Periorbital Injectables: Understanding and Avoiding Complications

Catherine J Hwang

Department of Ophthalmology, Division of Orbital & Oculofacial Plastic Surgery, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland OH, USA


Periorbital rejuvenation with neurotoxins and dermal fillers address several aging changes. Safe and effective results

require a thorough understanding of periorbital anatomy, proper injection techniques, and complications of these

products. Prompt recognition and treatment of complications can minimize their adverse impacts. Complications

can be divided into ischaemic and non-ischaemic effects. Hylauronidase, an enzyme that degrades hyaluronic acid,

may improve outcomes after intravascular hyaluronic acid fillers.


Periorbital rejuvenation with botulinum toxin and dermal fillers is increasingly used to address the changes associated with aging. Understanding the periorbital  anatomy, proper injection techniques and complications that can arise are important for every injector of this delicate area. However, even in the most skilled injectors, complications can arise and education, recognition and early treatment are of utmost importance.


Understanding the underlying anatomy and aging changes of the periorbital presents a critical component to successful rejuvenation of the periorbital region.[1] A detailed description of anatomy is beyond the scope of this article, but understanding the soft tissue, vascular and bony anatomy is crucial for successful rejuvenation in the periorbital area. The periorbital region is one of the most dynamic and unforgiving in relation to volume enhancements. The eyelid skin is the thinnest in the body that lacks subcutaneous fat and is a dynamic structure. Irregularities are more readily apparent in this area than other areas of the face. Understanding the complex periorbital anatomy is important to help avoid potential complications.

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Maximizing the result of full face volumization – Cecile Winter (timeline: 00:33:25)

Dr. Cecile Winter talks in-depth about facial anatomy, before beginning with the upper third of the face. Dr. Cecile Winter notes that the patient has some glabellar lines as well as a deflated temple region, so she begins by injecting small amounts of HA filler to reduce hollowness and lift the lateral part of the eyebrow.


Both botulinum toxin and dermal fillers have been widely used to address periorbital aging. Complications arising from botulinum toxin injections are usually transient and related to its effect on the affected muscles. Most patients with complications arising from botulinum toxin injections can be treated supportively with ocular drops and referral to an ophthalmologist or oculoplastic surgeon may be considered. Complications from dermal fillers are more varied and will be the main focus of this article. The classification of filler complications can be divided into early or late or into non‑ischaemic and ischaemic complications.[2,3] In this article, the latter classification will be used.

Dermal fillers have been used effectively in the periorbital area for over 20 years.[4,5] Various dermal fillers are available; however, in the periorbital area, the reversible and temporary hyaluronic acid (HA) fillers are preferred [Table 1]. Proper selection and placement of product can help avoid some complications.[5,6] The use of permanent, non‑reversible fillers are discouraged in the periorbital area as this area is constantly changing and complications with these fillers can be difficult to address. This article will mainly focus on non‑ischaemic and ischaemic complications associated with HA fillers. Of note, when injecting HA fillers, hyaluronidase should be available.


Non‑ischaemic complications include contour irregularities, bluish‑discoloration or Tyndall effect, inflammatory reactions, and infection/biofilm formation [Figure 1]. Transient oedema and bruising are expected after any periorbital injection and can be minimised by avoiding blood thinners 2 weeks prior to injection, applying numbing cream with a vasoconstrictor such as epinephrine prior to injection and the use of cool compresses after injection.

Figure 1: (a) Tyndall effect, (b) contour irregularity, (c) persistent oedema, (d) inflammation/granuloma

To help avoid contour irregularities, injections below the orbicularis or in the pre‑periosteal plane will help to allow more coverage of the filler product. In addition, placement of small amounts of filler product, in a cross‑hatched pattern or small amounts on the periosteum may be helpful.[5] To help avoid persistent oedema after HA fillers, it is important to note those patients that are prone to retaining fluid. Patients with fluid around their eyes prior to injection may not be ideal candidates for HA fillers and this should be discussed with the patient prior to treatment. If the contour irregularities or oedema does not resolve over time, dissolving the HA filler with hyaluronidase can be performed. In these cases, small amounts of hyaluronidase can be injected to the desired effect, usually around 15–50 IU.[7,8] 

The bluish‑hue or Tyndall effect is commonly seen in lighter thin skinner patients. Sometimes this bluish‑hue cannot be avoided and should be discussed with patients prior to injection. In addition, over time in some cases, there can be anterior migration of hyaluronic acid gel (HAG) filler product, causing more of a bluish hue. In these cases, the bluish‑hue can be addressed with dissolving of the HA filler product with hyaluronidase. 

