Keywords
infraorbital hollows - hyaluronic acid - filler - VYC-20L
Aging of the infraorbital region of the midface remains one of the most challenging
areas of the face to reliably and most effectively rejuvenate. The thin lower eyelid
skin, compromised lymphatic drainage, increased vascularity, and underlying orbital
bony remodeling create a multifactorial dilemma for the facial plastic and reconstructive
surgeon.[1]
[2] A number of different nonsurgical and surgical interventions have been used to treat
infraorbital hollowing, including filler injections, autologous fat transfer, topical
agents, laser resurfacing, and lower blepharoplasty with or without fat repositioning.[3]
[4]
[5] There continues to be a great trend in plastic surgery treatments toward interventions
that optimize the balance of efficacious long-lasting treatments, while minimizing
invasiveness and recovery time.[6]
[7]
The aged appearance of the infraorbital region of the face most commonly starts with
shadowing in the area of the orbitomalar ligament, leading to a tear trough deformity.
The infraorbital hollowing can be more specifically divided into the tear trough,
nasojugal groove, and palpebromalar groove.[1]
[3] Given the large volume of patients seeking correction of the infraorbital hollows,
there is an increasing need to be more objective about the assessment of pretreatment
severity and posttreatment correction. The Allergan Infraorbital Hollows Scale was
designed to meet that need, providing a validated and reliable scale for physician
rating of the infraorbital hollows.[4]
Much of the literature studying restoration of volume to infraorbital hollows with
nonsurgical interventions has emphasized the use of lower hyaluronic acid (HA) concentration
fillers.[1]
[8]
[9]
[10] Our recent retrospective study of VYC-20L demonstrated safe and efficacious use
of the higher HA concentration filler in the often-challenging infraorbital region.[11] We have continued to use VYC-20L (JUVÉDERM VOLUMA XC; Allergan Aesthetics, AbbVie
Inc, Irvine, CA), hereto referred to as VYC-20L, for off-label use in the infraorbital
hollows. The objective of this study was to evaluate the effectiveness of VYC-20L
for the treatment of infraorbital hollows, including objective measures and patient
satisfaction at 1 month after treatment.
Methods
A prospective cohort study was designed for patients seeking nonsurgical correction
of infraorbital hollowing at a single metropolitan private practice in the United
States (Buckingham Center for Facial Plastic Surgery, Austin, TX) from April 1, 2017,
to May 31, 2018. The study was designed and created to further explore and expound
upon the retrospective findings published in JAMA Facial Plastic Surgery by Hall et al, “Novel use of a volumizing hyaluronic acid filler for treatment of
infraorbital hollows.”[11] The difference of this study is the prospective nature, objective data collection,
and adverse event reporting. The study design was reviewed and granted approval by
IntegReview, an independent institutional review board, prior to commencement of patient
enrollment. A total of 21 patients, or 42 infraorbital injections, successfully completed
all required inclusion criteria for the prospective cohort study. All injections were
elective in nature and performed under the supervision of the senior author (E. D.
B.) by a certified facial plastic and reconstructive surgeon or a certified nurse
injector. Each patient underwent an initial consultation and discussion of the risks
and benefits of and alternatives to VYC-20L use for the correction of infraorbital
hollows. Patients were then informed of the opportunity to be included in the study,
for which participation was voluntary without any coercion. Each patient included
in the study signed our research study consent form, which included the use of their
medical records and patient photographs for the purposes of research. We did not receive
any external funding or ancillary benefit from any other institution as a part of
this study. Additionally, patients were not compensated for their participation.
