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MD Codes
MD Codes
MD Codes
Accepted Article
Authors: Dario Bertossi MD1, Pier Francesco Nocini MD1, Eqram Rahman MD2, Izolda Heydenrych MD3,4,
Krishan Mohan Kapoor MD5,6, Mauricio de Maio MD7
1Department of Oral and Maxillofacial Surgery, University of Verona, Policlinico G.B. Rossi, Verona, Italy
2University College London, London, UK
3Cape Town Cosmetic Dermatology Centre, Central Park on Esplanade, Century City, Cape Town, South
Africa
4Division of Dermatology, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch,
South Africa
5Fortis Hospital, Mohali, India
6University of London, London, UK
7Clinica Dr. Maurício de Maio, São Paulo, Brazil
Corresponding author:
Dario Bertossi, Department of Oral and Maxillofacial Surgery, University of Verona, Policlinico G.B. Rossi,
Piazzale L. Scuro, 10 – 37134, Verona, Italy; e-mail: dario.bertossi@univr.it; tel: +39 045 8126768; fax: +39
045 8127437
Conflicts of Interest: DB, IH and MDM are consultants and speakers for Allergan. KMK is consultant,
speaker and board member for Allergan. PFN and ER report nothing to disclose.
Acknowledgements: The authors thank Dr Timothy Ryder from Biological Communications Limited
(London, United Kingdom) for assistance in editing and submitting the final draft, funded by Allergan at
the request of the investigator. Neither honoraria nor payments were made for authorship.
This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process, which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1111/jocd.13596
This article is protected by copyright. All rights reserved
Accepted Article
PROF. DARIO BERTOSSI (Orcid ID : 0000-0002-8635-9967)
DR. KRISHAN MOHAN KAPOOR (Orcid ID : 0000-0002-3134-4266)
ABSTRACT
Background: Both age-related and congenital volume deficiencies may be addressed through the
injection of hyaluronic acid (HA) fillers. Deep injection provides structural support, more superficial
fat-tissue injection mediates contouring, and superficial intradermal use of HA filler and/or
onabotulinumtoxinA may be used for refinement.
Aims: To evaluate the clinical efficacy, patient satisfaction, and safety of the MD Codes approach as a
proposed standardized methodology for full-face rejuvenation.
Methods: This was a retrospective, single-center study of 250 consecutive adult patients undergoing
full-face rejuvenation with HA fillers (Vycross) and onabotulinumtoxinA based on the MD Codes
approach.
Results: The mean age was 39.4 ± 11.6 years and 80.4% were female. All patients were treated with
HA filler in the midface; 89.6% were also treated in the upper face, and 63.2% in the lower face. The
mean number of syringes used was 14 ± 4 (range 4–25), with more syringes typically required in
older versus younger patients. All patients received onabotulinumtoxinA treatment. Mean FACE-Q
Appearance-Related Psychosocial Distress score decreased from 54.3 ± 9.3 pre-treatment to 36.1 ±
8.9 at 3 months post-treatment (p<0.05). The most common complications were bruising (35.2%),
transient soft-tissue edema (14.0%), and prolonged periorbital edema (3.6%).
Conclusions: Full-face rejuvenation based on the MD Codes approach provides significant aesthetic
improvements, with no major safety issues observed.
Level of Evidence: IV
Keywords: botulinum toxin type A, dermal filler, hyaluronic acid, MD Codes, onabotulinumtoxinA,
Vycross
The treatment of facial aging has changed substantially over the past few decades, with patients now
desiring preventative treatment of changes previously considered inevitable, with the progressive
development of applicable technologies and techniques representing a contributory driver. Non-
surgical procedures based on injectable formulations of botulinum toxin type A (BoNTA) and
hyaluronic acid (HA) fillers are playing a pivotal role, with approximately 10 million injectable
procedures performed in 2018 in the US alone.5 Although injectable HA fillers and BoNTA may need
to be combined with surgical modalities for optimal facial rejuvenation, many patients prefer the
reduced invasiveness and short recovery time of non-surgical techniques alone. Two key outcomes
are typically desired – facial reshaping and the prevention of aging – both of which may be achieved
through biological and physiological intervention based on deep and superficial tissue re-modeling.
