Cosmetic Medicine

Aesthetic Surgery Journal

2020, Vol 40(5) 560–567
Premaxillary Injection for Perioral © 2019 The Aesthetic Society.
Reprints and permission:
Rejuvenation and Lip Enhancement journals.permissions@oup.com
DOI: 10.1093/asj/sjz108
www.aestheticsurgeryjournal.com

Thuy-Van T. Ho, MD ; Eric W. Cerrati, MD; Nimit D. Gandhi, MD;

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Arjun Kalbag, PhD; and Steven H. Dayan, MD, FACS

Abstract
Background:  This is the first study to evaluate the effect of premaxillary filler injection on nasal tip projection, upper lip
projection, and upper lip vermilion height.
Objectives:  The primary objective of this study was to analyze the change in nasal tip projection (measured by the Goode
ratio) and the change in upper lip projection (measured by the Z angle) following premaxillary hyaluronic acid injection.
A secondary objective was to measure the change in upper lip vermilion height. We hypothesized that treated subjects
will show an increase in nasal tip projection, upper lip projection, and upper lip vermilion height.
Methods:  Twenty volunteer patients with signs of perioral aging or poor upper lip projection were enrolled in this pro-
spective cohort study and underwent premaxillary hyaluronic acid filler injection between November 2017 and June 2018.
Nasal tip projection, upper lip projection, and upper lip vermilion height were assessed from baseline and posttreatment
photographs based on the Goode ratio, Z angle, and lip vermilion height ratio, respectively.
Results:  No significant change was noted between pre- and posttreatment Goode ratio measurements (P = 0.841). There
was a significant decrease in Z angle and therefore significant increase in upper lip projection with treatment (P < 0.001).
The lip vermilion height ratio demonstrated a trend of increased upper lip vermilion height but this did not achieve statis-
tical significance (P = 0.561).
Conclusions:  Premaxillary filler treatment resulted in a significant increase in upper lip projection. Premaxillary filler injec-
tion when performed in a safe manner is a valuable treatment option for perioral rejuvenation.

Level of Evidence: 4 

Editorial Decision date: March 27, 2019; online publish-ahead-of-print April 9, 2019.

