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INTERNATIONAL JOURNAL OF AESTHETIC AND ANTI-AGEING MEDICINE Special Supplement Autumn 2014 DERMAL FILLER INDUCED FACIAL ARTERY OCCLUSION BOTOX FOR DEPRESSION IS IT EFFECTIVE? THE DUBLIN LIFT TO TREAT THE AGEING FACE

PRIME Supplement - Dr. Patrick Treacy

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INTERNATIONAL JOURNAL OF AESTHETIC AND ANTI-AGEING MEDICINE

Special Supplement Autumn 2014

DERMAL FILLER

INDUCEDFACIAL ARTERY

OCCLUSION

BOTOX FOR DEPRESSION

IS IT EFFECTIVE?

THE DUBLIN

LIFTTO TREAT THE AGEING FACE

Page 2: PRIME Supplement - Dr. Patrick Treacy

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| CONTENTS

BOARD MEMBER SPECIALISM COUNTRYDr Claude Dalle Anti-ageing & aesth. medicine FranceDr Wilmar Accursio Endocrinology BrazilDr Firas Al-Niaimi Dermatology & laser surgery UKDr Ashraf Badawi Dermatology Egypt & CanadaDr Janethy Balakrishnan Aesthetic & anti-ageing medicine MalaysiaDr Lakhdar Belhaouari Plastic surgery FranceDr Anthony Benedetto Cosmetic Dermatology USADr Philippe Berros Oculoplastic surgery MonacoDr Dario Bertossi Maxillofacial surgery ItalyDr Pierre Bouhanna Dermatology – Hair surgery FranceDr Fahd Benslimane Plastic Surgery MoroccoProf Wayne Carey Dermatology CanadaDr Claude Chauchard Anti-ageing medicine FranceDr Christophe de Jaeger Geriatrics FranceDr Gerd Gauglitz Aesthetic Dermatology GermanyProf Ilaria Ghersetich Dermatology ItalyDr Kate Goldie Aesthetic Physician UKProf Eckart Haneke Dermatology GermanyDr Steven Hopping Plastic surgery USAProf Andreas Katsambas Dermatology GreeceDr Mario Krause Anti-ageing medicine GermanyDr Marina Landau Dermatology Israel

BOARD MEMBER SPECIALISM COUNTRYDr Gustavo Leibaschoff Cosmetic Surgery USADr Sohail Mansoor Dermatology UKProf Leonardo Marini Dermatology ItalyDr Sly Nedic Aesthetic & anti-ageing medicine South AfricaProf Daniel Pella Cardiology SlovakiaDr Chariya Petchngaovilai Dermatology ThailandProf Ascanio Polimeni Neuro-endocrinology ItalyDr Herve Raspaldo Facial plastic surgery FranceDr Christopher Rowland-Payne Dermatology UKDr Neil Sadick Dermatology USADr Hema Sundaram Dermatology USADr Pakpilai Thavisin Dermatology & Anti-ageing medicine ThailandDr Patrick Treacy Aesthetic surgery IrelandDr Mario Trelles Plastic surgery SpainDr Ines Verner Dermatology IsraelDr Octavio Viera Anti-ageing medicine SpainDr Jean-Luc Vigneron Aesthetic dermatology FranceProf Bernard Weber Genetics LuxembourgDr Sabine Zenker Dermatology GermanyCatherine Decuyper Industry expert & consultant FranceWendy Lewis Industry expert USAChristophe Luino Industry expert & consultant France

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Original articles previously published in Prime Journal, Europe edition

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Patrick Treacy considers the conflicting evidence of botulinum toxin use as a therapy for depression, and proposes that it all comes down to where the toxin is injected

THE ‘BOTOX PARADOX’: IS IT EFFECTIVE FOR DEPRESSION?

REVERSAL OF A DERMAL FILLER INDUCED FACIAL ARTERY OCCLUSION Patrick Treacy discusses the factors to consider to avoid adverse events after the use of a dermal filler as well as the best methods of treating complications, including steroids and hyaluronidase

Patrick Treacy presents a novel method for full facial rejuvenation, which combines a number of treatments to obtain the most optimum results

COMBINING THERAPIES FOR THE AGEING FACE:THE DUBLIN LIFT

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REVERSAL OF A DERMAL FILLER

INDUCED FACIAL ARTERY OCCLUSION Patrick Treacy discusses the factors to consider to avoid adverse

events after the use of a dermal filler as well as the best methods of treating complications, including steroids and hyaluronidase

KEYWORDS Localised adiposities, topical slimming treatment, botanical extracts, ultrasonography, in vivo assessment

ABSTRACT Soft tissue augmentation with dermal fillers has become an integral part of most aesthetic practices. Fortunately, adverse reactions are usually mild and transient. However, significant adverse events such as vascular occlusion also occur. Vascular compromise occurs

because of embolisation and/or compression material into/onto the vasculature. In this article, the author theorises that late onset vascular occlusion may occur not only due to embolisation but because hyaluronic acid (HA) expands due to its hydrophilic action and compresses the

facial artery or its branches. He proposes that intravenous steroids should be added to the accepted reversal protocol. His goal is not to promote this as a definitive measure but rather to establish a discussion on treatment protocols that may be helpful to other physicians in the future.

WITHIN THE PAST 15 YEARS, facial soft-tissue augmentation has become very popular in aesthetic clinics around the world. Although most biodegradable-type products

are considered safe, adverse events do occur that are time-limited. The products have been observed to have severe, persistent, and recurrent complications. Histological examinations in these cases, often show the presence and persistence of the filler1. Dermal filler complications are divided into ‘early’ and ‘delayed’ in terms of time of occurrence and ‘minor’ and ‘major’ in terms of severity1, 2. Minor complications occurring immediately or hours to days after injection include injection site reactions, such as bruising, erythema, pain and tenderness, swelling, and itching. These events usually resolve within a week without sequelae3, 4. Severe vascular adverse events have been reported in the glabellar and nasolabial regions after treatment with both biodegradable and non-biodegradable injectable fillers5.

Although rarely reported in the literature, complications related to interrupted blood supply to the nose can occur with nasolabial fold dermal injection. The exact mechanism of this event is unknown, however it is widely accepted that vascular compromise is a function of compression and/or embolisation of material into the vasculature. It has

PATRICK TREACY, Medical Director, Ailesbury Clinics Ltd and Ailesbury Hair Clinics Ltd, Dublin, Cork, London, and Middle East

email: [email protected]

been theorised that, as injected hyaluronic acid (HA) expands because of its hydrophilic action, the facial artery, angular artery, or its branches, become compressed. the facial artery runs in an oblique direction over the mandible toward the nasal sidewall. It passes under the zygomaticus muscles, crossing the nasolabial fold. It turns to run in the alar crease and along the lateral nasal wall, where it terminates in the angular artery, which continues toward the medial orbital rim6.

There are several important factors that may lessen the occurrence of adverse events. Before injecting any dermal filler, a thorough medical history including medication (especially blood thinners), allergies, and scarring history (e.g. tendency for keloids) should be taken. The injector should be well trained in injection technique and know which filler to implant at which depth. Understanding the anatomy, limitations of the filler and proper technique can reduce the risk of adverse effects. When complications occur, the practitioner should understand how to manage them from observation to surgical intervention7.

Preventing side-effectsThe best way to handle side-effects is to prevent them8. For optimum outcomes, aesthetic physicians should have: a detailed understanding of facial anatomy; the individual characteristics of available fillers; their indications, contraindications, benefits, and drawbacks; and ways to prevent and avoid potential complications9. Hyaluronic acid dermal fillers are the most widely used injectables to augment facial volume without surgery. They are popular because of their ease of administration, predictable effectiveness, good safety profile, and quick patient recovery10. Since its reformulation in mid-1999, the biologically engineered hyaluronic acid filler Restylane (Medicis Pharmaceuticals, Scottsdale, AZ, USA) elicits less than one allergic reaction in 1600 treatments. Skin

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Severe vascular adverse events have been

reported in the glabellar and nasolabial regions after

treatment with both biodegradable and non-biodegradable

injectable fillers.

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reactions, including granuloma formation with poly-L-lactic acid (Sculptra/formerly New Fill, Dermik Laboratories, Berwyn, PA, USA) is considerably less likely if a greater dilution and deeper injection technique are employed11. Inflammatory nodules are

likely to be caused by a low-grade infection maintained within a biofilm surrounding the hydrophobic silicone gel and the combination gels. Aquamid gel may prevent formation of a biofilm through its high water-binding capacity, explaining why late inflammatory nodules are not seen after injection of this polyacrylamide hydrogel product11, 12. All gels act as foreign bodies. Host response ranges from a few macrophages to an intense foreign-body reaction with fibrosis, depending on gel type. For polymer gels the filling effect stems from their volume. For combination gels it stems from the intended host foreign-body reaction to the microparticles. Infectious nodules must be treated with antibiotics. Granulomas must be treated with a combination of both steroids and antibiotics or excision12.

