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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
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| CONTENTS
BOARD MEMBER	 SPECIALISM	 COUNTRY
Dr Claude Dalle	 Anti-ageing & aesth. medicine	 France
Dr Wilmar Accursio	 Endocrinology	 Brazil
Dr Firas Al-Niaimi	 Dermatology & laser surgery	 UK
Dr Ashraf Badawi	 Dermatology	 Egypt & Canada
Dr Janethy Balakrishnan	 Aesthetic & anti-ageing medicine	 Malaysia
Dr Lakhdar Belhaouari	 Plastic surgery	 France
Dr Anthony Benedetto	 Cosmetic Dermatology	 USA
Dr Philippe Berros 	 Oculoplastic surgery	 Monaco
Dr Dario Bertossi 	 Maxillofacial surgery	 Italy
Dr Pierre Bouhanna	 Dermatology – Hair surgery	 France
Dr Fahd Benslimane	 Plastic Surgery	 Morocco
Prof Wayne Carey	 Dermatology	 Canada
Dr Claude Chauchard	 Anti-ageing medicine	 France
Dr Christophe de Jaeger	 Geriatrics	 France
Dr Gerd Gauglitz	 Aesthetic Dermatology	 Germany
Prof Ilaria Ghersetich	 Dermatology	 Italy
Dr Kate Goldie	 Aesthetic Physician	 UK
Prof Eckart Haneke	 Dermatology	 Germany
Dr Steven Hopping	 Plastic surgery	 USA
Prof Andreas Katsambas	 Dermatology	 Greece
Dr Mario Krause	 Anti-ageing medicine	 Germany
Dr Marina Landau	 Dermatology	 Israel
BOARD MEMBER	 SPECIALISM	 COUNTRY
Dr Gustavo Leibaschoff	 Cosmetic Surgery	 USA
Dr Sohail Mansoor	 Dermatology	 UK
Prof Leonardo Marini	 Dermatology	 Italy
Dr Sly Nedic	 Aesthetic & anti-ageing medicine	 South Africa
Prof Daniel Pella	 Cardiology	 Slovakia
Dr Chariya Petchngaovilai	 Dermatology	 Thailand
Prof Ascanio Polimeni	 Neuro-endocrinology	 Italy
Dr Herve Raspaldo	 Facial plastic surgery	 France
Dr Christopher Rowland-Payne	Dermatology	 UK
Dr Neil Sadick	 Dermatology	 USA
Dr Hema Sundaram	 Dermatology	 USA
Dr Pakpilai Thavisin	 Dermatology&Anti-ageingmedicine	 Thailand
Dr Patrick Treacy	 Aesthetic surgery	 Ireland
Dr Mario Trelles	 Plastic surgery	 Spain
Dr Ines Verner	 Dermatology	 Israel
Dr Octavio Viera	 Anti-ageing medicine	 Spain
Dr Jean-Luc Vigneron	 Aesthetic dermatology	 France
Prof Bernard Weber	 Genetics	 Luxembourg
Dr Sabine Zenker	 Dermatology	 Germany
Catherine Decuyper	 Industry expert & consultant	 France
Wendy Lewis	 Industry expert	 USA
Christophe Luino	 Industry expert & consultant	 France
PRIME JOURNAL EDITORIAL BOARD
International Journal of Aesthetic
and Anti-Ageing Medicine
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PatrickTreacyconsiderstheconflicting
evidenceofbotulinumtoxinuseasatherapyfor
depression,andproposesthatitallcomesdown
towherethetoxinisinjected
THE‘BOTOX
PARADOX’:
IS IT EFFECTIVE
FOR DEPRESSION?
REVERSAL OF A
DERMAL FILLER
INDUCED
FACIAL ARTERY
OCCLUSION
PatrickTreacydiscussesthefactorstoconsider
toavoidadverseeventsaftertheuseofadermal
filleraswellasthebestmethodsoftreating
complications,includingsteroidsandhyaluronidase
PatrickTreacypresentsanovelmethodforfull
facialrejuvenation,whichcombinesanumber
oftreatmentstoobtainthemostoptimum
results
COMBINING THERAPIES
FOR THE AGEING FACE:
THE DUBLIN LIFT
10
14
4
REVERSAL OF A
DERMAL FILLER
INDUCEDFACIAL ARTERY OCCLUSION
PatrickTreacydiscussesthefactorstoconsidertoavoidadverse
eventsaftertheuseofadermalfilleraswellasthebestmethodsof
treatingcomplications,includingsteroidsandhyaluronidase
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.
