A shot of history
Professor Nick Lowe guides us through 20 years of injectables
Injectables have revolutionised aesthetic treatments over the last 20 years. Looking at aesthetic procedures that have been used since 1997 (recorded by the American Plastic Surgery Society), botulinum toxins outpaced the frequency of use of the other categories of injectable.
Why injectable fillers?
One rationale of using injectable fillers is to restore the ageing face
to the contours of youth. This is one of the most frequent indications, but the other indication for volumising fillers by derma-
tologists and skin physicians, is for managing patients with atrophic scarring and lipodystrophy of the face.
Recent history of temporary tissue augmentation
This started with the advent of bovine collagen in the 1970s and 1980s when Collagen Corporation in California developed bovine collagen. The start of the hyaluronic acid fillers came in the mid-1990s, with avian-derived hyaluronic acid, Hylaform (HA). The next development was non-animal-derived hyaluronic acids, called NASHA hyaluronic acids. Several studies including some of our own showed that these produce much less allergy than the animal-derived HAs. Many HAs are now available. Neocollagenesis fillers with polymerised lactic acid was developed in response to HIV related facial atrophy. In the USA there are far fewer fillers than in the rest of the world, and as a result fewer complications. Only a relatively small number of fillers have been thoroughly researched to FDA requirements, which cannot be said for the UK and the rest of the world where—in my opinion—we have far too many fillers.
The other thing that’s popularised fillers more recently is knowing what else they can do. Fillers don’t just fill, with strategic placement of the fillers you can achieve useful lifting, volumisation and facial contouring changes. Years ago Bill Hanke and Gerhardt Sattler described the Tower method of injecting HA fillers with needles, and others have proposed variations on this. My own approach is I use needles for some areas to lift and I will use cannulas for other areas to volumise.
I can’t over-stress the importance of planning your injection sites for each patient. We can have patient do facial “grimacing” as well as static marking, to enhance the placement of these agents. This is what I do and I will select some areas for injection with needles and I’ll select other areas for the cannulas.
Over-simplifying where to place these fillers can be misleading because every patient’s face, as we know is quite different. You have facial asymmetry, facial anatomy differs, the patient desires differ and faces change considerably with age and weight.
I think using both cannulas and needles makes an enormous amount of sense. There are definite advantages to cannulas in some locations, vascular risk areas. For periosteal placement I think needles are more accurate, and for large areas of volume replacement cannulas are more logical. In a recent audit study at Cranley Clinic we showed that cannulas create less bruising than needles, and there are certain areas where you can use the cannulas to safely deliver correcting volumising filler and you can use them in combination with needles.
In my clinic we try to reduce the incidence of bruising by using a vascular viewing laser, which we find extremely useful. I mark out the vascularity; this laser picks up veins, adjacent veins and many arteries, so by marking these areas carefully we can target and avoid hitting those vascular areas. This is a very common area for bruising with fillers, and it’s these vascular areas in this area.
Swelling from fillers
Certain areas swell more than others—the lips area may swell more than other areas with some fillers than with others. We carried out a study where we injected 1.5cc of a hyaluronic into the upper and lower lips and measured the volume immediately afterwards. That increased volume was 2.8cc, which equates to almost as much oedema and swelling as the amount of filler. We found there can be a difference from one filler to another in the amount of immediate lip swelling.
I will usually use three types of HA filler: a high G-prime for
upper face and lifting, a volum-ising filler for the mid-face and atrophic scars, a lower viscosity filler for shallows in the perioral area. There are many fillers out there,
so you need to find ones you can trust and probably just stay with those.
Polymerised lactic acid
These have an important part to play for volumisation of the face, the correction of atrophic scars, facial asymmetry and lipodsytrophy. Polymerised lactic acid was used for this for years and in a study using three dimensional imaging, we proved that improved volumisation does occur after a series of polymerised lactic acid injections. One problem with polymerised lactic acid is that there are certain areas where it has a higher incidence of nodule formation. You can overcome this with increased dilution techniques.
Polymerised lactic acid also requires a series of treatments – usually about three to five – to get the maximum volumisation. Many of my patients don’t want to come for all those treatments. More recently I’ve been using another neocollagenesis filler, polycapralactone fillers.
Polycapralactone progressive re-volumises as the polycapralactone beads dissolve and create this progressive neocollangenesis. I’ve started using this for atrophic faces, hands. As yet haven’t seen any serious complications.
Fillers are not a replacement for face-lifting surgery, but they can be used in a very valuable way for treating facial atrophy, asymmetry, atrophic scars, nasolabial folds, and modest facial lifting. I advise always having hyalase available in your emergency filler tray to dissolve overcorrection. Nodules and papules can be permanent with non-HA fillers.
I’m wary of injecting some fillers too superficially, because some can give a bluish Tyndall effect, and also wary of reactions, with previous permanent fillers, if you inject near a previous filler there can be a problem with delayed reactions.
Necrosis is obviously a major potential problem but I feel there is much less risk of necrosis with cannulas because they tend to push vascular structures aside rather than piercing them. With use in the periorbital and nasal areas there is a small but tragic number of cases of reported blindness.
Early history of botulinum toxins
The innovative work of the American ophthalmologist Dr Alan Scott, using botulinum toxin for the correction of strabismus, initially in primates and then in humans began human use.
