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Vascular Complications after

Facial Filler Injection:
A Literature Review and Meta-analysis
ABSTRACT
by GIUSEPPE SITO, MD, PhD; VERONICA MANZONI, MD;
Background: Vascular occlusion during the and RAFFAELLA SOMMARIVA, MD
injection of facial fillers is uncommon, but can Prof. Sito is with the Prof. Professor Giuseppe Sito Clinic in Turin, Italy. Dr. Manzoni is with the Istituto Auxologico Italiano in
result in serious adverse events, including necrosis, Milan, Italy. Dr. Sommariva is a specialist in plastic surgery practicing in Acqui Terme, Italy and Genoa, Italy.
blindness, and stroke. Objectives: We explored
factors that influence the frequency and severity J Clin Aesthet Dermatol. 2019;12(6):E65–E72

N
of vascular complications during filler injections.
Methods: This was a meta-analysis that included
case reports and case series published during Nonsurgical cosmetic procedures are a hypopigmentation, infection, abscess formation,
the years 2004 to 2016 describing patients who growing trend worldwide. Included among these herpetic outbreaks, nodular masses, and
experienced any type of vascular complication minimally invasive techniques are botulinum paresthesia (if a nerve has been pinched during
after an aesthetic procedure. In addition to the
toxin and soft-tissue augmentation with fillers, the procedure).While these adverse reactions are
descriptive analysis of the variables retrieved,
a logistic regression for predicting the outcome
which are used restore tissue loss and correct usually transient, the common use of three-
of the vascular event was performed. Results: aging-related rhytides and folds. In 2011, dermal dimensional facial volume restoration techniques,
The analysis included 93 cases described in 30 fillers were used in nearly 1.6 million aesthetic where the filler material can be injected at any
articles. Blindness was the main consequence procedures, increasing to 2.3 million in 2013 and depth, has brought about infrequent but serious
of the vascular complications (n=57; 61%). The 5.5 million in 2014.1–3 and often irreversible vascular complications
reported outcome was partial or total recovery in Hyaluronic acid (HA) fillers are the most caused by symptomatic arterial occlusion.6,11–13
24 cases (28%) and no improvement in 61 cases commonly used injectable fillers, followed by These vascular complications can result in
(72%). Hyaluronic acid (HA) and autologous fat autologous fat. According to the American Society persistent skin necrosis, ophthalmoplegia,
were the two fillers most frequently involved in
for Aesthetic Plastic Surgery, nearly 900,000 soft- permanent unilateral or bilateral vision loss, and
vascular occlusions, with autologous fat showing
a stronger trend toward no improvement than
tissue augmentation procedures were performed stroke.11–13 Ocular and cerebral embolism occurs
HA. Involvement of the ophthalmic and retinal with HA in 2004.4,5 Other commonly used filler when the injected material travels from the distal
arteries was most frequently associated with no materials include bovine and human collagen to proximal retinal and ophthalmic arteries,
improvement.Conclusion: Injury to ophthalmic (active for 1–3 months before degradation); causing sudden, excruciating pain, persistent
and retinal arteries during the injection of facial poly-L-lactic acid, which stimulates endogenous blindness, and further tissue necrosis.11–13 In
fillers can result in irreversible serious adverse collagen production for up to 15 months; and addition to fillers accessing the vessel lumen,
events. Physicians performing facial filler injections calcium hydroxylapatite, which offers up to 2 vascular occlusion can occur by external
should have a proficient knowledge of anatomy. years of activity.3 These fillers can all be used for compression of the stiff gel bolus deposited in
KEYWORDS: Dermal fillers, vascular
volume replacement and enhancement, such as direct contact with the vessel wall.14–16
complications, hyaluronic acid, autologous fat,
collagen, adverse events
cheek and chin augmentation, tear trough valley Based on the available literature, some authors
correction, nose reshaping (rhinoplasty), midface have suggested that the injection technique,
volumization, and lip enhancement.1,5–7 Although site,and substance can have significant influence
these procedures are generally considered on the level of risk for an adverse vascular
safe, some local adverse events, aside from the event.2,5,7,11,12,17 However, most of these reviews
relatively common site-injection reactions (e.g., were not systematic, and the potential influence
swelling, tenderness, pain, bruising), have been of other variables on the incidence of adverse
observed.8–10 These include edema, erythema, events has not been addressed. Therefore,
scarring, granuloma formation, hyper- and we reviewed the literature regarding vascular

FUNDING: No funding was provided for this study.

DISCLOSURES: The authors have no conflicts of interest relevant to the content of this article.
CORRESPONDENCE: Prof. Giuseppe Sito; Email: mail@giuseppesito.it