W
ITHIN 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: ptreacy@gmail.com
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-effects
The 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
PEER-REVIEW | DERMATOLOGY |
4 prime-journal.com
Severe vascular
adverse events have been
reported in the glabellar and
nasolabial regions after
treatment with both
biodegradable and
non-biodegradable
injectable fillers.
prime-journal.com 5
| DERMATOLOGY | PEER-REVIEW
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 study
Patient 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
PEER-REVIEW | DERMATOLOGY |
6 prime-journal.com
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 O2
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.
Discussion
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. 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(usingcorticosteroidsandhyaluronidase),
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 of
HLA immediately
Massage the affected area
immediately
Apply warm packs of gauze
to area (microwave)
Apply nitro-paste or 10 mgs
transderm-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 of
75u to occluded area
Hydrocortisone 100mg
IV stat (if not an acute
ischaemic event)
Dexamethsone 4mgs daily
PO 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 artery
Dorsal nasal artery
Ophthalmic
artery
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.
| DERMATOLOGY | PEER-REVIEW
prime-journal.com 7
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 References
1.	 Lowe NJ, Maxwell CA, Patnaik R.
Adverse reactions to dermal fillers:
review. Dermatol Surg 2005; 31 (11 Pt
2): 1616–25
2.	 Gladstone HB, Cohen JL. Adverse
effects when injecting facial fillers.
Semin Cutan Med Surg 2007; 26(1):
34–9
3.	 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:
S128–35
4.	 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, 2007
5.	 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: 1629–34
6.	 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: 1635–40
7.	 Gladstone HB, Cohen JL. Adverse
effects when injecting facial fillers.
Semin Cutan Med Surg 2007; 26 (1):
34–9
8.	 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): 171–6
10.	 Christensen L, Breiting V, Janssen
M, Vuust J, Hogdall E. Adverse
reactions to injectable soft tissue
permanent fillers. Aesthetic Plast Surg
2005; 29(1): 34–48
11.	 Christensen L. Normal and
pathologic tissue reactions to soft
tissue gel fillers. Dermatol Surg 2007;
33 Suppl 2: S168–75
12.	 Lowe NJ, Maxwell A, Patnaik R.
Adverse Reactions to Dermal Fillers:
Review. Dermatologic Surgery 2005;
31(s4):1626–1633
13.	 Smith L, Cockerham K Hyaluronic
acid dermal fillers: can adjunctive
lidocaine improve patient satisfaction
without decreasing efficacy or
duration? Patient Prefer Adherence
2011; 5: 133–9
14.	 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): 276–281
15.	 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): 357–360
16.	 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.
PEER-REVIEW | DERMATOLOGY |
8 prime-journal.com
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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.
THE‘BOTOX
PARADOX’:
IS IT EFFECTIVE
FOR DEPRESSION?PatrickTreacyconsiderstheconflictingevidenceofbotulinum
toxinuseasatherapyfordepression,andproposesthatitall
comesdowntowherethetoxinisinjected
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: ptreacy@gmail.com
A
RECENT ARTICLE
byClaireColeman1
,
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
oneoftheleadingcausesofdisability
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.
Darwinevensoughtouttheopinions
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
popularityofBOTOXmadescientists
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
| DEPRESSION | OPINION
prime-journal.com 11
OPINION | DEPRESSION |
12 prime-journal.com
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 depression
A 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.
References
1.	 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): 645–9
3.	 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): 213–6
4.	 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: 321–38
5.	 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):537–42
6.	 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): 895–900
7.	 Neal DT, Chartrand TL.
Embodied emotion perception:
amplifying and dampening facial
feedback modulates emotion
perception accuracy. Soc Psychol
Personal Sci 2011; doi:
10.1177/1948550611406138
8.	 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
| DEPRESSION | OPINION
prime-journal.com 13
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
reducethesymptomsofmajordepression.
