Anatomic danger zones for facial injection of soft tissue fillers

INTRODUCTION — Complications associated with the injection of soft tissue fillers arise in most cases from injector inexperience or use of unapproved products. However, injection injuries to relevant anatomic structures, such as nerves and vessels, can occur even in the hands of experienced injectors while using US Food and Drug Administration (FDA)-approved products.

The incidence of vascular occlusion following soft tissue injection may be as high as 3 in 1000 [1]. In May 2015, the US FDA warned that the unintentional injection of soft tissue fillers into the blood vessels of the face can result in rare, but serious, adverse effects and advised providers without appropriate training or experience to refrain from injecting soft tissue fillers [2].

This topic will review the relevant vascular anatomy of the face and the danger zones at risk of vascular compromise from injection of soft tissue fillers. The types and clinical use of injectable soft tissue fillers are discussed separately. The anatomic danger zones for cutaneous surgery of the head and neck are also reviewed separately.

●(See "Injectable soft tissue fillers: Overview of clinical use".)

●(See "Injectable soft tissue fillers: Temporary agents".)

●(See "Injectable soft tissue fillers: Permanent agents".)

●(See "Anatomic danger zones for nerve injury in cutaneous surgery of the head and neck".)

VASCULAR COMPLICATIONS OF INJECTABLE FILLERS — Rare, but serious, complications following facial treatment with soft tissue fillers result from the accidental intravascular injection of filler material. Despite the fact that vessel diameter decreases as they travel more superficially, 30 or 27 gauge needles, which are usually provided in the manufacturer packaging of injectable fillers, can easily enter and occlude small vessels even in a very superficial location.

Acute arterial occlusion results in most cases in local and/or distant cutaneous ischemic necrosis (picture 1), which may be irreversible and lead to scarring and disfigurement [1,3,4]. In extremely rare instances, when the filler material has traveled retrogradely through the blood vessels exiting the periorbital area to the ophthalmic and/or retinal artery, embolic blindness and stroke may occur [5].

While unintentional injections into blood vessels may occur at any injection site on the face, certain injection locations at increased risk of arterial occlusion have been identified, based upon a US Food and Drug Administration (FDA) review of the literature and of the adverse event reports submitted to the US FDA [2]. These sites, in which relatively large caliber vessels run superficially, include the skin between the eyebrows and nose (glabella), in and around the nose, forehead, and around the eyes (periorbital region) (figure 1A). A systematic review of the literature identified 190 cases of filler-induced blindness between 2000 and 2018 [6]. The most frequent cause was autologous fat injection (47 percent), followed by hyaluronic acid (28 percent). The injection sites more frequently associated with this complication were the glabella complex, nose, nasolabial fold, and forehead.

Aesthetic filler injectors must have an in-depth understanding of the facial anatomy to achieve good cosmetic outcomes and avoid complications. The risk of complications should be discussed with the patient preoperatively, and informed written consent should be obtained. (See "Informed procedural consent".)

RISK FACTORS FOR VASCULAR COMPLICATIONS — The risk of vascular complications following the facial injection of soft tissue fillers is influenced by a number of factors, including [5]:

●Site of injection – Deep injection at the site or in the vicinity of named vessels, such as the facial artery and the angular artery (figure 2), carries an increased risk of unintentional intravascular injection. High-risk sites include the nasolabial fold, nose, and glabella, which have rich anastomoses with the internal carotid artery.

●Volume of the injected filler – The injection of large amounts of filler product in a single area, especially if using high pressure, may increase the degree of arterial occlusion.

●Type of filler – Permanent fillers that cannot be dissolved may cause a nonreversible vascular occlusion.

●Needle gauge – Small-gauge sharp needles can enter the lumen of an artery more easily than larger needles. In addition, aspiration of blood through a small needle is unreliable.

●Scarring – Scarring from previous procedures may have modified the local vascular pattern.

UPPER FACE DANGER ZONES — The upper face area includes the forehead and the temporal and upper periorbital regions [7].