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complications and performed a meta-analysis of TABLE 1. Characteristics of cases included in the meta-analysis
the variables that potentially affect the frequency
CHARACTERISTIC n %*
and severity of adverse events.
Female 84 90.3
Sex (n=93)
METHODS Male 9 9.7
Literature search and article selection. Hyaluronic acid 40 43.5
This meta-analysis included data from case Autologous fat 38 41.3
reports and case series of patients experiencing
any type of vascular complication after an Injected substance (n=92) Collagen 7 7.6
aesthetic procedure published during the years Calcium hydroxylapatite 4 4.3
2004 to 2016. The main source for article retrieval Poly-(L)-lactic acid 3 3.3
was the PubMed. Additional sources included Glabella 44 48.9
Google Scholar, where the search was restricted
Nose 41 45.6
to the article title, and a case series by Park et al,18 Injection site** (n=90)
which provided details from 19 cases previously Periocular 9 9.7
published as case reports. The database search, Frontal/temple area 11 12.2
performed on December 2016, combined the Ophthalmic artery 36 43.9
term filler with the following terms: injection (or
Central retinal artery 29 35.4
injected), blindness, visual loss, ophthalmoplegia, Affected blood vessel (n=82)
artery occlusion, embolism, ischemia (or ischemic), Nasociliary artery 8 9.8
necrosis, and complication. Only full-text articles Other 9 11.0
written in English were considered for eligibility. Blindness 57 61.3
To be included in the analysis, cases had to report Main consequence** (n=93) Visual loss 21 22.6
a vascular event occurring after an aesthetic
Skin necrosis 11 11.8
procedure on the human face.
Data extraction and management. Pain 32 47.1
Data for the meta-analysis were extracted Erythema 3 4.4
from each case and transferred to a predefined Concomitant symptoms** (n=68)
Ptosis 31 45.6
form containing the following variables: case
Edema 11 16.2
reference, age, sex, injected product, aesthetic
procedure, needle diameter, injected volume, Angiography 31 38.8
person who injected the product, injection site, OCT 4 5.0
blood vessel affected, main consequence(s) of Imaging diagnostic tests** (n=80) MRI 52 65.0
the vascular event, concomitant symptoms, Fundus imaging 15 18.8
time to symptom onset, intervention performed
to treat the vascular complication, and outcome. Ultrasonography 1 1.3
Additionally, diagnostic tests performed to < 1 hour 13 17.8
confirm the occurrence of vascular complications Time to symptoms onset (n=73) 1–24 hours 47 64.4
were recorded to address the quality of the > 24 hours 12 16.4
articles included in our review. The main
Total or partial recovery 24 28.2
consequences of a vascular complication were Outcome (n=85)
blindness, visual loss, necrosis, and other. No improvement 61 71.8
Blindness was only considered when explicitly * Percentages are shown based on available cases
stated in the text, whereas visual loss included a ** More than one category can apply to each case
reduction in visual acuity, the perception of light
only, and the perception of hand movement Statistical analysis. Categorical variables significant differences, a post-hoc analysis was
only. Time-to-onset values were grouped were described as frequency and percentage, performed by computing the chi-squared values
into three categories: less than one hour whereas quantitative variables were described as of the adjusted residuals and applying the
postprocedure, 1 to 24 hours postprocedure, and means and standard deviations (SDs). To assess Bonferroni correction, as described by Beasley et
more than 24 hours postprocedure. The final the factors possibly influencing the outcome of al.19 A prediction model (multivariate analysis)
outcome was categorized as no change, partial vascular complications, the percentages of cases for the vascular event outcomes was built using
recovery, or full recovery based on the progress with no improvement and those showing partial logistic regression. The multivariate analysis
of the main consequence of the vascular or full recovery were compared using the chi- included all variables regarding events occurring
complication. squared test. For variables showing statistically prior to any vascular complication, which showed

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prostaglandins injected into a vein, leading

to the improvement of signs and symptoms).
Conversely, in four cases, the physician failed to
identify the affected vessel despite performing
imaging diagnostic tests. Needle diameter,
injected volume, and the professional who
performed the injection were only reported in
11, 17, and 13 cases, respectively; due to their
low representation in the study sample, these
variables were excluded from analysis.
Case characteristics. Table 1 summarizes
the main characteristics of the cases described
in the selected articles. In most cases (n=57;
61.3%), blindness was the main consequence of
vascular complication. In five cases (5.4%), the
patients experienced blindness and skin necrosis
simultaneously. Whereas blindness was typically
assumed to be a consequence of a vascular
embolization of the filler material, necrosis
was sometimes attributed to compression
(Figure 2).2,39,45 However, none of these cases
reported evidence regarding the etiology of skin
necrosis, and compression was suggested based
on the time-to-onset or necrosis progression.
Nine patients (9.7%) experienced neither
necrosis nor visual loss or blindness despite a
diagnosis of vascular occlusion. Eight patients
FIGURE 1. Flow diagram of study inclusion. (8.6%) reported mild consequences (e.g., pain,
erythema), all of which resolved completely.
significant differences when comparing patients complications),18,40–44 and one observational One patient that was injected with autologous
without improvement and those with partial or trial (i.e., an article retrieving data from a fat in the glabella experienced occlusion of the
total recovery. The significant threshold was set at cohort of patients, including at least one patient retinal artery with concomitant brain infarction,
α=0.05 and all analyses were performed using experiencing a vascular complication).45 Most which resulted in hemiplegia and death.43
the Statistical Package for the Social Sciences cases (n=62; 66.7%) were reported in Korea, Theoretically, multiple blood vessels and
version 22.0 for Windows software program (IBM while 14 (15.1%) were reported in China, 10 nerves can be reached by the needle during
Corp., Armonk, New York). (10.8%) were reported in the United States, three filler injection (Figure 3). However, the paths of
(3.2%) were reported in Germany, three (3.2%) facial, nasal, temporal, and ophthalmic arteries
RESULTS were reported in Taiwan, and one (1.1%) was define anatomical areas with increased risk of
Study selection. The initial search (including reported in Japan. injury during filler injection (Figure 4). In the
articles retrieved from additional sources) yielded All cases had information regarding the case of the ophthalmic artery, the increased risk
143 articles, published during the years 2004 to injection site and main consequences of vascular included occlusion of one of its most important
2016, on vascular events potentially associated complications. Other key variables, such as branches: the retinal artery. In our analysis,
with the use of injected fillers (Figure 1). After injected substance, outcome, and affected blood the ophthalmic retinal arteries accounted for
removing duplicates and excluding non-English vessel were reported in 92 (98.9%), 85 (91.4%), 79.3 percent of the cases in which the affected
articles and those without full-text availability, and 82 (88.2%) cases, respectively. In 80 cases blood vessel was reported. In addition to the
86 were considered eligible. Of these, 56 either (86.0%), the vascular complication and identity nasociliary artery, other blood vessels affected
reported results at injection sites other than the of the affected blood vessel were confirmed by the aesthetic procedure were the choroid
face or did not report any vascular complication, by at least one of the following imaging vessels, the internal carotid artery, the middle
and thus were discarded. The final selection techniques: optical coherence tomography, cerebral artery, and the facial vein and artery.
included 30 full-text articles reporting 93 cases: magnetic resonance imaging, ultrasonography, The occlusion of the ophthalmic artery was
22 case reports (i.e., articles containing a full or fundoscopy. In six cases, the affected vessel mostly due to injections in the nose (n=18,
description of one or more cases),2,8,13,20–39 seven was deduced from the signs (e.g., necrosis 42.9% of all cases affecting the ophthalmic
case series (i.e., articles containing a tabulated affecting a skin area clearly irrigated by the artery). Conversely, the occlusion of the retinal
description of various cases with vascular facial artery) or the treatment outcome (e.g., artery was mostly due to injections in the