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.)
Conclusions
Thereisgrowingevidencethatbotulinum
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.
PatrickTreacypresentsanovelmethodforfullfacial
rejuvenation,whichcombinesanumber
oftreatmentstoobtainthemostoptimumresults
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 CO2
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: ptreacy@gmail.com
ABSTRACT
T
HE 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, CO2
laser resurfacing was
considered the ‘gold standard’ in treating
photodamaged facial skin6–11
. Cutaneous
laser resurfacing with a fractional (CO2
)
laser involves the vapourisation of the
entire epidermis, as well as a variable
thickness of the dermis. Many physicians
stated that the ultrapulsed CO2
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
COMBININGTHERAPIESFORTHEAGEINGFACE:
THE DUBLiN
LIFT
More
recently, patients
are seeking
effective facial
rejuvenation
procedures with
less downtime
and low risks.
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14 prime-journal.com
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 CO2
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
stimulation
It 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
CO2
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)areknowntoberelatedtothewound-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 methods
This 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 CO2
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 (CO2
) 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.
Interventions
The following treatment protocols were used for this study:
Lumenis ActiveFX CO2
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
■■ 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 CO2
laser (UltraPulse
ENCORE, Lumenis Ltd). Technical differences between
this non-sequential fractional device and the older
ultrapulsed CO2
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
| DERMATOLOGY | PEER-REVIEW
prime-journal.com 19
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,
thethicknessofthedermallayerandpresenceofcollagen
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
dermallayerforeachgroupwasusedforthecomparison.
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-red633 nmlight,andlow-energyUltraPulsefractional
CO2
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 (CO2
) 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.
PEER-REVIEW | DERMATOLOGY |
20 prime-journal.com
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
showingthedepthoflaserpenetrationandconsequential
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 CO2
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
moreeffectivethanconventionalablativelaserresurfacing
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 results
Re-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
| DERMATOLOGY | PEER-REVIEW
prime-journal.com 21
ARTICLE | FACIAL AESTHETICS |
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
thiswasaresultoftheconcentration
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.
Conclusions
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.
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
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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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Beauty Through
Science
Stockholm, Sweden
www.beautythroughscience.com
6–10 JULY 2015
18th World congress IPRAS
Vienna, Austria
www.ipras.org
31 OCT–1 NOVEMBER 2014
3rd Marrakech World
Aesthetic Conference
Marrakech, Morocco
www.mwacongress.com
14–16 NOVEMBER 2014
IMCAS India
Goa, India
www.imcas.com/en/india2014/congress
15–16 NOVEMBER 2014
10th National Laser &
Cosmetic Medicine
Conference
Melbourne, Australia
www.dcconferences.com.au/lcmc2014/
27–29 NOVEMBER 2014
1st AMWC
Latin America
Medellin, Colombia
www.euromedicom.com
EUROPE REST OF WORLDNORTH AMERICA
6–9 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, 2014
Cosmetic Surgery
Forum
Las Vegas, NV
www.cosmeticsurgeryforum.com
4–6 DECEMBER, 2014
The Cutting Edge
2014
New York, NY
www.nypsf.org
prime-journal.com 23
| EVENTS

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PRIME Supplement - Dr. Patrick Treacy

  • 1. 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