Forehead — The supraorbital and supratrochlear arterial branches of the ophthalmic artery and vein and their smaller branches fall in this region (figure 1B). They exit their foramen on the orbital rim and travel cephalically. Their deep origin divides soon into branches that travel much more superficially, such that vessels in the forehead region can be encountered at all injection planes.

The forehead anatomical layers from superficial to deep, included in the classic mnemonic SCALP, consist of the skin, connective tissue, aponeurosis, loose areolar connective tissue, and periosteum. The loose areolar tissue is a relatively avascular plane that lies deep in the forehead and scalp and connects the galea aponeurosis with the underlying periosteum. Revolumizing or reshaping of the forehead is often performed at this deeper level to try to minimize the risk of vascular occlusion.

In most cases, injections of soft tissue fillers in the forehead area are directed at effacing the horizontal lines created by the dynamic activity of the frontalis muscle (figure 1A). The injector should keep in mind that as one travels medially from the midpupillary line, one will encounter the supraorbital artery and the supratrochlear artery and their branches (figure 2). Therefore, even superficial injections may carry the risk of occlusion of the distal branches, resulting in cutaneous necrosis of the forehead and scalp (picture 1). If enough pressure is delivered during injection, a retrograde flow toward the orbit and ophthalmic artery can occur (figure 2), resulting in occlusion of the retinal artery and vision loss.

One cadaveric study examined the frontal branch of the superficial temporal artery (FBSTA), as it supplies blood from the lateral to medial forehead and crosses the temporal crest [8]. The FBSTA was classified into two types, based on the main trunk: Type I FBSTA (90 percent) took a sudden turn once passing through the temporal crest, whereas type II FBSTA (10 percent) barely turned at the temporal crest. A total of 319 arteries passed through the midline in 48 cadaver heads. For all cases, the distance from the supraorbital rim to the FBSTA on the temporal crest was 31.58±8.33 mm. It is important to note that the pattern and branching of the forehead arteries are quite variable. The authors also noted that for the midline forehead, there were many more superficial arteries than deep arteries (292 and 27, respectively). Therefore, one might consider deeper injection in the midline region to try to avoid intra-arterial occlusion. The authors also suggested an entry point for filler injection that is 0.5 cm medial to the temporal crest and approximately 1 cm above the lateral end of the eyebrow or approximately 3 cm above the orbital rim and recommend a 23 or 25 gauge cannula for forehead injections in this area.

Temple region — The temporal fossa is defined by the superior temporal line (anterosuperiorly), the frontal process of the zygomatic bone (anteroinferiorly), and the zygomatic arch (inferiorly). The fossa contains part of the temporalis muscle, the superficial temporal artery and vein, and the auriculotemporal nerve. The anatomical layers from superficial to deep include the skin, subcutaneous layer, superficial fascia, loose areolar tissue, deep temporal fascia, and temporalis muscle (picture 2) [9].

The superficial temporal fascia is a thin, pliable vascular layer tightly adhered to the overlying skin. The plane just above this fascia includes the superficial temporal artery, which is one of the terminal branches of the external carotid artery, and its branches [10]. The deep temporal fascia envelopes the temporal muscle and contains the middle temporal vessels.

The middle temporal vein (MTV) is an important and relatively unknown blood vessel that receives several veins, including the sentinel vein, and traverses the temporal fossa deep to the superficial layer of the deep temporal fascia. It then joins the superficial temporal vein just above the level of the zygomatic arch (figure 3) [11]. Inadvertent injection into the MTV may lead to cavernous sinus embolism amongst other complications.

The size and location of the MTV has been investigated in a cadaver study [11]. Based upon their measurements and the course of the MTV, the authors of this study proposed that the safest area for filler injection for temporal fossa augmentation is one finger width above the zygomatic arch (figure 3).

In addition, the temporal (frontal) branch of the facial nerve, the superficial temporal artery and accompanying vessels, as well as the sentinel and middle temporal vein, course in the area of temple augmentation [12]. Injections for temporal fossa augmentation may be performed effectively at different planes, all of which have their own advantages and risks [13]. Of note, there has been reported blindness from temporal injection of soft tissue fillers.

