Cosmetic Medicine

Aesthetic Surgery Journal

2022, Vol 42(6) 649–655
Efficacy of Percutaneous Intraarterial Facial/ © The Author(s) 2021. Published
by Oxford University Press on behalf
Supratrochlear Arterial Hyaluronidase of The Aesthetic Society. All rights
reserved. For permissions, please
Injection for Treatment of Vascular Embolism e-mail: [email protected]
https://doi.org/10.1093/asj/sjab425
www.aestheticsurgeryjournal.com
Resulting From Hyaluronic Acid Filler

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Cosmetic Injection

Can Zheng, PhD ; Qiang Fu, MS; Gui-wen Zhou, MS; Lin-ying Lai, MS;
Li-xia Zhang, MS; De-quan Zhang, PhD; Guo-jie Chen, MS; Li-ming Liang,
MD, PhD; and Min-liang Chen, MD, PhD

Abstract
Background: Vascular embolism is a serious complication of hyaluronic acid (HA) filler cosmetic injection, and
hyaluronidase injection has been proposed as the treatment. Until now, there has been a lack of adequate clinical evi-
dence regarding the benefits of treatment for HA filler-induced vascular embolism by percutaneous facial or supratrochlear
arterial hyaluronidase injection.
Objectives: The authors sough to evaluate the efficacy of percutaneous facial or supratrochlear arterial hyaluronidase
injection as a rescue treatment for HA filler-induced vascular embolism.
Methods: We included 17 patients with vascular embolism after facial HA filler injection. Intraarterial injection of 1500 units
hyaluronidase was performed via facial artery for 13 cases with skin necrosis and via supratrochlear arterial for 4 cases with
severe ptosis and skin necrosis but no visual impairment. Simultaneously, general symptomatic treatment and nutritional
therapy were performed.
Results: After hyaluronidase injection, facial skin necrosis in all cases was restored and ptosis in the 4 cases was also
significantly relieved. Patients were subsequently followed-up for 1 month to 1 year. The skin necrosis in 16 patients com-
pletely healed, and only 1 patient had small superficial scars.
Conclusions: It is effective to alleviate skin necrosis and ptosis resulting from HA filler embolism via percutaneous facial
or supratrochlear arterial hyaluronidase injection.

Level of Evidence: 4

Editorial Decision date: December 10, 2021; online publish-ahead-of-print December 27, 2021.

In recent years, with the increasing request for minimally

From the Senior Department of Burns and Plastic Surgery, the Fourth
invasive rejuvenation, there is a rising trend of people Medical Center of PLA (People’s Liberation Army) General Hospital,
receiving facial hyaluronic acid (HA) filler cosmetic injec- Beijing, China.
tion.1,2 HA filler is an ideal cosmetic filler due to its unique
Corresponding Author:
chemical-physical properties and versatility.3-5 Despite
Dr Min-liang Chen, 51 Fucheng Rd., Beijing 100048, P.R. China.
the overall safety of the agent, complications and serious E-mail: [email protected]
650 Aesthetic Surgery Journal 42(6)

adverse events can occur following injection even at the Helsinki. Written informed consent was provided, by which
hands of experienced injectors.6,7 Severe complications the patients agreed to the utilization and analysis of the data.
related to arterial occlusion have been reported, including
skin necrosis, eye and eyelid movement disorder, ptosis,
loss of visual field, and even blindness.8,9 The most com-
Percutaneous Facial or Supratrochlear
monly affected areas were the frontal, glabellar area, nose, Arterial Hyaluronidase Injection
alar base, and nasolabial folds. Hyaluronidases are sol- We enrolled 17 patients who underwent emergency
uble protein enzymes that degrade HA filler. Their role is therapy by injection of hyaluronidase via percutaneous fa-
to increase drug diffusion and reverse the effects of HA cial or supratrochlear artery:
fillers. There have been reports of the efficacy of subcu-
taneous hyaluronidase injection for the treatment of HA 1. Thirteen patients were treated with percutaneous fa-
filler-induced vascular complications.10 However, whether cial arterial hyaluronidase injection. The color doppler