  • 2. Register to PRIME online for FREE prime-journal.com Why Register: prime-journal.com Access the latest PRIME articles as soon as they are published ONLINE FIRST Peer-review articles, insightful analysis and key data all in one place ONE PLATFORM Watch the latest videos which interest you DIGITAL CONTENT Comment on articles, and review the opinions of your peers INTERACT The PRIME website is maximised for mobiles and tablets so you can read it on the go EASE OF USE
  • 3. prime-journal.com 3 | CONTENTS BOARD MEMBER SPECIALISM COUNTRY Dr Claude Dalle Anti-ageing & aesth. medicine France Dr Wilmar Accursio Endocrinology Brazil Dr Firas Al-Niaimi Dermatology & laser surgery UK Dr Ashraf Badawi Dermatology Egypt & Canada Dr Janethy Balakrishnan Aesthetic & anti-ageing medicine Malaysia Dr Lakhdar Belhaouari Plastic surgery France Dr Anthony Benedetto Cosmetic Dermatology USA Dr Philippe Berros Oculoplastic surgery Monaco Dr Dario Bertossi Maxillofacial surgery Italy Dr Pierre Bouhanna Dermatology – Hair surgery France Dr Fahd Benslimane Plastic Surgery Morocco Prof Wayne Carey Dermatology Canada Dr Claude Chauchard Anti-ageing medicine France Dr Christophe de Jaeger Geriatrics France Dr Gerd Gauglitz Aesthetic Dermatology Germany Prof Ilaria Ghersetich Dermatology Italy Dr Kate Goldie Aesthetic Physician UK Prof Eckart Haneke Dermatology Germany Dr Steven Hopping Plastic surgery USA Prof Andreas Katsambas Dermatology Greece Dr Mario Krause Anti-ageing medicine Germany Dr Marina Landau Dermatology Israel BOARD MEMBER SPECIALISM COUNTRY Dr Gustavo Leibaschoff Cosmetic Surgery USA Dr Sohail Mansoor Dermatology UK Prof Leonardo Marini Dermatology Italy Dr Sly Nedic Aesthetic & anti-ageing medicine South Africa Prof Daniel Pella Cardiology Slovakia Dr Chariya Petchngaovilai Dermatology Thailand Prof Ascanio Polimeni Neuro-endocrinology Italy Dr Herve Raspaldo Facial plastic surgery France Dr Christopher Rowland-Payne Dermatology UK Dr Neil Sadick Dermatology USA Dr Hema Sundaram Dermatology USA Dr Pakpilai Thavisin Dermatology&Anti-ageingmedicine Thailand Dr Patrick Treacy Aesthetic surgery Ireland Dr Mario Trelles Plastic surgery Spain Dr Ines Verner Dermatology Israel Dr Octavio Viera Anti-ageing medicine Spain Dr Jean-Luc Vigneron Aesthetic dermatology France Prof Bernard Weber Genetics Luxembourg Dr Sabine Zenker Dermatology Germany Catherine Decuyper Industry expert & consultant France Wendy Lewis Industry expert USA Christophe Luino Industry expert & consultant France PRIME JOURNAL EDITORIAL BOARD International Journal of Aesthetic and Anti-Ageing Medicine Informa, Christchurch Court, 10–15 Newgate Street, London, EC1A 7AZ www.prime-journal.com ISSN 2159-8908 (print) ISSN 2159-8916 (online) Managing Editor Nicola Whyke nicola.whyke@informa.com Editor Balraj Juttla balraj.juttla@informa.com Art Director David ‘Spike’ McCormack spike@spikedesigns.co.uk Sales Manager Christopher Keeling christopher.keeling@informa.com / +44(0)2033773183 Business Development Manager NA Meg McNeel meg.mcneel@informausa.com / +1 (212) 520 2745 Production Manager Jonathan Collard jonathan.collard@informa.com Graphic Designer Snehal Sanghani snehal.sanghani@informa.com Director of Audience Development NoraPastenkos nora.pastenkos@informausa.com Production & Ads Department  primeadverts@informa.com Please send your manuscripts and press releases to: balraj.juttla@informa.com All submitted manuscripts are evaluated on the basis of scientific quality, originality, appropriateness, contribution to the field and style. Suitable manuscripts are subject to peer-review. Manuscripts and accompanying files should be prepared in accordance with our Author Guidelines, which are available via www.prime-journal.com. All content © 2014 Informa UK Ltd Images © Shutterstock.com, unless otherwise stated For address changes, please contact Hallmark Fulfillment: primeinternational@halldata.com Original articles previously published in Prime Journal, Europe edition Subscription rates UK £295 Europe €370 Rest of world US$490 PatrickTreacyconsiderstheconflicting evidenceofbotulinumtoxinuseasatherapyfor depression,andproposesthatitallcomesdown towherethetoxinisinjected THE‘BOTOX PARADOX’: IS IT EFFECTIVE FOR DEPRESSION? REVERSAL OF A DERMAL FILLER INDUCED FACIAL ARTERY OCCLUSION PatrickTreacydiscussesthefactorstoconsider toavoidadverseeventsaftertheuseofadermal filleraswellasthebestmethodsoftreating complications,includingsteroidsandhyaluronidase PatrickTreacypresentsanovelmethodforfull facialrejuvenation,whichcombinesanumber oftreatmentstoobtainthemostoptimum results COMBINING THERAPIES FOR THE AGEING FACE: THE DUBLIN LIFT 10 14 4