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glabella (n=18, 55% of all cases affecting the

TABLE 2. Distribution of cases in variables potentially influencing the outcome
retinal artery).
In 12 cases (12.9%), vascular occlusion TOTAL OR PARTIAL NO IMPROVEMENT,
progressed to brain infarction, identified by VARIABLE RECOVERY, n=24 n=61 p-VALUE
magnetic resonance imaging. Two of these were n (%) n (%)
associated with ophthalmic artery occlusion, Female 21 (27.6) 55 (72.4)
Sex 0.719
whereas eight were associated with retinal artery Male 3 (33.3) 6 (66.7)
occlusion. With the exception of two cases—one Hyaluronic acid 16 (45.7) 19 (54.3)
leading to the patient’s death and another
Autologous fat 1 (2.7) 36 (97.3)
resulting in neurological sequelae—blindness
was the main consequence for all patients Injected substance Collagen 4 (66.7) 2 (33.3) <0.001
affected by brain infarction. Calcium hydroxylapatite 3 (75.0) 1 (25.0)
Full recovery was reported in seven cases Poly-(L)-lactic acid 0 3 (100.0)
(8.2%): one case of blindness, one of visual loss,
Nose 14 (35.9) 25 (64.1) 0.132
and five cases of vascular occlusion with minor
consequences. Temporary blindness was caused Glabella 8 (19.0) 34 (81.0) 0.063
Injection site*
by an HA injection in the eyebrow. The patient Periocular 1 (16.7) 5 (83.3) 0.519
reported foggy and hazy vision immediately after Frontal/temple area 3 (30.0) 7 (70.0) 0.883
the filler injection; 10 days later, the filler was Ophtalmic artery 2 (5.6) 34 (94.4)
successfully removed by irrigation and aspiration
after creating a temporal limbal incision in the Affected blood Retinal artery 6 (26.1) 17 (73.9)
0.004
affected eye. Eight days after removal, visual vessel Nasociliary artery 4 (50.0) 4 (50.0)
acuity was restored.27 Other 4 (50.0) 4 (50.0)
Hyaluronidase was used only in 10 of 40 cases <1 hour 5 (41.7) 7 (58.3)
in which HA was the cause of vascular occlusion.
Time to onset 1–24 hours 10 (22.2) 35 (77.8) 0.024
The time between symptom onset and
hyaluronidase injection exceeded three hours >24 hours 6 (66.7) 3 (33.3)
in all cases. The dose of hyaluronidase injected, *Patients could have more than one injection site
reported only in five cases, ranged from 1,000
to 9,000 units. In five of these cases, blindness improvement (p=0.001 for the chi-squared TABLE 3. Individual contribution of variables in the
was the main consequence of the vascular adjusted residuals; the significant threshold after logistic regression to predict the outcome of the vascular
complication
event; only one patient experienced partial the Bonferroni correction was set at α=0.006).
recovery,25 whereas the rest remained blind A post-hoc analysis of time-to-onset did not VARIABLE OR (95% CI) P-VALUE
despite attempts to remove the HA obstruction reveal significant differences in any of the three Injected substance 1.3 (0.7–2.5) 0.391
by injecting hyaluronidase. categories. Affected blood
Factors influencing outcome. To The injected substance, the affected blood 0.4 (0.2–0.8) 0.007
vessel
explore possible baseline factors influencing vessel, and the time to symptoms onset were Time to symptom
the outcome, cases with either visual loss included in a logistic regression analysis. onset
0.8 (0.2–2.6) 0.708
or blindness as the main consequence were The resulting model explained 22 percent of
CI: confidence interval; OR: odds ratio
grouped into two categories based on the the outcome’s variance, categorized as “no
outcome: total or partial recovery and no improvement” and “total or partial recovery” blood vessels affected, the ophthalmic artery
improvement (Table 2). A chi-squared test (R2=0.219; p=0.027). However, only the affected was significantly associated with irreversible
revealed significant differences in the injected blood vessel significantly contributed to the blindness.
substance, the affected blood vessel, and the overall model (Table 3). The risk of vascular complications associated
time to symptom onset. The post-hoc analysis with facial aesthetic procedures has been
of the injected substance showed that both DISCUSSION addressed previously in case reports, case series,
HA and autologous fat were significantly In this systematic review and meta-analysis and literature reviews. In an attempt to further
associated with no improvement (p=0.003 of patients with vascular complications occurring understand the factors influencing the risks
and p<0.001 for the chi-squared adjusted after aesthetic procedures, we found that and outcomes of vascular complications, we
residuals of HA and autologous fat, respectively; unilateral blindness was the most frequent extracted data from individual cases to provide
the significance threshold after Bonferroni vascular adverse event associated with cosmetic a quantitative approach. Moreover, considering
correction was set at α=0.005). Regarding fillers for facial tissue augmentation. Of these, that the number of products available for soft-
the affected vessel, only the ophthalmic autologous fat tended to cause more cases tissue augmentation has been progressively and
artery was significantly associated with no of permanent vascular damage. Among all continuously increasing for the last 10 years, our

