Donnerstag, 25. April 2013

Corrections of Nasolabial folds with a Monophasic Filler: Superior Efficacy and tolerability

Interview with Dr. Johannes Reinmüller, plastic surgeon in Wiesbaden, principal investigator of the study

What are the most important results of this study?
In my opinion there are predominantly three points of interest: Most importantly we  know that this monophasic filler is a safe product. As the correction of wrinkles by injection of HA-based fillers is an optional medical procedure and not a live-saving  treatment safety is a really important issue.  In treatments the like first and foremoste  we have to follow the motto: no harm.
A second really important result is that this treatment has a proven efficacy. In many other products we do not have any clinical studies. Here we know we have a reliable product.
Last but not least a comparison with a previously undertaken study[1] onh two competing dermal filler showed that the cohesive monophasic HA-bsaed filler is superior to the biphasic product and to collagen preparations.

Do you have an explanation for the long lasting treatment effect ?
It is certainly not the tale about the isovolumetric degradation. At the moment we do have only poor knowledge about the biodegradation of dermal fillers in-vivo. Most of our data are results from in-vitro-studies. Therefore I can only give you  my personal explaination which is in part a hypothesis and  not established knowledge. Injecting any kind of filler material you have to take into account that part of it, especially of  products containing particles,  solid or gel-like,  is migrating. Strictly speaking this is a loss of material at the site of implantation and not  biodegradation in the sense of enzymatic breakdown or lysis. As a result of migration or dislocation resp. the total amount of filler substance at the injection site is reduced during the entire observation time.
The remainder undergoes biodegradation, if possible. How this is accomplished on a molecular basis is not well understood in most biodegradable filler materials. My personal opinion in the case of HA and its derivatives is, that the material is degraded by macrophages and  cells of the immune system or RHS wether inside the cells or at the cell surface.

My explanation for the longevity of the cohesive monophasic product is, that the material is anchored in the tissue. As even finest fissures are filled with the cohesive material it is indented in the  the tissue. Migration is less probable and we do exspect more of the injected material keeping its position instead of filling  distant organs as a consequence of migration.

In the most used particulated biphasic fillers the medium size of the particle is 700 microns. This is the mean value but, a Gaussian distribution provided, there are lots of much smaller particles who are phagocytized  when smaller than 20 microns or shifted to the lymph vessels and lymph nodes by the mimic motions in the face. Once in the lymph vessels they are true rolling stones. May be they fill the lung but not the face and fortunately not on a long term.Additional we have gravitation forces acting on the particles which bias the migration down and backwards. Therefore I think that enhancement of duration of the therapeutic effect of the monophasic cohesive gel is the real benefit of the CPM-technology – an appropriate injection technique provided. On the base of case reports and histological findings this is my personal explaination for the superior results of the CPM-material.
Is the comparison between the present study with the monophasic filler and the study by Narins et al. valid? There are no head-to head comparisons between different hyaluronic acid fillers?
It certainly is. This comparison is valid, because the design of the present study is very similar to the study by Narins and coworkers. There was not only the same primary endpoint but also the patients and the nasolabial folds at baseline were similar. The only meaningful difference between these studies was the fact, that in the preceeding study two touch-up treatments  were allowed.
If you take a close look at the results of both studies, you notice that the monophasic filler is superior to the other. With a single treatment we achieved a better  effect compared to the competing products, where more than a third of patients got touch-up-treatments 
How was the tolerability in these studies?
You have to discriminate between side effects due to the product itsself and side effects due to the implantation procedure, e.g. bleeding, swelling or erythema. But even if you take this into account, the monophasic filler was better tolerated. There were more side-effects immediately after implantation in the preceeding study on a statistical base. Most patients in the study assessed the tolerability as good or very good.

Case Report:
Correction of Nasolabial folds with a monophasic filler
A 42 year old woman presented to the clinic with the wish for the correction of her nasolabial folds.  The otherwise healthy patient had a history of Nickel allergy.
Before treatment the investigator rated her nasolabial-folds to be SRS-grade 4 (Fig). A topical preparation of a local anaesthetic (EmlaTM)) was applied to the injection site before implantation to minimize pain during the procedure. The investigator injected the material via Stratum Technique.

Immediately after the procedure investigator and patients assessed that the folds had “very much improved”. Fig. 2 shows a marked improvement of the nasolabial folds The investigator rated the SRS-Score 2 after treatment.
The patient came to a control visit after 15 days. All further presentations on day 29, 82, 166 and 251 showed that the treatment effect was still evident, even 166 (Fig.3 ) and 251 (Fig. 4) days after the initial treatment. At each visit  the SRS-value was rated 2 by the investigator.
On every visit investigator and patient had the opinion the folds had much improved
The treatment was also judged by a blinded reviewer according to photo-documentations. In his opinion, the SRS-values at baseline were even 5. On the other visits he rated them to be 2, which comes to an improvement in the SRS-scale of 3 points.
 Noticeable was the long filling state of the nasolabial fold. The investigator judged the filling state to be  100% even at day 166 after implantation and 92% at the end of the follow-up treatment period.
Tolerability was fairly good. There were only mild side effects related to the injection like erythema, swelling and haematoma which resolved within a week.
The patient seeks no further treatment at the moment, because she is very content with the present situation.
This case report shows that in selected patients  the treatment effect of a monophasic filler on the basis of hyaluronic acid can last up to nine month.

Fig. 6: Portrait Dr. Reinmüller
Fig. 7 : Patient before treatment : Although the volunteer is only 42 years of age, there are pronounced and deep nasolabialfolds.
Fig. 7: Patient immediately after treatment. Folds are fare less evident.
Fig. 8. Patient on day 166: Filling state was still rated 100% after this time.
Fig. 9 Patient on day 251: The treatment effect is still evident. The patient sees no need for a further treatment at the moment.

[1] Rhoda S. Narins, et al. A randomized doubleblind multicenter comparison of the efficacy and tolerability of Restylane versus Zyplast for the correction of the nasolabial folds. Dermatol Surg 2003 ; 29 :588-595

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