In patients presenting with inflammatory signs after periorbital filler injection, infection should be highly suspected. True allergic reactions can occur but are less common. To minimise infection, thorough sterilisation of the treatment site should be performed prior to injection. Fillers should be treated as implants as that is what their use is approved as in the United States by the Food and Drug Administration. In those patients with possible infections, treatment with systemic anti‑biotics should be initiated and close follow‑up was performed. After the initial inflammation or infection is treated, hyaluronidase can be used to dissolve the HA filler product. Hyaluronidase is not recommended in cases of active infection because it could spread the infection.[9] In cases of suspected biofilm, more intense anti‑biotic regimens should be considered as well as potential consultation with an infectious disease specialist. Biofilms tend to have more of an indolent inflammation/infection and the causative bacteria can be elusive. Eventually, the HAG filler product should be dissolved. In cases of granuloma formation, the HA filler product can also be dissolved to prevent further foreign body reaction. In patients with a history of inflammatory reactions, further injections with filler products should be made with caution. Very rare complications including the inadvertent globe penetration with filler product has also been reported.[10] Using proper injection technique and being aware of the location of the needle tip at all times can help prevent globe penetration. Only injectors with the understanding  of the periorbital anatomy and its complications should  inject this complex region. 


Ischaemic complications related to filler injections, such  as soft tissue necrosis and visual compromise, can occur  and should be discussed with patients receiving any  filler injection.[11‑13] The incidence of vascular occlusion  has been reported to be up to 3 in 1000 injections.[9]  For HA injections, the incidence of vascular occlusion  may be a bit less at 3–9/10,000 injections.[12] The most  high‑risk areas include the glabellae and nasal area, but  can also occur anywhere arteries run including the lip,  nasolabial fold and temple.[11,13] There are tips to help  prevent accidental intra‑arterial injection of product but  no technique is 100% effective in avoiding ischaemic  complications [Table 2]. Some techniques that can be  useful are using local anaesthetics with epinephrine to  vasoconstrict vessels prior to injection, injecting small  volumes per pass, aspiration prior to injection, using  low injection pressure, avoiding scarred areas and  considering the use of blunt cannulas.[9,11,13] However, remember cannulas can also act similarly to needles,  especially those with smaller calibre and those used in  scarred areas where the vessels are more likely to be  tethered. 

The mechanism of action of filler‑associated ischaemia  is due to direct intra‑arterial injection of product.[14,15]  With injection, it is proposed that the filer product  enters the artery initially in a retrograde fashion then  once the plunger is released, anterograde embolisation  of filler product occurs. Because of this, a larger area  than the injection site along a vascular distribution is  affected. In the periorbital area, the vascular structures  to be aware of include the supraorbital, supratrochlear,  infraorbital and angular arteries. In cases of filler induced  ischaemia, early recognition and treatment is a key in  treating patients. 


Signs of soft tissue ischaemia include whitening or  blanching on injection, pain, mottling, blister formation,  bluish discoloration and later tissue necrosis.[16] Not all of  these signs may be present. The whitening or blanching  may be transient and unnoticed and pain may not be  present as anaesthetics are often concurrently present.  Mottling in the area of a vascular distribution larger  than the injected area is a clue that vascular ischaemia  is occurring [Figure 2]. In cases of blister formation,  ischaemia can be confused with a herpetic infection. In  these cases, it is important to note the location of the  vesicle formation and whether it respects a vascular  distribution. The mottled appearance can then change  

