Research

Original Investigation

Subcutaneous vs Intramuscular Botulinum Toxin

Split-Face Randomized Study
Eli A. Gordin, MD; Adam L. Luginbuhl, MD; Timothy Ortlip, MD; Ryan N. Heffelfinger, MD; Howard Krein, MD, PhD

IMPORTANCE Much has been published regarding rejuvenation of the upper face with
botulinum toxin A injection; however, the optimal target tissue layer has not been specifically
examined.

OBJECTIVE To seek a difference between subcutaneous (SC) and intramuscular (IM)

administration.

DESIGN, SETTING, AND PARTICIPANTS Prospective, randomized study at a tertiary care

university facial plastic surgery practice. Nineteen patients who underwent botulinum toxin A
treatment to the forehead were randomized so that each patient received IM injection on one
side of the face and SC injection on the contralateral side.

INTERVENTION Patients were assessed on the basis of eyebrow elevation before treatment,
and at 2 weeks, 2 months, and 4 months following injection. Patients also completed a
subjective questionnaire examining discomfort during injection, bruising, and tenderness, as
well as their perception of their appearance after treatment.

MAIN OUTCOME AND MEASURE Eyebrow height measurements between SC and IM

techniques.

RESULTS There was no difference in eyebrow height measurements between SC and IM

techniques (0.00 [95% CI, −0.02 to 0.02]). Patients did report greater discomfort when
receiving IM injections compared with SC injections (−0.76 [95% CI, −1.53 to 0.0005]).
Patient satisfaction scores did not demonstrate a statistically significant difference between
IM and SC techniques when measured on the first and second posttreatment visits; however,
there was a trend toward significance on the final follow-up visit.

CONCLUSIONS AND RELEVANCE Subcutaneous injection of botulinum toxin A is equally

effective in achieving paralysis of the underlying frontalis muscle as IM botulinum toxin A
administration. In addition, the SC route may result in less pain to patients receiving
botulinum toxin A injection for rejuvenation of the upper face.

LEVEL OF EVIDENCE 1.
Author Affiliations: Department of
Otolaryngology–Head and Neck
Surgery, Thomas Jefferson University
Hospital, Philadelphia, Pennsylvania
(Gordin, Luginbuhl); Jefferson
Medical College, Thomas Jefferson
University, Philadelphia, Pennsylvania
(Ortlip); Division of Facial Plastic and
Reconstructive Surgery, Department
of Otolaryngology–Head and Neck
Surgery, Thomas Jefferson University
Hospital, Philadelphia, Pennsylvania
(Heffelfinger, Krein).
Corresponding Author: Eli A.
Gordin, MD, Department of
Otolaryngology–Head and Neck
Surgery, Thomas Jefferson University
Hospital, 925 Chestnut St, Sixth
JAMA Facial Plast Surg. 2014;16(3):193-198. doi:10.1001/jamafacial.2013.2458 Floor, Philadelphia, PA 19107
Published online April 3, 2014. (eagordin@gmail.com).