The anatomic changes behind perioral aging have been
well studied and well described in the literature. As patients
age, they tend to experience flattening of the Cupid’s bow
and loss of definition of the philtral columns, resulting in the
appearance of a thin and elongated upper lip.1,2 One influ-
ential factor in this process is the atrophy of the orbicularis
oris muscle; relaxation of the muscle curvature over time
leads to a less acute vermilion border angle and adds to
the overall increase in lip length.3 Other perioral signs of
aging include deepening of the nasolabial and labiomental
Dr Ho is a Facial Plastic Surgeon and Dr Dayan is an Assistant
Professor and Facial Plastic Surgeon, Division of Facial Plastic and
Reconstructive Surgery, Department of Otolaryngology, University
of Illinois at Chicago, Chicago, IL. Dr Cerrati is an Assistant Professor
and Facial Plastic Surgeon, Division of Otolaryngology, University of
Utah, Salt Lake City, UT. Dr Gandhi is a Clinical Research Coordinator
and Dr Kalbag is a Statistician, DeNova Research, Chicago, IL.
Corresponding Author:
Dr Thuy-Van T. Ho, 569 West Lancaster Avenue, Haverford, PA
19041, USA.
E-mail: thuyvantinaho@gmail.com
Ho et al561
folds, development of perioral rhytids, downturning of the
oral commissures, and jowling associated with gravita-
tional effects and soft tissue volume loss.4,5
In addition to the soft tissue changes, maxillary bony
resorption is also implicated in perioral aging. Mendelson
et al,6 for example, discovered that the maxillary angle de-
creased by about 10° between younger (<30  years) and
older (>60  years) individuals. Furthermore, the piriform
aperture gradually widens with age and subsequently
contributes to visible signs of nasal aging that include in-
creased nasal length and drooping of the tip.7,8
Hyaluronic acid filler continues to be an increasingly
prominent treatment option for perioral rejuvenation.9
Hyaluronic acid filler injection is routinely performed in the
mid to deep dermis to improve the appearance of deep
facial wrinkles and folds such as nasolabial folds, perioral
rhytids, and prejowl sulci. However, there is limited litera-
ture regarding deeper injection of hyaluronic acid in the
perioral region to compensate for the muscle atrophy and
bony resorption aspects of perioral aging and to address
the elongated upper lip.
In 2017, Cerrati and Dayan10 demonstrated in their retro-
spective study of rhinoplasty patients that increased nasal
tip projection was significantly associated with increased
upper lip projection. Moreover, there was also a trend to-
wards increased upper lip vermilion height. In light of these
findings, and based on his own clinical experience with
filler injection, the senior author (S.H.D.) observed the po-
tential benefit of hyaluronic acid injection into the premax-
illary space as a technique to address the multiple factors
that contribute to perioral and nasal aging.
Therefore, the primary objective of this study was to as-
sess the change in nasal tip projection (as measured by
the Goode ratio) and the change in upper lip projection (as
measured by the Z angle) following perioral rejuvenation
with premaxillary hyaluronic acid filler injections. A  sec-
ondary objective was to measure the change in upper lip
height by comparing the pre- and posttreatment injection
ratio of upper lip vermilion height to lower lip vermilion
height. We hypothesized that subjects who are treated with
premaxillary filler injection will demonstrate an increase in
nasal tip projection, upper lip projection, and upper lip ver-
milion height.
METHODS
We conducted an open-label prospective study to assess
the effect of premaxillary hyaluronic acid filler injection on
nasal tip projection and upper lip position. From November
2017 to June 2018, 20 volunteer patients who presented
to a facial plastic surgery office desiring facial rejuvenation
were enrolled in this study. Subjects were deemed eligible
by the senior author (S.H.D.) if they were 21 years or older,
and filler naive with signs of perioral aging or poor upper
lip projection on examination. Exclusion criteria comprised
any history of rhinoplasty, upper lip augmentation within
the last 12  months, lip lift or other surgical procedures
involving the upper lip, chin augmentation, or orthognathic
surgery. Enrolled subjects were instructed to avoid perioral
neurotoxin treatment, perioral ablative resurfacing, facial
cosmetic surgery, and all subdermally directed aesthetic or
filler treatments other than the protocol intervention during
the study. All subjects provided informed written consent
including signed photography consent prior to enrollment.
All study procedures were carried out in adherence to the
Declaration of Helsinki Principles and were approved by
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the local ethical committee of Quorum IRB in Seattle, WA.
The hyaluronic acid filler used in this study was a gel
of hyaluronic acid produced by the Streptococcus spe-
cies of Gram-positive bacteria chemically cross-linked with
butanediol diglycidyl ether and suspended in phosphate-
buffered saline (pH 7) at a concentration of 20 mg/mL with
0.3% lidocaine (Restylane® Defyne).11 This hyaluronic acid
filler is among the newer injectable products available and
possesses a high lifting capacity. It is indicated for correc-
tion of moderate to severe deep facial wrinkles and folds
such as nasolabial folds and marionette lines in patients
over the age of 21 years.12
Hyaluronic acid filler injection was administered in the
facial plastic surgery office setting in accordance with
standard operating procedure. Each patient’s upper lip
and nasolabial areas were first cleaned with benzalkonium
chloride. Bilateral infraorbital nerve block was performed
with 3% mepivacaine local anesthetic to minimize patient
pain and discomfort. Although a routine filler injection via
cannula in the subdermal plane is often tolerated well
without local anesthesia, a premaxillary injection occurs
much deeper and closer to bone as well as the nasal base
and may be felt more by the patient. The hyaluronic acid
filler product was then injected by the senior author in the
premaxillary area in the supraperiosteal plane via a linear
threading technique from 1-mL vials with the use of a 22-G
cannula (SoftFil, Paris, France) through bilateral port sites
at the inferior aspect of the nasolabial folds created with a
20-G needle. The larger cannula size is preferred by the
senior author as it further reduces the risk of vascular in-
jury. The premaxillary space can be defined as the ana-
tomic region located between the maxilla and orbicularis
muscle spanning between the alar bases. Injection was
performed until sufficient aesthetic improvement was
achieved as deemed by the senior author according to the
Optimal Cosmetic Results (OCR) criteria (Figure 1). The an-
ticipated volume of filler product needed in total and for
each side was determined by the senior author based on
his clinical evaluation of the subject’s individual anatomy
and degree of immediate aesthetic improvement achieved
562 Aesthetic Surgery Journal 40(5)