Moreover, evolving clinical experience has led to a deepening understanding of the dynamic
influence of muscle behavior on facial features and rejuvenation, with treatment focus evolving from
static filling to the conscious addressing of both volume deficiency and muscle balance. The latter
approach may mediate both direct and indirect effects. Mauricio de Maio recently published the
concept of using dermal fillers to modulate muscle movement (myomodulation).6 Despite a current
paucity of objective literature detailing physiological muscle response to injectable fillers, it is
clinically evident that HA fillers, in addition to BoNTA, may be used to effectively influence muscle
movement.
Filler quantities have been selected and described as standardized ’active numbers‘, equating to the
volume ideally needed for reproducible results. By combining the available tools, reproducible, full
non-surgical facial treatment may be achieved.
To assess the safety and efficacy of this standardized approach, we analyzed outcomes in a group of
250 non-surgical patients undergoing full facial correction. Patients were divided into three different
age groups with varying overarching treatment goals: 20–34 years, improving facial features,
achieving beautification, and preventing aging; 35–49 years, improving and delaying aging; ≥ 50
years, maintaining improvement. Although high treatment volumes were injected in this study, a
sequential approach based on staged, incremental volumes may be effectively used in real-life
clinical practice.
Eligible individuals were adult females or males with signs of facial aging, who wished to undergo
non-surgical correction. Exclusion criteria included acute or chronic local infection, diabetes mellitus,
pregnancy, bleeding disorders, history of systemic autoimmune or oncologic conditions, or
psychiatric conditions that could affect treatment. Smokers and patients receiving chronic
corticosteroid therapy were also ineligible.
In the present study, dermal fillers were from the Vycross™ range (Allergan, Dublin, Ireland), which
incorporates varying mixtures of high and low molecular weight HA to deliver tailored physical
properties:11 high G’ (20 mg/mL; VYC-20; Voluma®), intermediate G’ (17.5 mg/mL; VYC-17.5; Volift®),
low G’ (15 mg/mL; VYC-15; Volbella®), or very low G’ (12 mg/mL; VYC-12; Volite®). Injections were
typically performed in a superior-to-inferior direction (from forehead to mandible). In most cases, no
pretreatment with topical anesthesia was given.
Where necessary, BoNTA (onabotulinumtoxinA, Vistabex®, Allergan) was also used, in accordance
with a recent Italian consensus on the aesthetic use of onabotulinumtoxinA.12
Upper Face
In the upper face, key indications for treatment included: temple voids (shadowing in the area above
the superior periorbital margin and inferior to the temporal crest); reduced nasofrontal angle
(evaluated to be less than the mean range, which is around 13–15 degrees in female patients);
reduced soft-tissue eyebrow projection; forehead lines; and ptosis of the eyebrow.
Treatment areas included the temple, forehead, eyebrow, and peri-orbit (Table 2). In the temple
(MD Codes alphanumeric: T1–2), patients were injected with 0.5–1.0 mL per side of VYC-20 using a
27G 13 mm needle (TSK Laboratory Europe, Oisterwijk, Netherlands), deep onto bone, 1.5 cm below
the temporal crest and 1.5 cm above the supraorbital bony margin. The forehead (F1–3) was
injected with 0.2–0.5 mL of VYC-17.5 or VYC-15, deep onto bone, 2 cm above the supraorbital bony
margin, using a 25G 5 cm cannula (TSK) inserted on the midpoint of the temporal crest area. In
addition, 20 U of onabotulinumtoxinA could be injected into the forehead at 5 points (4 U per point)
Midface
The main indication was midfacial deficit, resulting in reduced malar projection, tear-trough defect,
and more pronounced nasolabial folds.
Key treatment areas were the malar region, tear trough, lower cheek, and nasolabial fold (Table 2).