193

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 Research Original Investigation
B
otulinum toxin was first discovered as a causative agent
of food-borne illness in 1895 by Emile Pierre van Er-
mengem in Ellezelles, Belgium. Over half a century
would pass before its mechanism of action would be uncov-
ered as the inhibition of acetylcholine release from motor nerve
endings.1 During this time, 2 variants of botulinum toxin would
be classified and described by Burke in 19192 and several more
in the intervening decades before the isolation of crystallized
botulinum toxin A would finally occur in 1946.1
Since the first reported study by Carruthers and Carruthers3
in 1992 of botulinum toxin A examining its utility in rejuve-
nation of the forehead, the injection of botulinum toxin A has
become the most commonly performed cosmetic procedure
in the United States.4 The use of botulinum toxin A for the treat-
ment of facial rhytides been demonstrated to influence oth-
ers’ perception of a patient, mitigate the misunderstanding of
an aging patient’s facial expressions, and improve patients’
moods while decreasing feelings of anxiety and depression.5-8
One potential factor deterring patients from receiving botu-
linum toxin A treatments is the pain associated with injection.
Muscle is a consolidated space, enveloped by surrounding fas-
cia, and comprised of tightly joined cells. Muscle and skin both
contain a dense supply of nociceptive nerve endings. Cutane-
ous nociceptors are concentrated in the dermoepidermal junc-
tion, leaving the subcutaneous (SC) space relatively devoid of
pain receptors.9 Intramuscular (IM) administration of an inject-
able substance may result in increased pain when compared
with application into the SC space, which may more readily ac-
cept a fluid bolus.10 While much has been published regarding
the technique of botulinum toxin A injection in its use for re-
juvenation of the upper face, the optimal target tissue layer has
not been examined, and opinion varies as to whether injection
need take place within the specific muscle body being tar-
geted vs the immediately adjacent tissue planes.11-15 To pre-
vent dilution and spread of effect, it is also recommended that
higher concentrations be used in smaller volumes.16,17
Injection of botulinum toxin A into the SC space has been
reported anecdotally,15 although there is not, to our knowl-
edge, a controlled study that examines whether or not a dif-
ferential exists in terms of efficacy for botulinum toxin A in-
jected intramuscularly vs subcutaneously. Therefore, we
undertook a prospective, randomized, double-blind study,
using a split face control, to ascertain whether the SC and IM
routes possess equivalent effectiveness for facial rejuvena-
tion of the forehead targeting the frontalis muscle.
Methods
This was a double-blind, randomized, prospective trial, per-
formed on 19 participants from December 1, 2010, to June 1,
2011. Institutional review board approval was given by Thomas
Jefferson University. All patients provided appropriate writ-
ten informed consent prior to participation in the study. Each
received a total of 12 U of botulinum toxin A (Botox; Allergan
Inc) administered in a symmetrical fashion in 4 equal ali-
quots; 2 to the left forehead and 2 to the right. Each partici-
pant was randomly assigned a number, via a computer data-
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Subcutaneous vs Intramuscular Botulinum Toxin
base, to determine which side of the face would receive an IM
application of botulinum toxin, and which would receive an
SC injection. Botox was diluted with injectable normal saline
to a concentration of 4 U per 0.1 mL and injected through a 30-
gauge, 0.5-in needle. No manipulation was performed of the
injection sites following injection. If there was any bleeding,
light pressure was briefly held with gauze.
Exclusion criteria for this study included individuals
younger than 18 years as well as those older than 65 years, preg-
nant patients, patients with immunocompromised states, and
patients with any neurologic conditions. In addition, individu-
als were not included in the study if they had received prior fa-
cial cosmetic procedures within the year prior to injection. These