  • 4. REVERSAL OF A DERMAL FILLER INDUCEDFACIAL ARTERY OCCLUSION PatrickTreacydiscussesthefactorstoconsidertoavoidadverse eventsaftertheuseofadermalfilleraswellasthebestmethodsof treatingcomplications,includingsteroidsandhyaluronidase 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. W ITHIN 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: ptreacy@gmail.com 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-effects The 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 PEER-REVIEW | DERMATOLOGY | 4 prime-journal.com
  • 5. Severe vascular adverse events have been reported in the glabellar and nasolabial regions after treatment with both biodegradable and non-biodegradable injectable fillers. prime-journal.com 5 | DERMATOLOGY | PEER-REVIEW
  • 6. 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 study Patient 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 PEER-REVIEW | DERMATOLOGY | 6 prime-journal.com
  • 7. 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 O2 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. Discussion 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. 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(usingcorticosteroidsandhyaluronidase), 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 of HLA immediately Massage the affected area immediately Apply warm packs of gauze to area (microwave) Apply nitro-paste or 10 mgs transderm-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 of 75u to occluded area Hydrocortisone 100mg IV stat (if not an acute ischaemic event) Dexamethsone 4mgs daily PO 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 artery Dorsal nasal artery Ophthalmic artery 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. | DERMATOLOGY | PEER-REVIEW prime-journal.com 7
  • 8. 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 References 1. Lowe NJ, Maxwell CA, Patnaik R. Adverse reactions to dermal fillers: review. Dermatol Surg 2005; 31 (11 Pt 2): 1616–25 2. Gladstone HB, Cohen JL. Adverse effects when injecting facial fillers. Semin Cutan Med Surg 2007; 26(1): 34–9 3. 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: S128–35 4. 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, 2007 5. 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: 1629–34 6. 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: 1635–40 7. Gladstone HB, Cohen JL. Adverse effects when injecting facial fillers. Semin Cutan Med Surg 2007; 26 (1): 34–9 8. 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): 171–6 10. Christensen L, Breiting V, Janssen M, Vuust J, Hogdall E. Adverse reactions to injectable soft tissue permanent fillers. Aesthetic Plast Surg 2005; 29(1): 34–48 11. Christensen L. Normal and pathologic tissue reactions to soft tissue gel fillers. Dermatol Surg 2007; 33 Suppl 2: S168–75 12. Lowe NJ, Maxwell A, Patnaik R. Adverse Reactions to Dermal Fillers: Review. Dermatologic Surgery 2005; 31(s4):1626–1633 13. Smith L, Cockerham K Hyaluronic acid dermal fillers: can adjunctive lidocaine improve patient satisfaction without decreasing efficacy or duration? Patient Prefer Adherence 2011; 5: 133–9 14. 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): 276–281 15. 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): 357–360 16. 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. PEER-REVIEW | DERMATOLOGY | 8 prime-journal.com
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  • 10. 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.
  • 11. THE‘BOTOX PARADOX’: IS IT EFFECTIVE FOR DEPRESSION?PatrickTreacyconsiderstheconflictingevidenceofbotulinum toxinuseasatherapyfordepression,andproposesthatitall comesdowntowherethetoxinisinjected 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: ptreacy@gmail.com A RECENT ARTICLE byClaireColeman1 , 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 oneoftheleadingcausesofdisability 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. Darwinevensoughtouttheopinions 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 popularityofBOTOXmadescientists 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 | DEPRESSION | OPINION prime-journal.com 11
  • 12. OPINION | DEPRESSION | 12 prime-journal.com 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 depression A 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.
