Editor's Note:
Dermal fillers have been used as a nonsurgical option for facial rejuvenation for more than 2 decades. This field has seen great advances in the past few years. Jayashree Gokhale, PhD, Scientific Director of Medscape, spoke recently with Tiffani Hamilton, MD, Director of Atlanta Dermatology, Vein & Research Center, LLC, Alpharetta, Georgia, about the key essentials in this field. Dr. Hamilton presents a brief historical perspective on the development of dermal fillers and discusses their use in volumization, setting patient expectations, safety, patient follow-up, and the importance of educating patients about different treatments.

Medscape: Can you give us a brief historical perspective on the development of dermal fillers? Why is there a need for different types of fillers?

Dr. Hamilton: The first dermal filler was bovine collagen. That was developed back in the 1980s, and although it was a wonderful filler -- it did a good job with fine wrinkles and lips -- there were some problems with bovine collagen. The first problem was that a certain percentage of patients developed an allergic reaction to it because it was a foreign substance and not recognized as human. The other problem is it didn't have quite the longevity that one would want in a dermal filler. Sometimes it would only last up to 6 weeks in patients. Certain people got up to 3 months, but it was rare for the bovine collagen to last longer than that.

Then we really had a great advance in the filler arena in 2004 when the hyaluronic acids were FDA [US Food and Drug Administration]-approved. Hyaluronic acid is a normal substance of our dermis. They provide really good structural support to the tissue. So, they were a good true filler substance. Hyaluronic acids, and there have been several that have been FDA-approved, are really great fillers for wrinkles, discreet wrinkles, lips, around the eyes, infraorbital wrinkles, and support some volumization of the face. However, unlike other newer fillers, which I will discuss a little bit later, they do very little in the way of stimulating collagen. So, once the body degrades a hyaluronic acid, it is pretty much gone.

Now, there is some new research that there is a little bit of collagen stimulation when you put any filler in, but it is not really enough to give a long-lasting correction. The hyaluronic acids last about twice as long, 6-9 months, and sometimes a little bit longer than the collagen, so that was a really great advance there. Also, because hyaluronic acid is ubiquitous among species, there is very little risk for allergy and skin testing was not needed.

Then we progressed in 2005 with the FDA approval of poly-L-lactic acid (PLLA). It was and still is just FDA-approved for the correction of HIV lipoatrophy. Unlike the true fillers, which basically are space-occupying molecules, PLLAs are small particles that, when injected into the subcutaneous tissues, actually stimulate the production of collagen and lead to a volumization effect and a more long-lasting effect than true fillers. Not only that, but because it is the production of the body's own collagen, it ages very naturally with the patient, and it gives a very nice, natural correction that can last at least 2 years. In my clinical experience, it has lasted up to 4 years or more.

The other kind of crossover between volumization and a true space-occupying filler is calcium hydroxyapatite, which was approved in 2006, and that does give a little bit of collagen stimulation and also provides instant gratification, whereas PLLA, which does a lot of volumization, is delayed gratification. It takes several months for the collagen to build.

Then finally, this year, we have had the development of porcine collagen. It is a new method of producing collagen; they clip the ends and it is glycosylated into fibrils. So, the body actually interprets that collagen as human instead of porcine. Because of that, there is very minimal risk for allergies. Again, testing is not needed and it lasts quite a long time, and studies suggest that it lasts up to a year.

So, the filler arena has just really dramatically exploded since 2004, giving us a lot of good options where we were pretty much stagnant for the 20 years prior to that.

Medscape: Do these allergic reactions subside with standard treatment?

Dr. Hamilton: Allergic reactions to collagen do tend to subside with time. However, while the product is still in the patient, there can be a continued nodule or skin eruption in that area sometimes requiring systemic steroids or even systemic cyclosporine to keep the allergic reaction down to a minimum while that collagen is degrading. Because of that, a double skin testing is recommended for bovine collagen. The double-skin test, however, does not mean that you are never going to develop an allergy because an allergy can develop to anything at anytime, so even if a patient has used bovine collagen for years, there can always be that risk for allergy. There are risks for allergies or granulomas to the other filler products, but they are much less likely, and that is more of a rare hypersensitivity response.

The only other filler that is actually a permanent filler is a collagen gel with polymethylacrylate, or PMMA, particles in it -- and that was FDA-approved in 2007. That does lead to a permanent correction, and because it is bovine collagen, there is a need for allergy testing.

Medscape: What are the different types of fillers used today?

Dr. Hamilton: There are quite a few ways to define fillers. They can be defined on the basis of their longevity, whether it is replacement or stimulatory, and I like to think of it as either a replacement or a stimulatory filler. The replacement fillers are collagen, hyaluronic acid, and the stimulatory fillers are PLLA and calcium hydroxyapatite. The calcium hydroxyapatite does constitute both a replacement and stimulatory filler.