included skin peels, dermabrasion, injections of neuromuscu-
lar agents or fillers, as well as cosmetic surgery of any kind.
Prior to injection, all patients were photographed in the
dedicated photography room within our department’s center
for facial aesthetics and reconstructive surgery. All photo-
graphs were taken under identical lighting conditions using the
same digital camera (model D90, Nikon). Patients were pho-
tographed in the standard fashion, positioned along the Frank-
ford horizontal plane, in frontal, left, and right oblique, and
left and right profile views. In all positions, patients were pho-
tographed in both a relaxed, neutral expression, as well as while
exhibiting maximal voluntary eyebrow elevation.
Injections themselves were performed by the 2 senior au-
thors (R.N.H. and H.K.) who are board-certified facial plastic
and reconstructive surgeons. Injections were performed with
the use of an Accuguide injection electromyographic (EMG) de-
vice (Xomed Surgical Products Inc) to aid in confirmation of
the specific tissue layer being injected. When the needle was
in position, participants were asked to raise their eyebrows,
resulting in audible activity from the EMG probe when the
needle tip was within the frontalis muscle body, and no change
in activity when the needle was positioned in the SC plane
(Figure 1).
Immediately following injections, patients were asked to
answer a brief questionnaire, examining whether they had pre-
viously received botulinum toxin A treatments, as well as the
level of discomfort each person experienced during each in-
jection, as rated on a scale of 0 to 5. Patients were also asked
whether a difference was noticeable between the left- and right-
side injections, and whether the discomfort experienced was
less than, equal to, or more than what was anticipated. The in-
jecting physicians also completed an evaluation form in which
they commented on any difficulty in accessing the SC plane
and whether there was bleeding or bruising immediately fol-
lowing injection; they had space to write in additional com-
ments, at their discretion.
Appointments were made with all patients for return vis-
its taking place 2 weeks postinjection, as well at 2 and 4 months
postinjection. At the time of all follow-up appointments, pa-
tients were photographed in a manner identical to that de-
scribed during the initial visit, and an identical questionnaire
was administered at each appointment. Inquiries were made
as to whether patients perceived any change in their appear-
ance since injection, what those changes were, and if there was
a noticeable difference between the 2 sides of the face. Pa-
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 Subcutaneous vs Intramuscular Botulinum Toxin
Figure 1. Injection With Botulinum Toxin A
A B
tients were asked to declare whether any bruising or tender-
ness followed their injections, and they were asked to rate the
degree to which they were pleased with the results of the in-
jections, on a scale of 0 to 5, for the left and right side of their
faces, individually.
To quantify eyebrow height, all frontal view digital pho-
tographs were transferred to Adobe Photoshop (Adobe Sys-
tems Inc), where several measurements were taken. First, a
horizontal line was drawn through the lateral limbus of bilat-
eral lateral canthi. From this line, eyebrow height was ob-
tained by measuring the distance between the line and a point
taken at the superior-most aspect of the eyebrow, positioned
directly above the mid-pupillary axis (Figure 2). Measure-
ments were made at 150% magnification, viewing images on
an Apple Cinema HD with a 23-in display (Apple Inc) and a
screen resolution of 1920 × 1200 pixels.
The intercanthal distance was measured on each indi-
vidual picture that was used for eyebrow height analysis. The
intercanthal measurements were then used to normalize the
brow height from each photograph to account for differences
in the camera-to-patient distance, which would otherwise com-
promise the eyebrow height values. This resulted in a ratio of
brow height to intercanthal distance that was used for fur-
ther analysis, hereafter referred to as normalized brow height.
For each patient, values of normalized brow height measured