●A commonly chosen plane is the immediate subcutaneous plane, although there is a risk of injecting into the more superficial branches of the temporal artery.

●The loose areolar tissue plane, which is relatively avascular and lies between the superficial fascia and the deep temporal fascia, can be difficult to identify accurately. However, this may be an area where the MTV may be encountered.

●Another plane that is frequently chosen is the supraperiosteal plane, deep to the temporalis muscle and above the periosteum. It is important to note that the deep temporal arteries and veins lie just beneath the temporalis muscle.

Periorbital area — The zygomaticotemporal and zygomaticofacial arteries as well as the middle and lateral palpebral arteries that connect to the ophthalmic branch of the internal carotid artery system lie in this area.

Periorbital augmentation involves brow and upper eyelid injections. An attempt to lift the brow is often performed by injecting the filler beneath the orbicularis oculi along the supraorbital rim in the area of the retro-orbicularis oculi fat (picture 3). Care should be taken with these deep injections as one approaches medially the supraorbital and supratrochlear neurovascular bundles exiting their respective foramens. In addition, the retro-orbicularis oculi fat is the deep fat compartment that gives shape to the brow and upper eyelid above the supratarsal fold [14].

By contrast, injections to augment the superior sulcus of the upper eyelid, to address a skeletonized orbit, are often placed below the superior orbital rim, deep to the orbicularis oculi and superficial to the levator aponeurosis. Avoiding the horizontally travelling superior palpebral arteries is critical in this area. In all of these locations, injections carry the risk of vascular compromise as well as direct trauma to the eye globe.

MIDFACE DANGER ZONES — The midface area includes the nose, cheeks, and lower periorbital regions.

Nose — The vascularization of the nose is so rich that any and all injections in all planes carry a higher risk of necrosis than in other areas of the face. Injections of the nasal dorsum are often performed in the supraperiosteal or supraperichondrial plane, as these tend to be relatively avascular planes [15]. Injections for nasal shaping may be performed before or after rhinoplasty. Injections following rhinoplasty may carry a higher risk of necrosis from arterial occlusion due to the presence of scar tissue and reorganized vascular pattern in the area, as well as reduced pliability with volume injection [16].

Accidental injection into the dorsal nasal, lateral nasal and external nasal arteries (figure 1B), and their arcades can lead to skin necrosis and disfigurement; retrograde flow and retinal artery occlusion may result in blindness [5,16].

Cheeks and lower periorbital area — The infraorbital branches of the maxillary artery, the angular artery, the superior labial artery, and septal artery course in the areas of tear trough injection, nasolabial fold augmentation, and lip injection, respectively (figure 1B). The transverse facial artery, a branch of the external carotid artery, travels along the malar and midcheek above the zygomaticus and levator labii muscles to anastomose with the angular artery (figure 1B).

The anatomic layers of the midface, with some exceptions around the lower eyelid, consist of the skin, subcutaneous fat, superficial musculoaponeurotic system (SMAS), deep areolar tissue, and the mimetic muscles. The infraorbital hollow lies just beneath the medial aspect of the eye and is a common target for tissue augmentation. This area can be separated into a lateral and medial component based on the division created by the facial artery (angular artery) and vein (picture 4) located 4 to 6 mm medial to the midpupillary line [17].

The lateral aspect of the infraorbital hollow contains seven different identifiable layers (ie, skin, subcutaneous fat, orbicularis oculi, suborbicularis oculi fat, deep fascia, preperiosteal fat, and periosteum) (picture 5). The medial aspect is reduced to two layers: skin and orbicularis oculi muscle, which is attached to the bone in this medial location [18]. Medial injections are thus often submuscular as there is no subcutaneous fat plane for injection.

The cheek and the infraorbital hollow are generally highly vascularized areas due to the connection of multiple large named vessels, including the angular, the transverse facial, and the infraorbital arteries and their branches [19]. Since the angular artery anastomoses with the ophthalmic artery, the accidental injection into the angular artery while injecting the melolabial folds may result in retinal artery occlusion and blindness [4].