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A B significantly associated with a lower frequency

of improvement, but the latter showed a
stronger trend towards more severe outcomes.
This result is consistent with that of previous
reviews, which concluded that autologous
fat is the filler material that most frequently
causes permanent blindness.12,17,46 In a previous
review by Beleznay et al,12 autologous fat was
responsible for 47.9 percent of cases of unilateral
permanent blindness, followed by HA (23.5%),
collagen (8.2%), poly-L-lactic acid (3.1%), and
FIGURE 2. Etiological details of blindness caused by A) direct injection of the filler into the vessel lumen and B) skin calcium hydroxylapatite (2%).The increased risk
necrosis caused by either direct injection or vascular compression of major vascular complications associated with
autologous fat injections could be explained by its
A B
large particle size, enabling it to occlude relatively
large vessels, such as the ophthalmic artery.12,17
Regarding safety, one of the advantages of HA
is the availability of an effective rescue procedure
(i.e., hyaluronidase injection into or around the
occluded blood vessel).45,47,48 This is one of the
reasons why HA has been claimed as the safest
substance indicated for tissue augmentation.48,49
However, in our review, the number of cases in
which hyaluronidase was administered accounted
for only a quarter of all cases in which HA was
FIGURE 3. A) main vascular and B) nerve structures of the face used (10 vs. 40). Furthermore, although the
reduced number of cases limited our statistical
A B analysis, it is worth mentioning that only half of
these cases resulted in the total recovery of the
main outcome related to vascular occlusion. The
low recovery rate despite the use of hyaluronidase
could be partially explained by the excessive time
gap between symptoms onset and hyaluronidase
injection, ranging from 3 to 24 hours, with
five over seven cases exceeding the four-hour
threshold, below which significant differences
are seen.45 These observations suggest that the
safer profile of HA compared with autologous fat
might be better explained by the properties of
the filler material rather than the availability of
FIGURE 4. A) depiction of facial arteries illustrating the primary areas of risk and B) their associated anatomical a rescue procedure. Due to the different physical
structure properties of each substance, the injector’s ability
to inject the filler using the right pressure might
review aimed to present an updated picture of In terms of clinical correlation, one of the become an overriding factor influencing the risk
vascular complications associated with these most relevant variables was the filler injected. of vascular complications.12,50 Rapid injections
fillers. All analyses based on case reports are In our study selection, the absolute number of not only result in greater amounts of filler but
constrained by the amount and accuracy of the cases with vascular complications after the use also limit the capacity of the injector to identify
information published. Eighty-six percent of cases of HA and autologous fat was similar. However, and amend any vascular occlusion. Furthermore,
reported using imaging diagnostic techniques considering that HA is, by far, the most used various authors have proposed that, when
to verify the diagnosis of vascular occlusion, and filler in the world for aesthetic procedures,4,5 this exerting too much pressure on the plunger, even
most of them provided details regarding key observation suggests that autologous fat is more during the injection of small amounts of filler,
variables such as the injected substance, the often associated with vascular complications arterial pressure can easily be overcome, with
blood vessel affected, the outcome of the vascular than HA. Regarding the recovery rate of vascular the filler reaching deeper arteries.6,12 Of course,
complication, and the time to symptom onset. complications, both HA and autologous fat were injection pressure and rate cannot be monitored

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unless the professional performing the injection

TABLE 4. Recommendations for preventing and managing vascular complications associated with filler injections
uses a motorized injector to deliver the filler;
hence, this information could not be included PREVENTIVE STRATEGIES
in our analysis. Motorized injectors have been
proposed as a means to reduce injection risks, Practitioner
as they provide a comfortable flow rate and Deep knowledge of the vascular anatomy is key for preventing vascular complications. In addition to good
allow physicians to keep their attention on the anatomical background knowledge, practitioners should consider the following aspects:
patient.50,51 • Possible altered anatomical connections in patients with previous surgeries
Considering that shorter onset times are more • Possible anatomical variants during the development of some blood vessels; precaution should be taken in
likely to prompt early interventions, we expected all face areas, including the upper lip and the wing of the nose
time to symptom onset to influence the outcome. • Possible extended vascular anastomoses of the nasal region from the perioral to the periorbital region,
However, no significant differences were found which might spread the filler from one area to the other.
between the times before and after one hour. Filler choice
The importance of the time gap between the
vascular complication and the intervention was Use reabsorbable products appropriate for the type of correction and therefore for the implant level. Hyaluronic acid
investigated in animal models by Kim et al38 and fillers are typically noninflammatory products and have a purely mechanical effect, unlike collagen and autologous
fat, which seem to activate the “clotting mechanism.”
Cavallini et al,47 who found that rescue procedures
performed less than four hours after a filler Injection technique
injection significantly reduced the area of necrotic
• Use a delicate retrograde injection technique.
ear skin.However, these studies were based on • Use very slow injection rates.
hyaluronidase injections as rescue procedures, • Apply light pressure on the syringe plunger (consider the use of an electronic device).
which were barely used in our case collection. • Distribute the product in various points by injecting small amounts of it (i.e. <0.1 mL).
Notwithstanding the lack of correlation with • Use a microcannula for deep injections and very viscous products (strongly recommended).
other studies, two important drawbacks limited • Use fine needles only for superficial injections.
our analysis of the potential influence of the time- • Always aspirate before injection.
to-onset on symptom recovery. First, our dataset
did not include time frames more accurate MANAGEMENT OF COMPLICATIONS
than a 24-hour interval. Second, most of these Immediate pain and/or bleaching of the area (typically a few seconds after injection)
cases were reported by ophthalmologists with Immediately stop injecting; vigorously massage the area.
patients showing sudden blindness concurrent
Possible livedoreticularis or reactive hyperemia (it may occur up to 10 minutes after injection)
with filler injections; therefore, the time from the
aesthetic intervention to the onset of vision loss Treat immediately to restore the vascular flow.
or blindness was assessed retrospectively. Possible arterial insufficiency (slow capillary reloading with acupressure)
Our results also showed that the affected blood Apply warm gauzes, topical paste or patch of nitro-derivatives; inject hyaluronidase (independently from the type of
vessel significantly influenced the outcome of the filler injected) and apply a local massage.
vascular complication. Based on the statistical Dark-blue discoloration of the area (it may occur from ten minutes to hours)
analysis, ophthalmic artery occlusion was more
frequently associated with no improvement Contact your plastic surgeon and consider using systemic antibiotics, steroids, aspirin, low molecular weight heparin,
prostaglandin.
than that of other blood vessels, particularly
the nasociliary artery. However, individual case Blisters and boils after a few days
examinations revealed that the most dangerous Gently disinfect by swabbing the area; pierce the boils and gently favor the spillage of the serum; leave a gras
adverse events (i.e., cerebral infarctions) occurred gauze dressing with antibiotic on the skin for no more than three days, then remove it (with clamp and scissors),
as an ultimate consequence of retinal artery gently disinfect with 3% boric acid and medicate with a gras gauze dressing and antibiotic ointment until complete
occlusion. Since the retinal artery is a final branch repitelization of the area.
of the ophthalmic artery, it could be assumed
that an occlusion of the retinal artery is not Necrosis (can appear after days or weeks)
likely to have consequences at more central Apply antibiotic ointments until eschar demarcation; after removal of the necrotic tissue, apply products intended to
areas. However, as previously discussed, when improve tissue regeneration such as hydrocolloids gel, plates or collagen tablets on the loss of residual substance.
the tip of the needle penetrates the artery and
Ocular complications
pressure is applied to the plunger, the filler
can reverse the flow in it, moving as a column
Contact an eye surgeon immediately. In the meantime, try to reduce eye pressure through ocular massage, timolol
proximal to the origin of the retinal artery. If the drops, acetazolamide/manitol, steroids, haemodilution, oxygen therapy, antiplatelet/anticoagulant, thrombolysis,
injector exerts more pressure on the plunger for decompression of the eye anterior chamber.
a longer time, the column can reach the origin