during neutral brow positioning were subtracted from those
measured during active brow elevation, for both sides receiv-
ing the IM and SC injection techniques, yielding a value of nor-
malized brow elevation. This was calculated for pictures taken
immediately prior to injection, and at each follow-up visit.
Once this was calculated, mixed-effects linear regression
was used to model normalized brow height as a function of
treatment (IM vs SC) and visit (initial visit, as well as all 3 fol-
low-up visits). An interaction term between treatment and visit
was included to allow for separate comparison of the 2 treat-
ments at each visit. Random intercept terms were included to
account for correlation between the left and right sides of the
face at each visit and among repeated measurements over time.
These analyses were performed by the division of biostatis-
tics at Thomas Jefferson University.
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Original Investigation Research
A, Placement of injection needle into
the frontalis muscle before voluntary
contraction yields no
electromyographic (EMG) activity on
contacting the probe to the injection
needle. B, Contraction of the frontalis
muscle during eyebrow elevation
elicits heavy activity from the EMG
probe, which is placed in contact with
the injection needle.
Figure 2. The Method for Eyebrow Height Measurement
a
b
A horizontal line was drawn through bilateral lateral canthi. From this line, a
vertical line was drawn, passing through the center of the pupil, extending to
the superior limit of the eyebrow (distance from point a to point b). This
measurement was performed for bilateral eyes, on all photographs. Brow height
was then divided by the intercanthal distance, specific to each photograph to
yield a normalized brow height.
In addition to eyebrow height, statistical analysis was also
performed on the degree of discomfort, as reported by each
patient, rated on a scale of 0 to 5, for the injections performed
on each side of the patient’s face. Similarly, satisfaction scores,
as rated by the patients on a scale of 0 to 5 for each side of the
face on all follow-up appointments, were analyzed as well. A
paired t test was used to compare the discomfort ratings, as
well as the satisfaction scores, for IM and SC injection tech-
niques. Statistical analysis was not used for the remaining items
on the patient and physician questionnaires owing to the small
sample size and limited responses.
Results
Brow Height Measurements
The mean normalized brow elevation for the initial visit was
0.25 (95% CI, 0.20-0.29) for the IM injection, and 0.25 (95% CI,
0.21-0.29) for the SC technique, yielding a mean difference be-
tween sides of −0.01 (95% CI, −0.02 to 0.01), which was not sta-
tistically significant (P = .53) (Table 1). The mean normalized
brow elevation for the first follow-up visit was 0.1 (95% CI, 0.06-
0.15) for the IM side and 0.1 (95% CI, 0.06-0.15) for the SC
method, yielding a difference of 0.00 (95% CI,−0.02 to 0.01)
JAMA Facial Plastic Surgery May/June 2014 Volume 16, Number 3 195
 Research Original Investigation
Table 1. Mean Eyebrow Height Measurementsa
Injection
Visit IM SC
Initial 0.25 (0.2 to 0.29) 0.25 (0.21 to 0.29)
Follow-up 1 0.1 (0.06 to 0.15) 0.1 (0.06 to 0.15)
Follow-up 2 0.19 (0.14 to 0.24) 0.18 (0.13 to 0.23)
Follow-up 3 0.21 (0.15 to 0.27) 0.21 (0.15 to 0.27)
Table 2. Descriptive Statistics of 19 Patients at the Initial Visit
Question Value
Prior Botox treatment Yes
No
Discomfort level Less
Equal
More
Difference between sides noticeable? Yes
No
between techniques, which was not statistically significant
(P = .85). The mean normalized brow elevation for the sec-
ond follow-up visit was 0.19 (95% CI, 0.14-0.24) for the IM tech-
nique and 0.18 (95% CI, 0.13-0.23) for the SC injections, yield-
ing a difference of 0.01 (95% CI, −0.01 to 0.03) between injection
methods, which was not statistically significant (P = .19). Fi-
nally, the mean normalized brow elevation for the final fol-
low-up visit was 0.21 (95% CI, 0.15-0.27) for the IM side as well
as 0.21 (95% CI, 0.15-0.27) for the SC method, yielding a dif-
ference of 0.00 (95% CI, −0.02 to 0.02) between injection meth-
ods, which was not statistically significant (P = .82).
Initial Patient Questionnaires
