COSMETIC

Tear Trough Filler Techniques Utilizing

Hyaluronic Acid: A Systematic Review

Babar K. Rao, M.D.
AQ1
Lauren E. Berger, B.A.
Catherine Reilly, B.A.
Mahin Alamgir, M.D.
Hassan Galadari, M.D.
Somerset, N.J.; New York, N.Y.; and
Al Ain, United Arab Emirates
Background: Hyaluronic acid soft-tissue augmentation fillers are commonly
injected into multiple areas of the face, including the tear trough. Despite
well-documented risks, there is no standardized, evidence-based approach to
inject filler in this area, be it using a hypodermic needle or a microcannula. The
authors, therefore, sought to establish a preference between the two methods to
facilitate progression toward standardization and prevention of adverse events.
Methods: This is a systematic review of articles discussing hyaluronic acid tear
trough injection techniques performed in vivo and related outcomes. Searches
were conducted across The Cochrane Library, PubMed, Scopus, Web of Science,
and Embase to yield relevant articles published before February of 2020. All
selected articles incorporated discrete patient cases and were analyzed by a variety
of variables assessing evidence strength, outcomes, technique, and patient safety.
Results: After appraisal, 42 articles met eligibility criteria: 20 using needles, 12
using cannulas, and 10 focusing on adverse events. Level III was the most com-
monly awarded evidence grade, corresponding to retrospective, nonexperimental AQ3
descriptive studies. There were no statistically significant differences in reported
aesthetic results, patient satisfaction, or incidence of adverse events across the
needle-based and cannula-based articles. Some technique trends, such as targeted
anatomical plane and needle position, emerged in subsequent articles.
Conclusion: Given that there were no statistically significant differences in
patient safety or outcomes, an evidence-based preference for needle or cannula
injection into the tear trough cannot be made at this time. Current inconsisten-
cies make tear trough injection procedures difficult to replicate, making stan-
dardization based on avoidance of adverse events not feasible.  (Plast. Reconstr.
Surg. 149: 1079, 2022.)

