Vascular occlusion is a rare but severe and dreaded complication of soft-tissue fillers. It occurs because of inadvertent injection of the filler material in a blood vessel. This intravascular injection of fillers may lead to complications such as tissue ischemia and loss, blindness, pulmonary embolization,46 and even stroke.47 In a recent study published by Povolotskiy et al48 investigating the adverse events arising with various aesthetic fillers, vascular complications were cited to be among some of the commonly occurring complications. This study comprised 5,024 cases, out of which vascular complications were observed in 590 cases. Even though blindness caused by soft-tissue fillers is an infrequent event, it is a matter of great concern owing to its distressing consequences.49 The causative agents that may lead to blindness include autologous fat, HA, collagen, poly-L-Lactic acid, calcium hydroxylapatite, and even corticosteroid suspensions.50 Vision loss manifests as an immediate complication of facial filler injection with other associated signs and symptoms depending on the location of vascular occlusion.51
In a retrospective study conducted between January 1, 2008 and August 31, 2014, Kim et al53 also observed that the prevalence of diffuse occlusion of ophthalmic artery and its branches is less in HA-injected patients compared with autologous fat–injected group. This could be attributed to the difference in the particle sizes of the 2 fillers. Autologous fat has a variable particle size, whereas HA particles are approximately 400 μm in size. Hyaluronic acid fillers are more likely to block the central retinal artery (approximately 160 μm in size) or its smaller branches and fat more likely the ophthalmic artery (2 mm in diameter) due to the particle size and the amount of filler injected per injection site.53 Chen et al22 while studying fundus artery occlusion also found that the prognosis was found to be much worser in autologous fat than in HA.
Previous studies have also reported that injections with autologous fat are associated with a higher diffuse occlusion rate, resulting in a much worse visual prognosis and more frequent cerebral infarctions compared with HA.24,53
Currently, it is thought that an accidental injection of fillers into the blood vessel can lead to the formation of tissue filler emboli. Various authors have suggested that the mechanism of this is most likely through initially retrograde flow against the prevailing blood pressure to a point at or past the retinal branches. Consequent release of the syringe pressure allows the usual blood pressure to reestablish the antegrade blood flow carrying forward these emboli allowing them to enter the ophthalmic artery circulation. This embolus is responsible for retinal ischemic necrosis. The ophthalmic artery branches with cutaneous innervation (supplying the glabella, nose periorbital zone, and forehead) probably carry the greatest risk, but anastomoses between facial artery and branches of the ophthalmic artery have been shown in cadaveric studies.49
A cadaveric study published in June 2018 has suggested that retrograde HA filler emboli to the ophthalmic artery may be a result of the cannulation of the supratrochlear artery, primarily due to its superficial location surrounded by rich vasculature and a variable anatomy.54 Sufan et al55 published an article in 2017 which showed that in the glabellar region, the deep injection on the periosteum will be at a risk of entering the supratrochlear artery and supraorbital artery, whereas, in nasal dorsum and nasolabial folds, the subsuperficial musculoaponeurotic system layer injection has the possibility to enter the dorsal nasal artery, angular artery, and facial artery.
It has also been suggested that the volume of the filler injected, and the pressure of injection can impact the outcome of blindness by influencing the retrograde flow of the filler into the ophthalmic circulation. The amount of soft-tissue filler injected varies according to the type of filler used, for example, autologous fat is typically injected in larger volumes compared with HA fillers.56
Even though both fat and HA fillers may cause vision loss, the occlusion of the ophthalmic circulation vessels would vary due to the particle size and the amount of filler injected per injection site. This could explain why the case series by Park et al. showed that autologous fat was associated with a higher diffuse occlusion with worse visual prognosis and a higher incidence of concomitant cerebral infarction.13,23
The speed and pressure of injection have also been proposed to influence the flow of the filler after its inadvertent injection into the vessel. This has a direct impact on the speed and pressure of injection as the viscosity of the filler influences the extrusion force (injection pressure) used by the injector that will then determine the speed and pressure of injection finally affecting the flow of the filler within the vessel. A highly viscous filler (like fat) will require a higher extrusion force compared with a filler that is less viscous.
Another factor influencing the extrusion force is the size of the syringe and gauge of the needle/cannula which is determined by choice of the soft-tissue filler used. Typically, autologous fat is injected using large gauge needles and an increased force used to inject it would be easier to produce57 increasing the likelihood of a large bolus if intravascular penetration occurs.
Interestingly, the propensity of soft-tissue fillers in activating clotting mechanism also influences their effect. The noninflammatory fillers may purely cause a mechanical obstruction when placed within the blood vessel. However, others can activate an intravascular inflammatory reaction over and above the mechanical blockage accentuating the obstruction and consequently cause ischemia and blindness. In fact, it has been shown that HA may have heparin-like activity as opposed to collagens clot promoting action.58
It has been seen that hyaluronidase, an enzyme that degrades HA, may improve outcomes following an accidental intravascular HA filler injection. A review conducted by Carruthers et al59 showed that when hyaluronidase was injected next to a blood vessel clogged with HA, it catabolized the HA without needing to canalize the affected artery. It is also suggested that in the case of retinal artery embolization with the HA product, retrobulbar injection of a large volume of hyaluronidase might well be the single most effective option to dissolve the intraorbital intravascular hyaluronan in a time-sensitive manner.59
Although consensus recommendations for the avoidance and management of complications from HA fillers including blindness are available,60 there is no evidence that following the currently available guidelines would reverse the vision loss necessitating a need for a specific protocol that can be followed to universally reverse all cases of blindness secondary to HA fillers. However, it is worthy to note that this possibility of reversal of iatrogenic blindness is likely to be possible with HA fillers and not others like autologous fat, collagen, or calcium hydroxylapatite.
Inconsistencies in recommendations for safer injection technique and lack of evidence to correlate the impact of injection technique on the occurrence of blindness necessitate the need for exploratory research. Better reporting of cases of blindness through a registry with details of the injection technique provided, including type of filler, use of needle or cannula (with size), use of local anesthesia, etc., can help to better understand the mechanism for the causation of blindness retrospectively so that preventive measures can be put in place. Additionally, the effect of different fillers (including the various brands of HA fillers available worldwide) on the vessel wall can be studied in vitro to establish the safety profile of the differently available fillers.
This systematic review has many limitations. First, there was no uniformity in presenting the cases, and many important parameters or variables were not reported. Second, as with any case reports, the information regarding the rate, ratios, incidences, or prevalence cannot be generated because they are not representative of the population. Last, as with descriptive studies, one cannot deduce the cause–effect relationship; hence, the findings cannot be generalized.
Even though rare, vision loss due to HA injection is a disastrous event. When vision loss occurs, with limited time for restoration, early recognition and prompt treatment are crucial. There is no gold standard for the treatment of vision loss, and even though there have been consensus recommendations, no specific guidelines are available which have been universally successful in reversing this complication.
HA-based fillers appear to be relatively safer soft-tissue fillers, although it will be prudent to say that profound medical, anatomical, and product knowledge are required to minimize the occurrence of grave adverse reactions such as blindness associated with their use.
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