Injections in the upper midface (ie, upper cheek and tear trough) are usually performed in the supraperiosteal plane or deep subcutaneous plane, whereas the lower midface (ie, midcheek) is often injected in the dermis or subcutaneous space. In all of these locations, the underlying anatomy and the course of named vessels and their branches should be recognized and avoided.

In one cadaveric study examining the lumen of the facial artery after the branching of the superior labial artery, the mean lumen diameter was largest at the midpoint between the oral commissure and the lateral supra-alar crease (0.81±0.36 mm) and smallest at the midpoint between the lateral supra-alar crease and the medial canthus (0.43±0.23 mm) [20]. Mean cutaneous depth was greatest at the lateral supra-alar crease (5.06±1.84 mm) and most superficial at the midpoint between the lateral supra-alar crease and the medial canthus (3.13±2.07 mm). The size and depth must be considered when trying to avoid intravascular injections in this area. It is advised to avoid the largest part of the vessel, as it is easiest to enter with a needle or cannula.

In addition, it has been noted that the course of the facial artery varies from one individual to another. One cadaveric study revealed that 47 of 118 cadaveric hemifaces had detoured branching of the facial artery [21]. Two main arterial patterns were identified. In type I (29 of 47 cases), there were both detoured and nasolabial trunks where the facial artery originated, whereas in type II (18 of 47 cases), there was only a detoured trunk. The detoured trunk originated 32±5.3 mm from the midsagittal line, 5±2.8 mm from the occlusion plane, and 5.9±3.5 mm below the skin layer. The inflection of the detoured trunk was located 30±5.6 mm laterally, 26.2±4.4 mm superiorly, and 5.7±2.6 mm deep. The meeting point with the inferior orbital rim plane was located 17.1±3.4 mm laterally, 43.4±3.1 mm superiorly, and 2.8±1.7 mm deep.

LOWER FACE DANGER ZONES — The lower face includes the perioral and mandibular regions. The mental branch of the mandibular artery and vein and accompanying vessels and their course as well as the facial artery and its branches (inferior and superior labial arteries) should be considered when performing lower face injections or lip augmentation.

Perioral region — The facial artery is generally located approximately 3 cm anterior to the angle of the mandible and can be reliably felt pulsating at the anterior border of the clenched masseter muscle (figure 1B). This is the major arterial supply to the lower face and gives off the inferior and superior labial arteries as it courses toward the lateral aspect of the nose, where it becomes the angular artery and anastomoses with the infraorbital and dorsal nasal arteries (picture 6). The anastomoses in this area around the nose allow for communication between the external carotid system via the angular artery and the internal carotid system via branches of the ophthalmic artery.

While performing lip augmentation and effacement of vertical lip rhytides, as well as augmentation of the nasolabial area, it is important to avoid the superior labial artery, which runs deep in the lip mucosa and supplies also the septal branch to the nasal area, as well as the columellar branch of the nose [15].

A cadaveric study examining the ideal injection plane for lips revealed that the arterial supply of the lips shows marked anatomical variations among individuals and even between the two sides of the face in the same individual [22]. The dissections revealed a "safe area" for filler injections in the submucosal plane 3 to 4 mm above the vermilion-mucosa junction of the upper lip and 3 to 5 mm below the vermilion-mucosa junction of the lower lip.

In another cadaveric study, the author looked at the lumen size of the superior labial artery [23]. They reported that lumen diameter of the superior labial artery was largest at the labial commissure (0.85±0.34 mm) and smallest at the midline (0.56±0.21 mm). The greatest mean cutaneous depth of the superior labial artery was at its branch point from the facial artery (5.49±1.95 mm), whereas the most superficial mean cutaneous depth was at the midpoint between the labial commissure and peak of Cupid's bow (4.29±1.54 mm).

The mental artery as well as the labii inferioris branch of the facial artery are the two major vessels to avoid while injecting the lower perioral area (picture 7).

Jowl correction — Injections in the mandibular area for jowl correction are often performed deep along the periosteum of the mandibular line as well as at the mandibular ramus. In the mandibular region lies the large, square-shaped masseter muscle with its deep and superficial portions; the facial artery at its anterior border should be recognized and avoided. The facial artery appears approximately 3 cm anterior to the mandibular angle and can be felt pulsating at the anterior border of the masseter with a clenched jaw (picture 6 and figure 1B).