A B

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C D

Figure 1.  (A) Pretreatment lateral view photograph of a 49 year-old female subject. (B) Post-treatment lateral photograph
demonstrating Optimal Cosmetic Result criteria 4 weeks after premaxillary filler injection. (C) Pretreatment frontal view
photograph of the 49 year-old female subject and (D) posttreatment lateral photograph 4 weeks after premaxillary filler
injection.
Ho et al563
A B
Figure 2.  (A) Goode ratio for measurement of nasal tip projection (ratio of nasal height to nasal length). (B) Z angle for
measurement of upper lip projection.
after treatment. The nasolabial folds were not directly ad-
dressed with the premaxillary injection.
Upon enrollment, each subject presented for an initial
treatment visit. At a follow-up visit 2 weeks later, the patient
was re-evaluated. If optimal correction, as deemed by the
senior author, was not maintained, a second “touch-up” in-
jection of filler was performed. Each subject then returned
for a third visit at 4 weeks following the initial treatment.
Subjects were followed for any treatment-related adverse
events including pain, nodules, swelling, redness, bruising,
tenderness, itching, and headache as well as for pigmen-
tation changes, and/or keloid formation.
Photographs were captured of each subject before
hyaluronic acid filler injection at the initial treatment visit
and at all subsequent follow-up visits by the same coau-
thor (N.D.G.). Standardized frontal, oblique, and lateral
view photographs were taken with a Nikon D90 digital SLR
camera (Nikon, Tokyo, Japan) with a 105-mm lens at 1.5 m
and umbrella lighting at quarter strength. Subject photo-
graphs were saved to Mirror software.
Upon study culmination, tip projection, upper lip projec-
tion, and lip vermilion height ratio were measured for all
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pretreatment and 4-week posttreatment subject photographs
with the same methods used by Cerrati and Dayan.10 A deci-
sion was made to perform measurements based on standard
facial landmarks and distance ratios to avoid the influence
of variability in lighting, camera angle, facial orientation, and
camera distance that are often difficult to maintain consist-
ently in standardized portrait photography. All measurements
and calculations were performed solely by the primary author
(T.T.H.) to avoid potential bias from the treating senior author
and coauthor photographer. Adobe Photoshop 7.0 software
was utilized to perform comparative measurements of the
anatomic distances and angles described below.
The Goode ratio was used as a measurement of tip
projection and is defined as the ratio of nasal height to
nasal length (Figure  2A). For each subject’s right lateral
view photograph, the nasal height was measured as the
length of a line drawn from the alar-facial groove to the
tip-defining point, and the nasal length was measured as
the length of the line drawn from the nasion to the tip-
defining point. The nasal height value was then divided by
the nasal length value to determine the Goode ratio for a
given photograph.
564
Figure 3.  Lip vermilion height ratio: ratio of upper lip
vermilion height (A) to lower lip vermilion height (B).
Upper lip projection was assessed via measurement of
the Z angle, a method outlined by Merrifield13 in 1966. This
method was selected for assessment of upper lip projec-
tion because the corresponding measurements would not
be affected by posttreatment soft tissue or nasal changes.
On each subject’s right lateral view photograph, a profile
line was drawn tangential to the pogonion of the chin and
to the most anterior point of the upper lip. A second line
was drawn along the Frankfort horizontal plane. The re-
sulting angle at which these 2 lines intersected corres-
ponded to the Z angle (Figure 2B).13,14 A decrease in the Z
angle to a more acute value on posttreatment photographs
would correspond to an increase in upper lip projection.
Lip vermilion height ratio was calculated as the ratio