Table 2: Injection techniques to help avoid complications  

Understand periorbital anatomy  

Treat with local anaesthesia with epinephrine to vasoconstrict blood  vessels  Inject small volumes per pass and <0.1 ml in any one area  Keep the tip moving of the injection instrument  Attempt aspiration prior to injection, however, sometimes because of the  length of the needle or nature of the filler product, may not produce a  flashback  Use low injection pressure, do not force injection, especially in areas of  previous scarring, injection, or surgery  Consider the use of blunt cannulas, but remember they do not eliminate  the risk  Smaller needles and cannulas are more likely to penetrate vascular walls  Always know where the tip of the needle or cannula is in 3‑dimensions,  including depth (can use non‑dominant hand to protect globe and feel tip  of cannula prior to injection) 

Figure 2: Mottling in the area of a vascular distribution,  sometimes respecting the midline, larger than the injected  area  into a bluish discoloration, which may appear like a  large bruise [Figure 3]. With this, vascular dilation with  increased artery pulsation occurs and can be seen on  colour Doppler ultrasound [Figure 4]. Tissue necrosis  or eschar formation appears even later. Once the deep  dermal layers are affected, scarring will likely occur.  Various treatment protocols have been suggested  in cases of soft tissue ischaemia.[17] Treatments such  as aspirin to prevent platelet aggregation, warm  compresses to improve circulation, nitroglycerin paste,  other vasodilators, hyaluronidase and hyperbaric  oxygen have been reported to have been used.[12,18]  The use of nitroglycerinpaste is controversial in cases  of filler induced ischaemia. Nitroglycerin paste has  been used successfully in flap ischaemia; however, in  filler‑induced ischaemia, the vessels are occluded with  particles and dilation may cause further worsening  of ischaemia by further downstream embolisation of  product.[19,20] In addition, nitroglycerin paste is more  of a venodilator.[21] The use of topical nitroglycerin in  filler‑induced ischaemia has little evidence and may  have other unwanted systemic side effects; therefore, its  use is not necessary in cases of filler induced ischaemia. 

Figure 3: Soft tissue ischaemia can become a bluish  discoloration, which may appear like a large bruise  

The only proven treatment for soft tissue ischaemia  in cases of HA filler is the use of early high‑dose  hyaluronidase. In a rabbit ear animal model, high‑dose  hyaluronidase (750 IU) given in the area of ischaemia  within 4 h of ischaemia, resolved the filler‑induced  ischaemia; after 24 h, there was no benefit.[15] In our  experience, patients who have presented within 24 h  and treated with high‑dose hyaluronidase until the  resolution of ischaemia (in the range of 400–1500 IU;  can be repeated every 24 h) in the entire area of  the tissue ischaemia had no long‑term scarring or  sequlae. Even if patients present after 24 h, we still  recommend treatment with high‑dose hyaluronidase  as we have had success in reducing ischaemia and  scarring; however, the sooner the treatment the better  the outcome. We have had also some success with the  use of intra‑arterial and subcutaneous hyaluronidase  in the area of ischaemia with rapid resolution of  ischaemia [Figure 5]. Intra‑arterial hyaluronidase is not  necessary with soft tissue ischaemia but can help resolve  the ischaemia more rapidly and could be considered  in instances of visual compromise, which we will  discuss later. In the patients treated with intra‑arterial  hyaluronidase, we do discuss the risk of further  embolisation of product if the filler product does not  dissolve completely, so careful selection of patients is  warranted. Intra‑vascular hyaluronidase has been used  safely in patients with myocardial infarctions and the  half‑life in the circulation is approximately 2–5 min.[22,23]  Other experts have suggested the use of high‑dose  subcutaneous hyaluronidase hourly starting around  400 IU until normalisation of capillary refill of the  affected area (DeLorenzi C, presentation at American  Society of Ophthalmic Plastic and Reconstructive  Surgery Las Vegas November 2015).[24] The bottom line  is early treatment with high‑dose hyaluronidase in the  entire area of ischaemia in cases of HA associated filler  ischaemia is imperative.  