The parotid gland is also located at posterior edge of the masseter muscle, and the anterior border may cover part of the buccinator muscle. The parotid gland duct (Stensen duct) arises from the anterior portion of the gland and at the anterior border of the masseter and penetrates the buccinator muscle to enter the oral cavity (picture 8) [24]. Injury to the Stensen duct by laceration with a needle may lead to a sialocele with or without cutaneous fistula formation.

Injections of the prejowl sulcus are frequently performed along the mandibular line, the area along the bony edge of the mandible between the chin and the angle of the jaw. The layers in this area include the skin, superficial fat compartment, fibers of the platysma muscle, deep fat compartment, periosteum, and bone [25]. The jowl occurs posterior to the mandibular ligament and injections are often performed anteriorly to the ligament and in its vicinity. Although the deep supraperiosteal plane may provide some protection from accidental arterial penetration, the clinician should be aware of the high vascularity of this area, due to the course of the inferior labial artery, the mental and submental arteries, and their anastomoses (figure 1B).

STEPS TO MINIMIZE RISKS

General principles — For the clinician using injectable fillers, the first and most important step to minimize the risks associated with facial injections is to achieve an in-depth understanding of the vascular anatomy of the face and adequate training. A detailed awareness of the position and depth of named vessels in the treatment area is crucial to determine the appropriate site and plane of injection [26].

Along with understanding the relevant anatomy, using blunt-tipped cannulas rather than needles is an additional measure to reduce the risk of accidental penetration of arteries. Most cannulas are designed with a port that is located proximal to the far distal tip and are blunt in design. The location of the port, along with the blunt tip, may create further levels of protection from inadvertent intravascular injection.

In a small, randomized trial comparing blunt-tipped cannulas with standard needles for injection into nasolabial folds, participants reported fewer complications (pain, edema, hematoma, and redness) on the side injected with the cannula than on the side injected with the standard needle [27]. However, there are reports of accidental arterial penetration using blunt-tipped cannulas [28].

US Food and Drug Administration recommendations — The following is the US Food and Drug Administration (FDA) summary of recommendations to avoid complications while injecting facial fillers [29]:

●Do not inject soft tissue fillers if you do not have the appropriate training or experience.

●Make sure that you are familiar with the anatomy at and around the site of injection, keeping in mind that blood vessel anatomy can vary among patients [30].

●Before injection, thoroughly inform the patient of all risks of the procedure and the specific product you intend to use.

●Note that the approved indications for use of soft tissue fillers vary depending on the product. The US FDA may not have reviewed use of soft tissue fillers in some locations in the body [31].

●Take extra care when injecting soft tissue fillers; for example, inject the product slowly and apply the least amount of pressure necessary.

●Know the signs and symptoms associated with injection into blood vessels and have an updated plan detailing how to treat the patient if this should occur [16]. This may include on-site treatment and/or immediate referral to another health care provider for treatment.

●Stop immediately the injection if a patient exhibits any signs or symptoms associated with injection into a blood vessel, such as changes in vision, signs of a stroke, white appearance (blanching) of the skin, or unusual pain during or shortly after the procedure. (See "Injectable soft tissue fillers: Overview of clinical use", section on 'Early adverse effects'.)

●Tell patients that they should seek immediate medical attention after the procedure if they experience signs and symptoms associated with injection into a blood vessel.

●Educate health care facility employees on how to quickly assist patients that report signs and symptoms of filler complications. They must understand how to instruct the patient to receive appropriate medical care.

●Report to the US FDA and the manufacturer if you become aware of a patient experiencing an adverse event associated with unintentional injection of soft tissue filler into a blood vessel [2].

MANAGEMENT OF VASCULAR COMPROMISE

Recognizing signs and symptoms of vascular occlusion — The first step in the management of vascular occlusion following soft tissue injection is to recognize the signs and symptoms of vascular occlusion. Clinicians should have a plan for on-site treatment and/or immediate referral to another health care provider for treatment.

