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Year : 2022  |  Volume : 67  |  Issue : 2  |  Page : 204
Detection of the safe zone for upper eyelid hyaluronic acid injections

From the Department of Plastic Reconstructive and Aesthetic Surgery, Balıkesir University, Turkey

Date of Web Publication13-Jul-2022

Correspondence Address:
Bilgen Can
ÇağışCompaund, Bigadiç Street - 10145, Balıkesir
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijd.ijd_787_21

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Background: Hyaluronic acid (HA) injections for upper eyelid volumisation are safe procedures with short downtime and low complication rates. Nevertheless, the upper eyelid is a high-risk area for vascular complications because of its rich vascular network. After injection, bruising, an indicator of vascular penetration, develops very often and prolongs the short downtime. Aims: To describe a pain-controlled withdrawal technique for minimizing vascular complications and to examine the effects of topical anaesthesia administered prior to injection on complications related to vascular penetration. Methods: HA was injected into the upper eyelids of 25 patients using the pain-controlled withdrawal technique without topical anaesthesia. The patients' median age, complication rates, average amount of HA administered, and follow-up periods were evaluated. In addition, the patients were asked to evaluate their pain during injection using a numerical pain rating scale. Results: The patients' mean age was 40.4 ± 7.3 years. Minimal eyelid edema developed in all patients but did not prevent any of the patients' social activities. No bruising was detected in any of the patients, and no major vascular complications, such as blindness or cerebrovascular events, developed. The average amount of HA administered was 1.43 ± 0.45 cc. All patients evaluated their pain during injection as mild. Conclusions: With the pain-controlled withdrawal technique, none of the patients had minor or major complications due to vascular penetration. The procedure was well tolerated by the patients. The detection of the safe injection zone allowed the administration of more than the standard/accepted 01 cc HA (up to 0.3 cc) from one point.

Keywords: Bruising, deep superior sulcus deformity, injection, vascular complications technique

How to cite this article:
Can B, BetülGözel. Detection of the safe zone for upper eyelid hyaluronic acid injections. Indian J Dermatol 2022;67:204

How to cite this URL:
Can B, BetülGözel. Detection of the safe zone for upper eyelid hyaluronic acid injections. Indian J Dermatol [serial online] 2022 [cited 2022 Aug 9];67:204. Available from:

   Introduction Top

Loss of upper eyelid fullness due to various reasons causes skeletonisation of the orbit and deep and superior placement of the supratarsal fold. This deterioration, called 'sunken eye deformity', 'upper eyelid hollowing' or 'deep superior sulcus deformity', creates an old, tired facial expression.[1]

Hyaluronic acid (HA) filler injections are safe, have a short downtime, are low-cost and are practical for the restoration of upper eyelid fullness.[2] However, due to its rich vascularity, the upper eyelid is a high-risk area for complications related to vascular penetration.[3] Being close to the ophthalmic artery also increases the risk of blindness when an accidental-intravascular-injection-induced embolism reaches the ophthalmic artery easily.[4] Only one case of blindness developed after HA injection in the upper eyelid has been reported in the literature.[5] However, in most clinical studies, bruising indicating vascular penetration has been reported as the most common complication.[2],[6],[7],[8],[9]

Clinical and experimental studies aiming to increase injection safety have focused on the arterial anatomy of the upper eyelid.[3],[10],[11],[12] In relevant studies, the arterial topography of the upper eyelid has been established. However, the rich vascularity of the eyelid and the frequent appearance of vascular anatomic variations make it impossible to determine the precise localization of vascular structures without using any imaging method during the injection.

Arteries and nerves travel in the neurovascular bundle with proximity in the upper eyelid, and there are perivascular nociceptors around the small arterioles that can perceive the mechanical and chemical changes around the vessel. Preservation of this sensorial innervation around the vessel may enable the prediction of vessel localization in cooperation with the patient during injection. For this purpose, we described our injection technique called pain-controlled withdrawal technique, which we administered without using topical anaesthesia, and discussed the effects of topical anaesthesia on vascular complications.