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hyaluronidase can diffuse across the intact arterial wall is flow imaging was utilized to locate the facial artery
still controversial. Some scholars think that the intravas- and the puncture point was 1 cm from the mandible
cular HA filler could not be degraded by extravascular angle. The patients were supine with their heads tilted
treatment of hyaluronidase.11 to the healthy side. They received the facial disinfec-
Another feasible technique is percutaneous direct tion and local anesthesia at the puncture point (the
intraarterial hyaluronidase delivery. Injecting hyaluronidase ipsilateral infraorbital nerve blockade was performed
into the supraorbital and supratrochlear vessels would when necessary). Then, a 22-gauge arterial blood col-
seem logical and necessary to treat retinal artery emboli- lection needle or 19/23-gauge disposable venous infu-
zation.12 However, the clinical effectiveness of intravascular sion needle was inserted through the facial artery. The
facial or supratrochlear arterial injection of hyaluronidase angle between the needle body and skin is generally
still lacks adequate clinical evidence. Herein, we retrospec- 30° to approximately 45°. The needle was advanced 2
tively reviewed 17 cases of HA-induced vascular complica- to 3 mm until a positive blood aspiration was confirmed.
tions. From January 1, 2019, to May 31, 2020, 13 cases were Then, 1500 IU hyaluronidase (Shanghai Shangyao No.
treated with percutaneous facial arterial hyaluronidase 1 Biochemical Pharmaceutical Co., LTD., Shanghai,
injection and other 4 patients were treated with percuta- China) was slowly injected into the facial artery.
neous supratrochlear arterial hyaluronidase injection. We 2. Four patients were treated with percutaneous
summarized the methods and carefully analyzed the clin- supratrochlear arterial hyaluronidase injection: color
ical effects, which will contribute to the treatment of se- doppler flow imaging was also utilized to locate the
rious vascular embolism. supratrochlear artery and mark the point of the punc-
ture. Patients were supine with a positive head posi-
tion. Patients also received the facial disinfection and
local anesthesia. Then, the treatment was performed,
METHODS and 1500 IU hyaluronidase was slowly injected into
the supratrochlear artery. The patients’ vital signs were
Clinical Study closely monitored during the process of injection. If nec-
Between January 1, 2019, and May 31, 2020, patients with essary, patients with severe vascular complications could
vascular complications of HA filler were retrospectively re- be treated with 2 or multiple hyaluronidase injections.
viewed and 17 were included in our study, which were con-
firmed to have no visual impairment and life-threatening
Symptomatic Treatments
injuries such as hypertension, coagulopathy or intracra-
nial and external hemorrhaging. The participants were In addition to the intra-arterial channel being established
19 to 52 years old and received HA filler at private clinics. for all patients to provide the hyaluronidase injection, we
Demographics and injection sites are summarized in Table also provided symptomatic treatments via the routinely
1. General physical examination was performed for all pa- established vein channel. The symptomatic treatments
tients on arrival at our hospital, and local facial skin damage we applied were as follows: anti-inflammation treatment,
was assessed. The range of skin necrosis in these pa- glucocorticoid pulse therapy (dexamethasone sodium
tients spread along the surface branches of the facial ar- phosphate, 10 mg, ivgtt, qd, 3 d), neurotrophic treatment
tery or supratrochlear artery. The study was approved by (mecobalamin injection, 0.5 mg, ivgtt, qd, 90 d), and anti-
the Fourth Medical Center to Chinese People’s Liberation allergy treatment (loratadine, 10 mg, pol, qd). The epidermal
Army General Hospital (Beijing, China) ethical committee growth factor and a continuous vacuum sealing drainage
(2020KY043-KS001) and conducted in accordance with are employed to promote wound healing. Nasal scaffolds
country regulations and the principles of the Declaration of should be worn to prevent narrowing of the nostrils or alar
Zheng et al651

Table 1. Demographic and Clinical Characteristics Examined in This Studya

Patient Sex Age (years) Cosmetic injection Hyaluronidase Skin necrosis Ptosis
sites injection artery

1 M 36 Frontal Supratrochlear Yes Yes

artery

2 F 31 Nasolabial folds Facial artery Yes —

3 M 38 Frontal Supratrochlear Yes Yes

artery

4 F 52 Nose Facial artery Yes —

5 F 37 Nasolabial folds Facial artery Yes —

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6 F 37 Upper lip Facial artery Yes Yes