T
he demand for minimally invasive soft-tissue
augmentation procedures using fillers has
been on a steady increase in the United
States, growing from 652,885 procedures per-
formed in 2000 to 2,721,469 in 2019.1,2 Soft-tissue
fillers are commonly injected into multiple areas
of the face, including the cheeks, lips, chin, naso-
labial folds, forehead, and under the eye. While
each procedure has its own associated risk, the
area around the eyes is more sensitive to the possi-
bility of adverse events given the blood supply and
circulation. The tear trough, the natural under-
eye depression extending inferiolaterally from
the medial canthus, is an area that is commonly
From the Rutgers Robert Wood Johnson Department of
Dermatology; Department of Dermatology, Weill Cornell
Medicine; and the College of Medicine and Health Sciences,
United Arab Emirates University.
Received for publication August 25, 2020; accepted August
12, 2021.
Copyright © 2022 by the American Society of Plastic Surgeons
DOI: 10.1097/PRS.0000000000008990
injected.3–6 Age-related tear trough “deformity”
results from multiple anatomical changes, mainly
with the loss or herniation of subcutaneous fat
in the trough and an enhancement of the gap
between the levator labii superioris alaeque nasi
muscle and the orbicularis oculi muscle.7–11 There
is no established standardized evidence-based
Disclosure: The authors have no financial interests AQ2
to disclose. No funding was received for this article.
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technique for safe and effective soft-tissue injec-
tions to improve the tear trough deformity.
The facial vein and the infraorbital or
detoured branch of the facial artery run along
the nasojugal fold and are subsequently at risk of
inadvertent cannulation by the injecting needle
or cannula, which may result in embolization of
the product with disastrous consequences.12–22
Because of the high degree of vascular anatomy
variation in this area, the entry point and delivery
method of the filler material are considered to be
of critical importance in ensuring patient safety
and avoidance of potential adverse events.4,22,23
Although soft filler injection techniques have uti-
lized sharp hypodermic needles, several studies
have since provided some evidence that the use
of blunt-tip cannulas may decrease the likelihood
of complications.24–30 Thus far, two cadaver stud-
ies have supported this claim by directly compar-
ing needle-based and cannula-based tear trough
injection techniques.31,32 Several articles discuss-
ing the utilization of cannula injections explicitly
claim personal preference of cannula over needle
in their discussions.27,33–35 Sufficient in vivo clinical
evidence is lacking, however.
As hyaluronic acid filler injections burgeon
into a billion-dollar industry,2 with more people
seeking to adhere to societal standards of a youth-
ful appearance, it is imperative for physicians to
practice evidence-based, standardized procedures.
Since very few in vivo studies directly compare
needle and cannula approaches, we performed
a systematic review of the literature to establish
which, if any, of these two techniques is preferable
for patients and whether safety outcomes differed.
METHODS
Article Selection
A search for articles published before February
of 2020 was conducted across five databases (i.e.,
The Cochrane Library, PubMed, Scopus, Web of
F1
Science, and Embase), as depicted in Figure  1.
A list of predetermined search terms relevant to
undereye fillers, anatomical terminologies, inter-
ventions, and patient outcomes was applied to
each database. (See Table, Supplemental Digital
Content 1, which shows number of results yielded
from each search term across the 5 analyzed data-
bases. Combination search terms included “needle
and cannula,” “injection and cannula,” “needle
and cannula and filler,” “injection and cannula and
filler,” “needle and cannula and tear trough,” “injec-
tion and cannula and tear trough,” “needle and
cannula and infraorbital,” “injection and cannula
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Plastic and Reconstructive Surgery • May 2022
and infraorbital,” “needle and cannula and perior-
bital,” “needle and cannula and nasojugal,” “injec-
tion and cannula and nasojugal,” “injection and
cannula and palpebromalar,” “needle and cannula
and palpebromalar,” “injection and cannula and
under eye,” “needle and cannula and under eye,”
“injection and cannula and lower lid,” “needle and
cannula and lower lid,” “injection and cannula and
lower eye lid,” and “needle and cannula and lower
eyelid,” http://links.lww.com/PRS/F9.)
Search results were then filtered using pre-
defined inclusion and exclusion criteria (Fig. 1).
(See Table, Supplemental Digital Content 2, which
shows primary and secondary inclusion and exclu-
sion criteria, http://links.lww.com/PRS/F10.) While
calcium hydroxylapatite and hyaluronic acid have
both been applied to treat tear trough deformi-
ties,36,37 less viscous, low-concentration hyaluronic
acid derivatives are preferred for the under-eye
area to prevent nodule formation.38–42 This review,
therefore, focused solely on studies utilizing hyal-
uronic acid to minimize the adverse effects spe-
cific to filler composition.
Articles without discrete patient cases, such
as commentary pieces, cadaver studies, and panel
discussions, were also excluded to facilitate selec-
tion of articles with clinical, in vivo evidence. Two
investigators independently examined articles to
determine relevancy. Discrepancies between the
two authors were resolved by a third investigator.
Before analysis, selected articles were grouped
according to reported technique (needle or can-
nula). Articles focusing on adverse effects result-
ing from hyaluronic acid undereye filler injections
were also included.
Data Extraction
The angle and depth of injection is impor-
tant for minimizing adverse effects.43 Multiple
reported techniques utilized to release the filler,
including fanning, linear threading, feathering,
singular bolus, and retrograde techniques, were
analyzed.41,44
Data extraction was guided by the following pre-
determined checklist: study type, sample size, year
published, approximate years of experience of the
first author, filler type, injection entry site, method
of filler release, needle/cannula gauge, outcome
measured, photograph bias (defined as clinical
photographs lacking standardized lighting, angles,
proximity, and patient makeup across before and
after photographs), statistically significant results,
adverse effects, and levels of evidence grading. To
determine statistical significance, the Fisher exact
test of independence was performed across each
 Volume 149, Number 5 • Hyaluronic Acid Tear Trough Injections