   Patients and Methods Top

Approval was obtained from the Ethics Committee for this study. A total of 25 patients who received HA injection in the upper eyelid were examined in terms of age, complication rate, total amount of HA injected per patient and follow-up period. Data analysis was performed using IBM SPSS Statistics version 25.0 software (IBM Corporation, Armonk, NY, USA). Data are expressed as mean ± SD or median (min–max), where appropriate. In addition, the patients were informed about the technique before the administration and were asked to score the pain felt during skin penetration with a gauge-30 needle. A numerical pain rating scale was used for the pain scoring. Written and verbal informed consents were obtained from all participants.

Relevant anatomy

The upper eyelid exhibited rich vascularity, originating from the internal carotideal system and the external carotideal system. The supratrochlear and supraorbital arteries, which are the terminal branches of the ophthalmic artery, are located in the superomedial orbit, which is often called the 'danger zone' for upper eyelid filler injections.[3] These two arteries form the pathway for filler embolisms caused by inadvertent intravascular injections to reach the central retinal artery, which feeds the globe. The central retinal artery is the branch of the ophthalmic artery before it splits into the supraorbital and supratrochlear branches [Figure 1]. The link between the internal carotideal system and the external carotideal system is formed by the anastomoses between the medial palpebral and dorsal nasal branches of the ophthalmic artery and the branches that originate from the angular artery, which forms the terminal branch of the fasial artery, in the medial orbit. In the lateral orbit, this link is formed by the lateral palpebral branches of the ophthalmic artery from the internal carotideal system and the branches of the superficial temporal artery to the upper eyelid from the external carotideal system. This rich vascular network constitutes two arcades in the upper eyelid; the marginal arcade lies in the pretarsal space, 2 to 3 mm from the eyelid margin, while the peripheral arcade is located at the superior margin of the tarsus within the Müller's muscle.[13] Therefore, the preperiosteal space is relatively avascular and provides a plane for filler injections. Although injections in the superomedial orbit have the highest risk for complications related to inadvertent intravascular injection, embolism can occur anywhere in the eyelid and may reach the ophthalmic artery and the internal carotid system through these anastomoses between the external and internal carotid system.[10] In addition, the intense vascular density of the upper eyelid increases the risk of vascular penetration during injection. Despite the strong knowledge of the vascular anatomy, anatomic variations are common, which can make it difficult to determine the exact location of the vasculature and avoid it.
Figure 1: The common vascular origin of the arteries which feed the globe and upper eyelid (1) internal carotideal artery, (2) ophthalmic artery (3) optic nerve, (4) central retinal artery, (5) long ciliary arteries, (6) lacrimal artery, (7) palpebral artery, (8) supraorbital artery, (9) supratrochlear artery, (10) dorsal nasal artery, (11) facial artery, (12) angular artery

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Upper eyelid sensory innervation is provided by the ophthalmic branch of the trigeminal nerve. The supratrohlear nerve which is a branch of the ophthalmic nerve innervated the medial and central part of the upper eyelid and palpebral branches of the supraorbital nerve were distributed throughout the central and lateral areas of the upper eyelid.[13] Cutaneous branches of the lacrimal nerve also provided the sensation of the lateral eyelid. In the upper eyelid, sensorial nerves accompanied with the arteries and form a neurovascular bundle.[14]

Injection technique

The first phase of the technique is to ensure patient cooperation by describing the technique beforehand. Then, we used gauge-30, half-inch-length syringe needles with 1-mL injectors to administer low-viscosity HA (molecular weight of 20 mg/dL) to the participants; no topical or local anaesthesia was applied before the procedure.