7 M 37 Frontal Facial artery Yes —

8 F 37 Frontal Facial artery Yes —

9 F 26 Frontal Supratrochlear Yes Yes

artery

10 F 27 Glabella Supratrochlear Yes —

artery

11 F 45 Nose Facial artery Yes —

12 F 31 Nasolabial folds Facial artery Yes —

13 F 19 Nose Facial artery Yes —

14 F 26 Nasolabial folds Facial artery Yes —

15 F 41 Nasolabial folds Facial artery Yes —

16 F 30 Nasolabial folds Facial artery Yes —

17 F 36 Nasolabial folds Facial artery Yes —

aF = female; M = male.

collapse. In addition, local semiconductor laser irradiation 1 patient. Four patients presented severe ptosis combined
can promote cell metabolism and wound healing and ac- with weakness in opening their eyes, ocular pain, and skin
celerate revascularization. Patients with oral ulcer should numbness. Moreover, 2 patients presented ocular motility
eat liquid food and gargle soon after meals. disorders, but they had no visual impairment.

RESULTS
Percutaneous Facial or Supratrochlear
Demographics and Clinical Arterial Injection of Hyaluronidase
Manifestations Decreases HA-Induced Vascular
The demographic and clinical characteristics examined in
Embolism
this study are summarized in Table 1. We included 17 pa- All 13 patients receiving facial arterial hyaluronidase injec-
tients with HA filler embolism in this study: 14 women and tion presented a significant reduction in tension of skin le-
3 men (mean age, 32 years). HA filler was most injected sions during or after hyaluronidase injection. Skin necrosis
into the nasolabial folds (41% [7 of 17]), which leads to facial was relieved significantly 3 to 5 days later. The cases with
artery occlusion. The second-ranked area was the frontal oral ulcer experienced a significant relief of oral pain on
(29% [5 of 17]), which leads to supratrochlear artery occlu- the second day after the injection, and the oral ulcer was
sion. All 17 patients had skin necrosis or skin ecchymosis healed in 2 to 4 days. Four patients received benefits from
during or after HA filler injection. Five cases showed skin percutaneous supratrochlear arterial hyaluronidase injec-
necrosis combined with oral ulcer. Black scabs occurred in tion, and the ptosis and ocular motility of all patients were
652 Aesthetic Surgery Journal 42(6)

A B

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C D

Figure 1. The clinical manifestation of this 52-year-old female patient before and after percutaneous facial arterial
hyaluronidase injection. (A) She received 1 mL hyaluronic acid filler injections into the right nasolabial folds for cosmetic
treatment accompanied by skin swelling and necrosis for 2 days. (B) She received 2 percutaneous facial arterial injections of
1500 units hyaluronidase. Recovery of facial skin damage (C) 3 days later and (D) 6 months later.

completely relieved. These patients were followed up for 3 IU hyaluronidase (Figure 1B). The swelling and pain were
to 12 months, with an average follow-up of 5 months. The significantly relieved 1 day later. The skin necrosis was sig-
skin necrosis of 16 patients was completely healed and 1 nificantly relieved 3 days later (Figure 1C). The patient was
patient had only small, superficial scars remaining. discharged from hospital after 1 week of treatment, and
These results suggest that percutaneous facial or the reexamination showed that the skin necrosis was com-
supratrochlear arterial injection of hyaluronidase con- pletely healed 6 months later (Figure 1D).
tributes to the recovery of HA filler-induced vascular Patient II (26-year-old female) received forehead aug-
complications. This therapy significantly alleviated skin mentation with approximately 0.8 mL of HA filler. Her left
necrosis, skin ecchymosis, and ptosis. Furthermore, eye presented a complete ptosis combined with cor-
this therapy nearly restored the patients’ appearance neal and conjunctival hyperemia, ocular pain, and con-
to normal, leaving only small and superficial scars in a junctival edema for 2 days (Figure 2A). The patient had
few patients. The amelioration of these complications a skin necrosis, and the affected area was along the left
provided an almost normal appearance for the patients, supratrochlear artery course from the frontal to the gla-
which was of great importance for their psychological bellar area. The fundus photogram and optical coherence
rehabilitation. tomography revealed a healthy retina (Figure 2B) and
macula (Figure 2C) in her left eye. The patient received 2
percutaneous supratrochlear arterial injections of 1500 IU
Report of 2 Cases hyaluronidase in addition to general treatment (Figure 2D).
Patient I (52-year-old female) presented skin necrosis The ocular issues of the patient significantly improved fol-
for 2 days after an injection with 1 mL HA filler into her lowing hyaluronidase injection. Similarly, the ptosis of the
right nasolabial folds (Figure 1A). The patient had a fa- eyelid was significantly relieved 1 day later. Facial skin pain
cial skin necrosis along the right facial artery course from was no longer obvious 3 days later (Figure 2E). The patient
nasolabial sulcus, nasal dorsum to the glabella, and re- was discharged from hospital after 10 days of treatment,
ceived 2 percutaneous facial arterial injections of 1500 and her ocular motility improved to varying degrees. The
Zheng et al653

