Derek Jones, MD

In this presentation, Dr Jones reviews the data on Belotero, a novel therapeutic approach to dermal fillers.

CPM Technology

Belotero utilizes CPM Technology. This is the most important difference with regards to Belotero and other dermal fillers. Belotero utilizes CPM Technology, a key differentiator between  Belotero and other hyaluronic acid  dermal fillers. CPM Gel provides further cross-linking steps resulting in a coherent molecule with different density zones, resulting in a coherent molecule with unique density zones.

What does this mean clinically?

While particulate biphasic fillers may lift and enlarge dermal spaces leaving lumps, Belotero integrates into dermal spaces allowing for smooth transition between treated and untreated areas.

This is important clinically as it is hypothesized that using Belotero may reduce the Tyndall effect.

Belotero US Clinical Study

The Primary Phase was a 24 week initial study in comparison to Zyplast. 118 patients were enrolled and the researchers looked at the treatment of nasolabial folds (NLFs). The open-label extension phase (OLEX) was an extension of the evaluation from 24 weeks to 96 weeks that included 85 patients.

This is important as it was an FDA pivotal trial and Dr Jones encourages everyone to review the pivotal trials on Restylane and Juvederm as well to look at similarities and differences among the fillers.

The mean age on these studies was 52.4 and the subjects were predominantly female.

In order to be eligible for this study, patients had to be a two or a three on the Wrinkle Severity Rating Score (WSRS) and to be deemed a “responder” that had to have at least a one-point improvement on this scale that was persistent.

The results demonstrated that both Belotero and Zyplast performed similarly at week 2, but by week 24 the results greatly improved with the use of Belotero.

Regarding the responder analysis, well over 50% of the subjects had at least a one- point change on the WSRS by week 24 and the percentage of subjects maintaining correction from week two to week 24 was greatly superior for Belotero.

Efficacy measured in GAIS was significantly better with Belotero versus Zyplast. In looking at the Physician’s Preference Assessment, 100% of the physicians preferred Belotero to Zyplast with regards to storage and handling, 67% preferred Belotero regarding the comfort and design of the syringe, and 33% preferred Belotero regarding ease of injection “flow”. Overall, 83% of the physicians preferred Belotero to Zyplast.

Adverse events were very similar to what one would expect with a hyaluronic acid such as erythema, bruising, and swelling. The AEs observed were not statistically significant.

The results of the Primary Phase study conclude that Belotero is superior to Zyplast in the correction of the nasolabial fold when evaluated 12 weeks after treatment. More patients preferred Belotero and the treatments were safe and well tolerated.

Belotero Balance (OLEX)

This was an open-label extension trial consisting of treatment with Belotero on both sides at completion of the 24-week visit (visits at week 32, 48, 72, 96, after the last main study treatment). Patients received touch-up treatments with Belotero in both nasolabial folds at week 24 and could receive an optimal touch-up treatment at week 32 to balance an observed unevenness between the two sides. At each of the visits, adverse events and relevant medication use was noted. The subjects could also receive optimal touch-up injections at week 48 or week 72 if the WSRS on that side is two or three. Subjects who did not receive an optimal touch-up injection at weeks 48 or 72 had the option of receiving a touch-up at week 96.

After repeat treatment, the filler starts to hold and dermatologists can see that with the other fillers as well.

The mean GAIS score, as assessed by the treating physician, was between two (improved) and three (much improved) at all timepoints. The GAIS was greater on the side of the face previously injected with HA in the double-blind trial, indicating greater improvement on that side.

During the OLEX study, there was an injection-free phase of 48 weeks in 80.2% of the patients.

At all time points during the open-label extension the treating investigator assessed improvement by both the WSRS and GAIS on both NLF.

In conclusion, Belotero appears to be a safe and well-tolerated, novel dermal filler.







Filler Complications

Joel Cohen, MD

In this presentation, Dr Cohen reviews the complications that can occur when utilizing fillers and best practices on how to manage these various complications. Dermatologists use fillers across the world, millions of times per year, and most of the time, everything is fine; but understanding the complications and how to manage them is imperative for us aesthetic dermatologists.