The difference in durability really depends on how the body sees the molecule. As far as collagen goes, it sees it as a foreign substance because it is bovine, so it breaks it down relatively quickly. In regard to the new collagen that is porcine with the allergenic ends enzymatically clipped off, the body does not sense that as a foreign material, and it really intercalates those collagen fibrils into the body; therefore, there is much more durability there.

The stimulatory ones are much more durable because they are replaced by the body's own collagen. So although it is not a permanent molecule, the actual molecules that are stimulating the fibroblasts tend to degrade and are gone at 6-9 months. The clinical correction can last several months to several years.

Medscape: Is there any other treatment or emerging treatments using combinations of various classes, various groups of these fillers?

Dr. Hamilton: Yes; there are a few in research right now that are not approved. There is one that is probably the closest to approval, which is very exciting. It is hyaluronic acid gel with calcium triphosphate, and it does give some instant gratification with the hyaluronic acid carrier, whereas the carrier for the PLLA is just water, so you don't get instant gratification. Then, the gel for the current calcium hydroxyapatite does not last any longer than about 6-9 months.

Medscape: In your clinical experience and your opinion, who is an ideal candidate for this treatment? In other words, how do you decide which specific type of treatment would be beneficial for a particular patient? What factors do you consider?

Dr. Hamilton: When patients come into the office, I assess their case and also ask them what is bothering them. A lot of women in their 20s may want lip enhancement, and so, if they are going for lip enhancement, you want one of the hyaluronic acid products or a collagen product. The hyaluronic acids do a very nice natural lip enhancement and can have a good amount of durability [for about 3-9 months], whereas the bovine collagen, and even the initial human collagen, only last about 6 weeks.

Now, once women get into -- and even men -- their 30s or 40s, they start noticing volume loss, and as we age, particularly as thinner women, we tend to lose volume in our central face -- medial cheeks. When we lose that volume, then we start noticing that we have tear trough or the hollows under the eyes and also prominent nasal labial folds. So nasal labial folds are the result of loss of volume in the deep medial cheek fat pads.

The other area that in the 30s, 40s, and 50s we start losing a lot of volume in is the marionette lines of the chin, and also because of the overall loss of medial cheek volume and the descent of the tissues, we begin getting a gel appearance. Because of that, patients at that age range look more toward the volumizers.

Now, you can volumize with hyaluronic acid and calcium hydroxyapatite, which are the replacement fillers, and even collagen and the new long-lasting collagen. The problem with correcting volume loss with just a replacement filler is (1) it takes a lot of product to do that -- and it can be cost-prohibitive -- and (2) you don't have quite the longevity. However, for patients who do want instant gratification, or have minimal volume loss, then those fillers are appropriate. The various hyaluronic acids do a wonderful job with the tear trough and the hollows under the eyes, also putting it in the central cheek area for correction of the nasal labial fold, and the marionette lines.

For patients with significant volume loss or for patients who want a very natural correction and don't require instant gratification, then PLLA is a very nice choice. Before PLLA, the only way to really volumize significant loss was with fat transfer or fat grafting. Now, since the development of PLLA, I found in my clinic that I do very little fat transfer because unlike fat transfer, the PLLA volume correction is quite predictable; I don't have to worry about the second surgical fat harvesting that is required.

In the 60s, 70s, and even 80s where there is a lot of volume loss, the products that volumize are really the most important thing to look at. However, many of my patients want both instant gratification of the true space-occupying fillers and the long-lasting, but delayed, volumization that comes with Sculptra™ (PLLA), and so combination therapy is really where to go with most patients once they are beyond their 30s because we need that wrinkle -- that superficial wrinkle correction -- plus we need to fill that volume that we have lost.

Medscape: What is the timeframe for instant gratification?

Dr. Hamilton: With the hyaluronic acid products, hyaluronic acid is a very good plumper. It loves water, and so initially, the correction is actually too much. So, for anywhere from a few hours to several days, there can be some swelling. Then that goes down and the correction usually settles out at about 1 week, and the patient maintains that correction over several months. With the collagen, and particularly the new long-lasting porcine collagen, there is very little initial swelling. It is a pretty much immediate correction: What you see is what you get. There is no overcorrection needed, and that can last for up to a year.

The difference between hyaluronic acid and the porcine collagen -- as far as the instant gratification, there is also another nice point to the porcine collagen -- is that it does not promote bruising. A lot of times with the hyaluronic acid products, patients will leave; they will be looking great, and then wake up the next morning with terrible bruising. The reason behind that is because the hyaluronic acids are anticoagulants and collagen is a coagulant; therefore, you can see much more significant bruising. So, the patient can't always go immediately to an event.