Pretreatment photographs were obtained in the standardized fashion that all photographs
are taken at our center. All photos were taken with a Canon EOS Rebel T2i Digital
SLR camera in a professional studio with standard oblique frontal flashes, controlled
settings, patient positioning, and standardized views. Each enrolled patient was then
treated with cosmetic injection of VYC-20L for correction of infraorbital hollowing
bilaterally. The treatments begin with an infraorbital nerve block using lidocaine
1% via a gingivobuccal approach and 27-G 1.5-inch needle. The cheek and lower eyelid
are then cleansed with chlorhexidine followed by creation of the puncture site on
the anterior cheek with a 26-G 0.5-inch needle. The cannula, a 27-G 1.5-inch DermaSculpt
microcannula (DermaSculpt, Dublin, Ireland), is then introduced through the puncture
site and the filler is injected in a layered fashion in a supraperiosteal or submuscular
plane. Patients then returned for their posttreatment visits anywhere between 3 weeks
and 3 months for follow-up posttreatment photos. Photos were independently assessed
by two authors (S. W. S. and E. D. B.) and graded using the Allergan Infraorbital
Hollows Scale. In this study, only early adverse events were assessed at 3 days posttreatment
using the FACE-Q Recovery Early Symptoms questionnaire via telephone. Longer safety
data (mean follow-up, 12 months) were analyzed retrospectively in our previous study.[11] Patient-reported satisfaction outcomes were assessed using FACE-Q Satisfaction with
Eyes (pre- and posttreatment) and Satisfaction with Decision (posttreatment) surveys.
FACE-Q Satisfaction with Eyes and Satisfaction with Decision surveys were sent to
all patients via email at 1 month posttreatment. FACE-Q surveys are highly validated
and reliable patient-reported outcome questionnaires. The FACE-Q Satisfaction with
Eyes and Decision surveys are scored with a raw scale that is converted to an equivalent
Rasch transformed score (0–100), where higher scores reflect higher satisfaction and
better outcomes.[12] In this study, we report the transformed scores with a scale of 0 to 100.
Patient before and after photographs were then evaluated separately by two facial
plastics and reconstructive surgeons using the validated 5-point photonumeric Allergan
Infraorbital Hollows Scale (Grade 0 = none; Grade 4 = extreme). Each physician performed
graded scale assessments of the 21 patients (42 infraorbital regions). The two grading
physicians were blinded to one another's scores. [Table 1] and [Fig. 1] further describe and illustrate the Allergan Infraorbital Hollows Scale. Interrater
reliability was analyzed using Cohen's kappa coefficient. Paired sample t-tests (degrees of freedom = 20, two-tailed, significance level p = 0.05) were performed to test for statistical significance (FACE-Q Satisfaction
with Eyes and infraorbital hollows data). Survey data were tested for normality using
histograms and Shapiro–Wilk test, and were noted to be approximately normal. Surveys
were administered via Survey Monkey (www.surveymonkey.com). Data were then analyzed using Microsoft Excel (Redmond, WA) and SPSS (IBM Corp.,
Armonk, NY).
Table 1
Allergan Infraorbital Hollows Scale descriptors
|
Grade
|
Term
|
Descriptor
|
|
0
|
None
|
No visible hollowing or volume loss medially or laterally
|
|
1
|
Minimal
|
Presence of hollowing with some volume loss medial to the midpupillary line; smooth
lateral lid–cheek transition
|
|
2
|
Moderate
|
Defined hollowing extending laterally beyond the midpupillary line with moderate volume
loss; smooth lateral lid–cheek transition with mild volume loss
|
|
3
|
Severe
|
Defined hollowing extending laterally beyond the midpupillary line with moderate volume
loss creating a defined groove along the lid–cheek junction
|
|
4
|
Extreme
|
Defined hollowing extends from medial to lateral canthus; severe volume loss creates
a marked step along the lid–cheek junction
|
Source: Copyright Allergan Aesthetics.
Fig. 1 Allergan Infraorbital Hollows Scale (copyright Allergan Aesthetics).
Results
Initially, 38 patients were enrolled in this study. Twenty-one participants completed
all study requirements and were included in the data analysis. The remaining 17 patients
either did not complete follow-up photos within the allotted 3 months or did not complete
all surveys. Patient ages ranged from 27 to 77 years at the time of service, with
a mean (standard deviation [SD]) age of 48 (12.7) years. The study was composed of
19 females and 2 males.