Case studyPatient was a 37-year-old woman who received HA injection to the left nasolabial fold. She had an uneventful procedure but reported back to the clinic with an erythematous reaction and some pain in the nasolabial and malar area the next day. In view of the vascular compromise she was immediately treated with 150 units of hyaluronidase and nitropaste to the reticulated area. Because the patient presented 24 hours post-procedure she was given 100 mgs of cortisone IV and commenced on 4 mgs of Dexamethasone PO. It was also considered appropriate to inject 0.2 mls of a dilute solution of 50% dexamethasone 40 mgs/ml into the area where the hyaluronic acid was initially injected.

The patient became hypotensive during treatment and was temporarily referred to the emergency room until stable. This was considered secondary to the nitropaste gel. The hospital was willing to allow the patient to come back to the clinic for further steroid

Figure 1 Images demonstrating management of a patient over 7 days with impending necrosis owing to complications secondary to hyaluronic acid dermal filler injection

Figure 2 Branching patterns of facial artery

ILA

SLA

IAA

LNA

FB

Branching patterns of facial artery according to its termination (ILA, inferior labial artery; SLA, superior labial artery; IAA, inferior alar artery; LNA, lateral nasal artery; FB, forehead branch

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treatment and commencement of Chiroxy oxygenating skin cream (Auriga international, Belgium). Chiroxy oxygenating skin cream is designed to increase the oxygen content of your skin by delivering O

2 via

nanosomes. Her symptoms and signs disappeared within a 5 day period and 2 weeks later there was no evidence of any residual vascular deficit.

DiscussionFor the moment, there is no ideal dermal filler as they have widely varying properties, associated risks, and injection requirements that contribute to adverse events for the patient. The majority of adverse reactions are mild and transient, such as bruising and oedema secondary to trauma or the physical characteristics of the material itself.

However, although serious adverse events are rare, vascular complications either arterial or venous can occur that are related to volume of filler used and the technique of placement in the region of terminal vessels. It is possible that injected HA expands because of its hydrophilic action and the underlying facial artery, angular artery, or its branches, become compressed. This results in vascular compromise that can lead to skin necrosis unless it is immediately treated. The author proposes that intravenous steroids and anti-histamines should be given to all these patients.

There are also issues related to the recent use of adjunctive lidocaine in fillers that may make vessels more exposed to accidental infiltration. Lidocaine significantly decreases pain during injection and post-injection with corresponding increased patient satisfaction13. The efficacy and safety profile of the original filler may be compromised.

Rare complications with HA fillers include vascular compression during or after the event which results in reticulation some hours later and the author postulates the use of intravenous steroids in these patients. These patients normally show no evidence of vascular compromise during injection. The protocol outlined by Glaich et al14 calls for a coherent, sequential treatment for vascular compromise resulting from injections of hyaluronic acids. This protocol elaborates a sequence of events that use topical nitroglycerin, hyaluronidase, and other modalities to minimise the damage from impending necrosis. Other authors have also published guidelines for the treatment of impending necrosis following soft tissue augmentation following injections of hyaluronic acid15,16. Based upon the experience with hyaluronic acid occlusion, treatment for particular fillers that occlude vascular structures should seek to increase blood flow to the affected areas. This may be accomplished by decreasing pressure in the anatomic compartment (using corticosteroids and hyaluronidase), increasing blood flow (with sildenafil or similar drugs, aspirin, and nitroglycerin paste), and increasing the oxygen content to the affected tissues (hyperbaric oxygen)17.

Regarding reversal of a hyaluronic acid induced embolus, the author recommends starting at higher

Table 1

Author’s HLA

reversal protocol

Discontinue injection ofHLA immediately

Massage the affected areaimmediately

Apply warm packs of gauzeto area (microwave)

Apply nitro-paste or 10 mgstransderm-nitro patches(Novartis) for a period of

up to 12 hours

Mix 300 units of hyalase(0.2mls) with 0.2mls

(Wockhardt UK) of 2%lidocaine (Astra Zeneca)

Inject hyalase in 5–6 lots of75u to occluded area

Hydrocortisone 100mg IV stat (if not an acute

ischaemic event)

Dexamethsone 4mgs dailyPO X 3/7 (if not an acute

ischaemic event)

Table 2 Typical complication progression after accidental intra-arterial injection of hyaluronic acid

CLINICAL FINDINGS TIMING

Blanching: invariably immediate, usually seen during Lasting seconds to tens of the actual injection seconds

Livedo pattern or immediate reactive hyperaemia Minutes: sometimes up to if insufficient material injected to occlude the artery tens of minutes

Blue-black discolouration Tens of minutes to hours

Blister/bullae formation Hours to days

Skin breakdown, ulceration, demarcation, slough Days to weeks

Figure 3 Effects of a large filler bolus

Figure 4 Effects of a small filler bolus

When a large bolus of filler material enters a small- or medium-sized vessel, the material may flow retrograde to the blood flow’s normal direction after it has filled in the distal segment, because there is nowhere else for the filler to go. If the filler bypasses a tributary during its retrograde flow, it may enter this particular pathway and be carried to distant areas. This is probably the pathophysiology responsible for injury sites distant to the original injection site

Usually carried downstream by blood flow. May cause limited obstruction that can be bypassed via abundant collateral vessels. The problem is in a region with restricted collaterals (eg, the glabellar region). Effect depends on the presence or absence of enough collateral circulation in the target tissues

Micro volume of filler does not completely obstruct blood supply

Angular artery

Distal branches

Supratochlear arteryDorsal nasal artery

Ophthalmicartery

Facial artery

External carotid artery

Internal carotid artery

Distal branches

Collateral flow

Proximal branches

For the moment, there is no ideal dermal

filler as they have widely varying

properties, associated risks,

and injection requirements that

contribute to adverse events for

the patient.

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levels of hyalase, possibly in the region of 150 to 300 iu, and then treating repeatedly until the circulation returns. Repeated treatment, massage, and the other recommendations to promote vasodilation are continued. It is probable as the material starts to break down, it flows further downstream, where it probably opens collateral vessels, or it can flow further past these and obstruct a slightly different area. When it gets to the precapillary arterioles, it gets permanently stuck, unless it is bathed in more hyaluronidase (HYAL) and is hydrolysed.

There are so many variables in a typical case that it is impossible to be specific, since the manner of manipulation of the area, the quantity and nature of the filler within the vessel, and the actual location of the emboli all factor into the equation. The absolute quantity of hyaluronidase is probably irrelevant during an acute event, it’s the results that count.

Declaration of interest None

Figures 1 © Dr Treacy, 3-4 original artwork © Claudio De Lorenzi redrawn for Prime Journal © Kevin February

One of the most significant adverse events associated with injections of soft tissue augmentation products is vascular occlusion

Vascular complications with HA fillers include embolism or compression during or after the event which results in reticulation some hours later

The author postulates the use of higher doses of Hyalase than the normal protocols and the uses of intravenous steroids in these patients

Key points References1. Lowe NJ, Maxwell CA, Patnaik R. Adverse reactions to dermal fillers: review. Dermatol Surg 2005; 31 (11 Pt 2): 1616–252. Gladstone HB, Cohen JL. Adverse effects when injecting facial fillers. Semin Cutan Med Surg 2007; 26(1): 34–93. Baumann LS, Shamban AT, Juvederm vs. Zyplast Nasolabial Fold Study Group, et al. Comparison of smooth-gel hyaluronic acid dermal fillers with cross-linked bovine collagen: a multicenter, double-masked, randomized, within-subject study. Dermatol Surg 2007; 33 Suppl 2: S128–354. Pinsky MA, Thomas JA, Murphy DK, et al. Juvederm injectable gel: A multicenter, double-blind, randomized study of safety and effectiveness. Poster presented at the American Society for Aesthetic Plastic Surgery Annual Meeting, New York, NY, April 19–24, 20075. Bachmann F, Erdmann R, Hartmann V, Wiest L, Rzany B. The spectrum of adverse reactions after treatment with injectable fillers in the glabellar region: results from the Injectable Filler Safety Study Dermatol Surg 2009; 35 Suppl 2: 1629–346. Grunebaum LD, Bogdan Allemann I, Dayan S, Mandy S, Baumann L. The Risk of Alar Necrosis Associated with Dermal Filler Injection. Dermatol Surg 2009; 35 Suppl 2: 1635–407. Gladstone HB, Cohen JL. Adverse effects when injecting facial fillers. Semin Cutan Med Surg 2007; 26 (1): 34–98. Funt D, Pavicic T. Dermal fillers in aesthetics: an overview of adverse events and treatment approaches. Clin Cosmet Investig Dermatol 2013; 6: 295–316

