filler materials or with larger
amounts of filler used, the effectiveness of the treatment can be
enhanced. On the contrary, the results also reveal that the upper
face first injection algorithm is effective and is superior to the lower
face first algorithm.
When the side-­specific aesthetic improvement was evaluated,
the facial side treated with the upper face first algorithm was rated

HERNANDEZ et al.
significantly better than the lower face first algorithm. This outcome
was observed at all follow-­up visits throughout the study period. It
could be argued that the split-­face study design results in facial asym-
metries which are perceived as aesthetically unpleasant for the study
participants. To investigate this aspect, the aesthetic improvement was
compared between the left and right facial sides (not between the two
injection algorithms) when rated by the patient only. The results re-
vealed that the patients do not perceive their facial sides significantly
different from all values p > 0.05. This indicates that the study partici-
pants did not perceive the study design to result in facial asymmetries.
5 | CO N C LU S I O N
It can be summarized that the upper face first injection algorithm
results in superior aesthetic outcomes when directly compared to
the lower face first algorithm. Semi-­quantitative and objective out-
come measurements confirm its clinical effectiveness. However, the
results seem to depend on the rheologic properties and the duration
of the administered products; this can be regarded as a great oppor-
tunity for future large-­sampled clinical studies.
AC K N OW L E D G M E N T
Open Access funding enabled and organized by Projekt DEAL.
F U N D I N G I N FO R M AT I O N
The authors received no financial support for the research, author-
ship, and publication of this article. The products utilized in this
study were donated by the injectors for the purposes of this study.
C O N FL I C T O F I N T E R E S T
The authors declared no potential conflicts of interest with respect
to the research, authorship, and publication of this article.
DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from
the corresponding author upon reasonable request.
E T H I C A L A P P R OVA L
Authors declare human ethics approval was not needed for this
study.
ORCID
Konstantin Frank https://orcid.org/0000-0001-6994-8877
Michael Alfertshofer https://orcid.org/0000-0002-4892-2376
Sebastian Cotofana https://orcid.org/0000-0001-7210-6566
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How to cite this article: Hernandez CA, Zapata DEU,
Bermudez MP, et al. Clinical validation of the upper face first
principle—­A clinical, prospective, interventional split-­face
study. J Cosmet Dermatol. 2023;22:418-425. doi:10.1111/
jocd.15563