Hyaluronic Acid in Practice

By Allie Anderson / 07 Dec 2016

Allie Anderson explores the development of HA fillers, their application, best practice and management of complications

When it comes to beauty, people these days really are trying to keep up with the Kardashians. Last year, some aesthetic clinics reported that enquiries about lip fillers increased by as much as 70% after Kylie Jenner of the famous family confirmed she’d had the treatment.1 It’s no surprise then, that dermal fillers remained the most popular non-surgical treatment in the UK in 2015, with a 113% surge in enquiries.

Of course, people don’t just turn to fillers for plumper lips. They can be used to treat several facial aesthetic concerns, including: scars, crow’s feet, nasolabial folds, marionette lines, loss of volume in the cheeks, frown lines.3 as well as the ears, hands and the vaginal area. One of the most popular substances used in filler treatments is hyaluronic acid (HA), owing to its temporary nature and the fact that it can be reversed. But dermal fillers have not always been as sophisticated as they are today. 

For decades, the go-to substance for soft tissue augmentation was silicone, which enjoyed huge popularity throughout the 1950s and 60s. But silicone fillers were associated with numerous severe adverse events, including granuloma, nodules, tissue necrosis, infection, pain and migration of the injected substance.4 Moreover, the fact that silicone gave the fillers a lasting outcome made it attractive to consumers, but this also meant that any complications were especially difficult to manage, and silicone was banned by the US Food and Drug Administration (FDA) in 1991/1992.5 In the early 1980s, the FDA approved bovine collagen as a filling agent,6 and it enjoyed many years of popularity worldwide. However, derived from the hides of cows, bovine collagen requires double skin testing before treatment, meaning it’s not the quick fix many hope for, and is associated with a 3-5% risk of delayed hypersensitivity.

One solution emerged in the mid-1990s in the form of HA. The substance occurs naturally in the body’s cells and tissue fluids, and is a key molecule involved in maintaining the skin’s moisture.8 It
is this moisture-retaining capacity that makes the skin pliable and plump, and hence, the loss of moisture associated with ageing causes the skin to lose elasticity, making it prone to lines and wrinkles. HA fillers, therefore, have many applications in antiageing treatments. Since HA is also biodegradable and does not elicit
an immune response,9 it is now regarded by many as the most effective dermal filler substance. 

The right product for the job 

Aesthetic practitioner Dr Ravi Jain is a proponent of non-animal stabilised hyaluronic acid – known as NASHA, used in Restylane filler products. “The NASHA technology is the most widely studied technology globally,” he claims. “It’s been around for more than 20 years and, in my opinion, is the gold standard in treatment; I find it delivers excellent results when you’re looking at efficiency of product and maximum lift.” The NASHA products come in the form of a firmer, gel-like substance, which aims to give rise to a more pronounced lifting capacity. “I use this when I want a more targeted projection and lift in someone with thicker skin, or when I’m trying to alter the contour of the face, for example, the nose, chin, jawline and cheekbones,” Dr Jain adds.

 For older patients with thinner tissue coverage who would benefit from restoration as well as volumisation, Dr Jain advocates another HA technology, also used in Restylane. “I would turn to OBT – Optimal Balance Technology
– because these products have a more distributed rather than targeted tissue integration and give a softer, more even look.”
One of the main differences between types of HA fillers, says Dr Jain, is the degree of cross-linking and tissue integration. Variations in cross-linking technology coupled with particle size helps practitioners choose between products that provide more lift or more tissue integration.9

This cross-linking also determines the longevity of the product, says Dr Ayad Harb, who uses a hyaluronic acid product based on supreme monophasic and reticulated technology (SMART) properties called Princess by CHROMA-PHARMA. “The manufacturer has developed
a way of very cleverly manipulating the HA chains so that they are aligned very closely together to optimise their reticulation,” Dr Harb explains. “The HA gel is then cross-linked in the usual way with a
very low concentration of the non-HA constituent – 1 ,4-butanediol diglycidyl ether (BDDE) – which binds the HA chains together to give them more resistance and greater longevity.” 

The product is also homogenised to make it smoother, which, Dr Harb adds, “Means
it’s very easy to inject with minimal force, making it much more comfortable for the patient.” Many years of data support the use of BDDE-cross-linked HA fillers as a safe and highly effective choice of treatment;10 but some evidence – both empirical and anecdotal – suggests that the substance’s integrity can begin to decline within six months.11 For this reason, Dr Kathryn Taylor-Barnes opts to use Neauvia, a range of fillers that, rather than being cross-linked with BDDE, contain the biodegradable substance poly ethylene glycol (PEG). “Neauvia not only gives immediate hydration and structural support of the hyaluronic acid, but also the calcium hydroxyapatite helps to stimulate collagen in the longer term,” she comments. 

Molecular size is also important in choosing an effective HA filler, as Dr Milvia Di Gioia highlights. “I use a family of cross-linked monophasic HA, Regenyal Idea. The molecules are as small as 1-3 microns – where the average with monophasic fillers
is 40-50 microns, and the biphasic around 200 microns – and this allows the filler to integrate with the tissues where it is implanted and progressively diffuse all around,” she says, adding, “In my experience, the homogeneous distribution results in a very natural effect of the treatment, which also does not alter the facial expressions.” 

A patient-focused method 

Taking a holistic approach is key to Dr Di Gioia’s treatment protocol. This involves looking at the patient’s concerns in the context of the entire face with the aim of maintaining proportion. “We call this the 3D facial volumisation. We start with a full consultation about all the facial problems and the patient’s desires, and go through a full-face analysis with the aid of the full-face imagery; we offer a comprehensive treatment plan able to address all the different aspects,” she explains, adding, “The aim is to create new balance and harmony in the facial proportion and appearance.” To this end, Dr Di Gioia employs a nine- point injection technique to lift and reshape the middle and lower thirds of the face and to give a well-proportioned, natural result. According to the practitioners interviewed, this method reflects a shift in the general approach to dermal fillers over the last decade or so, where the focus now tends to be on the overall face and the causes of the patient’s concerns, rather than on tackling a specific problem
in isolation.