of the upper lip vermilion height to the lower lip ver-
milion height across the subject frontal photographs
(Figure 3). The upper lip vermilion height was measured
as the length of a vertical line drawn from the upper
lip vermilion border at the Cupid’s bow portion to the
stomion. The lower lip vermilion height was measured
as the length of a central vertical line drawn from the
stomion to the lower lip vermilion border. Each upper lip
vermilion height value was divided by the related lower
lip vermilion height value to determine the lip vermilion
height ratio for a given subject photograph. Statistical
analysis comprised a paired 2-tailed t test, with P < 0.05
considered significant.
RESULTS
A total of 20 female subjects, ranging from 42 to 75 years
in age with a mean age of 61 years (SD = 8.58 years), were
enrolled in this study. The mean follow-up period dur-
ation was 26.3 days (range, 12-47 days). All 20 subjects
completed the protocol without any complications.
Subjects were injected with a maximum of 4 syringes
of filler product to treat their premaxillary space. The
average volume of filler product injected was 2.35  mL
(range, 1.0-3.4 mL).
Aesthetic Surgery Journal 40(5)
The mean, standard deviations (SDs), and range values
of the Goode ratio, Z angle, and lip vermilion height ratio at
baseline and posttreatment are presented in Table 1.
The repeated-measures analysis of variance model
used to study the multivariate effect of the premaxillary in-
jection on outcome variables demonstrated significance
[Pillai’s trace  =  0.511, F(3,17)  =  5.911, P  <  0.001]. Follow-up
t tests conducted to assess the difference between
posttreatment and baseline values of the Goode ratio, the
Z angle, and the lip height ratio, however, detected only
a significant change in the mean Z angle measurement.
Significance level α for multiple comparisons from base-
line to posttreatment for each outcome variable was set to
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0.016 to avoid inflating the type I error rate.
The mean posttreatment Goode ratio of 0.601
(SD = 0.052) was neither greater nor significantly different
than the mean baseline Goode ratio of 0.603 (SD = 0.064)
[t(19)  =  –0.203, P  =  0.841]. On the other hand, the mean
posttreatment Z angle of 74.245° (SD  =  10.859°) was sig-
nificantly lower than the mean baseline Z angle of 77.070°
(SD  =  10.677°) [t(19)  =  –4.111, P  <  0.001]. From baseline to
posttreatment, Z angle measurements demonstrated a
mean decrease of 2.825° (95% CI: 1.387°-4.263°). Figure 4
illustrates an example patient who experienced a decrease
in Z angle after premaxillary filler injection. The mean
posttreatment lip version height ratio of 1.147 (SD = 0.375)
was higher than the mean baseline lip height ratio of 1.116
(SD = 0.393) but the difference did not reach statistical sig-
nificance [t(19) = 0.591, P = 0.561].
DISCUSSION
Although perioral aging is well understood and described in
the literature,1-5 treatment options that address all aspects
of the perioral aging process remain limited. Hyaluronic
acid filler is a popular nonsurgical treatment that is com-
monly used to improve perioral lines, jowling, and thin,
down-turned lips at the soft tissue level.9 Nevertheless,
the use of hyaluronic acid filler injection to combat pre-
maxillary bony deficiency has not been widely pursued or
studied.
In 2008, Ibhler et al15 conducted a magnetic resonance
imaging–based comparative study analyzing upper lip
changes with aging. They revealed that there is actually
no loss in volume in the upper lip as previously believed,
but rather a redistribution of upper lip thickness towards
length. They also found that the nasolabial angle deep-
ened in the older population, which highlights the contribu-
tion of premaxillary volume loss to the process of perioral
aging. Therefore, it is reasonable to conclude that hyalu-
ronic acid filler injection targeted at multiple levels of the
perioral region, including the premaxillary space, is most
beneficial. For this reason, a treatment aimed to address
Ho et al565