Descriptive Statistics
Of the 19 patients who participated in the initial study visit with
treatment, 13 (68%) denied any history of receiving botuli-
num toxin A injections. Overall, 6 patients (35%) described the
injections as being less painful than expected, while 10 pa-
tients (59%) stated that the injections were equal to their an-
ticipated discomfort level. One patient experienced more pain
than anticipated. Among the patients who had received pre-
vious treatments, 2 reported less pain than they anticipated,
while the remaining 4 described the pain as being equal to what
was expected (Table 2).
Discomfort Ratings
Fifteen patients (79%) claimed to feel a noticeable difference
in discomfort levels between sides of injection, while 4 (21%)
did not. The mean discomfort level, as rated on a scale of 0 to
5, immediately following the completion of both injections, was
1.97 (95% CI, 1.44-2.51) for the IM side and 1.21 (95% CI, 0.81-
1.61) for the SC side. The mean difference in rated discomfort
was −0.76 (95% CI, −1.53 to 0.0005), with P = .05.
Initial Physician Comments
The attending physicians administering injections noted no dif-
ficulty in accessing the SC plane to deliver medication. Bleed-
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Subcutaneous vs Intramuscular Botulinum Toxin
Difference P Value
−0.01 (−0.02 to 0.01) .53 Abbreviations: IM, intramuscular;
0 (−0.02 to 0.01) .85 SC, subcutaneous.
a
0.01 (−0.01 to 0.03) .19 The ratio of eyebrow height to
intercanthal distance was used for
0 (−0.02 to 0.02) .82
analysis.
ing was noted in 5 cases. In 3 of these cases, bleeding was bi-
lateral, while in 2 cases, bleeding was noted only on the IM side.
No. (%) Immediate bruising was noted in only 2 cases, both occurring
6 (32) on the IM side.
13 (68)
6 (35) Follow-up Questionnaire Responses
10 (59) First Follow-up Visit
1 (6) Eighteen patients returned for the first follow-up visit, 2 weeks
15 (79) postinjection. Fourteen patients (78%) noted an effect from
4 (21) their injections, while 4 (22%) did not. Effects written in by pa-
tients included a reduction in wrinkles, smoother forehead
skin, decreased forehead movement, as well as drooping eye-
lid skin in 1 patient, and a heavier eyelid in another. Eight pa-
tients (44%) reported a noticeable difference in appearance be-
tween sides, while the 10 remaining patients (56%) did not.
Two patients reported bruising on the side that received
the IM injection, while 1 patient reported bruising on the side
that received the SC injection. Similarly, 2 patients noted ten-
derness on the IM side, while 1 declared tenderness on the SC
side. The 2 patients with bruising from the IM injection were
the same 2 who reported tenderness from this technique.
Second Follow-up Visit
Sixteen patients presented for the second follow-up visit, 2
months postinjection. At this point, 10 patients (63%) noted
an effect from treatment, while 6 (38%) did not. Effects noted
by the patients were similar to those noted at the initial visit
and included decreased forehead wrinkles and lines, tighter
and smoother forehead skin, and reduced forehead move-
ment. Six patients (38%) claimed to notice a difference be-
tween sides, while 10 (63%) did not.
Final Follow-up Visit
Ten patients returned for the final follow-up visit at 4 months
postinjection. At this time, 8 patients (80%) noted an effect
from treatment, while 2 (20%) did not. Again, patients specifi-
cally noted reduced forehead lines and wrinkles, smoother
skin, improved appearance, and decreased eyebrow mobil-
ity, as well as 1 case of numbness. Five patients (50%) stated
that they could notice a difference between their right and left
sides, while the other 50% could not.
Patient Satisfaction Ratings
In addition to the variables mentioned herein, patients were
also asked to rate the degree to which they were satisfied with
the results seen on each side of their face, on a scale of 0 to 5.
For the IM injections, patients rated their satisfaction on fol-
low-up visits 1, 2, and 3 at 2.94 (95% CI, 2.01-3.86), 3.00 (95%
CI, 2.04-3.96), and 3.60 (95% CI, 2.43-4.77), respectively. For
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 Subcutaneous vs Intramuscular Botulinum Toxin Original Investigation Research