As Dr Harb says, a patient who seeks to remedy their problematic nasolabial folds or lower face jowls will ultimately be disappointed if you only consider that concern. “It’s easy to fill a line
or fix a shadow or crease, but that’s not addressing the underlying problem so it’ll recur pretty quickly. I always try to appreciate the ‘whys’ in facial aesthetics: why is the skin sagging, why are there fine lines, and why have the lips thinned out?” Treating the causes of these problems in combination tends to yield better outcomes and happier patients, he adds.

Aesthetic nurse prescriber Amanda Robertson commonly performs mid-face HA fillers, mainly treating the cheeks and lips. She says a thorough appreciation of the patient is an important consideration
in selecting the type and amount of product, as well as how and where you inject it. “I look at the person and their size, as well as their lifestyle,” she comments. “With someone tall, everything about them
is slightly bigger – their face, head and hands – so they tend to be able to take more filler than someone smaller. I would therefore often use more product for a taller person than someone shorter to achieve the same result; perhaps two 1ml vials instead of one to define the
lip border.” A light-handed approach is best, Robertson adds, with patients sometimes opting to return for a repeat treatment weeks later if, when the product has settled and initial swelling has subsided, the result is less pronounced than they had hoped.


One of the potential pitfalls with HA fillers, practitioners note, is the propensity to over-inject, leading to a puffy and sometimes lumpy appearance in the treated area. To combat this, Dr Taylor-Barnes
and Robertson both advise that the practitioner must take time to massage the area after it’s been injected, to shape the product and ensure it disperses rather than clumps together. “It’s important not to rush the procedure and certainly spend time moulding the product,” says Dr Taylor-Barnes. 

“The quality of the products today should mean it’s robust enough to withstand a degree of moulding and massaging without harming its integrity.” A filler that contains anaesthetic is advantageous in this regard because thorough post- injection massage can be painful and hard for patients to tolerate, adds Robertson. “I prefer an injection with lidocaine in it,” she says, “And if you take your time and allow the lidocaine to take effect, at
the end you can give a really good massage to eliminate any lumps and bumps and improve the result.” Of course, the added benefit
of HA is that it has a neutralising agent in the form of hyaluronidase. Administered via injection, it dissolves the HA thereby reversing its effects. So, in the event that a patient is unhappy with the outcome of their filler treatment, or if they experience any adverse reaction – such as allergy, infection or lumping – it can be easily managed.

Refining treatments 

The evolution of HA fillers over the years has enabled the industry to develop a wider range of applications for a diverse patient cohort. 

Dr Taylor-Barnes, for example, has among her armamentarium a HA product specifically aimed at men, Intense Man from Neauvia, which has a higher concentration of HA (28mg/ml) and is more viscous. It can therefore be considered more suitable for men’s thicker skin and can be used to restore volume in areas of sagging, as well as to fill areas of skin depression, including deep wrinkles and nasolabial folds.12 But as important as the formulation of the product itself, says Dr Taylor- Barnes, is the branding and packaging. “It’s nice to have a product that’s recognised for the male market, because when a male patient comes into an aesthetic clinic, everything is female-orientated,” she comments, adding, “These fine touches help your patient to be more receptive to treatments.” As products have advanced and become more sophisticated, so have practitioners’ skills, enabling many to develop signature treatments. One such treatment is the ‘three-point rhinoplasty’, designed by Dr Harb using HA fillers to alter the contour of the nose. 

This non-surgical nose correction involves an injection of HA filler at three points – the top, the bridge and the tip – to smooth out bumps, correct droopy tips and crooked profiles, and give a straighter, more proportioned nose. “I have used my experience as
a plastic surgeon and knowledge of the nasal anatomy to rationalise this non-surgical treatment of the nose, which is able to correct 90% of noses that present in my clinic,” says Dr Harb. “The procedure gives predictable, consistent results, without the complication of surgery and in a treatment that takes all of just 10 minutes.” Dr Harb uses a HA filler that typically lasts between 12 and 18 months, with the potential to last longer when placed in the nose, because, he explains, “It is not an area that is prone to rapid deterioration, since the nose doesn’t move in the same way as other parts of the face.” 

Looking ahead 

According to Dr Di Gioia, the future of facial rejuvenation remains firmly at the door of HA fillers, thanks to, “Its excellent performance in terms of results and biocompatibility.” She comments, “Companies are working hard to lower the amount of the cross-linking agent, giving rise to an even more biocompatible product.” Dr Jain adds that further developments are likely to result in the inclusion of more additives, such as antioxidants. While many ranges are nowadays formulated with analgesic, this is not standard – something that could improve
the usability of the product and the tolerability of the treatment. 

But Dr Taylor-Barnes believes that manufacturers will develop more HA- based products to treat different anatomical areas. “There’s a big trend towards vaginal rejuvenation, so I would expect there will be more ranges targeting the female genital area,” she concludes, adding, “I also think there is room for improvement in the products available for the periocular region.” While HA fillers continue to be outside the jurisdiction of prescription-only medicines, there remains the risk of sub-standard treatments performed by unqualified practitioners. But in the right hands, and with full understanding of treatment protocol and, crucially, complication management, HA fillers are sure to retain their place in aesthetic practice as a top treatment for many ageing concerns for a wide patient demographic. 

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