FACE-Q Satisfaction with Eyes surveys were administered pre- and posttreatment at
1 month. The pretreatment mean (SD) score was 47.1 (19.5), and posttreatment mean
(SD) score was 74.1 (22.7). FACE-Q Satisfaction with Eyes scores were significantly
higher after treatment, with a mean difference of 27.0 (95% confidence interval [CI],
14.1–39.8; p < 0.001). There were three patients whose posttreatment satisfaction scores were
lower than pretreatment. [Fig. 2] further illustrates the mean FACE-Q Satisfaction with Eyes scores before and after
treatment. The mean (SD) score of the FACE-Q Satisfaction with Decision survey was
74.1 (28.4) with a range of 21 to 100. Of these, 42.9% (n = 9) reported a satisfaction with decision score of 100.
Fig. 2 FACE-Q Satisfaction with Eyes.
Pre- and posttreatment photographs were evaluated independently by two authors using
the Allergan Infraorbital Hollows Scale. This scale is composed of a 0 to 4 grading
system, where higher grades indicate worse hollowing.[4] Left and right eyes were rated separately by each physician rater, both before and
after treatment. Analysis was conducted for each physician rater separately, as well
as the combined average between the two raters to test for meaningful differences
in infraorbital hollow grades. There were statistically significant improvements in
infraorbital hollows scores within both separate and combined analyses (p < 0.001 for all comparisons). The combined right eye pre- and posttreatment mean
(SD) scores were 2.38 (0.91) and 1.21 (0.75), respectively, with a mean difference
of −1.17 (95% CI, −1.38 to −0.95; p < 0.001). The combined left eye pre- and posttreatment mean (SD) scores were 2.45
(0.86) and 1.1 (0.69), respectively, with a mean difference of −1.36 (95% CI, −1.57
to −1.14; p < 0.001). Mean infraorbital hollows scores before and after treatment for each physician
rater are displayed in [Fig. 3], and as a combined mean in [Fig. 4]. Representative patient photographs before and after treatment are shown in [Fig. 5].
Fig. 3 Infraorbital hollows grading by individual rater.
Fig. 4 Combined infraorbital hollows grading.
Fig. 5 Patient photographs before and after treatment. (A) A 27-year-old woman before filler treatment of infraorbital hollows with 1 mL of
VYC-20L (0.5 mL per side). This was the youngest patient in our study. (B) The patient is shown at 1 month posttreatment. (C) A 39-year-old man before filler treatment of infraorbital hollows with 1 mL of VYC-20L
(0.5 mL per side). (D) The patient is shown at 2 months posttreatment. (E) A 64-year-old woman before filler treatment of infraorbital hollows with 2 mL of
VYC-20L (0.5-mL bilateral tear troughs and 0.5-mL bilateral cheeks). (F) The patient is shown at 1 month posttreatment. (G) A 77-year-old woman before filler treatment of infraorbital hollows with 1 mL of
VYC-20L (0.5 mL per side). This was the oldest patient in our study. (H) The patient is shown at 1 month posttreatment.
The Allergan Infraorbital Hollows Scale has been previously validated by Donofrio
et al and shown to have substantial interrater and intrarater reliability.[4] We evaluated interrater reliability for all four data sets in our study, which was
noted to be moderate to excellent (kappa values: 0.54, 0.78, 0.78, 1.0). There were
five infraorbital regions scored as no improvement, which was 100% consistent in the
scores of both physicians, as demonstrated with the high interrater reliability score.
Of the five infraorbital hollow regions with no improvement, there were two patients
with no improvement bilaterally (four regions) and one patient with no improvement
on one side (one region). The two patients with no improvement on either side had
the lowest FACE-Q Satisfaction with Eyes and Satisfaction with Decision scores within
the entire cohort, and one received additional touch-up filler. All other infraorbital
region scores (88%) demonstrated improvement.
Early adverse events were assessed at 3 days posttreatment using the FACE-Q Recovery
Early Symptoms questionnaire. The most common short-term adverse symptoms were tenderness
(14 [67%]), swelling (13 [62%]), bruising (11 [52%]), and soreness (9 [43%]). Only
three patients rated their adverse symptoms as “extreme,” those being swelling (n = 2) and tenderness (n = 1). Among the 11 patients who reported bruising, 6 patients rated the severity
as “a little” and 5 as “moderate.” Of all adverse symptoms reported, 77.2% were rated
as “a little” bothersome, 19% as “moderate,” and 3.8% as “extreme.” Adverse events
are reported in further detail in [Table 2]. Most patients were treated with 1-mL syringe of VYC-20L (0.5 mL per side), while
4 of the 21 patients (19%) ultimately were treated with an additional 1-mL syringe
for further correction or touch-up between 1 and 3 months following initial treatment.