To perform the pain-controlled withdrawal technique, the area was cleaned with chlorhexidine gluconate prior to the procedure, and the patients were seated in a reclining chair positioned at approximately 70°. The assistant was asked to apply traction to the eyebrow on the side to be treated toward the cephalic side as much as possible for equal elevation medially, in the middle, and laterally [Figure 2]. With this manoeuvre, depressed areas in the superior orbital rim were exposed. The middle part of the depressed area was selected as the target for filling, and the injector was inclined at 40° to reach the supraperiosteal plane. The patient was then asked to indicate if a sharp pain sensation occurred when the needle was slowly pushed to the depth of the first few millimeters. The feeling of pain with nerve contact can be easily perceived in patients with even high pain thresholds. The needle was then stopped in the first few millimeters, and if no pain was reported, the needle was advanced from the lateral to the medial side in the middle of the target area, with an injector inclination of 40° [Figure 3]. The needle was stopped in the plane between the muscle and bone, and at a time 0.1 to 0.3 cc of the filler was injected into this area by pulling back the injector stopper. Initially, a filler nodule was created, but it was spread over the area with finger pressure (push/scatter) applied to this point [Figure 4]. The other depressed areas were filled similarly. Usually, 3 to 4 entry points are required depending on the deformity. The eyebrow was released to its normal position, and the area was checked after each injection [Figure 5]. When pain was reported, the presence of pain was evaluated again by entering a few millimeters from the cephalic, inferior, or lateral side.
Figure 2: The figure shows the manoeuvre revealing the supraorbital rim

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Figure 3: The figure shows that the injector advanced into the supraperiosteal plane. In order to determine vascular localization, we checked the patient regarding pain while injecting

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Figure 4: The figure shows the hyaluronic acid nodule that was visible after hyaluronic acid injection (02 cc). Finger compression was used for spreading

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Figure 5: The right upper eyelid was filled with 06 cc hyaluronic acid. Comparison with left upper eyelid

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   Results Top

The study population consisted of 25 female patients with an age range of 30 to 55 years. The mean amount of HA per patient was 1.43 ± 0.45 cc. No minor complications, such as bruising, severe swelling, and hyperemia, or major complications, such as blindness, skin necrosis, and cerebrovascular events, occurred. The median follow-up period was 14 months, and the longest follow-up period was 24 months. Minimal edema developed in all patients but did not interfere with daily activities. No revision was required regarding the follow-up period of the patients [Figure 6] and [Figure 7]. Dermographic and clinical characteristics of the patients are summarized in [Table 1]. The procedure was well tolerated by all patients, and the pain felt during the penetration of the syringe needle into the skin was expressed as mild in all patients.
Figure 6: (a) Figure shows a 46-year-old patient with deep superior sulcus deformity, (b) upper eyelids were filled with 1 cc hyaluronic acid

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Figure 7: (a) Figure shows a 40-year-old patient with deep sulcus deformity, (b) just after upper eyelids were filled with 1.5 cc hyaluronic acid

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Table 1: Demographic and clinical characteristics of cases

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   Discussion Top

Upper eyelid fullness is essential for a healthy and youthful appearance. Reduced periorbital soft tissues due to ageing, previous fat-reducing blepharoplasty operations, and trauma may cause denudation of the orbit. This situation may occur in young patients with underdeveloped periorbital soft tissues and a distinct frontal prominence because of congenital reasons, resulting in an older, tired, and sickly appearance.[1]

HA injections have been used for upper eyelid volumization since 2009.[6] Since then, it has become increasingly popular as it is safe, has a short downtime, is low cost, and is an office-based procedure for this complex deformity. However, recent reports on life-altering complications with hyaluronic injections, such as skin necrosis, blindness, and cerebrovascular events, have raised concerns regarding the safety of office-based practical solutions.[15]