9. Andre P, Lowe NJ, Parc A, Clerici TH, Zimmermann U. Adverse reactions to dermal fillers: a review of European experiences. J Cosmet Laser Ther 2005; 7 (3–4): 171–610. Christensen L, Breiting V, Janssen M, Vuust J, Hogdall E. Adverse reactions to injectable soft tissue permanent fillers. Aesthetic Plast Surg 2005; 29(1): 34–4811. Christensen L. Normal and pathologic tissue reactions to soft tissue gel fillers. Dermatol Surg 2007; 33 Suppl 2: S168–7512. Lowe NJ, Maxwell A, Patnaik R. Adverse Reactions to Dermal Fillers: Review. Dermatologic Surgery 2005; 31(s4):1626–163313. Smith L, Cockerham K Hyaluronic acid dermal fillers: can adjunctive lidocaine improve patient satisfaction without decreasing efficacy or duration? Patient Prefer Adherence 2011; 5: 133–914. Glaich AS, Cohen JL, Goldberg LH. Injection necrosis of the glabella: protocol for prevention and treatment after use of dermal fillers. Dermatol Surg 2006; 32(2): 276–28115. Hirsch RJ, Cohen JL, Carruthers JD. Successful management of an unusual presentation of impending necrosis following a hyaluronic acid injection embolus and a proposed algorithm for management with hyaluronidase. Dermatol Surg 2007; 33(3): 357–36016. Dayan SH, Arkins JP, Mathison CC. Management of impending necrosis associated with soft tissue filler injections. J Drugs Dermatol 2011; 10(9): 1007–1012 17. Beer K, Downie J, Beer J . A treatment protocol for vascular occlusion from particulate soft tissue augmentation. J Clin Aesthet Dermatol 2012; 5(5): 44–7

It is probable as the material starts to break down, it flows further downstream, where it probably opens collateral vessels, or it can flow further past these and obstruct a slightly different area.

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Page 10: PRIME Supplement - Dr. Patrick Treacy

In 2003, Heckmann et al published data suggesting that

treatment of the glabellar region with botulinum toxin

could produce a change in facial expression from angry,

sad, and fearful to happy, and that this could impact on

emotional experience.

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THE ‘BOTOX PARADOX’: IS IT EFFECTIVE FOR DEPRESSION?Patrick Treacy considers the conflicting evidence of botulinum toxin use as a therapy for depression, and proposes that it all comes down to where the toxin is injected

PATRICK TREACY is Medical Director of Ailesbury Clinics Ltd and Ailesbury Hair Clinics Ltd; Chairman of the Irish Association of Cosmetic Doctors and Irish Regional Representative of the British Association of Cosmetic Doctors; European Medical Advisor to Network Lipolysis and the UK’s largest cosmetic website Consulti,ng Rooms. He practices cosmetic medicine in his clinics in Dublin, Cork, London and the Middle East

email: [email protected]

A RECENT ARTICLE by Claire Coleman1, published in the UK’s Daily Mail newspaper, has led to much confusion

with regard to the role of BOTOX® in treating or causing depression. The article was based on a study led by Dr Michael Lewis of the School of Psychology, Cardiff, Wales, who followed 25 people who had received BOTOX treatment for facial lines and examined the idea of facial feedback — where the expressions we make with our faces affect how we feel — and found that many women who have the treatment for cosmetic purposes feel depressed because they are no longer able to smile properly.

Previous studies, however, have found that the treatment of frown lines left patients feeling less depressed. In 2006, Dr Eric Finzi and Dr Erika Wasserman reported in Dermatologic Surgery that treating clinically depressed patients with BOTOX on their frown lines actually reduced patients’ feelings of depression2. Depression affects over 120 million people globally, making it one of the leading causes of disability in the world. Although there are a number of effective treatments,

therapeutic response remains unsatisfactory and depression can develop into a chronic condition in a considerable proportion of patients. An economic treatment option that could provide long intervals between treatments, and that is safe, would be very important to doctors. So, what is the truth? Is there an actual physiological reason to explain the different results?

The ‘grief’ muscles The story begins in 1872, when Charles Darwin recognised that negative emotions, such as anger, fear, and sadness — all prevalent in depression — are associated with hyperactivity of the corrugator and procerus muscles in the glabellar region of the face. Darwin called them the ‘grief muscles’ and formulated a new theory, known as the ‘facial feedback hypothesis’, which implied a mutual interaction between emotions and facial muscle activity. He published his new theory in The Expression of the Emotions in Man and Animals, which concerns the genetically determined aspects of behaviour.

In this book, Darwin aimed to trace the animal origins of human characteristics, such as the tightening of the muscles around the

eyes in anger and efforts of memory. Darwin even sought out the opinions of eminent British psychiatrists in preparation of the book, which forms Darwin’s main contribution to psychology. His theory implied a mutual interaction between emotions and facial muscle activity. Research into this stayed there during the great upheavals of both World Wars, until the rising popularity of BOTOX made scientists review his facial hypothesis.

In 2003, Heckmann et al3

published data suggesting that treatment of the glabellar region with botulinum toxin could produce a change in facial expression from angry, sad, and fearful to happy, and that this could impact on emotional experience. Many therapists argue that patients who had been treated in the glabellar area reported an increase in emotional wellbeing and reduced levels of fear and sadness beyond what would be expected from the cosmetic benefit alone.

In 1992, Larsen et al4 provided evidence that voluntary contraction of facial muscles could channel emotions, which were conversely expressed by activation of these muscles. Hennenlotter et al5 went one stage further and showed that botulinum toxin treatment to the

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glabellar area stopped the activation of limbic brain regions normally seen during voluntary contraction of the corrugator and procerus muscles. This indicated that feedback from the facial musculature in this region in some way modulated the processing of emotions. Many other researchers continued on this track, with Havas et al6 noting that the processing time for sentences with negative affective connotation was prolonged in women after botulinum toxin treatment to the glabellar, and Neal and Chartrand7 speculating that the treatment interfered with the ability to decode the facial expression of other people. This is where things remained, until recently, when some authors suggested that this capacity

to counteract negative emotions could be put to some clinical use during the treatment of depression.

Reducing symptoms of depressionA seminal article by Finzi and Wasserman2 postulated that botulinum toxin injected into the glabellar reduced the symptoms of depression. The authors provided data from an open case series of 10 female patients. The article contained a footnote from editor Alastair Carruthers, who stated that the report must be considered anecdotal as there were no appropriate methods of control used. In addition, there were other methodological weaknesses, including

limited follow-up, lack of randomisation, the absence of blind evaluation, and in particular, the small number of subjects included. Many felt that the methodology of evaluating depression should have been more rigorous.

At the time, I noted by letter that patients’ self-report of depressive symptoms by administration of the BDI-II (Beck Depression Inventory) introduced a significant bias. This is of more concern because of the potential for secondary cosmetic gain. While the BDI-II is an accepted method of evaluating an individual’s level of symptoms over time, self-report in isolation was not considered an acceptable method of diagnosing depression. It was concluded that in order to ensure that patients’ psychiatric symptoms are accurately classified, a thorough psychiatric interview must be conducted.

In 2012, the Psychiatric University Hospital of the University of Basel, Switzerland, and the Medical School Hanover, Germany, conducted a randomised, placebo-controlled, double-blind trial8. The authors hypothesised that facial psychomotor features associated with depression are not just epiphenomena, but integral components of the disorder, and may be targeted in its therapy. To explore whether attenuation of these features produces alleviation in the affective symptoms, they conducted a randomised controlled trial of botulinum toxin injection to the glabellar region as an adjunctive treatment of major depression. The study was investigator-initiated and carried out independently of any commercial entity.

Participants in the study were recruited from local psychiatric outpatient units and psychiatrists in private practice. In order to avoid attracting candidates who were primarily motivated by receiving this treatment for cosmetic reasons, botulinum toxin treatment was not explicitly mentioned. Exclusion criteria included psychotic symptoms, suicidal tendency, and clinical severity requiring immediate intervention. The same injection scheme was applied as that of the open case series2. At each study visit, participants were assessed using the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS), the BDI self-rating questionnaire, and the Clinical Global Impressions (CGI) Scale. To conceal

Havas et al noted that the processing time for sentences with negative affective connotation was prolonged in women after botulinum toxin treatment to the glabellar.