Table 2
Early adverse events
|
FACE-Q Recovery Early Symptoms survey
|
|
Not at all
|
A little
|
Moderately
|
Extremely
|
Total # with AE (%)
|
|
Tenderness
|
7
|
11
|
2
|
1
|
14 (66.7)
|
|
Swelling
|
8
|
7
|
4
|
2
|
13 (61.9)
|
|
Feeling bruised
|
10
|
6
|
5
|
|
11 (52.4)
|
|
Feeling sore
|
12
|
9
|
|
|
9 (42.9)
|
|
Feeling that your face is too tight
|
14
|
5
|
2
|
|
7 (33.3)
|
|
Discomfort
|
15
|
6
|
|
|
6 (28.6)
|
|
Numbness
|
17
|
4
|
|
|
4 (19.0)
|
|
Headaches
|
17
|
3
|
1
|
|
4 (19.0)
|
|
Pain
|
18
|
3
|
|
|
3 (14.3)
|
|
Feeling tired
|
18
|
2
|
1
|
|
3 (14.3)
|
|
Itching
|
19
|
2
|
|
|
2 (9.5)
|
|
Feeling lightheaded
|
19
|
2
|
|
|
2 (9.5)
|
|
Stinging
|
20
|
1
|
|
|
1 (4.8)
|
|
Tingling
|
21
|
|
|
|
0
|
|
Throbbing
|
21
|
|
|
|
0
|
|
Burning
|
21
|
|
|
|
0
|
|
Feeling feverish
|
21
|
|
|
|
0
|
Abbreviation: AE, adverse event.
Note: Five most common AEs in bold.
Discussion
The infraorbital hollow is one of the most common cosmetic concerns that new patients
present with today. As with any patient consultation, the most important component
of the assessment is identifying the cause of the perceived concern and developing
the appropriate solution.[5] Aging of the lower eyelids can be multifactorial and therefore appropriate identification
of a volume deficiency is paramount to achieving success with HA filler treatment
of the infraorbital region.[1] Correct assessment of the lower eyelid region requires facial examination from multiple
angles and dynamic assessment of the lower eyelid as it relates to the globe and infraorbital
rim. The hollows refer to the volume deficiency or curvilinear depression under the
eyes overlying the region of the inferior orbital rim, which can affect a wide range
of different age groups.
Successful filler treatment of the infraorbital hollow requires a strong comfort with
the use of different fillers as well as an understanding of the properties within
each filler. The ideal filler should be nonimmunogenic, biocompatible, stable with
long duration of benefit, and well-integrated into the surrounding tissue.[5] While the number of different filler types and different manufacturers have continued
to grow, VYC-20L continues to be the filler with the longest duration of action, which
can be up to 2 years.[13]
[14] Food and Drug Administration (FDA) approval for the use of VYC-20L continues to
be limited to cheek augmentation and more recently the chin; however, as with this
particular investigation, its off-label uses have expanded.[15] Many physicians avoid filler treatment of the infraorbital region due a higher rate
of complications and undesirable results. Criticisms of VYC-20L product use in the
infraorbital region include that it is too hydrophilic. In this author's experience,
however, injecting the filler in layered fashion in the supraperiosteal or submuscular
planes and not in bolus fashion has yielded excellent results and high patient satisfaction.
