30 years of neuromodulators

We speak to Dr Nick Lowe about his use of botulinum toxin over the years and what the future holds

DR NICK LOWE

Dr Nick Lowe is a consultant dermatologist at Cranley Clinic, London and clinical professor of Dermatology at UCLA School of Medicine, Los Angeles. He is a Fellow of the Royal College of Physicians, American Academy of Dermatology and American Society of Laser Medicine and Surgery. He has authored more than 450 clinical and research publications, 15 scientific and five educational books.

2020 marked 30 years of botulinum toxin for cosmetic use. Dr Nick Lowe was involved in some of the very early studies of the drug, and we wanted to find out more about how its development and continuing research over the years has impacted his aesthetic practice.

AM: Has a lot changed in 30 years? 

Dr Nick Lowe: Last year was the 30th anniversary of when we very first started using botulinum toxins for aesthetics. I’ve learnt a lot in the last 30 years and I have certainly refined how I use them, the dosages I use, sometimes the dilution, what sites I use them on and, very importantly, how I combine the toxins with other treatments to get optimum results for my patients. There will be developments in the future with a number of new toxins in the pipeline.

AM: How do botulinum toxins actually work?

 NL: All the toxins work by blocking the release of acetylcholine across the neuromuscular junction, therby reducing muscle action. The toxins target synaptic proteins: types A and E target SNAP-25 and types B,D, F and G target synaptobrevin. So, they all work in a similar way, they impair the release of the acetylcholine and thereby reduce neuromuscular action.

AM: More and more indications for the aesthetic use of toxins have emerged, taking their use way beyond forehead lines. What are the key indications you use them for?

NL: We can target a variety of different muscle activities of the upper face, such as glabellar frown lines, crow’s feet, horizontal forehead lines and infraorbital lines. We can also achieve brow lift in selected patients. For the mid and lower face, we can again target a number of different problems, ranging from nasal scrunch and flare, perioral lines, marionette lines and jaw line ptosis, to the mental creases, crinkly chins, platysmal bands, masseter hypertrophy and gum show. The novice injector needs to tread cautiously with lower faces and complex foreheads.

AM: What, in your view, is the optimal approach to patient selection?

NL: The optimal approach needs to include relevant history. What medications are they taking? For example, anticoagulants, aspirin, or steroid anti-inflammatories that may give bruising? Have they got any history of muscle weakness? We don’t want to treat a patient with myasthenia gravis.

Facial examination at rest and animation is very important for all our treatments, so we need to have a thorough knowledge of facial anatomy. We need to achieve facial harmony, taking into account different ethnic groups and what that means for individual patients. We also need to consider the goals of the patient. It’s important to select patients carefully and not over-treat.

AM: What advice can you give on injection sites? Is there a prescriptive approach with botulinum toxins?

NL: Many of these injection sites on training programmes have been standardised from research studies but patients vary considerably. We have to examine and carefully individualise different patterns of injections, depending on the patient’s face.

AM: The glabellar is one of the most commonly treated areas with toxin. What lessons have you learned through treating it over the years?

NL: Glabellar muscle patterns vary considerably, so we need to examine them at rest and frown. Examine for asymmetry, look for brow ptosis and look for the degree of brow elevation – this is very important. Mark treatment sites with ink spots and inject these areas; decide on and then record exactly how many unit doses you have used and where you’ve injected.

Target the brow depressor muscles at maximum frown. I have learned over the years that tiny amounts in the upper forehead (and sometimes just above the lateral brow) are important to avoid over-elevation of the brow, but I stress, tiny amounts. When the patient comes back 10 days or two weeks later you can always adjust. If you’ve put in too high a dose, then you are going to get long-term brow ptosis.

Consider less dilute-concentrated volumes in the glabellar procerus area in somebody who’s got very intense muscle action.

Photography is also very, very useful; it is essential pre-treatment so you can go back to those photographs when you next see the patient and adjust any injection sites for the following treatment.

AM: Do male foreheads need higher doses? 

NL: In general, yes. But you have to be careful not to create too much lateral brow lift. Many years ago I did a study with Dr Alastair Carruthers where we asked the study volunteers how pleased they were with the results. It was much easier to achieve 85% positive responder rates in females than in males because (in retrospect), we were not using high enough doses of toxin in males back then, which we can all correct now by examining the patients appropriately. So, most males definitely need higher doses than females to get the desired result.

AM: Is it more difficult to achieve an optimum result as people get older?

NL: I have learned over the years (and have had Botox treatment myself for 30 years) that it is more difficult for whoever is injecting me – my daughter, usually – to achieve what we feel is an ideal result and that’s true of most patients. When we looked at it in another study I did with Dr Carruthers, it showed quite clearly that the response rate is greater in the younger age group and is more difficult to achieve as patients get older. So, it’s important to address this when you’re examining the patient and when you are informing the patient of the likelihood of success.