Clinicians should be aware that there are new filler agents and new indications for the agents currently available, so it is important to understand these products and recognize what can potentially go wrong when using them in our patients.


Filler complications include:

  • Superficial injection
  • Vascular compromise
  • Bruising
  • Sensitivity
  • Granuloma
  • Infection (or possible ” biofilm”)
Superficial Injection

When injecting the peri-ocular area, it is critical that dermatologists understand the anatomy and how to inject these areas.  When Dr Cohen injects these areas, he defines them by either “infra-orbital hollow” or “tear trough”.

Approach to Infra-Orbital Hollow injection

This is a much less common injection than the actual tear trough. Dr Cohen uses anesthetic eye drops, a jaeger retractor to protect the globe, and a 32 gauge needle above the level of the muscle. He discusses the importance of the 32 gauge needle as he believes it slows down the injection, or alternatively a 30g cannula can be used as well to try to decrease the incidence of bruising. This is an off-label area of injection and should be done very superficially, but it is very important to avoid superficial nodules—so inject slowly and avoid depositing clumps.

Injecting the Tear Trough

Dr Cohen injects very deep, below the muscle on the level of the periosteum. An anterior approach may help to lessen bleeding encounters.

Persistent Swelling

Persistent swelling has been documented across the board with various fillers. It is important to remember that this is an off-label area and dermatologists choose their agents based on personal preferences.  Experts are not sure if the swelling is related to etiology, e.g., Botox a few weeks prior. Treatment for persistent swelling includes time, massage, caffeine, oral HCTZ, and hyaluronidase.   Hyaluronidase can be helpful for an area that was superficially injected (very localized).

When injecting the glabella, you would want to see a little bleeding, you absolutely do not want to see it blanche.  Bototulinum toxin immobilization prior to filler (sometimes a week or two prior), may provide a better, more durable response with the filler (Carruthers, Derm Surg, 2003).

Vascular Compromise and Necrosis

The glabella is an area at significant risk for impending necrosis. Vascular compromise and necrosis, albeit rare, are caused by compression and intravascular injection.  In 2006, Dr Cohen and colleagues published a prevention and treatment protocol for injection necrosis of the glabella (Derm Surg, Feb 2006).

Understanding the facial arteries is of great importance for dermatologists who do soft tissue augmentation.

If you see a blanche, immediately stop the procedure. With some warm tap water gauze, try to tap the area and the warmth will facilitate vasodilation. If you have nitro paste in your office, you can apply that as well along with giving your patient aspirin to manage the headache associated with nitro paste.

Understanding the vessels and patterns is important not only to dermatologists, but to patients and office staff as well. Hyaluronidase with multiple stabs and perhaps into the adjacent artery has been demonstrated as a novel treatment for impending necrosis. It is very important as a healthcare provider to intervene immediately and not “wait and see what happens” in the cases of impending necrosis. A new article in Derm Surg suggests prostaglandin E may be helpful, and many experts also recommend hyperbaric oxygen be considered in some cases as well.


Fillers can be for postsurgical depressed scars on the ears, nose, and cheeks. Dr Cohen and colleagues published various case reports in 2008 on the use of fillers for postsurgical depressed scars after skin cancer reconstruction. The use of hyaluronic acid and calcium hydroxylapatite has proven successful to fill and blend these scars.


Bruising may occur regardless of the injection site. The injection pattern is extremely important and it is critical that dermatologists understand the various approaches to injection. There are some things that patients can do to reduce bruising, such as avoiding non-therapeutic anticoagulant over-the-counter agents.. There are vitamins that can potentially interfere with bleeding; so again, something to keep in mind.  Clinicians need to be realistic with their patients, so they can expect some bruising and/or swelling which may last up to ten days. It is important to communicate this as a reality with patients prior to the procedure.


There are a few cannulas available in the US. Dr Cohen uses cannulas most often in the hands, cheeks, infra-orbital, and décolleté. They seem to decrease bruising along with potentially decreasing pain in some areas, and this has been seen in two preliminary studies (Hexsel and Barrone).



In conclusion, there are a variety of fillers available for patients. It is important that dermatologists understand the anatomy of the face in order to optimize injection results and minimize potential complications.