A B

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C D

E F

Figure 2. The clinical manifestation of this 26-year-old female patient before and after percutaneous supratrochlear arterial
hyaluronidase injection. (A) Clinical manifestations of the patient upon admission. (B) Color fundus photograph of the left
eye. (C) Ocular coherence tomography of the left eye. (D) Two percutaneous supratrochlear arterial injections of 1500 units
hyaluronidase. (E) Recovery of facial skin damage and ptosis after the second injection. (F) Recovery of facial skin damage and
ptosis at the time of discharge.

skin lesion and the conjunctival edema were significantly include skin necrosis, eye and eyelid movement disorders,
relieved (Figure 2F). blindness, cerebral embolism, and even death.13,14
In clinical practice, for patients with local skin ne-
crosis but without obvious visual impairment, hot appli-
DISCUSSION cation, vasodilators and glucocorticoid pulse therapy,
hyperbaric oxygen treatment, and subcutaneous injec-
HA filler facial injection is an increasingly common cos- tion of hyaluronidase were often applied.15,16 These treat-
metic procedure for noninvasive facial rejuvenation be- ments, however, have limited scope and poor efficacy.17
cause it is purported to be safe. However, because of the Furthermore, the long courses of treatment easily cause
multiple anastomoses between the vascular supply of wound infection and leave severe scars or pigmentation.
the face and orbit, potential risks for vascular embolism Our previous results indicated that intraarterial thromb-
do exist. HA filler-induced serious vascular complications olysis therapy was beneficial to patients suffering from
654 Aesthetic Surgery Journal 42(6)

blindness induced by HA embolism.18 However, this tech- alleviating the symptoms of tissue ischemia and necrosis.
nique demands an interventional facility and sophisti- Early utilization of neurotrophic drugs is an effective way to
cated skills, and thus is not widely available as a rescue protect the injured optic nerve and promote the recovery
treatment. of nervous system function. Anti-inflammation and anti-
HA filler was most injected into the nasolabial folds, allergy treatment could effectively control the inflamma-
the nasal ala, and lips, which are supplied by the branch tory and allergic reaction.
of the facial arteries (lateral nasal artery, upper labial ar- Unfortunately, this study is limited by a small number
tery, or lower labial artery). Inadvertent injection of HA of patients without a control group, because vascular em-
filler into these sites may lead to facial artery occlu- bolism is a rare complication of HA filler injection, and
sion.19,20 The frontal and glabella are also commonly af- the direct intraarterial hyaluronidase injection is our initial
fected areas, which are caused by supratrochlear artery attempt. But it is worth noting that before 2019, the sub-
occlusion.18,21 The typical patterns of skin necrosis in the cutaneous hyaluronidase injection was also our general