Table 3. Mean Patient Satisfaction Rating at Follow-up Visitsa

Visit IM SC Difference (95% CI) P Value

Follow-up 1 2.94 (2.01 to 3.86) 2.95 (2.01 to 3.89) −0.02 (−0.7 to 0.67) .96
Abbreviations: IM, intramuscular;
Follow-up 2 3.00 (2.04 to 3.96) 2.61 (1.64 to 3.58) 0.39 (−0.31 to 1.10) .27
SC, subcutaneous.
Follow-up 3 3.60 (2.43 to 4.77) 2.67 (1.47 to 3.87) 0.93 (0.05 to 1.80) .04 a
On a scale of 0 to 5.

the SC injection technique, satisfaction ratings were 2.95 (95% Table 4. Questionnaire Responses at Follow-up
CI, 2.01-3.89), 2.61 (95% CI, 1.64-3.58), and 2.67 (95% CI, 1.47-
Follow-up Patients, No. (%)
3.87) for those same visits. The differences in patient satisfac-
Question 1 2 3
tion were not statistically significant on follow-up visits 1 and
Any effect resulting
2, although on the final follow-up visit, the difference of 0.93 from injections?
(95% CI, 0.05-1.8) was statistically significant (P = .04) (Table 3 Yes 14 (78) 10 (63) 8 (80)
and Table 4). No 4 (22) 6 (38) 2 (20)
Noticeable difference
between sides?
Yes 8 (44) 6 (38) 5 (50)
Discussion No 10 (56) 10 (63) 5 (50)
There is variation among health care practitioners in the spe- Bruising?
cific technique of botulinum toxin A injection, with some ap- IM
plying the toxin directly into the body of the muscle being tar- Yes 2 (13) 2 (13) 1 (10)
geted and others injecting into adjacent tissue layers, such as No 14 (88) 14 (88) 9 (90)
the SC space.11-14 Small volumes of high-concentration botu- SC
linum toxin A are administered to minimize diffusion of the Yes 1 (6) 1 (6) 0
toxin throughout surrounding tissues.11 Anecdotal reports of No 15 (94) 15 (94) 10 (100)
equivalent efficacy using a SC injection exist15; however, to our Tenderness?
knowledge, there exists no randomized study specifically in- IM
vestigating a difference between the 2 techniques. Theoreti-
Yes 2 (13) 1 (6) 0
cal advantages of a SC injection include decreased pain on in-
No 14 (88) 15 (94) 10 (100)
jection and reduced bruising and tenderness.
SC
In this study we were able to use an EMG probe to deter-
Yes 1 (6) 0 1 (10)
mine whether the tip of the injection needle was within the
No 15 (94) 16 (100) 9 (90)
frontalis muscle. Anecdotally, this practice is not used by health
care practitioners performing SC injection. We feel that an ex- Abbreviations: IM, intramuscular; SC, subcutaneous.
perienced facial plastic surgeon can gauge the tissue level
reached by a needle during needle placement and differenti- consuming, and contact dermatitis can result.19,20 There have
ate between muscle, skin, and the SC space. We had no objec- also been trials of remedication with analgesics, such as non-
tive means of ensuring that we were not performing an intra- steroidal anti-inflammatory drugs or acetaminophen.
dermal injection when targeting the SC space, and we relied This study represents a randomized, double-blinded in-
on the experience of the attending surgeon performing the in- vestigation, using a split-face, side-by-side comparison of botu-
jections. We do not intend that an EMG device be used in prac- linum A toxin injected intramuscularly vs subcutaneously. No
tice when performing a SC injection, just as it is not currently statistical difference was noted between the 2 techniques of
relied on for an IM injection. injection by using the magnitude of active brow elevation as
Additional methods of anesthesia include the use of small an objective metric. In fact, results from the 2 methods were
diameter needles, such as 30 to 32 gauge, slow needle inser- nearly identical.
tion, insertion of the needle tip through a pore, and slow in- In accordance with our hypothesis, patients generally
jection. The reconstitution of botulinum toxin A using nor- found the SC application of botulinum toxin A to be less pain-
mal saline containing benzyl alcohol preservative has also been ful than the IM technique, rating their discomfort at 1.21 and
noted to reduce pain associated with treatments.18 Alterna- 1.97, respectively, on a 0 to 5 scale. This difference was signifi-
tive methods of anesthesia include massaging adjacent skin cant, although by no means large. Interpretation of this scale
and the application of vibratory tactile stimulation to the sur- is somewhat limited as well, owing to the nature of this sub-
rounding area,18 as well as thermal techniques, such as cool- jective question.
ing sprays, ice packs, and heating devices. As far as issues with bruising and tenderness are con-
Several pharmacologic measures have been described to cerned, there were more reports of these occurrences with the
lessen the pain of botulinum toxin A injections, including IM injection; however, most patients experienced neither, and
creams and sprays containing compounds such as lidocaine no actual difference could be ascertained.
hydrochloride, prilocaine hydrochloride, tetracaine hydro- Responses were nearly split down the middle regarding the
chloride, and benzocaine, although these practices are time presence of a noticeable difference in appearance between the