Fig. 1. Flow diagram outlining the literature search and selection process.

set of variables using Stata software (StataCorp,

Table 1.  Levels of Evidence Based on the Journal of
LLC, College Station, Texas) to generate two-tailed the American Academy of Dermatology Guidelines
p values. Results with a p value of less than 0.05 were
deemed statistically significant. Levels of evidence Grade Definition
were based on the Journal of the American Academy of Level IA Meta-analysis or systematic review of
Dermatology guidelines (Table 1).45 randomized controlled trials
T1 Level IB ≥1 randomized controlled trial
Level IIA ≥1 controlled study without randomization
Level IIB ≥1 other type of experimental study
RESULTS Level III Nonexperimental descriptive studies, such as
comparative studies, correlation studies, and
case control studies
General Results Level IV Expert committee reports or opinions or
Out of the 16,302,063 articles identified from clinical experience of respected authorities,
or both
the database search, 32 were included in the

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 Plastic and Reconstructive Surgery • May 2022

systematic review; 20 utilized only hypodermic
needles (needle-based),46–65 and 12 utilized only
blunt-tip cannulas (cannula-based).24,27,33–36,66–71
One study met inclusion criteria but was ulti-
mately excluded from the analysis as the injec-
tion method of delivery was not systemized.72 The
majority of the articles were retrospective case
F2
series (Fig. 2, above). The median patient sample
sizes were 23 and 35.5 patients for needle and
cannula-based studies, respectively. Temporal
analysis highlighted the slightly more recent
emergence of cannula-based articles when com-
pared to needle-based articles (Fig.  2, below).
Years of experience across first authors did not
significantly differ, averaging 11.2 years among
the needle-based articles and 13.1 years across
the cannula-based articles. Study type (Fig.  2),
sample size, and
Journal of the American Academy of Dermatology
guidelines grade were analyzed to assess the over-
all evidence strength. (See Table, Supplemental
Digital Content 3, which provides a detailed sum-
mary of the incorporated studies and highlights
injection method, measured outcomes, relevant
results, level of evidence grades, and adverse
events, http://links.lww.com/PRS/F11.)
Evidence Strength
The most commonly afforded grade among
both study types was level III. Only one cannula-
based article met level IB standards, whereas no
studies met level IA criteria. (Table 2)35 T2

Fig. 2. (Above) Prospective versus retrospective study type for needle-based and cannula-based articles.
(Below) Temporal breakdown of included articles by published year.

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 Volume 149, Number 5 • Hyaluronic Acid Tear Trough Injections