Figure 4: Colour Doppler ultrasound: Vascular dilation  (arterial) on affected side (b). (a) Affected side  


More cases of visual compromise including vision loss,  decreased eye movements or ophthalmoplegia, droopy  eyelid or ptosis and cerebral infarct are being reported  with filler injections.[11,25‑32] When visual compromise  occurs, it is immediate and usually associated with  pain. It can also be associated with soft tissue ischaemia.  Beleznay et al. compiled cases from 1906 to 2015 and  found a total of 98 reported cases of dermal filler eye  related complications, with most reported in the past  5 years. Twenty‑three cases were found to be associated  with HA filler injection. Most cases of visual compromise  have been reported from South Korea, perhaps secondary  due to their large volume of facial filling and/or location  of facial augmentation.[11]  

In 2014, our institution conducted a nationwide survey  of retinal specialists with the American Society of Retina  Specialists, similar to that performed by the Korean  Retina Society.[26] The survey was carried out after the  Institutional Review Board approval using the Survey  Monkey system from October 15, 2014 to December 1,  2014. From this survey, 127 of the 720 retinal specialists  responded. The survey captured a total of four cases;  however, three had been reported previously.[30] The additional case was that of an unreported filler product  injected in an unreported location of the face by a  plastic surgeon. The patient had a branch retinal artery  occlusion (BRAO) and their initial visual acuity was  20/20. Our survey suggests perhaps the incidence of  visual compromise in the United States is less than in  Korea, but could still be underreported. A method to  anonymously report complications may help improve  case reporting. With the increasing use of fillers  worldwide, we are likely to see more cases of visual  compromise.  

The most high‑risk injection areas associated with visual  compromise include the glabellae, forehead, nasal region, nasolabial folds and temple.[11]

Figure 5: Patient after treatment with intra-arterial and  subcutaneous hyaluronidase with rapid resolution of  ischaemia. (a) Initial presentation, (b) 12 h post-intra-arterial  and subcutaneous hyaluronidase, (c) 72 h post-intra-arterial  and subcutaneous hyaluronidase  

The arteries in  these high‑risk areas have direct communication with  the ophthalmic artery.[33] The mechanism of action of  visual compromise is thought to be that product is  pushed retrograde thru an artery with connection to the  ophthalmic artery higher than arterial pressure. Once the  plunger is released the circulation takes over and the filler  particles travel anterograde and enter the ophthalmic  artery and its various branches, causing vision loss, ophthalmoplegia, ptosis and/or ocular ischaemia. If the  filler product is pushed further retrograde, it can enter  the brain circulation and cause cerebral infarction via  the internal carotid artery.[29]  

Park et al. described six types of visual compromise  based on the postulated level of occlusion of the  ophthalmic artery and patient symptoms: Ophthalmic  artery occlusion (OAO), generalised posterior ciliary  artery occlusion (PCAO) with relative central retinal  artery sparing, central retinal artery occlusion (CRAO),  localised PCAO, BRAO and posterior ischaemic optic  neuropathy (PION). They were also divided into diffuse  occlusions (OAO, generalised PCAO, CRAO) and  localised occlusions (localised PCAO, BRAO, PION).  Most of the patients presenting with OAO, a more diffuse  occlusion had undergone autologous fat injections. The  occlusion of the ophthalmic artery, with an approximate  diameter of 2 mm, would require a larger particle  size such as autologous fat; however, they did report  three cases of OAO with HA.[26,34] In addition, a majority  of the patients with OAO and fat injection had cerebral  infarction, which may be due to the larger volume and  injection pressure used during autologous fat injections.  In contrast, the central retinal artery is approximately  160 ìm in diameter.[35] In the study by Park, six of the  eight CRAO had undergone fat injections, one with  HA gel and one with collagen filler.[26] Still, with HAG  filler products, care should be taken to inject slowly and  under low injection pressure to reduce the potentiation  of particles retrograde into the ophthalmic artery. The  smaller HAG filler particles can potentially travel further  anterograde for a more localised effect and occlude the  central retinal artery, branch retinal artery, or posterior  ciliary arteries.[26] Beleznay et al. also showed that HA filler  injections have less serious ocular outcomes and central  nervous changes, most likely related to the smaller particle  size; however, if there was visual loss initially, there would  likely be no improvement in visual outcome.[11]