AM: Which treatments do you find most successful combined with toxins, and would you always perform the toxin first?

NL: We’ve got quite a few treatments in our armamentarium and the crow’s feet is just one area where toxins are splendidly combined with other treatments such as resurfacing, milder chemical peels and topicals, such as topical retinoids. My favourite lasers for this area are fractional lasers, either the 1550 nm for mild-to moderate photodamage and laxity; and fractional carbon dioxide lasers for more intense damage.

Radiofrequency skin tightening is very helpful and some can be used in the periorbital area. I tend not to use highintensity focused ultrasound (HIFU), I prefer radiofrequency because it can be used in this area, and we also use radiofrequency microneedling with very small microneedles in the periorbital area. We have also started using the Endolift around the ocular area to improve infraorbital skin laxity, and of course we have the injectable stem-cell treatments such as PRP/PRF. They can all be combined with botulinum toxin.

If possible, always inject the toxin first. The rationale for injecting botulinum toxin two weeks before laser or radiofrequency rejuvenation is that it reduces frequent wrinkling during dermal remodelling, reducing the need for more aggressive laser settings. It also shortens the healing time and gives fewer complications. It’s important to bring the patient back into clinic, if we are really looking for optimum results, about three months later for further treatment with botulinum toxin, because, if you keep that constant wrinkling and folding of the skin reduced, you will get a more sustained uniform neocollagenesis.

While it’s common to combine toxin with filler, if possible, don’t inject fillers in the same session as the botulinum toxin to the same area. I have seen a greater risk of diffusion, for example in the perioral area, so it’s best to separate them. Do the toxin first and bring the patient back a week or 10 days later for the filler. Do the same with lasers.

AM: How do you approach the platysma?

 NL: One of the concepts that has certainly been stressed at recent American Dermatology Society meetings is how platysma is in fact not only a muscle that controls neck movement but it’s also is a lower facial movement muscle. Essentially, it is a pair of flat muscles over the anterolateral neck and lower lateral face, interdigitating into the perioral muscles and with other muscles, such as the depressor anguli oris, risorius, and orbicularis oris, so one has to think about it as a lower face and neck muscle.

I get my patients to make a sad face so I can see and feel the depressor anguli oris muscle under your finger or thumb and you can actually inject while you’re feeling it contracting.

I will often inject at different sites in the platysmal band. I mark them with the ink marking pen and inject four units of onabotulinum toxin A or equivalent into each site of the band, usually separating them by about 2-3cm apart, injecting as I go down the neck.

Don’t inject doses that are too high – err on the side of caution initially because you can always go back and inject more. Some patients have mild dysphagia, some subtle changes of the voice after treatment. Be particularly careful if your patient is a lecturer, an actor, or a singer, etc., where it’s critically important that they have full control over their pharynx and larynx. Go cautiously and don’t overdo it. I’ve seen reports of several hundred units being injected into the neck. This is quite unnecessary and can lead to problems. Remember, you can always go back and inject more.

AM: For the best part of its 30-year history there have been three major players in the toxins market in the UK: Botox, Dysport/Azzalure and Xeomin/Bocouture. Now though, we are looking at multiple new toxins entering the market. What can you tell us about these?

NL: The current toxins are as you note. There is a new one that’s been available for about a year in the United States called prabotulinum toxin A (Juveau) that will apparently be coming here in the future.

There are also a whole variety of other type A toxins supposedly in the pipeline trade named as: Hugel, Nuceiva (EU), Meditox and Chinatox. Some claim equivalents to the existing toxins but we need a well-designed study on them for safety

A Californian company called Revance has developed Daxibotulinum toxin A, which is linked to a peptide that supposedly increases the duration of benefit of the toxin. In one of the studies they found 24 weeks’ median duration of efficacy, however, they were injecting 40 units to the glabellar area. Direct comparison studies are needed with other type A toxins.1

There’s also a new liquid toxin coming from Galderma, a liquid Dysport, and that has shown efficacy compared to placebo. Liquid botulinum toxins have to be kept at an acid pH and injections can sting more than the normal pH of the type A toxins or the powder/lyophilised toxins where we dilute with a normal pH saline. So, this could be like the type B toxin where the stinging pH is painful.2 Personally, I’m not sure why I would use a liquid toxin but there may be some practitioners who would.

Also on the horizon is this future type E toxin that has rapid-onset short action, which could be used for a number of situations for a transient or temporary effect for aesthetic improvement of facial lines, or patients who want to see the benefits to determine whether treatment is for them before embarking on a botulinum toxin A that will last for several months. I think there may be some other interesting uses as well.