Now, the calcium hydroxyapatite effect does not cause as much swelling as the hyaluronic acid. However, there can be a little more bruising than with the porcine collagen, kind of in-between there. Also, the difference between the calcium hydroxyapatite and the porcine collagen -- as far as the location or placement -- is that you cannot put those 2 products in the lips. They are too large of molecules, and they tend to coalesce into nodules or lumps in the lips. So you have to avoid those in that area -- same with PLLA.

Medscape: Is the treatment similar for male and female patients?

Dr. Hamilton: Yes; there is really no difference. It is all where the volume loss is. It does not matter, male or female.

Medscape: In your opinion, who should not receive these treatments?

Dr. Hamilton: One class of patients or one type of patient who should not get any dermal fillers are those patients with a condition called sarcoidosis, which is a condition where anything foreign injected into the skin or any foreign substance injected into the skin has a chance of turning into a granuloma or a red angry swelling. So, any patient with sarcoidosis, I tend to really avoid using dermal fillers. There is also a theoretical risk in using dermal fillers, particularly the collagen products, in any patient with autoimmune collagen disorders because they do not have antibodies to collagen. However, many patients with autoimmune disorders have done fine with fillers, but it is something that you really need to consider.

Another thing that you need to consider is herpes simplex virus (HSV). The augmentation of the lips can initiate or can lead to a recurrence of HSV. Also, there is some theoretical basis to the fact that HSV, when activated, can lead to a hypersensitivity granulomatous reaction. So, you really have to be careful in people with a history of HSV to appropriately treat with antiviral therapy.

Cheloid patients or patients with a history of cheloid, you always have to be concerned there. However, in a study or in my clinical experience, I have not had a problem in pigmented skin as far as increased cheloid risk with any of the fillers. However, I always do tell my patients that it is always a risk. As far as pigmented skin is concerned, any time you puncture the skin or cause disruption of the skin, there is a chance of temporary or more longer-lasting hyperpigmentation or darkening of the skin, although very unlikely with the fillers, but also something that you have to keep in mind.

Medscape: When the patient comes into your office, how do you describe the process or the treatment options, and how do you set the patient expectations depending on what the patient wants to achieve?

Dr. Hamilton: First, I ask patients what is bothering them. When looking at a patient, there are several things that may bother me that I want to correct, but if that is not what is bringing them to the office, then I really have to consider what their concerns are. However, sometimes they don't realize what their concerns are. They may say that they don't like their nasal labial folds, but when I point out that the reason they have them is the loss of cheeks, then it really fine-tunes our treatment options. So first and foremost, I try to determine what it is that they are really after.

The other thing that I want to know is whether they need instant gratification, or whether they are someone who can have kind of delayed gratification, and we can slowly improve their appearance either with a slow-building volumizer or just gradually volumize certain areas and fine-tune. Some patients actually prefer the delayed gratification and the slow change because they don't want people to know what they are doing. They just want people -- a few months from now -- to think that they are looking more rested or better than they did before, but then, they are always those patients who need to look good now and want to look different right now. So, the product I choose will depend on whether they require that instant gratification.

The other thing that I discuss with them is whether they are a novice to the filler. You may want to -- I tell them that they may want to consider a shorter-acting product and just try it out -- go for a test drive, if you will, for the filler. Not all patients like the look of themselves with that extra volume. It is rare, but you don't want to put something that is very long-lasting into patients and then have them be very disappointed with that. So, those shorter-lasting fillers are nice. Hyaluronic acid is nice in that way as well because we are able to actually melt it away with hyaluronidase, so if a patient does not like the correction -- or for whatever reason wants the filler gone -- we can dissolve it. Thus, it is a quick fix, and we can take it away if the patient does not like it. So that is a nice feature. For the new patients who are hesitant, just testing the waters, a hyaluronic acid product might be where they want to start.

The other thing is I tell patients that 1 syringe of a filler is not going to correct every wrinkle that they have, and that the costs really can get significant if they are looking for the filler to replace a face-lift, a surgical face-lift. So I always want to set their expectations to know exactly what each filler will do and the amount of correction that they can achieve with what product is in their budget and how much of the product is within their budget.

Medscape: Are patients familiar with the range of treatments that can be available, or do they decide that after you have educated them?

Dr. Hamilton: There has been a lot of direct-to-consumer advertising lately, which has really driven patients into the office. Patients come in with some sense of seeing products that are out there. However, they don't always know what product is best for the problem that they are seeing on their own face. So, just getting them in is nice, and when they are in, then we can discuss just exactly what is bothering them, and then describe the full range of this wonderful armamentarium that we have now with the dermal fillers and what would best suit their needs. Some patients just come in and want what they saw in the magazine or want what their friends have, and I guess that is okay, but I do believe as a physician and as the expert that it is my responsibility to choose the most appropriate filler for the patient and not just what they saw in the magazine or what their friend has. So education, I think, is key to patient satisfaction.