  • 13. References 1. 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): 645–9 3. 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): 213–6 4. 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: 321–38 5. 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):537–42 6. 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): 895–900 7. Neal DT, Chartrand TL. Embodied emotion perception: amplifying and dampening facial feedback modulates emotion perception accuracy. Soc Psychol Personal Sci 2011; doi: 10.1177/1948550611406138 8. 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 | DEPRESSION | OPINION prime-journal.com 13 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 reducethesymptomsofmajordepression. 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.) Conclusions Thereisgrowingevidencethatbotulinum 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.
  • 14. PatrickTreacypresentsanovelmethodforfullfacial rejuvenation,whichcombinesanumber oftreatmentstoobtainthemostoptimumresults 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 CO2 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: ptreacy@gmail.com ABSTRACT T HE 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, CO2 laser resurfacing was considered the ‘gold standard’ in treating photodamaged facial skin6–11 . Cutaneous laser resurfacing with a fractional (CO2 ) laser involves the vapourisation of the entire epidermis, as well as a variable thickness of the dermis. Many physicians stated that the ultrapulsed CO2 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 COMBININGTHERAPIESFORTHEAGEINGFACE: THE DUBLiN LIFT More recently, patients are seeking effective facial rejuvenation procedures with less downtime and low risks. PEER-REVIEW | DERMATOLOGY | 14 prime-journal.com
  • 15.
  • 16. 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 CO2 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 stimulation It 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 PEER-REVIEW | DERMATOLOGY | 16 prime-journal.com
  • 17. 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 CO2 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)areknowntoberelatedtothewound-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 methods This 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 CO2 Table 1 Patient treatment (positive) scoring chart Table 2 Patient treatment (negative) scoring chart yellow-grey | DERMATOLOGY | PEER-REVIEW prime-journal.com 17
  • 18. 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 (CO2 ) 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. Interventions The following treatment protocols were used for this study: Lumenis ActiveFX CO2 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) PEER-REVIEW | DERMATOLOGY | 18 prime-journal.com Figure 4 Patients before (A, C) and after (B, D) the DUBLiN Lift
  • 19. ■■ 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 CO2 laser (UltraPulse ENCORE, Lumenis Ltd). Technical differences between this non-sequential fractional device and the older ultrapulsed CO2 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 | DERMATOLOGY | PEER-REVIEW prime-journal.com 19
  • 20. 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, thethicknessofthedermallayerandpresenceofcollagen 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 dermallayerforeachgroupwasusedforthecomparison. 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-red633 nmlight,andlow-energyUltraPulsefractional CO2 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 (CO2 ) 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. PEER-REVIEW | DERMATOLOGY | 20 prime-journal.com
  • 21. 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 showingthedepthoflaserpenetrationandconsequential 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 CO2 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 moreeffectivethanconventionalablativelaserresurfacing 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 results Re-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 | DERMATOLOGY | PEER-REVIEW prime-journal.com 21 ARTICLE | FACIAL AESTHETICS |