Table 2.  Levels of Evidence Grade Distribution
among Needle-Based and Cannula-Based Articles
No. of Needle-Based No. of Cannula-
Grade Articles Based Articles
Level IA 0 0
Level IB 0 1
Level IIA 0 0
Level IIB 3 2
Level III 13 7 adverse effect, appearing within a minimum of 48
Level IV 4 2
Preference of Needle versus Cannula
Results, presence of photograph bias, and
reported incidence of adverse effects were ana-
lyzed to determine preference for method of
T3 delivery (Table  3). The primary outcome mea-
sured most often was clinical improvement via
F3
photographs (Fig. 3).
Average patient satisfaction was slightly higher
under the needle-based method (90 percent ver-
sus 86 percent for cannula-based method) (p >
0.05). Multiple articles blinded reviewers prior
to photographic assessment.53,55,70 Fifty-five per-
cent of needle-based articles and 20 percent of
cannula-based articles applied at least one of the
following scales: Likert-type Scale,53 Infraorbital
Hollowness Score,47 visual analogue scale,70 Global
Aesthetic Improvement Scale,24,47,48,55,56,70 Hirmand
Classification System,64 Allegran Infraorbital
Scale,48 and Barton Grading System.71 Though
articles using these scales reported significant
improvements in aesthetic and patient outcomes,
the subjective nature of photonumeric scales led
to highly variable results and made it difficult to
assess for grading consistency.24,71
Photograph bias was more common among
needle-based articles, but the difference was not
statistically significant (p = 0.07). Edema was the
most commonly observed adverse effect under
both methods (Table 3). Though distinct adverse
effects occurred at varying frequencies across the
two methods, there were no statistically significant
differences noted. Most observed adverse effects
were short-term, resolving completely by 2-weeks
after injection. However, cases of delayed-onset
hours after injection, were reported in multiple
needle-based and cannula-based articles.73–75
For the 10 studies focusing on adverse effects
observed with hyaluronic acid fillers, the evidence
grades were levels III and IV.15–17,19,73–78 Needles
were used in six articles, cannulas in two, and two
did not specify technique. Serious adverse effects
(e.g., vascular and skin necrosis) were more com-
monly reported among needle-based articles,
but the difference was not statistically significant
(p > 0.05).
Technique Trends
Reported aesthetic injection site, needle/can-
nula gauge, and method of release were analyzed,
and the following trends emerged (Table 4). The T4
most frequently reported injection site was the
tear trough across needle-based articles, and the
lateral orbital rim hollow across cannula-based
articles. Other injection sites included the medial
infraorbital area, nasojugal groove, palpebroma-
lar groove, upper malar area, and frontal-tempo-
ral point of entry.
Needle size ranged from 27 gauge to 32 gauge,
with the 30-gauge needle being the most frequent
(65 percent). Size range was larger among the
cannula-based articles (18 to 30 gauge). The ana-
tomical plane into which the filler was released
was almost always superficial to the periosteum
and deep to the orbicularis muscle, often referred

Table 3.  Results, Photograph Bias, and Reported Incidence of Adverse Effects across Needle-Based and
Cannula-Based Articles
Prevalence among Prevalence among
Category Variable Needle-Based Articles Cannula-Based Articles
Results Visual improvement in photos 100% (13/13) 100% (9/9)
Average patient satisfaction 90% 86%
Photograph bias Lack of lighting, proximity, angle, or patient
makeup standardization across photographs 54% (7/13) 11% (1/9)
Adverse effects Edema, swelling 55% (n = 11) 58% (n = 7)
Bruising 40% (n = 8) 33% (n = 4)
Erythema 25% (n = 5) 17% (n = 2)
Nodule(s) 15% (n = 3) 8% (n = 1)
Pain 10% (n = 2) 17% (n = 2)
Contour irregularities 10% (n = 2) 8% (n = 1)
Tyndall effect 5% (n = 1) 8% (n = 1)
Cellulitis 5% (n = 1) 0% (n = 0)
Migraine 5% (n = 1) 0% (n = 0)
Asymmetry 5% (n = 1) 0% (n = 0)
Hematoma 0% (n = 0) 17% (n = 2)

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 Plastic and Reconstructive Surgery • May 2022

Fig. 3. Percentage of articles reporting the three most frequently measured outcomes.

to as either preperiosteal tissue or the supraperi-
osteal plane.
Most often, needles were oriented perpendic-
ular to the skin and inserted down to the inferior
orbital bony rim surface.46,47 Cannulas were either
perpendicular to the skin33,66 or oriented superi-
orly from a malar insertion point.24,35,67 Filler was
then released in single or multiple aliquots by
means of an array of techniques.24,27,33,35,49,51–54,66,68,69
DISCUSSION
Although sometimes seen in younger indi-
viduals, tear trough development can be an early
sign of aging and is commonly associated with a
fatigued appearance.43 Hyaluronic acid has been
promoted as the filler of choice for the under-
eye area due to its decreased elasticity and vis-
cosity and its ability to be dissolved with Hyalase
(Wockhardt UK, Wrexham, United Kingdom), if
needed. A low-concentration hyaluronic acid gel
with small particles is recommended for this area
to avoid excessive volumizing.40,41 At this stage, the
evidence supporting use of cannulas over needles
to inject hyaluronic acid into the tear trough
derives primarily from weak, indirect comparisons
and anecdotal recommendations.
The majority of studies analyzed in our review
met only level III or IV evidence criteria, repre-
sentative of retrospective, descriptive articles. This
exemplifies the gaping absence of high-quality, ran-
domized, controlled and prospective studies to guide
the best approach for undereye filler injections.
Results were also challenging as most stud-
ies measured clinical improvements by means of
photographs. Although validated scales were used
in some studies, it was difficult to establish grad-
ing consistency across these scales. In addition,
because there were no statistically significant dif-
ferences in aesthetic outcomes, patient satisfac-
tion rates, or incidence of adverse effects between
the needle-based and cannula-based studies, a
clear preference for either technique cannot be
made at this time.