Table 1.  Descriptive Statistics for the Goode Ratio, Z Angle, and Lip Vermilion Height Ratio

Goode ratio Z angle Lip vermilion height ratio

Pretreatment Post-treatment Pretreatment Post-treatment Pretreatment Post-treatment

Mean 0.603 0.601 77.070° 74.245° 1.116 1.147

Standard deviation 0.064 0.052 10.677° 10.859° 0.393 0.375

Range 0.486-0.737 0.475-0.717 54.2°-95.1° 49.9°-90.2° 0.391-1.908 0.397-1.720

A B

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Figure 4.  (A) Pretreatment photograph of a 52-year-old female subject. (B) Post-treatment photograph illustrating decrease in Z
angle 4 weeks after premaxillary filler injection.

only one aspect of the perioral area, such as thin lips,
would result in an unnatural, duck-like appearance.
It is vital to have a thorough understanding of the rele-
vant facial anatomy and associated significant risks when
performing premaxillary filler injection. The premaxillary
space is near several large facial vessels, including the
lateral nasal artery and superior labial artery. Intravascular
injection can result in serious complications including
necrosis and blindness.16 The senior author strongly re-
commends the use of 22-G cannulas for injection and
placement of fillers into the deeper tissues, such as the
supraperiosteal plane, to minimize the risk of vascular
complications. Strict adherence to clean techniques is also
advocated to avoid potential complications of infection
and biofilm formation.
The hyaluronic acid filler used in this study is a newer
injectable product with multiple potential advantages
for addressing the premaxillary space. Compared with
its older counterparts, this hyaluronic acid filler demon-
strates a high lifting capacity (or high G′) due to its unique
XpresHAn Technology and is thus indicated for deeper
injection into the mid-to-deep dermis to provide more
566
support and projection in the correction of moderate to se-
vere facial wrinkles and folds.12 The unique cross-linking
nature of the filler also promotes its ability to support nat-
ural facial expressions. A multicenter, noncomparative trial
of 63 subjects treated with this filler product indicated
that facial movements and expressions remained intact at
1 month after treatment; in fact, 89% of patients treated felt
they looked natural when smiling and relaxed.17 A phase III
comparator trial revealed 64% of subjects maintained their
results after 12  months.18 Therefore, the advantageous
properties of high G′, flexibility, and longevity possessed
by the hyaluronic acid filler product used in this study
make it an ideal filler option for restoring volume in the
deeper premaxillary space without affecting natural facial
expression in the perioral region.
This is the first study to assess the effect of premaxillary
filler injection on nasal tip projection, upper lip projection, and
upper lip vermilion height. Although the premaxillary filler
treatment did not significantly affect nasal tip projection, it
resulted in a significant increase in upper lip projection with a
measurable trend towards an increase in lip vermilion height
ratio and therefore upper lip vermilion height. Additional
study is warranted to further delineate a causal relationship
between premaxillary injection and upper lip height, as our
study did not demonstrate statistical significance.
Our study possesses several inherent limitations.
Although the baseline and pretreatment photographs
were taken in similar fashion by a single photographer,
there were some inconsistencies in facial orientation
in the photographs, particularly in lateral view. In some
photographs, the external auditory canal was obscured;
subsequently the lines created for the Z angle measure-
ment were less precise and may have affected the angle
values. Furthermore, some lateral-view photographs were
more tilted compared to their baseline or posttreatment
counterparts, which may have distorted the accuracy of
the measurements. Although all measurements and cal-
culations were performed by one reviewer to avoid bias
created by the treating senior author, the inclusion of mul-
tiple reviewers for photograph assessment may have re-
duced the potential for human error. Finally, we used only
2-dimensional methods to analyze the premaxillary space,
a 3-dimensional area. Future studies that can assess the
3D changes in the perioral region may characterize more
accurately the specific changes produced by premaxillary
filler injection.
CONCLUSIONS
This is the first study to evaluate the impact of premaxillary
filler injection on nasal tip projection, upper lip projection,
and upper lip vermilion height. We found that premaxillary
filler treatment resulted in a significant increase in upper
lip projection with a trend towards increased upper lip
Aesthetic Surgery Journal 40(5)
vermilion height as well. These findings confirm the bene-
ficial effect of premaxillary filler injection for nonsurgical
treatment of the perioral region. Premaxillary filler injection
when performed in a safe manner is a valuable adjunct
treatment option for perioral rejuvenation.
Disclosures
Dr Dayan received equipment, materials, and medications as
well as funding from Galderma Laboratories, LP to support this
research. The other authors declared no potential conflicts of
interest with respect to the research, authorship, and publica-
tion of this article.
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Funding
This study was supported by a grant from Galderma
Laboratories, LP to the senior author (S.H.D.). This was an
investigator-initiated trial in which the collaborator Galderma
Laboratories, LP did not create the design or conduct the study
and was not involved in the collection management, analysis,
and interpretation of the data. Galderma Laboratories, LP did
participate in the preparation of this manuscript following the
draft by reviewing content for scientific accuracy of their prod-
ucts and approval of the manuscript and was involved in the
decision to submit this manuscript for publication.
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