Filler embolism caused by accidental intravascular injection may occlude skin perforators and cause skin necrosis if the embolism travels in an antegrade fashion.[11] In this case, the patient will experience proportional pain at the injection site, and the injector observes the skin bleaching following vascular tracing. Immediate hyaluronidase injection in the area of filler, application of warm compresses, and administration of aspirin tablets and nitroglycerin ointments or patches are recommended.[16] If embolisms travel in a retrograde fashion, visual loss, ophthalmoplejia, and/or ptosis may develop, depending on which branches of the ophthalmic artery are occluded.[17] Mental status changes and stroke may develop if the embolism travels more proximally in the carotideal system and occlude the vertebral arteries.[18] The consensus gathered in 2019 presented a guideline for the acute treatment of vision loss resulting from filler injections.[19] Accordingly, high-dose hyaluronidase (1500 ıu) should be administered at the medial supraorbital margin where the supratrochlear and supraorbital arteries are located. Retrobulbar injection of hyaluronidase is also suggested if the injector has the required expertise. Treatment with intraocular pressure-lowering agents, such as acetazolamide and mannitol, may also be used before transferring the patient to a specialized eye centre. Intravenous methylprednisolone, rebreathing the patient in a paper bag or carbogen to ensure vasodilatation in the central retinal artery, sublingual glycerol trinitrate, and ocular massage are other suggested bedside treatments. Simultaneously, the transfer of the patient to a specialized eye centre must be organized. Despite all these treatments, although various degrees of improvement have been reported in ophthalmoplegia and ptosis, visual loss is irreversible in reported cases; therefore, preventative measures are essential.[20]

The fact that the upper eyelid is considered a high-risk area for the aforementioned life-altering complications because of rich vascularity mostly coming from the internal carotid system and is fed by the same main artery with the globe, safe injection in the upper eyelids can be challenging and requires additional measurements.[4],[15],[21]

Studies conducted on the prevention of vascular complications have focused on upper eyelid vascular anatomy.[3],[10],[11],[12] However, it is impossible to determine the precise localization of the vascular structure during injection due to the intense vascularity and the frequent appearance of anatomical variations.[3]

In this study, the neurosensory innervation of the eyelid was regarded as a guide for determining vascular localization. Upper eyelid HA injections normally do not cause pain as they are performed in the supraperiosteal plane.[22] The patient feels pain only if the injector is in the vicinity of the vessel or nerve, or if these structures are breached. The supratrochlear and supraorbital nerves in the upper eyelid bundle are located around the supratrochlear and supraorbital vascular structures.[14] This proximity can be regarded as a guide for determining vascular localization by means of the pain felt, so long as the sensorial innervation is preserved. The injection is avoided when the patient feels pain, with the painful area considered as an unsafe area containing vascular structures. The probability of penetration is reduced by changing the injection localization.

Furthermore, free nerve endings called 'nociceptors' located around the small vessels enable the mechanical and chemical changes that occur in the vicinity of the vessels to be perceived as pain.[23] Preservation of the sensory innervation of the eyelid also causes the patient to feel pain when the injector is in the vicinity of the small vessels. As a safe zone was determined, up to 0.3 cc of HA was injected while withdrawing the injector within this zone. Administering HA up to 0.3 cc in the safe injection zone allowed sufficient volumization using two to three entry points. Using fewer entry points during the procedure also decreased the risk of vascular penetration.

In the relevant studies, a topical eutectic mixture of local anaesthetics (EMLA) cream was applied for 20 to 60 min before the procedure.[2],[7],[9],[24] These studies indicated that topical anaesthesia was applied to prevent pain caused by the penetration of the syringe needle into the skin. Occlusion studies conducted with EMLA cream have also demonstrated that when EMLA is applied to 3.30-mm-thick skin, it provides 3.11-mm-deep analgesia within 60 min.[25] It has been reported that the drug penetration and depth of analgesia increase as skin thickness decreases. The upper eyelid has been reported to be 1.27 microns in the subbrow area, which is the thickest part of the eyelid.[26] The supraorbital and supratrochlear nerves, which provide sensorial innervation of the upper eyelid, have an approximate distance of 2.8 mm from the skin.[12] Thus, it is likely that topical anaesthesia can provide analgesia in the supraperiosteal plane, which is used for HA injections in the upper eyelid. This indicates that pain cannot be used as a guide for determining vascular localization and avoiding vascular penetration. Studies in which EMLA was used before injection[2],[7],[9],[24] indicated that the procedure was well tolerated by all patients, yet bruising was identified as the most common complication. Therefore, patients who developed bruising may not have felt any pain during injection because of loss of sensory innervation, even if vascular penetration injury occurred.