The malar region and zygomatic arch (Ck1) were injected with 0.1–0.3 mL per side of VYC-20, deep
onto bone using a 27G 13 mm needle; the most prominent soft tissue area of the malar bone (Ck2)
with 0.2–1.0 mL per side of VYC-20 using a 25G 38 mm cannula; or in the most medial area (Ck3)
with 0.1–1.0 mL per side of VYC-20 using a 25G 38 mm cannula. The infraorbital area (Tt1–3) was
injected respectively with 0.2, 0.2, and 0.1 mL (each point) of VYC-15 using a 25G 38 mm cannula
below the sub-orbicularis oculi fat, deep onto bone. The lower lateral cheek (Ck4–5) was treated
with 0.5–1.0 mL of VYC-20 per point using a 25G 5 cm cannula, into the superficial fat compartment.
The nasolabial area (NL1–3) was treated with 0.2–0.4 mL per side and in each point with VYC-20,
deep onto bone in the pyriform aperture (NL1), using a 27G 13 mm needle; and with 0.25–0.5 mL of
VYC-17.5 injected superficially using a 25G 38 mm cannula (NL2–3). Finally, to improve skin quality,
1.0 mL per side of VYC-12 could be injected intradermally with a 32G 4 mm needle.
Lower Face
In the lower face, the main indications for treatment were marionette lines, jawline deficit, and chin
defects (e.g. deficits in projection < 3–4 mm or chin asymmetries).
Key treatment areas were the lips, labio-mental sulcus, chin, marionette lines, and the jawline (Table
2). The lip vermilion, body, and surrounding areas (Lp1–8) were treated with 0.05–1.5 mL of VYC-
17.5 using a 30G 13 mm needle, injected intradermally, into the superficial fat compartment, or deep
to the orbicularis oris muscle with a 25G 38 mm cannula. The labio-mental sulcus (C1) was treated
Finally, the neck could be also treated, using 1.0–2.0 mL of VYC-12 injected intradermally using a 32G
4 mm needle, and with 40 U of micro-botulinum toxin (onabotulinumtoxinA) injected into the
superficial skin using a Juvapen and 32G 4 mm needle.
All of these areas were injected through calculation of the so-called ’active numbers‘ (Table 2) that
underlie the MD Codes indications.
Assessments
Patient-reported outcomes were assessed pre-treatment and at 3 months post-treatment using the
FACE-Q Appearance-Related Psychosocial Distress tool.13 Complications were recorded immediately
post-treatment and during routine follow-up visits. Follow up lasted for up to 24 months.
Statistical Analyses
Statistical analyses were performed using Stata 14 (StataCorp LP, College Station, TX). Data provided
include mean, standard deviation and range for continuous variables, and frequency and percentage
for categorical variables. Pre- and post-treatment scores on FACE-Q were compared using the t-test
for paired data, with p<0.05 considered as statistically significant.
RESULTS
A total of 250 patients were enrolled with a mean age of 39.4 ± 11.6 years (range: 20–65). All were of
Caucasian ethnicity. Two hundred and one patients (80.4%) were female, and 49 (19.6%) were male
(Table 3). The age breakdown was as follows: 41 patients (35 females and 6 males) were aged 20–34
The mean number of syringes used was 14 ± 4 (range 4–25). In each age bracket, mean numbers of
syringes were: 20–34 years, 10 syringes; 35–49 years, 15 syringes; ≥ 50 years, 18 syringes.
All included patients were treated in the midface, and most were also treated in the upper face
(n=224; 89.6%). Around two-thirds were treated in the lower face (n=158; 63.2%) (Table 3). All
patients also received BoNTA treatment. Example before-and-after images are provided in Figures 2,
3 and 4.
Patient-reported outcomes were improved after treatment, as assessed using the FACE-Q
Appearance-Related Psychosocial Distress tool. The mean score decreased from 54.3 ± 9.3 (95%
confidence interval [CI]: 50.5–56.8) pre-treatment to 36.1 ± 8.9 (95% CI: 32.3–38.8) at 3 months post-
treatment (p<0.05).