Usually, an immediate onset of skin blanching will occur during the injection, and this may or may not be associated with significant pain. Of note, because many fillers have lidocaine mixed into the product, pain may be delayed for several hours. The blanching may only last a few minutes and can be followed by a livedo pattern and then by a deep blue or purple discoloration with diminished capillary refill [5,32].

In the event of retinal artery occlusion, ocular pain, vision changes, and blindness will often occur and may present in both or, more commonly, in one eye only. Blindness following filler injection requires immediate attention and may have a low success rate of reversal. A review of the literature found 98 cases of vision changes from fillers [33]. The sites that were reported as high risk for complications were the glabella (39 percent), nasal region (26 percent), nasolabial fold (13 percent), and forehead (12 percent). Autologous fat was the most common filler type to cause this complication (48 percent of cases), followed by hyaluronic acid (24 percent). The most common symptoms were immediate vision loss and pain. Most cases of vision loss did not recover. Central nervous system complications were seen in 24 percent of the cases. No treatments were found to be consistently successful in treating blindness.

Management — Although protocols for the management of vascular complications from filler injection have been published, there is very limited evidence to support their recommendations [34,35]. However, in the event of an occlusion, it is reasonable to stop the injection and use heat and massage to the area to try to increase blood flow.

For hyaluronic acid-based fillers, there is evidence that hyaluronidase injection within four hours may reverse impending necrosis [36,37]. Duplex ultrasonography can help in locating the intra-arterial obstruction and delivering hyaluronidase into the hyaluronic acid deposit [38].

In the author's experience, injecting hyaluronidase directly into the affected vessel as well as the surrounding path of the vessel and its terminal branch may be critical to successful reversal of the impending necrosis. The units of hyaluronidase necessary to reverse hyaluronic acid occlusion have not been determined. Some experts may suggest 300 international units, while others may suggest greater than 1000 international units. It is this author's experience that the number of units should not be predetermined. The end goals are either to bathe the occluded vessel and allow for transmural absorption or to cannulate the vessel directly. In situations of impending necrosis or blindness, as many attempts as necessary seem appropriate rather than limit the number of units arbitrarily. In the event of impending blindness, some authors have suggested attempting to directly cannulate the supratrochlear and or supraorbital arteries to reach the retinal artery [39]. Cadaver studies have shown that the supraorbital and supratrochlear arteries can be cannulated and support this approach to retinal artery occlusion [40].

Other proposed treatments include prostaglandin E1 [41,42], nitroglycerin ointment and hyperbaric oxygen [43,44], aspirin, sildenafil, and prednisone [34]. However, their efficacy remains unproven.

SUMMARY AND RECOMMENDATIONS

●Vascular complications of soft filler injection – Rare, but serious, complications following facial treatment with soft tissue fillers result from the accidental intra-arterial injection of filler material. Acute vascular occlusion may result in local or distant cutaneous necrosis (picture 1) and scarring or, in worst cases, blindness or stroke. (See 'Vascular complications of injectable fillers' above.)

●Facial areas at increased risk of vascular complications – Areas at increased risk of vascular compromise from compression or obstruction of blood vessels include the glabella (supratrochlear artery), the periorbital region (angular artery, supratrochlear artery), and the nasolabial folds (angular artery) (figure 1A-B). (See 'Forehead' above and 'Cheeks and lower periorbital area' above.)

●Minimizing risks – In-depth understanding of the vascular anatomy of the face and adequate training are of utmost importance for clinicians using injectable fillers. Utilizing blunt-tipped cannulas rather than needles may be helpful. (See 'Steps to minimize risks' above.)

●Management – Clinicians should be able to recognize the early signs and symptoms associated with vascular occlusion (eg, immediate blanching of the skin, purple discoloration, ocular pain, vision changes) and have a plan for on-site treatment and/or immediate referral to another health care provider for treatment. For hyaluronic acid-based fillers, there is evidence that hyaluronidase injection within four hours may reverse impending necrosis. (See 'Management' above.)