CPD: Analysing Facial Rejuvenation Treatments

Facial ageing is believed to be caused by intrinsic (genetic) and extrinsic (environmental) factors, including sun exposure, pollution, smoking, diet and general lifestyle elements.¹ Ageing may also be defined as a complex process brought about by cultural and societal factors reflecting biological, environmental and genetic influences.² Cutaneous changes include wrinkles, pigmentation and loss of elasticity, which often vary according to ethnic origin.2 Pollution may also play a role.³ 

Rejuvenation treatments include any injectables or skin intervention that makes the face appear younger.⁴ When considering a patient for facial rejuvenation, it is important to focus on facial harmony and realistic aims and outcomes.⁵ There is significant evidence to support implementing different methods to effectively rejuvenate the face in a variety of ways, and that combining two therapies together often yields more profound and longer-lasting results.^6-13 

In this article, I discuss four popular treatment options and present recent, relevant clinical data for each therapy with the aim of highlighting efficacy in treating specific issues.

Botulinum toxin

Botulinum toxin A (or BoNT-A) has its roots in ophthalmology, where it was first utilised in strabismus (squint) treatment.¹⁴ Allergan acquired the rights to distribute the drug in 1988, and the drug has been used cosmetically to reduce and prevent wrinkles in the upper face, periorbital and perioral regions since 1989.¹⁴ Its uses have expanded to treatment of the neck platysma bands, gummy smile and masseter muscles.¹⁵ It exerts its ‘muscle-relaxing’ action by gradually blocking release of the neurotransmitter Acetylcholine from presynaptic terminals of neuromuscular junctions at injection sites.¹⁶ 

From my readings, the highest proportion of trials provide evidence for the efficacy of BoNT-A in glabellar treatment. One open-label, phase 4 study (n=42) provided evidence that 85.4% of subjects displayed significant reduction in frown lines two days after treatment with 20U of the toxin Nabota.¹⁷ A larger scale American trial (n=156) treated and assessed healthy subjects in the glabellar, (GFL – 20U), frontalis (HFL – 10-20U) and periorbital line (LPL – 24U) regions, using a percentage scoring system.¹⁸ At 30 days post-treatment, a mean improvement of 71.3% across all treated areas was recorded in the study group, versus mean of 0.06% improvement in the control group.¹⁸ Another multicentre randomised, controlled trial conducted over five months and employing the four-grade facial wrinkle scale (FWS) focused on aesthetic results of treatment of the crow’s feet with 24 units of BoNT-A in 445 subjects. Findings provided evidence that the BoNT-A-treated group experienced a 66.7% wrinkle reduction at day 30, versus 6.7% in the placebo group.¹⁹

The effects of toxin may also go beyond wrinkle smoothing, with one study (n=40) providing evidence that female subjects who received a solitary treatment displayed significant improvements in cutaneous hydration, elasticity and a reduction in trans epidermal water loss (TEWL) at week 12 post-treatment, compared to the control group.¹² The same study also provided evidence that toxin therapy had positive effects on quality of life and psychological benefits on study group subjects, scoring significantly higher on the physician‘s global assessment and subject satisfaction score, compared to the control group.¹²

BoNT-A results vary according to a number of factors:^16,20

1) Antibody resistance – the lowest possible dose to attain the optimal outcome should always be used, and treatment intervals of more than three months should be instated

2) Sex – outcomes of BoNT-A treatment may vary between males and females due to differing muscle anatomy

3) Age – there is evidence to suggest that patients over 51 may require significantly higher doses

4) Length of toxin storage after reconstitution.

There is some data to support the theory that the type of toxin used affects the dosage required to reach optimum results; for example, one trial used 50U of Dysport (Azzalure) in the glabellar to achieve an average 86% improvement,²¹ whilst one Japanese trial provided evidence that lower doses of Botox – 10 to 20U – are required to achieve effective subject and physician-rated results up to a period of 16 weeks.²² This variation could be attributed to the presence or absence of complexing proteins across different brands, with protein-free toxins requiring lower dosage to achieve results.²³ On the other hand, a single-blind, split-face trial compared two toxin brands with 10 female subjects and reported no significant difference in clinical results.²⁴ Therefore, further large-scale, specific trials are required to substantiate this.