Till date, there are no proven treatments for visual  compromise secondary to filler injections. Many  theories have been postulated but none proven.[11]  For more diffuse occlusions, perhaps measures to  restore ophthalmic artery flow can be tried. Injection  of hyaluronidase either into the orbit (retrobulbar)  has been proposed but to date has not been reported  to be successful. With orbital or retrobulbar injection  of hyaluronidase, if the ophthalmic circulation is not  flowing, it will not likely reach distally into the retinal  circulation to improve perfusion. Direct hyaluronidase  injection into the vitreous cavity to dissolve product  in the retinal circulation could potentially be another  option; however, no cases have been reported of its use in  humans. Hyaluronidase injection into the vitreous cavity  for other indications has been used in the past safely.[36‑38]  Direct intra‑arterial injection to the ophthalmic artery,  via interventional neuroradiology, or cannulating the  supraorbital or supratrochlear arteries has also been  proposed.[39,40] We have had success in cases of soft  tissue ischaemia and could be a potential avenue of  treatment. Further investigation into potential uses of  hyaluronidase in cases of visual compromise is needed  and treatment may be a combination of the above.  

Current treatments for filler‑induced CRAOs attempt to  dislodge the emboli from the retinal circulation. These are  the same measures used in non‑filler‑associated CRAOs  including lowering the intra‑ocular pressure with drops  and or systemic medications such as acetazolamide and  mannitol, anterior chamber paracentesis and ocular  massage.[26] Other treatments that have been reported  but are unproven are corticosteroids, thrombolysis,  vasodilatory agents and anti‑coagulants.[12,41] If visual  compromise is encountered, patients should be  referred promptly to an eye specialist, preferably a  retina specialist, within 90 min.[31] Unfortunately, even  with early recognition and treatment, the visual loss  associated with filler injections is largely irreversible.  Ophthalmoplegia and eyelid ptosis usually recover,  likely due to the rich collateral circulation of the muscles  and the lack of sensitivity to reduced blood flow. 

When injecting filler products, it is important to  remember to use low injection pressure as well as use  small volumes per pass or area. Even though there are  lower reports of ischaemic events in the periorbital area,  care should be taken when injecting this vascular area.  In addition, perhaps the lower reporting of vascular  complication in the periorbital area is that only injectors  who are comfortable with this region and understand  the anatomy inject this area.  


When injecting HA fillers, hyaluronidase is beneficial  to aid with corrections as well as severe complications  such as vascular compromise.[9,42,43] There are two classes  of hyaluronidase: Human recombinant or animal  derived (bovine or ovine).[44,45] The duration of action of  hyaluronidase in soft tissue is approximately 24–48 h  and intravascularly around 3–5 min.[23]  

In patients with vascular compromise, skin testing  is not needed but could be considered in non‑urgent  cases for allergic reaction in a non‑urgent situation can  be performed.[23,43] In addition, there is no documented  adverse effect of high‑dose hyaluronidase on native  tissue. We have treated patients with over 1500 IU in a  single session without sequlae. Further investigations  into the optimal dose, formulation and timing of  hyaluronidase treatment for each complication,  especially vascular compromise, needs to be  performed. In addition, HA fillers have different  degradation responses to hyaluronidase and should  be considered when dissolving each individual  product.[43,46,47] We recommend having hyaluronidase  available in any formulation available when injecting  HA fillers.  


Periorbital rejuvenation with injectables, primarily HA  fillers, can be effective in addressing periorbital aging.  Because of the increasing use of periorbital fillers, more  complications, both non‑ischaemic and ischaemic,  will be encountered. Understanding the complex  periorbital anatomy and proper injection techniques  can help avoid complications, but are no guarantee. In  addition, education of both patients and injectors of these  potential complications are important as well as having  hyaluronidase on hand.  


Consultant for Merz Pharmaceuticals, Ischemic  Complications Advisory Board for Allergan.  Acknowledgement  I would like to acknowledge Jerome Comet Klein MD  Foundation.  

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.  

Financial support and sponsorship  


Conflicts of interest  

There are no conflicts of interest. 

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