  • 22. 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 thiswasaresultoftheconcentration 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. Conclusions 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. 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 References 1. 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): 134–42 2. Cohen JL, Bar A. Fillers for Facial Rejuvenation. In: Hirsch RJ, Cohen JL, Sadick N. Aesthetic Rejuvenation: A Regional Approach. China: McGraw-Hill Companies, 2009 3. 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): 218–25 5. 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): 120–8 7. Williams EF 3rd, Dahiya R. Review of nonablative laser resurfacing modalities. Facial Plast Surg Clin North Am 2004; 12(3): 305–10 8. Grema H, Greve B, Raulin C. Facial rhytides — subsurfacing or resurfacing? A review. Lasers Surg Med 2003; 32(5): 405–12 9. 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): 401–11 10. Fitzpatrick RE, Goldman MP, Satur NM, Tope WD. Pulsed carbon dioxide laser resurfacing of photo-aged facial skin. Arch Dermatol 1996; 132(4): 395–402 11. Hamilton MM. Carbon dioxide laser resurfacing. Facial Plast Surg Clin North Am 2004; 12(3): 289–95 12. Fitzpatrick RE. CO2 laser resurfacing. Dermatol Clin 2001; 19(3): 443–51 13. Fitzpatrick RE. Maximizing benefits and minimizing risk with CO2 laser resurfacing. Dermatol Clin 2002; 20(1): 77–86 14. Taylor CR, Stern RS, Leyden JJ, Golchrest BA. Photoaging/ photodamage and photoprotection. J Am Acad Dermatol 1990; 22(1): 1–15 15. Lavker RM. Cutaneous aging: chronological versus photoaging. In: Gilchrest BA. Photodamage. Cambridge, MA: Blackwell Science, 1995 16. Fife DJ, Fitzpatrick RE, Zachary CB. Complications of fractional CO2 laser resurfacing: four cases. Lasers Surg Med 2009; 41(3): 179–84 17. Nanni CA, Alster TS. Complications of carbon dioxide laser resurfacing. An evaluation of 500 patients. Dermatol Surg 1998; 24(3): 315–20 18. 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): 39–42 19. Alster TS. Cutaneous resurfacing with CO2 and erbium: YAG lasers: preoperative, intraoperative, and postoperative considerations. Plast Reconstr Surg 1999; 103(2): 619–32 20. Alster TS, Lupton JR. Treatment of complications of laser skin resurfacing. Arch Facial Plast Surg 2000; 2(4): 279–84 21. Sullivan SA, Dailey RA. Complications of laser resurfacing and their management. Ophthal Plast Reconstr Surg 2000; 16(6): 417–26 22. Berwald C, Levy JL, Magalon G. Complications of the resurfacing laser: retrospective study of 749 patients. Ann Chir Plast Esthet 2004; 49(4): 360–5 23. 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): 25–34 25. Bjerring P. Photorejuvenation — an overview. Med Laser Appl 2004; 19: 186–95 26. 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–159e 28. 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): 263–7 29. Sclafani AP. Applications of platelet-rich fibrin matrix in facial plastic surgery. Facial Plast Surg 2009; 25(4): 270–6 30. 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): 6–10 31. 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): 196–200 32. 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: 69–76 33. Fabbrocini G, De Vita V, Pastore F et al. 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PEER-REVIEW | DERMATOLOGY | 22 prime-journal.com
  • 23. eventsIndustryeventsin2014–15 fortheaestheticand anti-ageingmarket 24–25 OCTOBER 2014 2nd AMEC Paris, France www.euromedicom.com 19–21 NOVEMBER 2014 myRhinoplasty 2014 London, UK www.aesculap-academia.co.uk 26–28 NOVEMBER 2014 BAPRAS Winter Scientific Meeting 2014 London, UK http://tinyurl.com/p8nwkeg 29–30 NOVEMBER 2014 BODY Conference & Exhibition London, UK www.bodyconference.co.uk 29 JANUARY–1 FEBRUARY 2015 IMCAS Paris Paris, France www.imcas.com 5–8 MARCH 2015 12th EADV Spring Symposium Valencia, Spain www.eadv.org 7–8 MARCH 2015 ACE 2015 London, UK www.ace2014.co.uk 26–28 MARCH 2015 13th AMWC Monte Carlo, Monaco www.euromedicom.com 4–6 JUNE 2015 Beauty Through Science Stockholm, Sweden