A 2022 study (n=40), provided evidence that combining toxin with hyaluronic acid dermal filler yielded a lower FWS in glabellar treatment, compared to toxin alone.²⁵ Another provided significant evidence that combining application of cosmeceutical hyaluronic acid (HA) serum with toxin injections lengthened the duration of action of the BoNT-A.²⁶ Study reviews have shown toxin to be a well-tolerated and safe treatment option for facial rejuvenation.²³ Uncommon adverse side effects include ectropion, ptosis, heavy upper eyelids, bruising and transient headaches.¹⁶

Hyaluronic acid dermal filler

Injectable dermal fillers are commonly used to treat signs of facial ageing and provide enhancement in specific areas. There is much evidence to suggest that injection of HA filler improves skin volume, texture, elasticity, smoothness and hydration, as well as greater type I collagen expression, and can be used to attain natural, youthful results.^27-29,30-35 HA is a linear glycosaminoglycan containing a disaccharide unit³⁶ and is hygroscopic, meaning it has the capacity to absorb water extensively, creating lift and volume in the face.²⁷ Dermal filler products can be classified as biphasic or monophasic, based on the type of cross-linking technology they possess; cross-linking is essential in maintaining product longevity and stability.^27,37 Products will also vary based on HA concentration, particle size, gel consistency, viscosity and hardness, plus water solubility.³⁷ There is evidence to suggest that monophasic HA fillers are more cohesive, cause less localised erythema and display less risk of migration compared to biphasic fillers following injection.^38,39

Understanding the rheological properties of dermal filler – viscoelasticity and cohesivity – assists practitioners in selecting the correct product for treatment of a particular part of the face.⁴⁰ A thorough knowledge of facial anatomy, ideal proportions, bone degradation, and the facial fat pads and vasculature, is essential to attain optimal results and safety when injecting.^29,41

Tear trough rejuvenation is a popular choice of treatment with HA filler.³⁰ Under-eye hollows are believed to occur due to anatomical changes including descent of the cheek and underdevelopment of the infraorbital malar complex.^27,42 Natural, effective results can be achieved in this area through depot, periosteal HA placement.²⁹

An American study (n=100), assessed tear trough treatment outcomes based on patient satisfaction, downtime and side effects following injection of Perlane 0.59ml beneath each eye. The mean downtime was one day, 85% reported marked or moderate satisfaction, and 10% were dissatisfied.³¹ A recent prospective study assessed 24 subjects treated with Teosyal PureSense Redensity 2 in the medial tear trough. At two and four weeks post-procedure 75% were satisfied with the outcome, whilst 25% required further filler to be satisfied, and side effects such as bruising and swelling were mild and minimal.³² A systemic review has highlighted that complications of tear trough treatment can occur up to a mean of 52 months following initial treatment, including lumps, migration, discolouration and swelling.⁴³ Thorough consultation, patient selection incorporating skin analysis in the lower eyelid and rigorous consent help to reduce risks.²⁹

Mid-face rejuvenation and volume replacement with HA filler is essential in establishing rejuvenation in other areas, particularly in the nasolabial and lower face regions, and requires a thorough understanding of facial anatomy, particularly of the vasculator.^34,44 Successful treatment in this area should combine deep fat injections with periosteum placement, considering the sex and natural bone structure.⁴⁴

Zygomatic region rejuvenation using biphasic HA filler has shown improvements in elasticity, zygomatic curvature, volume and skin smoothness, as well as a high level of subject satisfaction at three months following treatment.³³ One split-face study highlighted that placing HA filler lateral to the line of ligaments versus medially in 12 subjects created a sculpted cheek, successfully volumised the infraorbital and upper cheek areas, whilst also achieving optimal patient satisfaction.⁴⁵

In terms of the efficacy of hyaluronic acid in combination with other treatments, a recent small-scale trial (n=12) provided evidence of 25-50% improvement in acne scarring following HA filler and ablative laser therapy,⁴⁶ whilst an earlier trial in 2013 highlighted greater improvement in static perioral rhytids when treated with a combination of HA filler, lipolysis injection and ablative laser, compared to HA and lipolysis alone.⁴⁷

The most common reactions to HA filler include erythema, swelling and bruising, and less frequently, Tyndall effect, migration and vascular occlusion.⁴⁸ Appropriate patient selection, skin preparation and a sterile technique are essential in preventing infections.²⁷

Microneedling

Microneedling is a minimally-invasive procedure implementing fine needles to repeatedly puncture the epidermis, with limited risk of adverse effects.⁴⁹ Dating back to 1905, the micro-wounds created during the needling process stimulate the release of growth factors and induce collagen production.⁴⁹ Improvements in scars, discolouration and skin texture brought about by microneedling were accidentally discovered during camouflage tattoo treatments to hypopigmented facial scars.⁵⁰ 