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of the ophthalmic artery, and part of the filler technique, which was identified as the main of the facial artery, particularly the retinal
embolus can access the internal carotid artery and cause of iatrogenic vascular occlusion.Other artery, almost invariably leads to unilateral, and
subsequently reach cerebral circulation (Figure variables that could not be analyzed because of occasionally bilateral, blindness. The incidental
2).6,12 The use of motorized devices, which enable data omission, despite their potential interest, occlusion of the retinal artery most frequently
accurate pressure control, has been proposed to include the specialty of the person performing occurs when treating the nose, but this artery
minimize this risk.50,51 We found no differences the injection, the characteristics of the device can also be reached from the glabella. Thus, to
in the outcome when the occlusion occurred in (e.g., needle, cannula), and the concentration of prevent vascular adverse effects, it is essential
other blood vessels, particularly the nasociliary hyaluronidase used in the rescue procedure. In that the physician performing the filler injections
and facial arteries. Although this observation addition to a few poor-quality case reports, some has a proficient knowledge of anatomy.
is consistent with the larger diameter of these of the cases analyzed were not reported by the
vessels, due to the limited number of cases in physician injecting the filler but rather by the ACKNOWLEDGMENTS
which there was occlusion in blood vessels other ophthalmologist who treated the complication, The authors gratefully acknowledge the time
than the ophthalmic and retinal arteries, no firm thus omitting details of the initial aesthetic and effort of Dr. Patrice Delobel, Dr. Kévin Legent,
conclusions could be reached. procedure. The variables most affected by this and Dr. Luana Consolini, who provided scientific
Finally, we addressed the influence of the lack of data were time-to-onset, initial rescue advice and helped with laying the groundwork
injection site on the outcome of the vascular treatment, and concomitant symptoms, which, of this research. The authors also thank the i2e3
event. Previous studies reported the glabella and in most cases, were retrospectively reported by Biomedical Research Institute team for providing
the forehead as areas more frequently associated the physician treating the complication. Another statistical and medical writing assistance.
with blindness and visual loss than the nose.5,7,11 potential source of inaccuracy was the ad-hoc
However, in our analysis, injections in the nose data transformation. The heterogeneity in the REFERENCES
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indicated that the nose might not be a safer simplicity and clarity to our conclusion. 2013;6(1):295–316.
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suggested that the dorsal nasal artery (i.e., the quantitative perspective of vascular complications of alar necrosis associated with dermal filler injection.
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might be responsible for the transmission of obtained in our analysis might serve to support 3. Bailey SH, Cohen JL, Kenkel JM. Etiology, prevention,
emboli following injections in either the glabella a few recommendations to help clinicians who and treatment of dermal filler complications. Aesthet
or the area proximal to the nasal root.Other perform filler augmentation procedures avoid Surg J. 2011;31(1):110–121.
injection sites did not yield significant results vascular adverse events or minimize their 4. Matarasso SL, Carruthers JD, Jewell ML. Consensus
upon comparing the outcomes of the vascular consequences. Table 4 provides a list of key recommendations for soft-tissue augmentation with
procedures. However, it is worth mentioning recommendations for preventing and minimizing nonanimal stabilized hyaluronic acid (Restylane).
that our analysis was compromised by the fact vascular adverse events when performing filler Plast Reconstr Surg. 2006;117(Suppl 3):3S–34S;
that a single patient could be injected at various injections. However, as mentioned before, our discussion 35S–43S.
sites, which precludes the identification of the analysis has important limitations associated with 5. Glogau RG, Kane MAC. Effect of injection techniques
precise injection responsible for the vascular the accuracy and diversity of data presentation in on the rate of local adverse events in patients
complication. the source articles. Hence, the recommendations implanted with nonanimal hyaluronic acid gel
Limitations. The fact that our meta-analysis we present in Table 4 should not be interpreted dermal fillers. Dermatologic Surg. 2008;34(Suppl
was based mostly on case reports implies some as being strictly supported by the results of our 1):S105–S109.
limitations that should not be dismissed. Case meta-analysis; our recommendations are also 6. Carruthers A, Carruthers J. Non-animal-
reports do not always provide all details of the based on our own insights gained from our based hyaluronic acid fillers: scientific and
procedures performed. This was particularly extensive experience as plastic surgeons. technical considerations. Plast Reconstr Surg.
notable for some variables identified as risk 2007;120(6):33S–40S.
factors for vascular complications, such as CONCLUSION 7. Weinberg MJ, Solish N. Complications of hyaluronic
injection technique, injected volume, pressure This meta-analysis provides an up-to-date acid fillers. Facial Plast Surg. 2009;25(5):324–328.
applied, and needle diameter, which were overview of vascular complications associated 8. Bachmann F, Erdmann R, Hartmann V, et al. The
omitted in most cases. Some of these factors were with the injection of facial fillers. Our results spectrum of adverse reactions after treatment with
investigated by Glogau et al,5 who concluded support the hypothesis that autologous fat is injectable fillers in the glabellar region: results from
that low injection pressures (i.e., flow rates of more likely to cause serious vascular events than the injectable filler safety study. Dermatologic Surg.
less than 0.3mL/minute) and small volume HA, irrespective of the use of hyaluronidase 2009;35(Suppl 2):1629–1634.
injections (i.e., less than 0.5mL) might prevent to treat the vascular occlusion. In light of the 9. McCracken MS, Khan JA, Wulc AE, et al. Hyaluronic
retrograde embolization of the filler; the authors information published in the literature, it seems acid gel (Restylane) filler for facial rhytids: lessons
also recommended avoiding the fan-like that accidental injection in the terminal branches learned from American Society of Ophthalmic Plastic

JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY June 2019 • Volume 12 • Number 6
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and Reconstructive Surgery member treatment occlusion: a cautionary tale and emphasis for of collagenous material. Dermatologic Surg.
of 286 patients. Ophthal Plast Reconstr Surg. early intervention. J Drugs Dermatol. 2013;12(10): 2010;36(7):1196–1199.
2006;22(3):188–191. 1181–1183. 38. Kim YJ, Kim SS, Song WK, et al. Ocular ischemia
10. Zielke H, Wölber L, Wiest L, Rzany B. Risk profiles of 24. Kim EG, Eom TK, Kang SJ. Severe visual loss and with hypotony after injection of hyaluronic acid gel.
different injectable fillers: results from the Injectable cerebral infarction after injection of hyaluronic acid Ophthal Plast Reconstr Surg. 2011;27(6):E152–E155.
Filler Safety Study (IFS Study). Dermatologic Surg. gel. J Craniofac Surg. 2014;25(2):684–686. 39. Tracy L, Ridgway J, Nelson JS, et al. Calcium
2008;34(3):326–335. 25. Hu XZ, Hu JY, Wu PS, et al. Posterior ciliary artery hydroxylapatite associated soft tissue necrosis: a
11. Lazzeri D, Agostini T, Figus M, et al. Blindness occlusion caused by hyaluronic acid injections into case report and treatment guideline. J Plast Reconstr
following cosmetic injections of the face. Plast the forehead: a case report. Medicine (Baltimore). Aesthetic Surg. 2014;67(4):564–568.
Reconstr Surg. 2012;129(4):995–1012. 2016;95(11):e3124. 40. Park SW, Woo SJ, Park KH, et al. Iatrogenic retinal
12. Beleznay K, Carruthers JDA, Humphrey S, Jones 26. Sung MS, Kim HG, Woo KI, Kim YD. Ocular ischemia artery occlusion caused by cosmetic facial filler
D. Avoiding and treating blindness from fillers: a and ischemic oculomotor nerve palsy after vascular injections. Am J Ophthalmol. 2012;154(4):653–662.
review of the world literature. Dermatologic Surg. embolization of injectable calcium hydroxylapatite 41. Park TH, Seo SW, Kim JK, Chang CH. Clinical
2015;41(10):1097–1117. filler. Ophthal Plast Reconstr Surg. 2010;26(4): experience with Hyaluronic acid-filler complications. J
13. Chen YY, Wang WY, Li JP, et al. Fundus artery occlusion 289–291. Plast Reconstr Aesthetic Surg. 2011;64(7):892–897.
caused by cosmetic facial injections. Chin Med J (Engl). 27. Kim DY, Eom JS, Kim JY. Temporary blindness after an 42. Kim YK, Jung C, Woo SJ, Park KH. Cerebral
2014;127(8):1434–1437. anterior chamber cosmetic filler injection. Aesthetic angiographic findings of cosmetic facial filler-related
14. Loh KTD, Chua JJ, Lee HM, et al. Prevention and Plast Surg. 2015;39(3):428–430. ophthalmic and retinal artery occlusion. J Korean Med
management of vision loss relating to facial filler 28. Roberts SAI, Arthurs BP. Severe visual loss and orbital Sci. 2015;30(12):1847–1855.
injections. Singapore Med J. 2016;57(8):438–443. infarction following periorbital aesthetic poly-(L)- 43. Hong JH, Ahn SJ, Woo SJ, et al. Central retinal artery
15. Walker L, King M. This month’s guideline: visual loss lactic acid (PLLA) injection. Ophthal Plast Reconstr occlusion with concomitant ipsilateral cerebral
secondary to cosmetic filler injection. J Clin Aesthet Surg. 2012;28(3):e68–e70. infarction after cosmetic facial injections. J Neurol Sci.
Dermatol. 2018;11(5):E53–E55. 29. Kim YJ, Choi KS. Bilateral blindness after filler 2014;346(1–2):310–314.
16. Urdiales-Gálvez F, Delgado NE, Figueiredo V, injection. Plast Reconstr Surg. 2013;131:298e–299e. 44. Lee SK, Kim SM, Cho SH, et al. Adverse reactions to
Lajo-Plaza J V, et al. Treatment of soft tissue filler 30. Kwon SG, Hong JW, Roh TS, et al. Ischemic oculomotor injectable soft tissue fillers: memorable cases and
complications: expert consensus recommendations. nerve palsy and skin necrosis caused by vascular their clinicopathological overview. J Cosmet Laser Ther.
Aesthetic Plast Surg. 2018;42(2):498–510. embolization after hyaluronic acid filler injection: a 2015;17(2):102–108.
17. Feinendegen DL, Baumgartner RW, Vuadens P, et al. case report. Ann Plast Surg. 2013;71(4):333–334. 45. Kim DW, Yoon ES, Ji YH, et al. Vascular complications
Autologous fat injection for soft tissue augmentation 31. Kim SN, Byun DS, Park JH, et al. Panophthalmoplegia of hyaluronic acid fillers and the role of hyaluronidase
in the face: a safe procedure?. Aesthetic Plast Surg. and vision loss after cosmetic nasal dorsum injection. in management. J Plast Reconstr Aesthetic Surg.
1998;22(3):163–167. J Clin Neurosci. 2014;21(4):678–680. 2011;64(12):1590–1595.
18. Park KH, Kim YK, Woo SJ, et al. Iatrogenic occlusion 32. Kassir R, Kolluru A, Kassir M. Extensive necrosis 46. Rzany B, DeLorenzi C. Understanding, avoiding, and
of the ophthalmic artery after cosmetic facial filler after injection of hyaluronic acid filler: case report managing severe filler complications. Plast Reconstr
injections: a national survey by the Korean Retina and review of the literature. J Cosmet Dermatol. Surg. 2015;136(5S):196S–203S.
Society. JAMA Ophthalmol. 2014;132(6):714–723. 2011;10(3):224–231. 47. Cavallini M, Gazzola R, Metalla M, Vaienti L. The role
19. Beasley TM, Schumacker RE. Multiple regression 33. Carle M V, Roe R, Novack R, Boyer DS. Cosmetic facial of hyaluronidase in the treatment of complications
approach to analyzing contingency tables: post hoc fillers and severe vision loss. JAMA Ophthalmol. from hyaluronic acid dermal fillers. Aesthet Surg J.
and planned comparison procedures. J Exp Educ. 2014;132(5):637–639. 2013;33(8):1167–1174.
1995;64(1):79–93. 34. Kim SG, Lee CJ, Kim YJ, Lee S Il. Salvage of nasal skin 48. Buhren BA, Schrumpf H, Hoff NP, et al. Hyaluronidase:
20. Kim SK, Kim JH, Hwang K. Skin necrosis of the in a case of venous compromise after hyaluronic acid from clinical applications to molecular and cellular
nose after injection of ribose cross-linked porcine filler injection using prostaglandin E. Dermatol Surg. mechanisms. Eur J Med Res. 2016;21(1):5.
atelocollagen. J Craniofac Surg. 2015;26(7): 2011;37(12):1817–1819. 49. Vartanian AJ, Frankel AS, Rubin MG. Injected
2211–2212. 35. Lee CM, Hong IH, Park SP. Ophthalmic artery hyaluronidase reduces restylane-mediated cutaneous
21. Chou CC, Chen HH, Tsai YY, et al. Choroid vascular obstruction and cerebral infarction following augmentation. Arch Facial Plast Surg. 2005;7(4):
occlusion and ischemic optic neuropathy after facial periocular injection of autologous fat. Korean J 231–237.
calcium hydroxyapatite injection—a case report. Ophthalmol. 2011;25(5):358. 50. Carey W, Weinkle S. Retraction of the plunger on a
BMC Surg. 2015;15(1):21. 36. Park SH, Sun HJ, Choi KS. Sudden unilateral visual loss syringe of hyaluronic acid before injection: are we
22. Lin YC, Chen WC, Liao WC, Hsia TC. Central retinal after autologous fat injection into the glabellar area. safe?. Dermatologic Surg. 2015;41(c):S340–S346.
artery occlusion and brain infarctions after nasal filler Clin Ophthalmol. 2008;2(3):679–683. 51. Cassuto D, Papagni M. Anteis injection system:
injection. QJM. 2015;108(9):731–732. 37. Kwon DY, Park MH, Koh SB, et al. Multiple positive results of a preliminary clinical evaluation.
23. McGuire LK, Hale EK, Godwin LS. Post-filler vascular arterial embolism after illicit intranasal injection Updat Plast Surg. 2010;3:5–8. JCAD

JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY June 2019 • Volume 12 • Number 6
E72
 M E TA - A N A LY S I S

and Reconstructive Surgery member treatment occlusion: a cautionary tale and emphasis for of collagenous material. Dermatologic Surg.
of 286 patients. Ophthal Plast Reconstr Surg. early intervention. J Drugs Dermatol. 2013;12(10): 2010;36(7):1196–1199.
2006;22(3):188–191. 1181–1183. 38. Kim YJ, Kim SS, Song WK, et al. Ocular ischemia
10. Zielke H, Wölber L, Wiest L, Rzany B. Risk profiles of 24. Kim EG, Eom TK, Kang SJ. Severe visual loss and with hypotony after injection of hyaluronic acid gel.
different injectable fillers: results from the Injectable cerebral infarction after injection of hyaluronic acid Ophthal Plast Reconstr Surg. 2011;27(6):E152–E155.
Filler Safety Study (IFS Study). Dermatologic Surg. gel. J Craniofac Surg. 2014;25(2):684–686. 39. Tracy L, Ridgway J, Nelson JS, et al. Calcium
2008;34(3):326–335. 25. Hu XZ, Hu JY, Wu PS, et al. Posterior ciliary artery hydroxylapatite associated soft tissue necrosis: a
11. Lazzeri D, Agostini T, Figus M, et al. Blindness occlusion caused by hyaluronic acid injections into case report and treatment guideline. J Plast Reconstr
following cosmetic injections of the face. Plast the forehead: a case report. Medicine (Baltimore). Aesthetic Surg. 2014;67(4):564–568.
Reconstr Surg. 2012;129(4):995–1012. 2016;95(11):e3124. 40. Park SW, Woo SJ, Park KH, et al. Iatrogenic retinal
12. Beleznay K, Carruthers JDA, Humphrey S, Jones 26. Sung MS, Kim HG, Woo KI, Kim YD. Ocular ischemia artery occlusion caused by cosmetic facial filler
D. Avoiding and treating blindness from fillers: a and ischemic oculomotor nerve palsy after vascular injections. Am J Ophthalmol. 2012;154(4):653–662.
review of the world literature. Dermatologic Surg. embolization of injectable calcium hydroxylapatite 41. Park TH, Seo SW, Kim JK, Chang CH. Clinical
2015;41(10):1097–1117. filler. Ophthal Plast Reconstr Surg. 2010;26(4): experience with Hyaluronic acid-filler complications. J
13. Chen YY, Wang WY, Li JP, et al. Fundus artery occlusion 289–291. Plast Reconstr Aesthetic Surg. 2011;64(7):892–897.
caused by cosmetic facial injections. Chin Med J (Engl). 27. Kim DY, Eom JS, Kim JY. Temporary blindness after an 42. Kim YK, Jung C, Woo SJ, Park KH. Cerebral
2014;127(8):1434–1437. anterior chamber cosmetic filler injection. Aesthetic angiographic findings of cosmetic facial filler-related
14. Loh KTD, Chua JJ, Lee HM, et al. Prevention and Plast Surg. 2015;39(3):428–430. ophthalmic and retinal artery occlusion. J Korean Med
management of vision loss relating to facial filler 28. Roberts SAI, Arthurs BP. Severe visual loss and orbital Sci. 2015;30(12):1847–1855.
injections. Singapore Med J. 2016;57(8):438–443. infarction following periorbital aesthetic poly-(L)- 43. Hong JH, Ahn SJ, Woo SJ, et al. Central retinal artery
15. Walker L, King M. This month’s guideline: visual loss lactic acid (PLLA) injection. Ophthal Plast Reconstr occlusion with concomitant ipsilateral cerebral
secondary to cosmetic filler injection. J Clin Aesthet Surg. 2012;28(3):e68–e70. infarction after cosmetic facial injections. J Neurol Sci.
Dermatol. 2018;11(5):E53–E55. 29. Kim YJ, Choi KS. Bilateral blindness after filler 2014;346(1–2):310–314.
16. Urdiales-Gálvez F, Delgado NE, Figueiredo V, injection. Plast Reconstr Surg. 2013;131:298e–299e. 44. Lee SK, Kim SM, Cho SH, et al. Adverse reactions to
Lajo-Plaza J V, et al. Treatment of soft tissue filler 30. Kwon SG, Hong JW, Roh TS, et al. Ischemic oculomotor injectable soft tissue fillers: memorable cases and