In studies applying topical anaesthesia before injection, gauge-30 needles were used for injection.[2],[7],[9] In this study, injections were performed with gauge-30 injectors, and the patients were asked to rate the penetration pain they felt. All patients rated the pain as mild, demonstrating that injection without topical anaesthesia can be tolerable, given the fact that it is useful for preventing vascular complications.

Injection without local anaesthesia has another benefit, apart from the use of sensory innervation in determining a safe injection zone. Studies conducted with EMLA cream demonstrated that the skin has a biphasic vascular response to the EMLA.[27] Vasoconstriction that occurs in the administration area in the first 0.5 to 1.5 h of the application is followed by vasodilation. Nevertheless, EMLA may have a faster effect in cases where the epidermal thickness decreases and penetration increases.[25],[28] The thin structure of the eyelid results in both increased penetration depth and accelerated effect; as such, 30- to 60-min applications may induce vasodilation. In this study, topical anaesthesia was not used; thus, vasodilation was prevented. Vasodilation caused by topical anaesthesia may also affect vascular penetration-based bruise occurrence as the most common complication.

It has been reported that HA with a higher molecular weight and viscosity provides a better volumetric augmentation for deep facial injections, and products with low molecular weight should be preferred for superficial subcutaneous injections.[29] However, this study indicates that it is safer to use low-viscosity and low-molecular-weight HA, even if the injection is performed in the deep supraperiosteal plane in the upper eyelid. Performing injections in this area using thin cannulas or syringe needles and high-viscosity products increases the injection pressure. The literature includes many studies that have used low- and high-viscosity products.[8],[13],[30] HA with low viscosity and low molecular weight was used in this study, which allowed volumetric augmentation with approximately 0.7cc HA in most of the patients. The amount of HA used is similar to that used in other studies conducted with high-viscosity products,[22],[30] indicating that using HA with low viscosity does not make a difference in terms of augmentation. In this regard, it is recommended to use low-viscosity HA to provide controlled injection by reducing the injection pressure, even if the injection plane is deep.

The pain-controlled withdrawal technique requires full patient cooperation, which is a disadvantage in this regard. Accidental intravascular injection may occur if patients do not report the pain that they feel in the deep plane. Thus, the importance of pain felt during the procedure, other than that induced by the penetration of the needle, should be described in detail to the patient before the procedure. The relevant technique may not be applicable to patients with high anxiety and psychological instability, thus preventing full cooperation. Furthermore, this technique is not suitable for patients who have undergone a surgical procedure that may affect eyelid sensation, as the reliability of the technique will decrease. Therefore, the aetiology of an existing sunken eye deformity should be investigated, and this technique should not be used in cases of deformity due to blepharoplasty surgery.

In conclusion, the upper eyelid is a high-risk area for vascular complications that may occur following HA injections. In relevant studies, bruising was reported as the most common complication, indicating vascular penetration. In this study, upper eyelid sensory innervation was preserved to reduce complications from vascular penetration, and pain felt in the perivascular area was used as a guide to determine a safe injection zone. Thus, vasodilation caused by topical anaesthesia was also avoided. No vascular complications occurred in any of the patients in this study. The pain-controlled withdrawal technique can be a safe and well-tolerated technique to avoid vascular complications.


We thank Editage for language editing assistance.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]

  [Table 1]


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