There are two types of microneedling devices. Roller devices have a cylindrical head which is rolled back and forth to induce tiny incisions over the skin; electronic pen devices have adjustable settings to control speed and depth of needle penetration.⁵¹ One review paper has provided evidence that roller devices are more likely to cause adverse effects, particularly erythema and pain, however, a 2015 pilot trial (n=22) used a roller device to improve facial melasma and reported no adverse side effects.^52,53

Few studies are available that focus purely on the effects of microneedling on overall facial rejuvenation, with most implementing combination therapies, making it difficult to analyse the benefits of microneedling alone.^53-57 This could be because a performance bias is inevitable because blinding subjects and practitioners for the procedure is impossible.⁵¹ The most widely researched area is acne scarring, and most trials analyse results using computerised images, optical profilometry, biopsy, visiometer and exometers.^51,53,55,56 From my readings, biopsy and resulting histological staining provides the clearest view of the impact microneedling has on epidermal changes at a cellular level.^57-59

Skin darkening and pigmentation have shown significant improvement for up to 24 months following a combination of two sessions of microneedling treatment, using 1.5mm depth and topical skin lightening agents.³⁴ However, it is difficult to substantiate the exact effect of the needling in this case.⁵³ One Korean trial (n=25) provided evidence that a combination of stem cell and microneedling therapies at a depth of 0.25mm had a significant impact on wrinkles and hyperpigmentation following five treatments.⁵⁴ There is evidence to suggest that hypertrophic and atrophic acne scarring is significantly improved with three to six treatments of microneedling alone, reporting the most significant results three to 12 months following treatment.^51,55,58

A small 2015 study (n=10) administered six roller needling sessions spaced two weeks apart, at 1.5mm depth to subjects with atrophic scars.⁵⁸ The biopsy results highlighted a favourable effect on enhancing collagen formation, particularly collagen III, which increased significantly between one and three months following treatment.⁵⁸

A 2014 German murine study used biopsy to compare changes in epidermal thickness and collagen synthesis in 30 rats divided into five equal groups.⁵⁷ Increases in epidermal thickness and growth factor occurred across groups C to E with a clear, significant trend. Group C experienced epidermal growth of 115% after one session of microneedling at 1mm depth, versus group D with an increase of 205% following four needling sessions at 1mm depth. Group E received four sessions at 1mm depth plus skincare and exhibited growth of 658% compared to control. The same trial also observed that skin tightening occurred in all microneedling groups.⁵⁷

Furthermore, a small-scale human study (n=10) treated subjects with six microneedling sessions at 14-day intervals, and provided evidence that various types of collagen – specifically I, III and VII – plus tropoelastin significantly increased (P<0.05) in response to treatment. This led to a reduction in wrinkles in all subjects.⁶⁰

When combined with chemical peels and platelet-rich plasma therapy, microneedling may yield faster and more profound results in treating acne scarring, due to increased upregulation of growth factors.^61,62

Microneedling is usually well tolerated with minimal risk of side effects.^53,57,63 Deeper treatment depth leads to longer recovery periods due to erythema and swelling.⁶⁴ Post-inflammatory hyperpigmentation should be considered as a realistic potential side effect, particularly in patients with darker skin, and therefore, microneedling should be avoided in patients with obvious signs of sun exposure.⁶⁵

Intense pulsed light

The basic principle of intense pulsed light (IPL) devices is selective thermal damage of tissue and chromophores – water, melanin and haemoglobin – to boost cellular rejuvenation.⁶⁶ IPL devices use light and filters to emit incoherent high-intensity pulsed light at a specific wavelength range, fluence, pulse duration and intervals, making it suitable for treatment of a wide range of skin issues associated with ageing.^66,67 The patient’s skin type must be recorded according to the Fitzpatrick scale pre-treatment⁶⁸ as well as its specific condition, as this determines the choice of suitable cut-off filters and therefore the spectrum of wavelengths to be emitted.⁶⁶ Photo documentation is highly recommended at each IPL session.⁶⁶

For this review, I have focused on data specifically linked to the effects of IPL on pigmentation, wrinkles and epidermal thickness. From my readings, IPL shows significant efficacy in skin rejuvenation, although differences in devices, wavelengths, numbers and intervals of treatments present limitations in comparing and drawing conclusions about the efficacy of IPL.^66-72 Additionally, trials with greater subject numbers, different skin types and longer-term follow ups are required to assess the prevalence of skin changes.⁶⁶ Trials have used a range of techniques to assess IPL efficacy, including patient and physician assessment photography and biopsy,^68-73 blinded evaluation of pre- and post-treatment photographs,⁶⁸ Fitzpatrick Wrinkle Severity Score⁶⁷ and Melasma Area Severity Index (MASI).⁶⁹