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References1. Coleman C. Is Maria’s story proof Botox can make you depressed? London, UK: Daily Mail, 2013. http://tinyurl.com/bv2y3kr (accessed 21 May 2013)2. Finzi E, Wasserman E. Treatment of depression with botulinum toxin A: a case series. Dermatol Surg 2006; 32(5): 645–93. Heckmann M, Teichmann B, Schröder U, Sprengelmeyer R, Ceballos-Baumann AO. Pharmacologic denervation of frown muscles enhances baseline expression of happiness and decreases baseline expression of anger, sadness, and fear. J Am Acad Dermatol 2003; 49(2): 213–64. Larsen RJ, Kasimatis M, Frey K. Facilitating the furrowed brow: an unobtrusive test of the facial feedback hypothesis applied to unpleasant affect. Cognition Emotion 1992; 6: 321–385. Hennenlotter A, Dresel C, Castrop F, Ceballos-Baumann AO, Wohlschläger AM, Haslinger B. The

link between facial feedback and neural activity within central circuitries of emotion--new insights from botulinum toxin-induced denervation of frown muscles. Cereb Cortex 2009; 19(3):537–426. Havas DA, Glenberg AM, Gutowski KA, Lucarelli MJ, Davidson RJ. Cosmetic use of botulinum toxin-a affects processing of emotional language. Psychol Sci 2010; 21(7): 895–9007. Neal DT, Chartrand TL. Embodied emotion perception: amplifying and dampening facial feedback modulates emotion perception accuracy. Soc Psychol Personal Sci 2011; doi: 10.1177/19485506114061388. Wollmer MA, de Boer C, Kalak N et al. Facing depression with botulinum toxin: a randomized controlled trial. J Psychiatr Res 2012; 46(5): 574–81

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cosmetic changes from psychometric raters, participants wore an opaque surgical cap, which covered the glabella and forehead during examinations.

The study concluded — for the first time — that a single botulinum treatment of the glabellar region with BOTOX could reduce the symptoms of major depression. This effect developed within a few weeks and persisted until the end of the 16-week follow-up period. The effect sizes in the study were large and the response and remission rates high. It is still unknown how botulinum toxin actually reduces depression and it is postulated that a number of mechanisms may be involved. As a result of the clinical data relating to botulinum toxin treatment on emotional perception, it is assumed that reduced proprioceptive feedback from the paralysed facial muscles is a relevant mechanism of mood improvement.

As the authors did not include patients who were cosmetically concerned about their frown lines, it is unreasonable to assume that an aesthetic benefit was the major cause of mood improvement. There is a small possibility of either placebo effect or central pharmacological botulinum toxin effects, including possible pharmacodynamics or pharmacokinetic interactions with concomitant antidepressant therapy.

The ‘Botox Paradox’So, who is correct? Does Botox reduce or augment depression? How can the findings of Dr Lewis be in complete contrast to those of other researchers? I

believe that both are correct, and that the answer to tise apparent medical paradox lies with the original theories of Darwin.

Dr Lewis and colleagues found that people treated for another muscle (around the crows’ feet) left patients feeling more depressed. This does not contravene Darwin’s original hypotheses; in fact it supports it. The muscles around the eye are related to happiness and smiling, and to restrict their movement must interfere with the facial feedback hypotheses in a converse way to those in the glabellar area. We can only assume that reduced proprioceptive feedback from these paralysed facial muscles is a relevant mechanism of mood deterioration, and this is why they may increase depression. Accordingly, happiness can make you smile and smiling can make you happy. It is obvious that the facial musculature not only expresses, but also regulates, mood states. Botulinum toxin injection interferes with the ‘facial feedback hypothesis’ originally postulated by Darwin. (Perhaps it was my sixth sense, but I never felt right about totally removing crow’s feet around a patient’s eyes.)

ConclusionsThere is growing evidence that botulinum toxin injection to the glabellar region may be an effective, safe, and sustainable intervention in the treatment of depression. The reason for this has not yet been fully evaluated, but we must consider the concept that the facial musculature not only expresses, but also

regulates, mood states. Owing to the longer intervals between treatments, it may also be an economic option, and the safety and tolerability record of botulinum toxin injections to the glabellar region is excellent.

However, further studies are required, including focus on muscles in the lower sections of the face. It is possible that treatment of the depressor angularis oris and the mentalis muscles, for example, may also have mood-elevating effects, and may enhance the clinical effect of the glabellar injection of botulinum toxin.

Modulation of mood states with botulinum toxin may also be effective in the treatment of other clinical conditions involving negative emotions, like anxiety disorders. There have also been recent studies investigating the possibility of botulinum toxin for bipolar disorder and post-traumatic stress disorder (PTSD).

It is paramount to remember that botulinum toxin to the glabellar region may be an effective, safe, and sustainable intervention in the treatment of depression. The reason for this has not yet been fully evaluated, but we must consider the concept as depression affects a huge number of people, making it one of the leading causes of disability worldwide.

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Patrick Treacy presents a novel method for full facial rejuvenation, which combines a number

of treatments to obtain the most optimum results

KEYWORDS fractionalised laser resurfacing, platelet-rich plasma, microneedling, Omnilux 633 nm light, neurotoxin

Objective The DUBLiN Lift: To establish the clinical effectiveness of combining five treatments in the rejuvenation of the ageing face in an effort to increase aesthetic effect, patient safety, and reduce laser downtime.

The face is the area for which the majority of patients seek cosmetic rejuvenation as the convex lines of a youthful appearance tend to flatten and droop as one grows older. The younger face is characterised by a balance captured in the classic shape of the inverted triangle. The reversal of this

‘triangle of beauty’ as ageing proceeds is considered generally less aesthetically appealing1. At present, a variety of different dermatologic and volumising treatments are available for facial rejuvenation. These include chemical peels, dermal fillers, intense pulsed light and radiofrequency lasers, platelet-rich plasmas (PRP) microneedling, microdermabrasion, botulinum toxin injections, and laser resurfacing. Each treatment has its own relative benefit, as well as risks2, 3.

In recent years, facial rejuvenation has been revolutionised with the development of CO

2 fractional laser skin

resurfacing. This procedure benefits from faster recovery time, more precise control of ablation depth, and reduced risk of post-procedural problems. However, there have been cases of hypopigmentation, hypertrophic scars and skin mottling, most often seen on the face, neck and chest when the laser parameters are used more aggressively4. Furthermore, the technique does not attend to chronological ageing problems such as volume deficits resulting from the loss and repositioning of facial fat.

This article examines the possibility of combining five established therapies

in an attempt to address these deficits. The facial rejuvenating therapies include microneedling, low-dose UltraPulse laser, PRP growth factors, Omnilux 633 nm light, and neurotoxins. The technique is called the DUBLiN facelift as an acronym of the procedures involved: Dermaroller, UltraPulse laser, Blood growth factors, Light (near-red 633 nm), and Neurotoxin.

The author compared this method to fractional laser skin resurfacing with regard to the reduction of photoageing and overall aesthetic effect. Neurotoxin was used in both arms of the study.

DR PATRICK TREACY is Medical Director of Ailesbury Clinics Ltd and Ailesbury Hair Clinics Ltd; Chairman of the Irish Association of Cosmetic Doctors and Irish Regional Representative of the British Association of Cosmetic Doctors; European Medical Advisor to Network Lipolysis and the UK’s largest cosmetic website Consulting Rooms. He practices cosmetic medicine in his clinics in Dublin, Cork, London and the Middle East

email: [email protected]

ABSTRACT

THE FACE, AND particularly the eyes, is very important for contact between humans, as this area provides a window to the rest of society with

regard to a patient’s level of health, tiredness and emotional status, as well as interest in others4. Many health professionals consider the periorbital area of the face as the most important area of rejuvenation as eye-to-eye communication occurs in approximately 80% of all human interactions6. Both areas present a barometer of a patient’s chronological and environmental age, and mastering the proper evaluation and execution of their aesthetic rejuvenation is paramount for all cosmetic doctors.

More recently, patients are seeking effective facial rejuvenation procedures with less downtime and low risks7. This change in attitude has been prompted by a realisation of both doctors and patients

that the much hyped non-ablative methods were often subject to extravagant claims in terms of efficacy2–4. For many years, CO

2 laser resurfacing was

considered the ‘gold standard’ in treating photodamaged facial skin6–11. Cutaneous laser resurfacing with a fractional (CO

2)

laser involves the vapourisation of the entire epidermis, as well as a variable thickness of the dermis. Many physicians stated that the ultrapulsed CO

2 laser was

the most effective method of laser resurfacing12–13. Photodamaged skin is the result of years of exposure to harmful ultraviolet light and is clinically demonstrated as a gradual deterioration of cutaneous structure and function. This results in the epidermis and upper papillary dermis having a roughened surface texture, as well as laxity, telangiectasias, wrinkles and variable degrees of skin pigmentation14–15.

Although ultrapulsed CO2 resurfacing

lasers were considered the best

COMBINING THERAPIES FOR THE AGEING FACE:

THE DUBLiNLIFT

More recently, patients are seeking effective facial rejuvenation procedures with less downtime and low risks.

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noted in these areas25. Scarring after fractional CO2 laser

therapy is considered mainly a result of overly-aggressive treatments and a lack of technical finesse. Physicians have also recorded post-operative infections leading to scarring, although it is generally felt that these may be prevented by careful history-taking, vigilant post-operative monitoring, and/or the use of prophylactic antibiotics26, 27.