Our intent of this study was to provide an objective assessment for the use of VYC-20L
in the infraorbital hollow. The validated Allergan Infraorbital Hollows Scale allowed
for a more objective grading for the ultimate degree of improvement achieved from
patient to patient.[4] The use of objective validated metrics allows the data collected in this study to
be compared with other similar studies in the future. The number and type of early
adverse symptoms in this study were comparable to other studies using HA fillers in
the infraorbital region.[8]
[9]
[13]
[16]
In our initial retrospective study, bruising was documented in 10% of patients. In
this study, mild-to-moderate bruising was reported in 52% of patients. It is important
to note that adverse events were measured differently between these two studies. In
our first study, adverse events were assessed using retrospective chart review, and
recorded events were those noticed by physicians and included prolonged episodes,
those requiring intervention, or those that were objectionable to the patient. In
the present study, adverse events were measured at 3 days postinjection and were patient
reported. Thus, it is expected that there would be a higher frequency of patient-reported
minor or temporary adverse events in this prospective study. In summary, our previous
study aimed to measure more long-term adverse events documented by the physician,
while a secondary aim of this study was to assess short-term adverse events reported
by the patient. This difference accounts for the discrepancy in adverse event frequency
between our two studies.
Objectively assessing the degree of patient satisfaction is equally as important.[17] FACE-Q surveys are among the most established and the most widely cited patient-reported
outcomes scales in aesthetic medicine.[12] These validated surveys allow for researchers to provide strong and more complete
assessments of patient perception of treatment success. The high rate of patient safety
and satisfaction initially introduced in our retrospective study is further supported
with the prospective and objective data generated from this prospective cohort. FACE-Q
Satisfaction with Eyes and FACE-Q Satisfaction with Decision to Treat surveys allowed
for validated quantification of patient's happiness with their treatment. Three of
the patient's surveys did demonstrate a perceived worse appearance or happiness with
their outcome. Among the three patients who had worse FACE-Q Satisfaction with Eyes
scores after treatment, one patient had objective improvement in infraorbital hollows
scores but after treatment had a MOHS (Micrographically Oriented Histographic Surgery)
defect along the right nasojugal groove present at the time of follow-up photos. Another
patient had no objective improvement in infraorbital hollows scores and did not receive
any additional touch-up filler. The third patient did not have any clear reason or
confounding factors as to why the posttreatment FACE-Q Satisfaction with Eyes score
was lower and did have objective improvement of infraorbital hollows scores. The main
reasons stated for dissatisfaction were no appreciable change or underwhelming degree
of improvement. The high degree of patient satisfaction (74.1%) in our current study
is similar to other studies treating the infraorbital hollows and tear troughs with
HA filler.[7]
[11]
[13]
[18]
[19] In our retrospective study, satisfaction with decision was slightly lower at 65.6%,
although there was only a 42% response rate.[11] Overall, this study demonstrated a high degree of objective improvement and patient
satisfaction of the infraorbital hollows with VYC-20L.
Limitations
This study is limited by a smaller sample size of 21 patients with treatment at a
single private ambulatory facial plastic surgery office, thus reducing statistical
power and generalizability. Given the open-label design, there is potential for performance
and detection bias. There were multiple injectors as well as injectors of variable
degrees of experience, and interinjector differences are unable to be accounted for.
However, all injectors followed the same protocol and injection technique as described
earlier. As for the timing of photoanalysis, an effort was made to have all patients
to follow up at the office 1 month postinjection for photos, but this was not feasible
in some cases due to patient-related factors, and photos ranged from 3 weeks to 3
months posttreatment. It should be noted that while efforts are made to ensure that
photos taken before and after treatment are consistent and standardized, precise control
of in-office photodocumentation is not possible, and there may be limitations to its
accuracy. Thirty-eight patients were initially enrolled in the study; however, only
21 (55%) completed all study requirements within the allotted time period. Lack of
timely follow-up for the study was higher than expected. This raises the possibility
of attrition bias as the incomplete data may represent a population with different
characteristics or outcomes from the study group. Long-term safety data were not evaluated
in this study and thus do not account for possible late adverse events such as delayed-onset
edema. Finally, there was no control group due to the within-subject design of the
study.
Conclusion
Nonsurgical infraorbital rejuvenation remains a debated topic within aesthetic medicine.
There remains a lack of consensus among providers regarding the unanimous HA filler
of choice for infraorbital region. Our experience with the product VYC-20L as a soft-tissue
filler for the treatment of infraorbital hollowing has yielded a high degree of objective
improvement and patient satisfaction with a low rate of adverse effects. Future studies
with consistent long-term follow-up are needed to better assess the safety profile
and duration of patient satisfaction when using VYC-20L for the treatment of infraorbital
hollows.