Before treatment of pigmentation, lesions must be identified as non-malignant and precisely diagnosed. Darkening and sloughing of treated spots can be expected in the days following IPL.⁶⁶ Q-Switched ruby laser (QSRL) therapy is often recognised as the gold standard in pigmentation treatments;⁷⁴ one trial (n=25) combined IPL with QSRL in Korean females with >2 pigmented lesions, at three to four-week intervals. A good to excellent improvement in lesions was reported by 76% of the subjects, whilst physician analysis reported 60% of subjects displayed 76-100% improvement in lesions.⁶⁹ Yet a larger Chinese trial (n=89) yielded similar results in hyperpigmented subjects treated with IPL alone at wavelengths ranging from 560-640 nm; from patient analysis, 70.8% reported improvement of 50% or higher, whilst the physician’s report provided evidence that 77.5% of subjects experienced improvements of 51-100%.⁷⁰ 

Another trial (n=58) used biopsy and photography to analyse skin changes following three sessions of IPL therapy.⁷¹ Marked improvements in wrinkles and pigmentation were displayed in 62.1% and 84.6% of patients respectively, whilst pathological examination provided evidence of an increase in fibroblast activity, a rise in types I and III collagen, but a decrease in elastin fibres.⁶⁶ Conversely, a quantitative murine study highlighted significant increases in both collagen and elastin fibres directly proportionate to the number of IPL treatments administered. This could explain the physical changes behind the improvement in skin texture we see following IPL, but further trials are required to clarify exact cellular changes.⁶⁶

The effects of IPL on wrinkles are unclear. One open-label study (n=38), treated periorbital rhytids with three IPL sessions using 572 nm at four weekly intervals, and provided data to show that 30.3% of subjects reported considerable to excellent improvement in the wrinkling in this area, whilst 27.2% were dissatisfied or noticed little or no improvement.⁷³ Similarly, another small-scale, split-face trial (n=32) provided evidence that application of three sessions of monthly IPL therapy at 530-750 nm had no significant effect on rhytids, although pigmentation and skin texture improved with optimum results recorded one-month post-treatment.⁸ However, the effects of IPL on epidermal thickness appear promising; a 2018 trial provided evidence that five sessions of IPL significantly improved thickness of the stratum corneum, epidermis, basal layer and dermal papillae in 10 Asian subjects.⁷³

Combination treatment involving three sessions of IPL and continuous fractional radiofrequency showed significant improvements in wrinkles, pigmentation and vascular lesions at six and 12 weeks in 11 subjects.⁷⁵ The trials I have reviewed provide evidence that IPL is generally well tolerated and safe, with the most common side effects recorded being transient erythema and discomfort. Transient post-inflammatory hyperpigmentation, linear hypopigmentation, swelling and blistering also occur in rare cases.^8,66-75

Consider your treatment options

This article has presented data available on the efficacy, safety and limitations of four different clinical approaches to facial rejuvenation. BoNT-A is highly effective in reducing wrinkles in the glabellar area,18 improving skin tone and texture.^12,24 Dosing and brands vary between studies making evaluation difficult and extensive research into the effects of BoNT-A on other facial muscles and longer-term skin improvements is limited.¹⁶ Microneedling possesses the strongest evidence for long-term increase in both collagen production leading to greater epidermal thickness and wrinkle reduction^54,57-59 although patients should be made aware of potential downtime following each treatment.⁶⁴

HA dermal fillers can restore fat and skeletal depletion in the mid and lower face, improve skin hydration and promote collagen production.^{27- 35} Care should be taken in patient selection, and treating conservatively and appropriately according to age and sex to maintain facial harmony.^34,44

In trials, IPL has comparable results to laser in facial rejuvenation, particularly in treatment of pigmentation and collagen stimulation,^69-73 whilst its effect on wrinkle reduction is controversial.^8,73 Most of the trials reviewed used IPL wavelength 530-650 nm, and as there is much variation between devices, this presents a challenge in assessing optimum wavelengths for different skin issues, and larger scale studies with long-term follow-up are required.⁶⁶ 

This review also suggests that if implemented appropriately, combinations of these modalities used together in patient treatment programmes could help to rejuvenate the facial skin and structure longer term, although more large-scale trials are required to substantiate this.