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 Research Original Investigation Subcutaneous vs Intramuscular Botulinum Toxin

2 sides of the patients’ faces. When patients were specifically
questioned regarding their posttreatment satisfaction as it re-
lated to each side of the face, both techniques achieved nearly
identical scores when rated on a scale of 0 to 5 at follow-up ap-
pointments 1 and 2. The third follow-up appointment did yield
a difference in satisfaction scores, with the patients noting a
better appearance on the side receiving IM injections. Strictly
speaking, this difference was more of a strong trend than a sig-
nificant difference, as overlap was noted between the 95% CIs.
While subjective grading of rhytides and skin appearance
was not performed, it was felt that a purely objective analysis
of muscular activity as it related to brow height on active el-
evation was the most appropriate metric for analysis of the ef-
ficacy of botulinum toxin A treatments. Considering that the
mechanism involved in the reduction of facial lines is the ac-
tual weakening of muscular contraction, quantifying the de-
gree of weakness by measuring brow movement should func-
tion as a suitable surrogate.
Our method of calculating a normalized brow elevation ra-
tio based on the intercanthal distance was adopted from Kim
et al,21 who devised a similar method of brow height measure-
ment, with the main difference being that those authors’ ra-
tio was calculated by dividing the brow height (as measured
from a horizontal line drawn through the medial canthi) by the
distance between the lateral limbus of the iris and the medial
canthus. We decided to use a completely fixed anatomic land-
mark for our calculations because we felt that this would more
reliably account for any fluctuations in the distance between
patient and camera among individual photographs.
Conclusions
The SC administration of botulinum toxin A achieves efficacy
equivalent to that attained by IM injection in treating brow
lines. Patients report less discomfort on injection of botuli-
num toxin into the SC plane relative to the IM space. Subcu-
taneous injection can therefore be used as a technique to miti-
gate the pain associated with the IM injection of botulinum
toxin A without compromising the compound’s efficacy.

ARTICLE INFORMATION
Accepted for Publication: September 9, 2013.
Published Online: April 3, 2014.
doi:10.1001/jamafacial.2013.2458.
Author Contributions: Drs Krein and Heffelfinger
had full access to all the data presented in the study
and take full responsibility for the integrity of the
data and the accuracy of the data analysis.
Study concept and design: Gordin, Luginbuhl,
Heffelfinger, Krein.
Acquisition of data: All authors.
Analysis and interpretation of data: All authors.
Drafting of the manuscript: Gordin, Luginbuhl,
Ortlip, Krein.
Critical revision of the manuscript for important
intellectual content: Luginbuhl, Heffelfinger.
Statistical analysis: Luginbuhl, Ortlip.
Obtained funding: Heffelfinger.
Administrative, technical, and material support:
Gordin, Luginbuhl, Heffelfinger, Krein.
Study supervision: Luginbuhl, Heffelfinger, Krein.
Conflict of Interest Disclosures: None reported.
Funding/Support: Funding for this project was
supplied by Department of Otolaryngology–Head
and Neck Surgery, Thomas Jefferson University
Hospital.
Additional Contributions: The Division of
Biostatistics, Thomas Jefferson University, assisted
with the statistical analysis.
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Role of the Sponsor: The funder had no role in the
design and conduct of the study; collection,
management, analysis, and interpretation of the
data; preparation, review, or approval of the
manuscript; and decision to submit the manuscript
for publication.
Previous Presentation: This work was presented
at the American Academy of Facial Plastic and
Reconstructive Surgery section of the Combined
Otolaryngology Spring Meeting; April 19, 2012;
San Diego, California.
J Cosmet Dermatol. 2009;8(1):24-26. 20. van den Hove J, Decroix J, Tennstedt D,
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