A quiver full of fillers

By Ruth Carol, contributing writer

There has been an influx of dermal fillers approved by the Food and Drug Administration (FDA) in recent years. But these aren’t just any fillers. The latest fillers target moderate to severe wrinkles and/or folds in specific anatomic locations. But are they really that different? You bet they are.

“The filler world is rapidly changing,” said Seth L. Matarasso, MD, who practices cosmetic and medical dermatology in San Francisco. When Dr. Matarasso started practicing more than 20 years ago, there was one collagen source — bovine — and one or two hyaluronic acid injectable fillers on the horizon. “Now, there are more than 20 fillers on the market with more on the way,” he added.

While there are only a handful of manufacturers of FDA-approved dermal fillers, each one has as many as five different products in their product lines. “Each manufacturer has a baseline of three products, a superficial filler followed by a medium and deep filler,” said Dr. Matarasso, who is also clinical professor of dermatology at the University of California School of Medicine in San Francisco. More recently, manufacturers have started adding fillers designed to treat specific areas, predominantly of the face.

“The results we can accomplish with these products are really remarkable — from the earlobes to the mouth to the chin, from the cheeks to the forehead to the temples,” he said. “You can use them on women or men, on light skin and dark skin, which you couldn’t do with the older fillers. We have so many FDA-approved products that are safe and effective to offer our patients, it’s almost an embarrassment of riches.”

Real differences

There may be an abundance of products, but are there really differences? Yes, the FDA approvals are based on real differences in the products, explained Hassan I. Galadari, MD, a cosmetic dermatologist in Dubai. The gold standard by which most fillers are compared are studies in the nasolabial fold because there is a standardized scale that allows for comparison in that anatomic location. More scales are becoming available for other areas such as the cheeks, lips, and even tear troughs. That allows for the creation of fillers with varying rheological properties to address different facial areas.

The rheological properties vary based on the dermal product’s viscosity, elasticity, and cohesivity. The first two properties are measured by the G’, or G prime. Fillers with high G prime are firmer and tend to keep their shape. In contrast, fillers with low G prime are thinner, more fluid, and spread easier. “If you put pressure on a filler with high G prime, it will press back and resist. A filler with low G prime will collapse under your fingers and spread out,” said Sue Ellen Cox, MD, a dermatologic surgeon who practices in Chapel Hill, North Carolina. “A filler that has high cohesivity will stick together without spreading out whereas a filler with low cohesivity will form to the bone more easily.” Another important characteristic for a filler is how integrative it is, she said. A filler that integrates with the patient’s collagen and elastic fibers effectively fills etched-in facial lines by acting as structural support that melds with them, essentially erasing the lines.

Each product has its own characteristics suited for special effects in specific locations, Dr. Cox said. “You couldn’t achieve the effects on the face you wanted to if you didn’t have all of these different products.” Additionally, she points out that no two faces are the same. “To create lift in the cheeks, you would have to use a different product on a woman in her 80s with thin skin than you would use for a man with a beard and thick skin,” Dr. Cox said.

Dr. Matarasso concurs that the newer fillers offer a lot of flexibility and diversity when treating site-specific areas. A high G prime product is wonderful for thicker, more sebaceous skin to obtain volume and lift as opposed to chasing a line. A lower G prime filler is ideal for use around the periocular area and lips and in some of those very etched-in lines. A medium G prime product works well in the temples.

Some hype

Although Kavita Mariwalla, MD, who practices medical and cosmetic dermatology in West Islip, New York, acknowledges that there are rheological differences in the latest filler products, she also believes there is a lot of hype being generated about using a specific filler for a particular area. “Going after other indications is a bit of a marketing ploy,” she said. It’s an opportunity for a manufacturer to say its filler is the one and only FDA-approved filler for a certain area, which can impact the number of injectors it attracts and build patient confidence, she said. Even Dr. Mariwalla admits to having fallen for the hype and purchased new fillers that promised to last longer than other products only to find out they don’t.

Ultimately, it’s the manufacturers that win, Dr. Matarasso said. Whenever a new filler comes out, there is a marketing blitz, and he gets telephone calls from patients asking about it. “But just because it’s new doesn’t mean it’s better,” he said. “It just gives us a bigger palate to use.”

Many of these companies are marketing directly to consumers, which generates interest in the product, but also confusion, Dr. Cox said. Patients come in asking for a specific product, not understanding that it might not be the best one for the aesthetic effect they desire. Even for one anatomic region, such as the lips, several products may be indicated, depending on whether the patient wants more volume, larger lips, or a smidge of a vermillion border. “Once we educate patients about these products,” she said, “we can offer them the optimum products for the best results.”

MORE DERMAL FILLERS ON THE WAY

More dermal fillers targeting specific anatomic areas are expected to make their way to the United States in the near future.

Three out of the four Teosyal resilient hyaluronic acids (RHAs) by Teoxane Laboratories were approved by the Food and Drug Administration (FDA) in the U.S in December 2017. The fourth filler, RHA1 used for fine lines around the eyes, neck, and decollete, should make its way to America soon, said Hassan I. Galadari, MD. The volumizer Volyme and lip filler kYss are also on the way.

Only one Belotero product, Belotero Balance for wrinkles and folds in the nasolabial fold, forehead, and around the mouth and lips, has been FDA-approved in the U.S., but three other products in the Belotero line are expected to land here soon, noted Andre Braz, MD, who practices aesthetic surgery and cosmetic dermatology in Rio de Janeiro, Brazil. They are Belotero Volume for restoring volume in areas such as the cheeks, chin, and temples; Belotero Intense for correcting deep lines in the nasolabial folds and around the mouth and lip; and Belotero Soft for superficial wrinkles in the perioral area, lips, around the eyes, and forehead. All come with lidocaine or without. The one that Dr. Galadari is most excited about is the polycaprolactone-based biostimulatory filler that is bioresorbable and exists in four forms based on its longevity when injected. “More fillers in the pipeline will incorporate certain technologies to make them longer and reversible,” he added.