Medscape: What is your advice to new students who are just starting to use the injection technique?

Dr. Hamilton: Well, the first thing I tell any new injector is to know your facial anatomy, know where the structures are, and where the muscles are, the nerves, the fat pads, the compartments, and really learn how to look at the face and see what is creating the wrinkle and not just focus on the wrinkles. Once you do that, then the rest of the job is pretty easy. When you first start out, probably the best filler to start out with is the hyaluronic acid family of fillers. The reason it is so good to start out with is that it is easy to inject; it feels very natural for the patient. If you do happen to put too much product in one area, there is always hyaluronidase, which can melt the product. It is moldable and really pliable. So starting out with a good hyaluronic acid filler, particularly in the nasal labial folds, is a good place to start when you are just starting out.

As you get more comfortable with holding the syringe and the feel of injecting in the tissues and knowing what level you are in, then of course you can branch out to more aesthetic filling of the face with the combination of different fillers, combination of replacement and stimulatory fillers. Thus, it is really all about once you are comfortable with the syringe, you are comfortable injecting, and you know where the levels of the skin are, the most important thing is knowing your facial anatomy and knowing the area of the face, if you put volume in a certain area, what that is going to lead to, and how that is going to change the draping of the skin.

So when there are students in my office or other physicians in the office, you can talk about the fact that it is the underlying structures that are becoming volume-deficient, and we have to redrape the skin. You can't just focus on the wrinkles.

Medscape: What are the most common complaints you hear from patients? Could you describe the follow-up visits, and the safety considerations?

Dr. Hamilton: Probably the most common complaint from patients is bruising, and now, there are lots of tricks that we will use to try to prevent some of the bruising. The most important thing is what they are taking: aspirin, ibuprofen, vitamin C, and vitamin E. What has become a really big problem in my area are the omega-3's and flaxseed oil; everybody is on those and they do potentiate a lot of bruising. So just asking patients to hold off on that for a week to 10 days with those things really helps with bruising. Patients will get very frustrated when they have an important event and they just have a huge bruise that shows up 2 or 3 days later because they are on those products.

The other complaint is unmet expectations or unrealistic expectations. Some people think that they are going to have Angelina Jolie lips with 1 syringe of a hyaluronic acid product, and that falls on the physician or the injector. It is very important to educate patients on what they can expect within their budget. If they can only afford 1 syringe of a filler, they are not going to get much correction, or they may not get a full correction. So education is key.

Another problem with the thicker fillers, such as calcium hydroxyapatite or the new porcine collagen, is that those thicker fillers can be felt; therefore, some patients don't like the feel of that thicker substance. Now, with the porcine collagen, that tends to go away after several weeks and feels just like normal skin. Calcium hydroxyapatite is a great filler, but occasionally the patient will feel that fullness. I just tell my patients that it is a filler; we are filling it with something. It is not as soft as your hyaluronic acid, but because it is not as soft, it gives that much more structural support when they have those deep marionette lines or deep nasal labial folds.

Appropriate use of massage helps prevent lumpiness, and so, that really is just more of an injection-technique issue. I don't get many complaints about that; however, patients referred or who sort of come from other offices have stated in the past that they don't like that filler because it lumps up, and you just have to educate patients that there are appropriate areas to put the filler -- and maybe it migrated or who knows -- but it does not necessarily mean that the filler is bad; it just may not have been in an appropriate location.

The other thing with any product: Granulomas or nodules can develop. It is rare luckily, but that can occur. There are treatment options; for example, you can inject it with a dilute steroid; the nodules can be broken up, so they can be treated. However, that is a risk and can occur. If you are going to inject fillers, it is very important that you know how to handle complications.

Extremely rare but something that, if you are an injector, you have to keep in mind is that intravascular injection of a filler can result in occlusion of the vessel, and then necrosis of the overlying tissues. So it is important to keep a lookout of that, and that is why anatomy is very important and why appropriate injection technique is also important to prevent that problem. If you are unfortunate enough to have that experience, then having topical nitroglycerin onboard to dilate the vessels is good to have in your office.

As far as follow-up visits go, for my patients with just a replacement filler, I don't necessarily have them follow up in 2-3 weeks. Some physicians like to have patients follow up in 2 weeks for fine-tuning or subtle correction. I leave that up to my patients as far as whether they want more; I tell them that this is what you get with one: "If you have any questions, come on back and we will decide whether to put more in."

PLLA is a stimulatory filler that requires multiple sessions at 8- to 12-week intervals. For correction, I have those patients back every 8-12 weeks and assess whether more filler is necessary. Then, I just tell patients that it is best to touch up or do a repeat session before all of the filler is gone.

This activity is supported by an independent educational grant from Dermik.