Drs Alistair and Jean Carruthers noticed that patients treated with strabismus showed improvement in some of their periorbital wrinkles. That led to development studies with the botulinum toxins from the 1990s onwards. A series of double blind studies resulted in the modern use of the botulinum toxins. In the 1990s and early
2000s there were two botulinum toxins: type A Botox – the American-derived toxin from the Fort Detrick warfare station in Maryland in the United States; then Dysport, named after Porton Down, the biologic warfare station on Salisbury Plain in the UK. The approved uses have gradually expanded, initially blepharospasm, cervical dystonia, strabismus, cerebral palsy, hemifacial spasm, and moving to the treatment of glabellar lines and hyperhidrosis and numerous other indications.
From 1996 onwards, clinical evidence was gathered of botulinum toxin A in glabellar lines. I was a participant in early double blind controlled placebo studies, BotoxTM was eventually approved for use for glabellar lines in the United States in April 2002. In some patients we noticed that in addition to improving the mid-forehead frown lines we also saw significant brow lifting which led to a series of observations and uses based on strategic placing of BTX-A. The whole concept of brow lifting with the botulinum toxins, is now very firmly established; the key is knowing where to place toxin, otherwise you’ll get brow drop and heaviness of the brows.
As the treatments evolved, we realised that some heavily muscular, heavy brows, particularly males, needed more botulinum toxin units, above the 20 units of the approved dosage. Fortunately we can use it outside of the indicated doses. From 2006 onwards, other botulinum toxins became available and we have now three available at the moment in Europe and the USA.
Units of BTX-A with the botulinum toxins are not interchangeable, they are quite different. Different formulations have different protein loads and different delivery – there are key differences pharmacologically between the botulinum toxins. In my clinic we use Botox to Dysport with roughly a 1:2.5 unit conversion. With Xeomin there’s been some really interesting studies around levels of glabellar strain suggesting 1 unit of Xeomin has less duration than 1 unit of Botox.
Crow’s feet was the next area researched. I did the first study in 2002, which was a pilot study. Our dosages were confirmed by a large multi-centre study. I use between 12 and 18 units of Botox units, or the equivalent times 2.5 Dysport units for each crows feet area.
An important use of botulinum toxins is for hyperhidrosis. There is greater diffusion of botulinum toxins in subcutaneous tissue than in muscle. Several factors govern diffusion – e.g. dilution and volume. Injecting in a dense, bulky muscle it diffuses less than into subcutaneous tissue.
This occasionally occurs; in general it’s much more common in the larger dosages for neurologic use. We have seen a group of patients who have developed resistance to type A toxins. I see about two patients a year, with acquired type A resistance from aesthetic use and a few more with hyperhidrosis. The reason, for this is when one type A is resistant they all are. The enzyme targets are different – there’s a snap 22 target for the type A and there’s a different one for type B, so they’re all working through the different synaptic proteins.
There are problems with type B botulinum toxin too. It is more expensive, unless you modify the pH it gives a lot of injection pain, and also it doesn’t last nearly as long as BTX-A for muscle activity. Interestingly, although it doesn’t last as long in muscles, it may last longer against hyperhidrosis.
Reducing BTX Bruising
A few patients get bruising after botulinum toxins, particularly in the crow’s feet area, which led us to use a vein viewing near infrared laser system to identify the vascular elements, mark the vascularity, and then make a point of where to inject the toxin. For anybody that we think is at risk for bruising we will use this routinely, and I think it is useful for both toxins as well as fillers.
Other side effects
There are side effects from Botox, but fortunately relatively few when it is injected, some lower eyelid oedema, and facial asymmetry from an over-action in some areas compared to the others. Occasionally we also see diplopia. There have been reports of using too much botulinum toxin in the cervical area and resulting dysphagia and dysphonia. Very rarely, hypersensitivity reactions, have been reported.
Combining BTX with other treatments
Combination treatments of botulinum toxins with appropriate fillers can lead to good results. If you use botulinum toxins in association with lasers or pulse lights, my advice is do the botulinum toxin at least a week before or after. I tend not to do them at the same time because of an increased bruising and diffusion risk. You certainly can inject BTT the same time as fillers.
The future of botulinum toxins
A topical botulinum toxin developed in the USA has been reportedly abandoned recently. There are acetylcholine inhibitors that could be promising for the control of hyperhidrosis. Time and effort may lead to new alternative treatments.
Professor Lowe is a Consultant Dermatologist at Cranley Clinic, London, and Clinical Professor of Dermatology at UCLA School of Medicine, Los Angeles. He is Fellow of numerous societies and Colleges, including the Royal College of Physicians, American Academy of Dermatology, American College of Physicians, American Society of Laser Medicine and Surgery, Royal Society of Medicine and is a past President of both the Pacific Dermatology Association and the Cosmetic Dermatology Group of the British Association of Dermatology. Prof Lowe is a prolific author, with over 450 clinical and research publications, 15 scientific and five educational books for the public. He is on a number of editorial boards is a reviewer of International Journals and is founding editor of the Journal of Cutaneous and Laser Therapy. Over the last 30 years he has undertaken clinical research and treatment of general dermatology, acne, ageing skin, laser skin therapy, photo protection, phototherapy, psoriasis and skin rejuvenation procedures.