www.beautythroughscience.com 6–10 JULY 2015 18th World congress IPRAS Vienna, Austria www.ipras.org 31 OCT–1 NOVEMBER 2014 3rd Marrakech World Aesthetic Conference Marrakech, Morocco www.mwacongress.com 14–16 NOVEMBER 2014 IMCAS India Goa, India www.imcas.com/en/india2014/congress 15–16 NOVEMBER 2014 10th National Laser & Cosmetic Medicine Conference Melbourne, Australia www.dcconferences.com.au/lcmc2014/ 27–29 NOVEMBER 2014 1st AMWC Latin America Medellin, Colombia www.euromedicom.com EUROPE REST OF WORLDNORTH AMERICA 6–9 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, 2014 Cosmetic Surgery Forum Las Vegas, NV www.cosmeticsurgeryforum.com 4–6 DECEMBER, 2014 The Cutting Edge 2014 New York, NY www.nypsf.org prime-journal.com 23 | EVENTS
  • 24. INTERNATIONAL JOURNAL OF AESTHETIC AND ANTI-AGEING MEDICINE July/August 2014 Volume 4 ❙Issue 5 Farjo Hair Institute ❚Hair Restoration Market ❚Patient Testimonials ❚Product News ❚Events ACNE AND ACNE SCARS ENERGY BASED TREATMENTS MALE BODY IMPLANTS MUSCULAR ENHANCEMENT ACNE IN ADULT WOMEN CAUSES, TRIGGER FACTORS AND TREATMENT OPTIONS HAIRLOSS withpolynucleotides Treatingfemalehormonal INTERNATIONAL JOURNAL OF AESTHETIC AND ANTI-AGEING MEDICINE September 2014 Volume 4 ❙Issue 6 Hand Rejuvenation ❚ISAPS Surgical Relief Teams ❚AMEC Preview ❚Industry News ❚Events Thefightagainst SKINAGEING Dietandnutraceutical interventions DERMAL FILLER INDUCED FACIAL ARTERY OCCLUSION SUSPENDING THREADS FOR FACIAL REJUVENATION A NEW TOPICAL SLIMMING TREATMENT CLINICAL EFFECTIVENESS Has now been published for 4 years and has received high acclaim from its thousands of regular readers around the world for its unique coverage of the latest news, features, reports, and products in the field of aesthetic and anti-ageing medicine. ➲PRIME will provide you with access to the best peer-reviewed information available to keep you at the cutting-edge of the industry. ➲PRIMEdraws on expertise from across the aesthetic and anti-ageing medical market. ➲PRIME is the only publication to provide comprehensive coverage of the global aesthetic and anti-ageing disciplines. ➲PRIMEwill give you practical information and case studies, enabling you to provide your patients and clients with the latest techniques and best possible care. If you wish to receive PRIME in hard copy printed format for the next 12 months please contact: Brian Waller, Prime Journal, Informa Business Information, Christchurch Court, 10–15 Newgate Street, London EC1A 7AZ, UK. Email: brian.waller@informa.com Subscription rates UK £295 Europe €370 Rest of world US$490
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  • 27. eventsIndustryeventsin2014–15 fortheaestheticand anti-ageingmarket 24–25 OCTOBER 2014 2nd AMEC Paris, France www.euromedicom.com 19–21 NOVEMBER 2014 myRhinoplasty 2014 London, UK www.aesculap-academia.co.uk 26–28 NOVEMBER 2014 BAPRAS Winter Scientific Meeting 2014 London, UK http://tinyurl.com/p8nwkeg 29–30 NOVEMBER 2014 BODY Conference & Exhibition London, UK www.bodyconference.co.uk 29 JANUARY–1 FEBRUARY 2015 IMCAS Paris Paris, France www.imcas.com 5–8 MARCH 2015 12th EADV Spring Symposium Valencia, Spain www.eadv.org 7–8 MARCH 2015 ACE 2015 London, UK www.ace2014.co.uk 26–28 MARCH 2015 13th AMWC Monte Carlo, Monaco www.euromedicom.com 4–6 JUNE 2015 Beauty Through Science Stockholm, Sweden www.beautythroughscience.com 6–10 JULY 2015 18th World congress IPRAS Vienna, Austria www.ipras.org 31 OCT–1 NOVEMBER 2014 3rd Marrakech World Aesthetic Conference Marrakech, Morocco www.mwacongress.com 14–16 NOVEMBER 2014 IMCAS India Goa, India www.imcas.com/en/india2014/congress 15–16 NOVEMBER 2014 10th National Laser & Cosmetic Medicine Conference Melbourne, Australia www.dcconferences.com.au/lcmc2014/ 27–29 NOVEMBER 2014 1st AMWC Latin America Medellin, Colombia www.euromedicom.com EUROPE REST OF WORLDNORTH AMERICA 6–9 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, 2014 Cosmetic Surgery Forum Las Vegas, NV www.cosmeticsurgeryforum.com 4–6 DECEMBER, 2014 The Cutting Edge 2014 New York, NY www.nypsf.org prime-journal.com 23 | EVENTS