With regard to facial rejuvenation, CO2 laser light at a

10 600 nm wavelength results in vapourisation with thermal denaturation of type I collagen, collagen shrinkage and later, collagen deposition. However, in very deep rhytides, acne scarring and severe elastotic changes from sun damage, fractional CO

2 therapy

requires multiple treatments to achieve the same results as the older lasers28. A number of studies have evaluated using different laser combinations in the same session in order to improve collagen deposition, with a wider zone of fibroplasia6–9, 28. Owing to the inherent risks of fractional laser skin resurfacing and its inability to deal with some evidence of chronological ageing, it was advocated to here establish the clinical effectiveness of using a multi-procedural approach to volumisation and collagen regeneration. The author used microneedling with low energy laser, and platelet rich plasma (PRP) to address these issues.

Collagen remodelling and fibroblast stimulationIt is recognised that the most important rejuvenation process for photoaged skin is the collagen remodelling process, and dermal fibroblasts are known to have the most important function29. Rejuvenation of skin injury caused by UV light is a complex process that organically involves cytokines interacting with a number of growth factors and control proteins28. The procedures evaluated included PRP, microneedling, and Omnilux 633 nm near-red light, with neurotoxins as an adjunct to low-level fractional laser skin resurfacing. Cells in the epidermis and dermis can be targeted by microneedling and

Care should be taken when

treating sensitive areas such as the

eyelids, upper neck, and

especially the lower neck and chest, by using

lower energy and density, as scarring has been noted in these areas.

Figure 1 Omnilux 633 nm light for fibroblast stimulation

Figure 2 Blood post-centrifuge, showing the platelet layer Figure 3 Injecting PRP in the periorbital area

treatment option, they had many post-procedural problems16, 17, including prolonged post-operative recovery, pigmentary changes, and a high incidence of acne flares and herpes simplex virus (HSV) infection18, 19. Many patients complained of oedema, burning, and erythema that sometimes lasted for many months20, 21. The implied risks and long downtime made many patients reluctant to accept this method of treatment22, 23. More recently, fractional resurfacing lasers have addressed many of these earlier problems with benefits of faster recovery time, more precise control of ablation depth, and reduced risk of post procedural problems8. These lasers are extremely versatile, in that they can be used for the treatment of facial rhytides, acne scars, surgical scars, melasma and photodamaged skin, and many have entered the market at the same time24.

With the advent of fractional laser skin resurfacing, the number of completely ablative resurfacing cases has declined for most practitioners. However, care should be taken when treating sensitive areas such as the eyelids, upper neck, and especially the lower neck and chest, by using lower energy and density, as scarring has been

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Patient histology Carbon dioxide laser ablative fractionalisation

near-red light, resulting in fibroblast stimulation. Omnilux Revive™ (633 nm) therapy stimulates fibroblast activity, leading to faster and more efficient collagen synthesis and extracellular matrix (ECM) proteins. It also increases cell vitality by increasing the production of cellular adenosine triphosphate (ATP) and stimulates the contractile phase of the remodelling process producing better lineated collagen30–33. Collagen induction therapy is an aesthetic medical procedure that involves repeatedly

Parameter 0 1 2 3 4

Global score Area of Area of Area of Area of Area of roughness roughness roughness roughness roughness x 0 x 1 x2 x3 x4

Fine lines None Rare Several Moderate Many

Pigmentary None Patchy Moderate Heavy Marked

problems

Touch Even Rare Mild Moderate Severe problems

Facial veins None Rare Several Moderate Severe

Coarse lines None Rare Several Moderate Many

Complexion Pink Pale Grey Slightly Distinct yellow-grey

Parameter 0 1 2 3 4

Erythema severity None Rare Several Moderate Severe

Infective outbreak None Rare Several Moderate Severe(herpes/acne)

Crusting None Rare Several Moderate Severe

Pain of None Mild Tolerable Moderate Severe procedure

Improvement None Minimal Fair Good Excellent

Group 1 patient showing ablative CO

2 laser penetration to 118 nm.

Depth range 113 microns

Group 2 patient showing collagen formation at 3 months, representing a skin biopsy from a Group 2 patient 3 months post-treatment. Depth range 118 microns

Group 2 patient at Phase 3. Depth range 85 microns

Group 1 patient showing collagen formation at 3 months. Depth range 700 microns

All skin biopsies show the effect of thermal treatment with thermal coagulation of the epidermis and superficial dermis

puncturing the skin with tiny, sterile needles. Typically, this is done with a specialised instrument called a microneedling device.

Controlled studies have suggested that the application of autogenous PRP can enhance wound healing in both animals and humans29. Five major growth factors such as transforming growth factor (TGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF) are known to be related to the wound-healing processes28. These growth factors are released from platelets, and the production of collagen and fibroblasts is stimulated by IGF, EGF, Interleukin-1 (IL-1) and tumour necrosis factor (TNF)-α34, 35. In vivo studies report TGF-β to be the most stimulative growth factor. PRP may be used for dermal augmentation and Sclafani observed aesthetic improvements of the nasolabial fold in less than 2 weeks, and the results lasted for up to 3 months28, 29.

Research design and methodsThis multi-centre randomised study included 44 patients of skin types 1 and 2 aged between 39 and 68 years, presenting with photoageing of the skin, 37 of whom were women and seven were men. The subjects presented with the typical hallmarks of chronological and photoageing, such as expression lines, rhytides, wrinkles, eyelid skin laxity, dermatochalasis, lowered brows, lateral hooding, and prominent fat pads. All patients were subjected to a programme of skin tightening and neocollagenesis by one of two methods: conventional fractional laser skin resurfacing (Group 1) or the DUBLiN Lift (Group 2). The mean patient age in Group 1 was 49 years (range 37–71 years) and in Group 2 was 55 years (range 41–76 years).

Fifteen patients underwent Lumenis ActiveFX™ with settings as (energy) 125 mJ and (rate) 19 w CPG 3/5/4. Twenty-nine patients received the DUBLiN Lift, a three-phase combination of established treatments with microneedling, platelet growth hormones, near-red 633 nm light, and low-energy UltraPulse fractional CO

2

Table 1 Patient treatment (positive) scoring chart

Table 2 Patient treatment (negative) scoring chart

yellow-grey

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laser skin tightening. All patients received Dysport® in three areas 1 week prior to the other treatments as an adjunct to the laser resurfacing.

The DUBLiN Lift was introduced as three phases over a period of 3 weeks. Phase 1 included Dysport® at dilution 3.5 : 1 to three areas — glabellar, frontalis and periorbital. Phase 2 introduced intense fibroblast stimulation and modification through microneedling, PRP growth factor induction, and near-red phototherapy. Phase 3 administered the low–level (CO

2) UltraPulse laser at

100 mJ 14 w CPG 3/5/2, and adjunct near-red 633 nm phototherapy. The study evaluated post-procedural aesthetic results at 2 weeks, 4 weeks and 12 weeks. The length of downtime, patient discomfort and adverse side-effects were noted for each phase.

Clinical assessment of patients in each group was made at 2 weeks, 1 month and 3 months post-operatively in the presence of two aesthetic staff. The degree of improvement in photoageing was based on the degree of re-epithelialisation rate, reduction of rhytides, reduction of tactile roughness, and loss of hyperpigmentation and telangiectasias. The prolongation and severity of erythema as well as the presence of negative side-effects (e.g. herpes) were also recorded.

The efficacy of treatment was evaluated using a variation of the five-point scale (Table 1) originally suggested by Dover et al36. Investigators and patients evaluated efficacy using palpability assessments and change from baseline score at 0, 6 and 12 weeks. A total

DEGREE DESCRIPTION

5 Extreme Extremely deep and long folds, detrimental to facial appearance

4 Severe Very long and deep folds; prominent facial features; less than 2 mm visible

3 Moderate Moderately deep folds; clear facial feature visible at normal appearance, but not when stretched

2 Mild Shallow but visible fold with a slight indentation; minor facial feature

1 Absent No visible nasolabial fold; continuous skin, injectable implant alone

DEGREE DESCRIPTION

1 Exceptional improvement Excellent corrective result at week 12. No further treatment required

2 Very improved patient Marked improvement of appearance, but not completely optimal

3 Improved patient Improvement of the appearance, better compared with the initial condition. Touch-up is advised

4 Unaltered patient The appearance substantially remains the same compared with the original condition

5 Worsened patient The appearance has worsened compared with the original condition

global score was recorded in each patient based on the addition of points obtained from six photodamage variables. The degree of perceived improvement in overall aesthetic effect reflecting chronological age was assessed separately by patients and physicians using the Wrinkle Severity Rating Scale (WSRS) and the Global Aesthetic Improvement Scale (GAIS). The WSRS is recognised as a valid and reliable instrument for quantitative assessment of facial skin folds, with good inter- and intra-observer consistency5. Wrinkle severity is measured using a wrinkle severity rating scale with 1 being absent and 5 being extreme. By allowing objective grading of data, these proved useful clinical tools for assessing the effectiveness of facial volumisation with PRP and microneedling–633.