Currently, Dr. Cox is conducting clinical trials on a filler for chin augmentation and one for use under the eyes.

Typically, dermal fillers are introduced in Europe and other parts of the world before they are introduced in the U.S. One reason is that the companies making these products are European, Dr. Galadari said. The only American manufactured filler he knows of is Radiesse and even that received its European approval two years before getting approved by the FDA. The other reason is that the FDA approval process is relatively expensive and more rigorous regarding clinical trials and manufacturing guidelines, he said. “A lot of these companies simply may not have the resources to attempt an FDA approval without partnering with an American company.”

A substantial lag time often occurs between the time a filler is introduced in other countries and the U.S. It takes approximately 18 months to two years to receive FDA approval for most hyaluronic acid-based fillers, Dr. Galadari said. But the timing depends on how quickly the FDA-approval process is started, among other factors. Teoxane’s RHA line was approved in Europe in 2013 and received its FDA approval in 2017. The application for FDA approval, however, occurred in 2015. If the manufacturer is seeking approval for a longer duration indication, he said, the process might take a bit longer.

Juvederm Voluma was launched in Brazil and other Latin American countries six years earlier than in the U.S., Dr. Braz noted. Juvederm Volbella was introduced in Brazil and other Latin American countries four years earlier than in the U.S.

ART OF INJECTING

Using fillers is as much about the injector as the product being injected, Dr. Mariwalla said. Sodium hyaluronate is her “go to” filler. “I can make it work for me the way I want it to. In my hands, it is reliable and predictable, and I get good results.”

Similarly, Dr. Matarasso doesn’t believe that there is a remarkable difference between, for example, hyaluronic acid with lidocaine and sodium hyaluronate. “My feeling is that it’s the injector, not the injectable material,” he said. Experienced injectors know the right volume, speed, technique, and materials to use. They know when to use a cannula versus a needle or when a blended material will work best. Many dermatologists have started to tailor their fillers by adding a little lidocaine or saline to bring down the G prime so the product becomes a little more malleable, Dr. Matarasso said. “This is where the art meets the science of injectables,” he added.

“The science of being a great injector is that you have to know the anatomy cold,” Dr. Cox noted. “You have to know where the important nerves, arteries, and veins are to avoid injecting into them and causing [an adverse event]. The art is about applying the ideals of beauty, and how to make the patient’s face in front of you look five or 10 years younger than when the patient walked into your office.”

COULD CAUSE HARM

Not knowing the science can result in harm to the patient if the wrong dermal filler is used in the wrong anatomic location. Among the potential adverse effects are swelling, lumps, nodules, depressions, and the Tyndall effect that makes the skin appear bluish when the filler is placed too superficially. Using a high G prime filler, such as calcium hydroxyapatite, under the eyes or lips can cause horrible lumpy nodules that can’t be dissolved, Dr. Cox said. Conversely, using a low G prime filler to create some definition or lift in the cheek, jawline, or chin won’t have any effect. While the latter isn’t harmful, it will anger the patient who just spent money to have a cosmetic procedure that failed to yield the desired result.

Dr. Matarasso sees profound complications from site-specific fillers being injected inappropriately on a fairly regular basis. One patient recently came to him after going to a local spa where an aesthetician injected her face with four different fillers all made by different manufacturers. The aesthetician used a high G prime filler around the woman’s eyes and an even higher G prime product around her mouth, which made no sense, he said. She used two other fillers around the patient’s lips and eyebrows. When the patient returned to the spa to have the overcorrection fixed, she was injected with large amounts of cortisone. “They didn’t select the appropriate treatment which is to dissolve the hyaluronic acid nodule with the enzyme hyaluronidase, so the result was atrophy with a significant concave depression in her face,” Dr. Matarasso said. “It looked like a Picasso painting. There were lumps, nodules, and depressions where there shouldn’t have been.” Using four or five different products for one facial improvement is not in the patient’s best interest, he stated. It’s hard to tell which filler worked best for the patient, and if an adverse reaction occurs, it’s impossible to determine which product caused the problem.

ADVICE FOR DERMATOLOGISTS

To learn about all of the latest fillers and their indications, Dr. Cox advised dermatologists to read as much as they can in the medical literature and attend conferences that offer filler courses, such as those run by the AAD and American Society for Dermatologic Surgery (ASDS). She also recommended doing a year-long cosmetic fellowship offered through the ASDS, or a preceptorship, also offered through the ASDS. “There is no substitute for time spent one-on-one with a physician watching how an expert injector uses the different fillers,” Dr. Cox said. Dr. Matarasso suggested calling manufacturers to ask for a demonstration of their products. “You want to see how the syringe feels in your hand, the resistance of the injection, and the flow pattern of the fillers,” he said.

For novice injectors, Dr. Matarasso recommended starting out by using one baseline filler in one area, such as the nasolabial folds. Gain some versatility with the filler before moving on to other areas. “Once you have familiarity with the anatomy and know what to look for, add another filler or two,” he said. “It’s all about learning technique.” Dr. Matarasso prefers using one product line on a patient, if possible, to ensure consistent and predictable results. Another advantage to using one brand is if a problem arises, he can call the manufacturer to ask what to do about it.

Although it’s an exciting time because of all the fillers available on the market, it can also be overwhelming to keep straight which ones work best where. Dr. Matarasso urged dermatologists to start cautiously because patient safety is paramount. “Every product has a safety and risk profile,” he said. “You need to manage that ratio to see what’s appropriate for the patient.”

New approvals target specific anatomic locations