Table 4.  Technique Analysis Results

Variable Needle-Based (n) Cannula-Based (n)
Most frequently reported injection entry site Tear trough (11) Lateral orbital rim hollow (5)
Most common instrument size 30-gauge needle (13) 25-gauge cannula (4)
Method of release Deep scaffolding (1), fanning/layering (1), Retrograde (4), anterograde
retrograde linear threading (2), (1), fanning (3)
push-ahead (1), deep fill (1)
n, number.

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 Volume 149, Number 5 • Hyaluronic Acid Tear Trough Injections
Some technique trends did emerge across
multiple studies, however. Most authors reported
aiming for the anatomical plane superficial to the
periosteum and deep to the orbicularis muscle,
which has previously been described as being
largely avascular.79 Retrograde technique was the
most commonly reported method, but an array
of release mechanisms was suggested. While 65
percent of needle-based articles utilized 30-gauge
needles, cannula size ranged from 18 gauge to 30
gauge, despite previous evidence that 27-gauge
cannulas are no safer than 27-gauge needles.30
Furthermore, the variation in reported injection
points likely arose from the application of incon-
sistent terminology associated with this anatomi-
cal area.80 These inconsistencies make tear trough
injections difficult to replicate, which is likely to
disproportionately challenge physicians new to
the procedure and may further complicate a pro-
cedure already deemed high risk.81 An analysis of
the reported short-term adverse effects revealed
that a higher percentage of needle-based studies
reported bruising, erythema, and nodule forma-
tion, whereas pain and edema were more often
reported under the cannula method, but these dif-
ferences were not statistically significant. Multiple
studies also reported occurrence of the Tyndall
effect, which is believed to result from placing the
filler too superficially.82,83
Delayed adverse reactions were reported in
multiple studies and included lower eyelid edema
or nodule formation. Cases of granulomas, skin
necrosis, and vision loss have also been reported,
emphasizing the serious risks associated with this
procedure.18,19,75 These serious adverse effects
have been reported more frequently following
injection with a needle, but more data from can-
nula-based procedures are needed to determine
whether this difference is statistically significant.
Although most adverse effects resolved without
intervention, hyaluronidase proved to be an effec-
tive antidote for vascular occlusion.15,17,19,74,77,78
Definitive conclusions regarding the safest or
most effective method to inject tear trough fillers
cannot be drawn from currently published data, and
a standardized evidence-based approach cannot be
established. Method of delivery, injection entry site,
and release technique seem to be up to the discre-
tion of the injector. In addition, a preference of nee-
dle or cannula method cannot be made because of
inconsistencies across present data. Future impar-
tial, blinded, and prospective studies directly com-
paring the two methods in vivo may help to more
clearly establish one. Alternatively, such studies may
reveal a third, novel method that provides greater
Copyright © 2022 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
patient satisfaction and could be more closely rep-
licated in the clinic. Until then, any conclusions
drawn from the present literature should be consid-
ered with an abundance of caution.
Babar K. Rao, M.D.
1 Worlds Fair Drive, Suite 2400 AQ4
Somerset, N.J. 08873
babarrao@gmail.com
Twitter: @DrBabarRao
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