InterventionsThe following treatment protocols were used for this study: Lumenis ActiveFX CO

2 laser, Traylife PRP, Omnilux 633 nm

red light, Dermaroller®, and Dysport®. All participants received selective regional anaesthesia blocks with 2% lignocaine plus adrenaline, a topical combination anaesthetic of 23% lignocaine, and prophylactic Valtrex 500 mg twice daily for 8 days. Valium 5–10 mg stat was given as a pre-medication to some patients. A post-procedural advice sheet and Nurofen or codeine with paracetamol — as required — was also given to patients.

Clinical assessment of patients in each group was made at 2 weeks, 1 month and 3 months post-operatively in the presence of two aesthetic staff.

Table 3 Wrinkle Severity Rating Scale (WSRS) patient scoring chart

Table 4 Global Aesthetic Improvement Scale (GAIS)

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Figure 4 Patients before (A, C) and after (B, D) the DUBLiN Lift

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■ Infraorbital nerve block. 1 cc of 1–2% Lidocaine injected into the buccal cavity with the needle directed towards the infraorbital foramen

■ Mental nerve block. 1 cc of 1–2% Lidocaine injected into the mental foramen just above the bone level.

Group 2: DUBLiN lift Phase 1 Dysport® treatment to three areas: glabellar, frontalis and periorbital.

Phase 2 (Week 2) Microneedling Topical anaesthesia: benzocaine 20%, Lidocaine Base 6%, and tetracaine 4%.

Each patient received Chiroxy cream post-procedure to reduce erythema and inflammation. Tepid water

Figure 5 Patient in differing phases of DUBLiN Lift

The ActiveFX is a protocol of settings applied in conjunction with an improved computer pattern generator to the ultrapulsed CO

2 laser (UltraPulse

ENCORE, Lumenis Ltd). Technical differences between this non-sequential fractional device and the older ultrapulsed CO

2 include tissue bridges left between spots,

resulting in faster healing time, and less thermal damage to the basal cell membrane. The device has a smaller spot size (1300 mm rather than 2500 mm), resulting in less post-procedure erythema.

The computer pattern generator lays down a random series of spots rather than a sequential sequence resulting in less overheating of the treated tissue. This application is termed ‘Cool Scan’, and was used with every patient in the study.

The Traylife Kit (PRP) (Promoitalia Wellness Research) provides blood plasma enriched with a concentrated source of autologous platelets that releases a number of growth factors and other cytokines that stimulate the healing of soft tissue.

Omnilux Revive™ (633 nm) (Photo Therapeutics, Inc., UK) stimulates fibroblast activity, leading to faster and more efficient collagen synthesis and extracellular matrix proteins.

Dermaroller™ Collagen Induction Therapy (CIT) (AesthetiCare®, UK) is a minimally-invasive cosmetic procedure that involves the use of a micro-needling device.

Scoring charts are presented in Tables 1–4.

Group 1: fractional laser skin resurfacing Phase 1 Dysport® treatment to three areas: glabellar, frontalis and periorbital.

Phase 2 (Week 2) Lumenis ActiveFX with settings (energy) 125 mJ (rate) 1 9w CPG 3/9/4

In the pre-laser procedure, the author typically prescribes Valium (Diazepam 5–10 mg orally) for anxiety, administered 45 minutes before the procedure.

For infection prophylaxis, Famvir (famciclovir) 750 mg daily or Valtrex (valcyclovir) 500 mg twice per day for 7 days, was prescribed for every patient starting 3 days before procedure. If the patient had a strong history of acne, By-Mycin (doxycycline 100 mg daily) or Keflex (cephalexin 500 mg twice per day) was prescribed for 7 days, beginning on the day of surgery. Diflucan (fluconazole 150 mg) was not routinely prescribed in any patient.

The patients were treated under topical and regional anaesthesia. Topical anaesthesia comprised benzocaine 20%, Lidocaine Base 6%, and tetracaine 4%. Regional anaesthesia was three-fold:

■ Supraorbital and supratrochlear nerve block. The supraorbital foramen was located and 1 cc of 1–2% Lidocaine injected just above the bone laterally, with the needle directed medially, parallel to the brow and toward the nose

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was used to cleanse the face for the following 48 hours, and dried gently. It was recommended that make-up was not applied for 12 hours after the procedure. After the procedure, a broad-spectrum UVA/UVB sunscreen with SPF 50 was recommended for use.

PRP preparation Draw blood (4 ml for each tube), then centrifuge tubes at 2000 rpm for 5 minutes. Take the syringe, insert the needle and withdraw 0.5 ml DNA Activator (10% calcium chloride). Withdraw platelets and mix with the DNA Activator.

Multiple injections (0.05–0.1 ml for a single injection) were applied to the intra/sub dermis using the ‘multi-pricking’ or retrograde linear techniques

Omnilux 633 nm LED This was applied for 20 minutes per session (126 J/cm2).

Phase 3 (Week 3) Low-level UltraPulse Lumenis ActiveFX with settings (energy) 100 mJ (rate) 14 w CPG 3/5/2.

Omnilux 633 nm LED This was applied for 20 minutes per session (126 J/cm2).

Histology Skin biopsies were obtained from five of the patients intra-operatively, before Phase 2 of the treatment and at 3 months post-operatively, and were performed to determine the amount of epidermal damage, subsequent inflammation, and new collagen synthesis. The extent of neocollagenesis was

Figure 6 Cachexic patient with volumisation post PRP/DUBLiN Lift

compared with data on file for patients who had skin biopsies for laser resurfacing and neurotoxin alone in 2007. Each 1 cm by 1 cm piece of skin was fixed with 10% formalin solution, neutral buffered. After treatment with polyester wax, the skin samples were sliced into 6 μm thicknesses. The sliced sections were treated with haematoxylin and eosin statin (H&E) and Masson’s trichrome staining solutions. Through tissue evaluations, the thickness of the dermal layer and presence of collagen fibres were observed. The thickness of the dermal layer was calculated by measuring five different sites from each section, and the mean value of the thickness of the dermal layer for each group was used for the comparison.

Results Over 3 months, 29 subjects (Group 2) were selected to compare the effect of low energy fractional laser skin resurfacing with adjunctive treatments to conventional ablative laser resurfacing. These patients received a three-phase combination of established treatments with neurotoxin, microneedling, platelet growth hormones, near-red 633 nm light, and low-energy UltraPulse fractional CO

2 laser skin tightening over a 3-week period. Phase 1

included the administration of Dysport® neurotoxin to the upper face. Phase 2 introduced fibroblast stimulation from microneedling and PRP growth factor induction with near-red phototherapy, and Phase 3 included low-level (CO

2) UltraPulse laser with adjunct

near-red 633 nm phototherapy. Results were compared to the remaining 15 patients (Group 1) who received fractional laser skin resurfacing (125 mJ; 19 w CPG 3/5/4), and

Over 3 months, 29 subjects (Group 2) were selected to compare

the effect of low energy fractional laser skin resurfacing with adjunctive

treatments to conventional ablative laser resurfacing.

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Investigator-based and patient-based ratings using both the WSRS

and GAIS indicated that the DUBLiN lift was more effective than conventional ablative laser

resurfacing in creating cosmetic correction to the lower face.

whose data was already on file. Patients in both groups were administered Dysport® neurotoxin 1 week prior to treatment to complement and preserve the overall aesthetic effect. The study evaluated post-procedural aesthetic results at baseline, 6 weeks and 12 weeks by means of a scoring system based on Dover’s photoageing scale, as well as using the WSRS and GAIS.

Histological results were obtained from both groups showing the depth of laser penetration and consequential formation of new collagen. All skin biopsies showed thermal coagulation of the epidermis and superficial dermis in a depth ranging from 85 to 113 μ. The zone of residual thermal (coagulative) damage was less in the Group 2 patients, in whom less laser energy was used. The best neocollagenesis results — at 3 months — were evident in Group 1 where one patient had evidence of effect at 700 μ. This was reflected in the patient’s skin, which continued to improve over the period. Owing to the variance in energy of the CO

2 laser in Group 1 and

Group 2, it was expected that the documented depth of histological ablation and thermal effects would vary between them. Responses of aesthetic effect were evaluated at 6 and 12 weeks after baseline.

