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218
Fig. 6.11 Degradation of hyaluronic acid ller in blood vessel by inltration of hyaluronidase
Table 6.4
Repeated hyaluronidase treatment is effective The interval should be as short as 15–30min It is effective to use high doses of hyaluronidase
Hyaluronidase usage recommendations
6 Side Eects andTreatment Methods ofFiller Procedures
injection using a rabbit model. Flaps were made in rabbit ears to block blood vessel anastomosis, and then llers were injected into the auricular artery. Necrosis of the ear was induced after which hyaluronidase was injected at various intervals.
The results of the experiment were as follows (Table6.4).
The hyaluronidase usage guidelines have changed over time. In the past, it was recom­mended to repeat the procedure every day. Recently, re-evaluation and re-administration at 1h intervals are recommended. This study found that in emergency situations such as intravascular injections, frequent administrations at 15 min intervals are more desirable.
Based on these ndings, we expect that new evidence-based guidelines will be coming soon.
To compare the difference between in vivo and invitro experiments, the authors conducted a similar experiment for the use of hyaluroni­dase in the laboratory. Unlike in vivo experi-
ments, the ller degradation effect of hyaluronidase was related to the total amount of hyaluronidase used. In summary, there was no difference between the group administered 750 units at once and the group administered 250 units divided into 3 injections at 15 min intervals. Repeated administration did not show better results. This is thought to be associated with the inactivation of hyaluronidase invivo (Fig.6.12).
(6) Massage the area after injection.
Borders and Raftery (1968) reported that the molecular weight of hyaluronidase is 61,000Da. Khorlin et al. (1973) report four subunits of 14,000 each and a total molecular weight of 55,000Da. Hyaluronidase has a large molecular weight; it dissolves on the outer surface of the ller material when it encounters hyaluronic acid ller. Naturally, the contact surface must be large for effective enzymatic degradation. After hyal­uronidase injection, the area of contact should be widened through massage. As mentioned earlier, because hyaluronidase activity decreases in the body, it is recommended to massage after injec­tion to effectively facilitate contact between the ller and hyaluronidase.
The authors performed hyaluronic acid ller degradation test and observed the difference of solubility according to massage.
< Experimental condition>
(a) It was performed at 36.5 degrees Celsius to
match the enzyme activity.
(b) The authors performed a seal after hyaluroni-
dase mixing to prevent evaporation of water
during the experiment. (c) A monophasic ller was used. (d) The group without massage was compared
with the group which received the massage at
the same time. (7) When injecting into a nodule or granuloma,
make sure to penetrate the capsule and inject
into the center of the mass.
Nodules or granulomas are caused by a vari-
ety of factors. Thick brous capsules form
6.3 Use ofHyaluronidase forDegeneration ofFillers
Fig. 6.12 Comparison of hyaluronidase usage invitro test
219
a
Fig. 6.13 Degradation difference between the non-massage and massage group after 24h of mixing 750units of hyaluronidase
around the ller when it is due to the poor qual­ity of the ller itself or by abnormal immune responses (Fig.6.13).
Even when nodules or granulomas are pres­ent, hyaluronidase is recommended for primary treatment. When the brous capsule around the nodule or granuloma is not thick, it is adequate to inject a sufcient amount of hyaluronidase into
b
the area around the lesion and massage it. However, in cases where the capsule is very thick and severely inamed with calcication, injec­tion and massage of hyaluronidase around the mass cannot effectively dissolve it. Only hyal­uronic acid llers in connective tissues along the periphery of normal tissues can be dissolved, but the mass will not disappear.
220
6 Side Eects andTreatment Methods ofFiller Procedures
Although surgical removal may be consid­ered, surgical removal often leaves scars on the face. Therefore, efforts to dissolve using hyal­uronidase should not be easily abandoned.
When treating a hard nodule or granuloma with hyaluronidase, the hyaluronidase must be injected into the center of the mass to dissolve it from the inside (Figs.6.14 and 6.15).
It is important to know whether hyaluronidase is properly injected into the center of the mass during the procedure. If it is not injected in the right place, not only does the mass not dissolve; it can cause unwanted side effects.
There is a way to determine if the needle tip is properly positioned in the center of mass.
It is one of the most important details in treat­ing ller side effects (Table6.5).