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glabellar region have a vertical dimension arising from treatment to reverse HA embolism. But according to our
the medial brow, which corresponded to the course of the approximated statistics, the average healing time of these
supratrochlear arteries.21-23 Furthermore, supratrochlear patients with skin necrosis is approximately 2 weeks.
artery occlusion also leads to ptosis. Therefore, we con- Significantly, the average healing time of the cases with
sidered that hyaluronidase injection via percutaneous fa- the direct intraarterial injection of hyaluronidase is approx-
cial or supratrochlear artery might alleviate embolism and imately 1 week. The average recovery time for ptosis was
recover the blood supply. also shortened from 1 week to 4 days. These data seem to
The facial artery arises in the carotid triangle from the suggest that the direct intraarterial hyaluronidase injection
external carotid artery, above the lingual artery, and passes could accelerate wound healing. The exact answer awaits
obliquely up beneath the digastric and stylohyoid muscles, future studies.
over which it arches to enter a groove on the posterior sur- There is a risk to perform percutaneous facial or
face of the submandibular gland. It then curves upward over supratrochlear arterial hyaluronidase injection, so plastic
the body of the mandible at the antero-inferior angle of the surgeons should have a complete knowledge of the un-
masseter, passes forward and upward across the cheek to derlying facial anatomy. This treatment can be assisted by
the angle of the mouth, and terminates as the angular artery, the color doppler flow imaging and palpation and should
upper lip artery, or lower lip artery.24 The facial arterial pulse be employed with extreme caution. Furthermore, al-
is palpable at the junction of the lower margin of the man- though consensus recommendations for field injection of
dible and the anterior margin of the masseter muscle, and hyaluronidase have been formed, there is no standard of
the diameter is approximately 2.3 mm, which is wider than care for intravascular injection.26 Before intravascular in-
the diameter of the needle (0.57-0.92 mm). Therefore, in- jection of hyaluronidase, we first conduct a skin test to en-
jection should be aimed into the junction. In the 13 patients, sure the patient is not allergic, and then we utilize a high
direct injection of a high concentration of hyaluronidase into concentration of hyaluronidase to make sure that the em-
the facial artery accurately and slowly could rescue the skin bolus is completely dissolved to prevent smaller volumes
necrosis and promote effective hydrolysis of the HA filler. of emboli flowing into other sites of the eye circulation
The supratrochlear artery comes out from the and causing another embolization. We refer to the recom-
supratrochlear hole or the supratrochlear incision, and mended dosage for subcutaneous injection in the manual,
it was approximately straight and close to the inner and and it is also determined by our plastic surgeons based on
upper vertical direction. The artery goes subcutaneously experience. After the injection treatment, it is confirmed to
after the frontal muscle penetration point and is anasto- be safe and effective. We will continue to verify the safety
mosed to the supraorbital artery and frontal branches of of this concentration in future studies and hope that con-
the superficial temporal artery.25 It may be that direct intra- sensus recommendations based on this fact will be formed
vascular hyaluronidase injection into the superficial areas at an early date.
of supratrochlear artery is necessary. The ptosis of 4 other
patients was ultimately relieved after hyaluronidase in-
CONCLUSIONS
jection. The cornea was transparent, and the conjunctival
edema disappeared. The skin necrosis was completely Our study reported that timely percutaneous facial or
healed, leaving only small superficial scars. supratrochlear arterial hyaluronidase injection could re-
Undeniably, percutaneous facial or supratrochlear ar- duce the HA filler-induced vascular complication. Adjuvant
terial hyaluronidase injection is the most important ther- therapies including early hormone shock, neurotrophic
apeutic procedure. However, the general symptomatic drugs, and anti-inflammation and anti-allergy treatment are
therapies are also necessary for patients’ recovery. The necessary. According to our study, we recommend per-
glucocorticoid and dehydrating drugs may contribute to cutaneous facial or supratrochlear arterial hyaluronidase
Zheng et al655

injection as an effective treatment for vascular compli- on intravascular hyaluronic acid embolism in the rabbit ex-
cations caused by HA filler facial injection, which can be perimental model. Aesthet Surg J. 2020;40(3):319-326.
widely available in general medical institutions. 12. Goodman GJ, Clague MD. A rethink on hyaluronidase
injection, intraarterial injection, and blindness: is there
Acknowledgments another option for treatment of retinal artery embolism
caused by intraarterial injection of hyaluronic acid?
Drs Zheng and Fu contributed equally to this work as co-first
Dermatol Surg. 2016;42(4):547-549.
authors.
13. He MS, Shen MM, Huang ZL, et al. Sudden bilateral vision
loss and brain infarction following cosmetic hyaluronic acid
Disclosures injection. JAMA Ophthalmology. 2013;131(9):1234-1235.
The authors declared no potential conflicts of interest with re- 14. Woodward J, Khan T, Martin J. Facial filler complications.
spect to the research, authorship, and publication of this article. Facial Plast Surg Clin North Am. 2015;23(4):447-458.
15. Glaich AS, Cohen JL, Goldberg LH. Injection necrosis of

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Funding the glabella: protocol for prevention and treatment after
The authors received no financial support for the research, use of dermal fillers. Dermatol Surg. 2006;32(2):276-281.
authorship, and publication of this article. 16. Dufly DM. Complications of fillers: overview. Dermatol
Surg. 2005;31(11):1626-1633.
17. Rzany B, Becker WP, Bachmann F, et al. Hyaluronidase
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