The two methods appeared to produce different clinical improvement of lesions and rhytides. The GAIS for photoageing for the DUBLiN lift improved from 13.2 to 10.2 at day 30. This compared to 13.8 at baseline and 9.6 at day 30 for conventional fractional laser skin resurfacing alone. The score for fine lines was the most significant reduction, dropping from 3.6 at baseline to 1.4 at day 30. The score for reduction of coarse wrinkles (3.2 at baseline to 2.2 at 6 weeks) was more difficult to interpret in this heterogeneous age grouping, with older patients requiring the conventional ActiveFX settings rather than the ‘softer’ settings.

According to investigator-based WSRS and GAIS assessments at 3 months after baseline, the DUBLiN lift was superior in 62% and 55.2% of patients respectively, while fractional laser skin resurfacing was superior in 33.3% and 34.4% of patients. (P < 0.0004). An ‘optimal’ cosmetic result was achieved in a higher percentage of patients in Group 2 compared with Group 1.

Investigator-based and patient-based ratings using both the WSRS and GAIS indicated that the DUBLiN lift was more effective than conventional ablative laser resurfacing in creating cosmetic correction to the lower face. This resulted from the volumising effect of adding PRP to the larger folds in this area. At 3 months post-treatment, a higher proportion of patients showed a greater than or equal to 1-grade improvement in WSRS with the DUBLiN Lift compared with fractional laser skin resurfacing. The author suspects the PRP may have a longer aesthetic effect when used in association with microneedling and 633 nm light than previously noted27, 29. However, the results were almost reversed whenever periorbital rejuvenation was assessed alone, with almost every patient (93%) favouring conventional fractional laser skin resurfacing. Investigator-based GAIS assessment of this region at 3

months after baseline indicated that fractional resurfacing was superior in 93% of patients, while the DUBLiN Lift was superior in 6.8% of patients (P = 0.0025).

Objective resultsRe-epithelialisation occurred in all laser-treated areas of both groups by day 7, and this appeared to be clinically similar for both procedures. Mean duration of erythema was 6.9 days after resurfacing (range 4–10 days) in Group 1 and 4.2 days in Group 2 (range 3–7 days). This appeared to be in keeping with previous studies37. All patients reported having no ‘crusting’

effect remaining on their face after 6 days. Residual erythema remained in one patient in Group 1 for a

Further reading ☛ Alster TS, Nanni CA. Famciclovir prophylaxis of herpes simplex virus reactivation after laser skin resurfacing. Dermatol Surg 1999; 25(3): 242–6

☛ Alster TS. Side effects and complications of laser surgery. In: Alster TS. Manual of Cutaneous Laser Techniques. Philadelphia: Lippinco, 2000

☛ Avram MM, Tope WD, Yu T, Szachowicz E, Nelson JS. Hypertrophic scarring of the neck following ablative fractional carbon dioxide laser resurfacing. Lasers Surg med 2009; 41(3): 185–8

☛ Baez F, Reilly LR. The use of light-emitting diode therapy in the treatment of photoaged skin. J Cosmet Dermatol 2007; 6(3): 189–94

☛ Berlin AL, Hussain M, Phelps R, Goldberg DJ. Treatment of photoaging with a very superficial Er:YAG laser in combination with a broadband light source. J Drugs Dermatol 2007; 6(11): 1114–8

☛ Bernstein LJ, Kauvar AN, Grossman MC, Geronemus RG. The short- and long-term side effects of carbon dioxide laser resurfacing. Dermatol Surg 1997; 23(7): 519–25

☛ Bonan P, Campolmi P, Cannarozzo G et al. Eyelid skin tightening: a novel ‘Niche’ for fractional CO2 rejuvenation. J Eur Acad Dermatol Venereol 2012; 26(2): 186–93

☛ Burkhardt BR, Maw R. Are more passes better? safety versus efficacy with the pulsed CO2 laser. Plast Reconstr Surg 1997; 100(6): 1531–4

☛ Cotton J, Hood AF, Gonin R, Beeson WH, Hanke CW. Histologic evaluation of preauricular and postauricular skin after high-energy, short-pulse carbon dioxide laser. Arch Dermatol 1996; 132(4): 425–8

☛ Day DJ, Littler CM, Swift RW, Gottlieb S. The wrinkle severity rating scale: a validation study. Am J Clin Dermatol 2004; 5(1): 49–52

☛ Doddaballapur S. Microneedling with dermaroller. J Cutan Aesthet Surg 2009; 2(2): 110–1

☛ Goldberg D. Reduced Down-time Associated with Novel Fractional UltraPulse CO2 Treatment (Active FX) as Compared to Traditional Resurfacing P3115. Presented at the 65th Annual American Academy of Dermatology Meeting

☛ Fitzpatrick RE, Ruiz-Esparaza J, Goldman

MP. The depth of thermal necrosis using the CO2 laser: a comparison of superpulsed mode and conventional mode. J Dermatol Surg Oncol 1991; 17(4): 340–4

☛ Fitzpatrick RE, Tope WD, Goldman MP, Satur NM. Pulsed carbon dioxide laser, trichloroacetic acid, Baker-Gordon phenol, and dermabrasion: a comparative clinical and histologic study of cutaneous resurfacing in a porcine model. Arch Dermatol 1996; 132(4): 469–71

☛ Kauvar ANB, Waldorf HA, Geronemus R. A histopathologic comparison of char-free lasers. Dermatol Surg 1996; 22: 343–8

☛ Lask G, Keller G, Lowe N, Gormley D. Laser skin resurfacing with the SilkTouch flashscanner for facial rhytides. Dermatol Surg 1995; 21(12): 1021–4

☛ Lee SY, Park KH, Choi JW et al. A prospective, randomized, placebo-controlled, double-blinded, and split-face clinical study on LED phototherapy for skin rejuvenation: clinical, profilometric, histologic, ultrastructural, and biochemical evaluations and comparison of three different treatment settings. J Photochem Photobiol B 2007; 88(1): 51–67

☛ Majid I. Microneedling therapy in atrophic facial scars: an objective assessment. J Cutan Aesthet Surg 2009; 2(1): 26–30

☛ Pierce GF, Brown D, Mustoe TA. Quantitative analysis of inflammatory cell influx, procollagen type I synthesis, and collagen cross-linking in incisional wounds: influence of PDGF-BB and TGF-beta 1 therapy J Lab Clin Med 1991; 117(5): 373–82

☛ Rubach BW, Schoenrock LD. Histological and clinical evaluation of facial resurfacing using a carbon dioxide laser with the computer pattern generator. Arch Otolaryngol Head Neck Surg 1997; 123(9): 929–34

☛ Smith KJ, Skelton HG, Graham JS, Hamilton TA, Hackley BE Jr, Hurst CG. Depth of

morphologic skin damage and viability after one, two and three

passes of a high-energy, short-pulse CO2 (Tru-Pulse) laser in pig skin. J Am Acad Dermatol 1997; 37(2 Pt 1):

204–10

☛ Trelles MA, Allones I. Red light-emitting diode (LED) therapy accelerates wound

healing post-blepharoplasty and periocular laser ablative resurfacing. J Cosmet Laser Ther 2006; 8(1): 39–42

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period of 14 days, but this was minimal. Post-operative erythema was most intense in the areas treated with the ActiveFX at an energy level above 125 mJ.

The mean pain sensation (Table 2) felt during the DUBLiN lift was 2.2 compared to conventional fractional resurfacing treatment, which was 3.4. The author noted that most patients did not feel much pain at all with the ActiveFX until the energy level crosses 100 mJ. No patient experienced any adverse reaction to laser skin resurfacing, except one case of herpetic infection in each group (Group 1 6.6%; Group 2 3.4%). Both treatments were well tolerated. Clumping of platelets occurred in 10% of patients treated with PRP and the author felt that this was a result of the concentration of solution used. In fact, anecdotal evidence suggests that most cosmetic physicians are using PPP (platelet-poor plasma) in most areas of the face, rather than the higher concentrations used by orthopaedic surgeons.

ConclusionsFacial ageing is a consequence of many interacting intrinsic and extrinsic factors. The most important of these include sun exposure or photoageing, and the

intrinsic changes associated with chronological ageing. Over time, the muscles of facial expression produce dynamic and static facial lines and folds. Laser

resurfacing has long been recognised as a skin rejuvenation procedure for tissue that has lost

its elasticity and become less able to resist stretching. However, despite the advent

of newer fractionalised lasers, it has adverse risks and does not

adequately address the problems associated with chronological

ageing as gravity exerts its toll on the facial structures. It is important to apply supplementary methods, such as dermal fillers or PRP, to address nasolabial or marionette lines and volume

deficits resulting from the loss and repositioning of facial fat.