complications: expert consensus recommendations. nerve palsy and skin necrosis caused by vascular their clinicopathological overview. J Cosmet Laser Ther.
Aesthetic Plast Surg. 2018;42(2):498–510. embolization after hyaluronic acid filler injection: a 2015;17(2):102–108.
17. Feinendegen DL, Baumgartner RW, Vuadens P, et al. case report. Ann Plast Surg. 2013;71(4):333–334. 45. Kim DW, Yoon ES, Ji YH, et al. Vascular complications
Autologous fat injection for soft tissue augmentation 31. Kim SN, Byun DS, Park JH, et al. Panophthalmoplegia of hyaluronic acid fillers and the role of hyaluronidase
in the face: a safe procedure?. Aesthetic Plast Surg. and vision loss after cosmetic nasal dorsum injection. in management. J Plast Reconstr Aesthetic Surg.
1998;22(3):163–167. J Clin Neurosci. 2014;21(4):678–680. 2011;64(12):1590–1595.
18. Park KH, Kim YK, Woo SJ, et al. Iatrogenic occlusion 32. Kassir R, Kolluru A, Kassir M. Extensive necrosis 46. Rzany B, DeLorenzi C. Understanding, avoiding, and
of the ophthalmic artery after cosmetic facial filler after injection of hyaluronic acid filler: case report managing severe filler complications. Plast Reconstr
injections: a national survey by the Korean Retina and review of the literature. J Cosmet Dermatol. Surg. 2015;136(5S):196S–203S.
Society. JAMA Ophthalmol. 2014;132(6):714–723. 2011;10(3):224–231. 47. Cavallini M, Gazzola R, Metalla M, Vaienti L. The role
19. Beasley TM, Schumacker RE. Multiple regression 33. Carle M V, Roe R, Novack R, Boyer DS. Cosmetic facial of hyaluronidase in the treatment of complications
approach to analyzing contingency tables: post hoc fillers and severe vision loss. JAMA Ophthalmol. from hyaluronic acid dermal fillers. Aesthet Surg J.
and planned comparison procedures. J Exp Educ. 2014;132(5):637–639. 2013;33(8):1167–1174.
1995;64(1):79–93. 34. Kim SG, Lee CJ, Kim YJ, Lee S Il. Salvage of nasal skin 48. Buhren BA, Schrumpf H, Hoff NP, et al. Hyaluronidase:
20. Kim SK, Kim JH, Hwang K. Skin necrosis of the in a case of venous compromise after hyaluronic acid from clinical applications to molecular and cellular
nose after injection of ribose cross-linked porcine filler injection using prostaglandin E. Dermatol Surg. mechanisms. Eur J Med Res. 2016;21(1):5.
atelocollagen. J Craniofac Surg. 2015;26(7): 2011;37(12):1817–1819. 49. Vartanian AJ, Frankel AS, Rubin MG. Injected
2211–2212. 35. Lee CM, Hong IH, Park SP. Ophthalmic artery hyaluronidase reduces restylane-mediated cutaneous
21. Chou CC, Chen HH, Tsai YY, et al. Choroid vascular obstruction and cerebral infarction following augmentation. Arch Facial Plast Surg. 2005;7(4):
occlusion and ischemic optic neuropathy after facial periocular injection of autologous fat. Korean J 231–237.
calcium hydroxyapatite injection—a case report. Ophthalmol. 2011;25(5):358. 50. Carey W, Weinkle S. Retraction of the plunger on a
BMC Surg. 2015;15(1):21. 36. Park SH, Sun HJ, Choi KS. Sudden unilateral visual loss syringe of hyaluronic acid before injection: are we
22. Lin YC, Chen WC, Liao WC, Hsia TC. Central retinal after autologous fat injection into the glabellar area. safe?. Dermatologic Surg. 2015;41(c):S340–S346.
artery occlusion and brain infarctions after nasal filler Clin Ophthalmol. 2008;2(3):679–683. 51. Cassuto D, Papagni M. Anteis injection system:
injection. QJM. 2015;108(9):731–732. 37. Kwon DY, Park MH, Koh SB, et al. Multiple positive results of a preliminary clinical evaluation.
23. McGuire LK, Hale EK, Godwin LS. Post-filler vascular arterial embolism after illicit intranasal injection Updat Plast Surg. 2010;3:5–8. JCAD

JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY June 2019 • Volume 12 • Number 6
E72