6.3.2 SONO-Guided Techniques
forHyaluronidase Injections
6.3.2.1 Dissolving Hyaluronic Acid
Fillers
Hyaluronic acid llers can be dissolved using hyaluronidase. In cases where the injected ller causes nodules or granulomas, dissolution may
Table 6.5
injected into the center of mass
1. If the needle tip is located at the center of mass
2. When the injection is successful, you can feel that
3. You can feel the mass swell and burst while the
4. If it is properly injected and then promoted again
How to make sure hyaluronidase is correctly
correctly, it is difcult to inject hyaluronidase due to the higher injection force than when the needle tip is located at the surrounding normal tissue
the size of the mass has increased immediately after the injection. If the central injection fails, swelling simply occurs in the periphery
injection is successful. Fibrous capsules are inated due to hyaluronidase injected into the body and cannot withstand pressure and burst
after several minutes, it can be seen that the rigidity of the mass is reduced and the size is reduced. If you feel the capsule pops out, you can see that the mass itself is gone
Fig. 6.14 When injected outside the mass: hyaluronidase cannot pass through the thick brous capsule of the nod­ule and thus cannot remove the mass
Fig. 6.15 Hyaluronidase is injected and dissolved in the center of the mass. Hyaluronidase is injected directly through the brous capsule via a needle and then directly inside
6.3 Use ofHyaluronidase forDegeneration ofFillers
221
be necessary. Typically, these injections are per­formed blindly by hand. However, the use of ultrasound can enable a more effective dissolu­tion process.
By employing ultrasound guidance, the exact location of the ller can be identied, allowing for precise administration of hyaluronidase. This method improves the accuracy of the treatment and increases the likelihood of successful resolu­tion of nodules or granulomas caused by the ller.
6.3.2.2 Sonographic Finding ofHA
Filler Nodule
On ultrasound, hyaluronic acid ller nodules typ­ically present as homogenous, anechoic (black) masses. The absence of internal echoes indicates a uid-like consistency, which is characteristic of HA llers. These ndings are generally well­dened with smooth borders, making them dis­tinguishable from other types of tissue irregularities.
6.3.2.3 Sonographic Appearance
ofGranulomas
In contrast, granulomas induced by HA llers present as heterogeneous and irregular masses on ultrasound. These formations show mixed echo­genicity, with both hypoechoic (dark) and hyper­echoic (bright) areas. The irregular echo patterns indicate a more complex internal structure, often due to chronic inammation and brosis.
Granulomas may also exhibit poorly dened borders and a “dirty” appearance, reecting the disorganized nature of the inammatory response. The presence of these irregularities makes granu­lomas distinct from the more uniform appearance of HA ller nodules.
Hyaluronidase can be effectively used to dissolve HA llers, and ultrasound guidance enhances the precision of this intervention. For granulomas, additional treatments such as intralesional ste­roids may be required to address the inamma­tory component.
6.3.2.5 Sonographic Findings inCases ofSkin Impending Necrosis Following Filler Injection
Sonographic andDoppler Finding inIschemic Areas
In cases of ischemia following ller injection, affected areas exhibit reduced blood ow on Doppler ultrasound. This reduction in blood ow is indicative of vascular compromise, which, if not addressed, can lead to tissue necrosis. The ischemic area may show altered echotexture compared to healthy tissue, reecting underlying tissue distress (Fig.6.16).
a
b
6.3.2.4 Clinical Implications
The ability to accurately differentiate between HA ller nodules and granulomas using ultra­sound is crucial for appropriate management.
Fig. 6.16 (a) Sonographic image of ischemic forehead area (b) Sonographic image of the contralateral normal forehead area
222
6 Side Eects andTreatment Methods ofFiller Procedures
a
b
Fig. 6.17 (a) Sonographic image of the treated ischemic forehead area post-hyaluronidase (b) Sonographic image of the contralateral normal forehead area post-hyaluronidase
Sonographic Improvements Post­hyaluronidase Treatment
Hyaluronidase is an enzyme that can dissolve hyaluronic acid llers, thereby alleviating the compression on blood vessels and restoring blood ow. After hyaluronidase treatment, Doppler ultrasound typically shows an improve­ment in blood ow to the previously ischemic area. The echotexture of the tissue also returns to a more normal appearance, reecting the recov­ery of the affected tissues (Fig.6.17).

Further Reading

1. Haddock NT, et al. The tear trough and lid/cheek junc-
tion: anatomy and implications for surgical correction. Plast Reconstr Surg. 2009;123:1332–40. discussion
1341.