Declaration of interest None

Figure images © Patrick Treacy

References1. Raspaldo H. Volumizing effect of a new hyaluronic acid sub-dermal facial filler: a retrospective analysis based on 102 cases. J Cosmet Laser Ther 2008; 10(3): 134–422. Cohen JL, Bar A. Fillers for Facial Rejuvenation. In: Hirsch RJ, Cohen JL, Sadick N. Aesthetic Rejuvenation: A Regional Approach. China: McGraw-Hill Companies, 20093. Hirsch RJ. Dermal Fillers. In: Sadick N, Moy R, Lawrence N. Concise Manual of Cosmetic Dermatologic Surgery. China: McGraw-Hill Companies, 2008 4. Clementoni MT, Gilardino P, Muti GF, Beretta D, Schianchi R. Non-sequential fractional ultrapulsed C02 resurfacing of photoaged skin. J Cosmet Laser Ther 2007; 9(4): 218–255. Rohrich RJ, Pessa JE. The fat compartments of the face: anatomy and clinical implications for cosmetic surgery. Plast Reconstr Surg 2007; 119(7): 2219–27 6. Sadick NS. Update on non-ablative light therapy for rejuvenation: a review. Lasers Surg Med 2003; 32(2): 120–87. Williams EF 3rd, Dahiya R. Review of nonablative laser resurfacing modalities. Facial Plast Surg Clin North Am 2004; 12(3): 305–108. Grema H, Greve B, Raulin C.

Facial rhytides — subsurfacing or resurfacing? A review. Lasers Surg Med 2003; 32(5): 405–129. Manuskiatti W, Fitzpatrick RE, Goldman MP. Long-term effectiveness and side effects of carbon dioxide laser resurfacing for photoaged facial skin. J Am Acad Dermatol 1999; 40(3): 401–1110. Fitzpatrick RE, Goldman MP, Satur NM, Tope WD. Pulsed carbon dioxide laser resurfacing of photo-aged facial skin. Arch Dermatol 1996; 132(4): 395–40211. Hamilton MM. Carbon dioxide laser resurfacing. Facial Plast Surg Clin North Am 2004; 12(3): 289–9512. Fitzpatrick RE. CO2 laser resurfacing. Dermatol Clin 2001; 19(3): 443–5113. Fitzpatrick RE. Maximizing benefits and minimizing risk with CO2 laser resurfacing. Dermatol Clin 2002; 20(1): 77–8614. Taylor CR, Stern RS, Leyden JJ, Golchrest BA. Photoaging/photodamage and photoprotection. J Am Acad Dermatol 1990; 22(1): 1–1515. Lavker RM. Cutaneous aging: chronological versus photoaging. In: Gilchrest BA. Photodamage. Cambridge, MA: Blackwell Science, 199516. Fife DJ, Fitzpatrick RE, Zachary CB. Complications of fractional CO2 laser resurfacing: four cases. Lasers

Surg Med 2009; 41(3): 179–8417. Nanni CA, Alster TS. Complications of carbon dioxide laser resurfacing. An evaluation of 500 patients. Dermatol Surg 1998; 24(3): 315–2018. Alster T, Hirsch R. Single-pass CO2 laser skin resurfacing of light and dark skin: Extended experience with 52 patients. J Cosmet Laser Ther 2003; 5(1): 39–4219. Alster TS. Cutaneous resurfacing with CO2 and erbium: YAG lasers: preoperative, intraoperative, and postoperative considerations. Plast Reconstr Surg 1999; 103(2): 619–3220. Alster TS, Lupton JR. Treatment of complications of laser skin resurfacing. Arch Facial Plast Surg 2000; 2(4): 279–8421. Sullivan SA, Dailey RA. Complications of laser resurfacing and their management. Ophthal Plast Reconstr Surg 2000; 16(6): 417–2622. Berwald C, Levy JL, Magalon G. Complications of the resurfacing laser: retrospective study of 749 patients. Ann Chir Plast Esthet 2004; 49(4): 360–523. Trelles MA, Mordon S, Svaasand LO, Mellor TK, Rigau J, Garcia L. The origin and role of erythema after carbon dioxide laser resurfacing: a clinical and histologic study. Dermatol Surg 1998; 24(1): 25–9

24. Fitzpatrick RE, Rostan EF. Reversal of photodamage with topical growth factors: a pilot study. J Cosmet Laser Ther 2003; 5(1): 25–3425. Bjerring P. Photorejuvenation — an overview. Med Laser Appl 2004; 19: 186–9526. Chapas AM, Brightman L, Sukal S et al. Successful treatment of acneiform scarring with CO2 ablative fractional resurfacing. Lasers Surg Med 2008; 40(6): 381–6 27. Eppley BL, Pietrzak WS, Blanton M. Platelet-rich plasma: a review of biology and applications in plastic surgery. Plast Reconstr Surg 2006; 118(6): 147e–159e28. Sadick NS. A study to determine the efficacy of a novel handheld light-emitting diode device in the treatment of photoaged skin. J Cosmetic Dermatol 2008; 7(4): 263–729. Sclafani AP. Applications of platelet-rich fibrin matrix in facial plastic surgery. Facial Plast Surg 2009; 25(4): 270–630. Bhat J, Birch J, Whitehurst C, Lanigan SW. A single-blinded randomised controlled study to determine the efficacy of Omnilux Revive facial treatment in skin rejuvenation. Lasers Med Sci 2005; 20(1): 6–1031. Russell BA, Kellett N, Reilly LR. A study to determine the efficacy of combination LED light therapy (633

nm and 830 nm) in facial skin rejuvenation. J Cosmet Laser Ther 2005; 7(3–4): 196–20032. Kim JW. Clinical trial of non-thermal 633nm Omnilux LED array for renewal of photoaging: Clinical Surface Profilometric Results. Journal of the Korean Society for Laser Medicine and Surgery 2005; 9: 69–7633. Fabbrocini G, De Vita V, Pastore F et al. Collagen induction therapy for the treatment of upper lip wrinkles. J Dermatolog Treat 2012; 23(2): 144–5234. Stebbins WG, Hanke CW. Ablative fractional CO2 resurfacing for photo aging of the hands: pilot study of 10 pateints. Dermatol Ther 2011; 24(1): 62–7035. Goldman MP, Marchell N, Fitzpatrick RE. Laser skin resurfacing of the face with a combined CO2/Er: YAG laser. Dermatol Surg 2000; 26(2): 102–436. Dover JS, Bhatia AC, Stewart B, Arndt KA. Topical 5-aminolevulinic acid combined with intense pulsed light in the treatment of photoaging. Arch Dermatol 2005; 141(10): 1247–5237. Lowe NJ, Lask G, Griffin ME, Maxwell A, Lowe P, Quilada F. Skin resurfacing with the Ultrapulse carbon dioxide laser. Observations on 100 patients. Dermatol Surg 1995; 21(12): 1025–9

Facial ageing is a consequence of many interacting intrinsic and extrinsic factors. The most important of these

include sun exposure or photoageing, and the intrinsic changes associated with chronological ageing.

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events Industry events in 2014–15 for the aesthetic and anti-ageing market

24–25 OCTOBER 20142nd AMEC

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19–21 NOVEMBER 2014myRhinoplasty 2014

London, UKwww.aesculap-academia.co.uk

26–28 NOVEMBER 2014BAPRAS Winter Scientific

Meeting 2014London, UK

http://tinyurl.com/p8nwkeg

29–30 NOVEMBER 2014BODY Conference &

ExhibitionLondon, UK

www.bodyconference.co.uk

29 JANUARY–1 FEBRUARY 2015IMCAS ParisParis, Francewww.imcas.com

5–8 MARCH 201512th EADV Spring

SymposiumValencia, Spain

www.eadv.org

7–8 MARCH 2015ACE 2015

London, UKwww.ace2014.co.uk

26–28 MARCH 201513th AMWC

Monte Carlo, Monacowww.euromedicom.com

4–6 JUNE 2015Beauty Through

ScienceStockholm, Sweden

www.beautythroughscience.com

6–10 JULY 201518th World congress IPRAS

Vienna, Austriawww.ipras.org

31 OCT–1 NOVEMBER 2014

3rd Marrakech World Aesthetic ConferenceMarrakech, Morocco

www.mwacongress.com

14–16 NOVEMBER 2014

IMCAS IndiaGoa, India

www.imcas.com/en/india2014/congress

15–16 NOVEMBER 2014

10th National Laser & Cosmetic Medicine

ConferenceMelbourne, Australia

www.dcconferences.com.au/lcmc2014/

27–29 NOVEMBER 20141st AMWC

Latin AmericaMedellin, Colombiawww.euromedicom.com

EUROPE REST OF WORLDNORTH AMERICA6–9 NOVEMBER 2014

QMP’s 10th Aesthetic

Surgery Symposium Chicago, Illinois

www.qmp.com

6–9 NOVEMBER 2014

ASDS Meeting 2014

San Diego, California

www.asds.net

3–6 DECEMBER, 2014Cosmetic Surgery

ForumLas Vegas, NV

www.cosmeticsurgeryforum.com

4–6 DECEMBER, 2014The Cutting Edge

2014New York, NY

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