Complications are listed in Table 4. The most common was bruising (n=88; 35.2%; usually in the
upper or lower face), followed by transient soft-tissue edema (n=35; 14.0%) and prolonged
periorbital edema (n=9; 3.6%). One patient experienced infection, which was managed with
ciprofloxacin 500 mg every 12 hours for 10 days, and one individual experienced skin discoloration.
There were no cases of paresthesia.
DISCUSSION
This analysis demonstrated excellent patient-assessed aesthetic outcomes in a cohort of 250 patients
undergoing full facial rejuvenation based on the MD Codes approach. To the best of our knowledge,
it is the first large-scale study to provide long-term results using a full-face approach based on a
standardized protocol.
All patients received injectable dermal fillers and BoNTA, based on an entirely non-surgical treatment
plan. In general, combining fillers and BoNTA may offer superior outcomes to using either alone.15
Our practice has evolved towards greater use of the full-face approach having been convinced that
treatment of some parts of the face – such as the cheek and temple – can greatly influence other
areas. Thus, we moved away from single-area treatment to a more comprehensive approach.
The present study was conducted using the Vycross range of dermal fillers combined with
onabotulinumtoxinA. Our data add to the substantial body of evidence demonstrating the efficacy
and safety of these treatments.23–34
Many patients are reluctant to undergo cosmetic surgery due to the complication risk, long recovery
times, and high upfront costs, thereby making injectable treatments a satisfactory alternative.
Results that are comparable to surgery can often be achieved – albeit temporarily – and injectables
may even offer a means of ‘test driving’ some of the more permanent changes attainable with
surgery.35 However, it is important that patients have realistic expectations and realize that although
injectables can restore balance, enhance appearance, and minimize the signs of aging, facial features
cannot be completely changed.
Surgical procedures such as facelift have a high upfront cost, but after a recovery period of 1.5–2
months, the results are typically long-lasting (≥ 5 years).36,37 By contrast, in our experience, full-face
injectable treatment has a more moderate upfront cost even though relatively large volumes may
initially be required to create structure and modulate muscle behavior. Subsequent treatment
sessions typically require substantially lower amounts of filler for maintenance of results.
Nonetheless, regular maintenance is essential, with results typically lasting for 4–18 months
depending on the type of product(s) used,26,28,30,34 although the requirement for multiple visits each
year generally declines over time. Ultimately, injectables usually require a similar financial outlay as a
facelift for a similar duration of effect.
In the present study, three different age groups were treated, each with different goals. It is notable
that around a sixth of patients (n=41/250) were younger individuals aged 20–34 years, a
demographic that has not traditionally been viewed as a key treatment group. However, in recent
years, the ‘millennials’ that comprise a large segment of this demographic have begun to take a
more proactive approach to anti-aging and to self-care in general.38 They may be more likely than
previous generations to consider aesthetic medicine acceptable, achievable, and part of normal life.
Among the commonly reported filler injection techniques (e.g. serial puncture, threading, fanning
and cross-hatching), there is no algorithm for choosing the most appropriate. Although certain
situations may lend themselves to a particular technique, the decision is ultimately based on clinical
judgement, injector experience, size and location of the treatment area, and the specific filler being
used. Based on our experience, we have found that a needle is best used in the temple, superficial or
deep nasolabial fold, malar region, and lips; other areas of the face can typically be treated with a
cannula, particularly with fanning and cross-hatching techniques used to fill larger areas.41 A needle
may be preferable for local precise augmentation or superficial placement of fillers along wrinkles or
into the tear trough. This selection of injection device corresponds with the MD Codes
recommendations.
As with any procedure, soft-tissue augmentation is not risk-free. Various complication types have
been reported, with the literature providing somewhat contradictory complication profiles. Injector
inexperience, suboptimal patient selection, defect/filler mismatch, and suboptimal technique most
likely play an integral role in this variation. Incorrect placement depth, location, volume, or product
choice may contribute to untoward skin and color changes, palpable bumps, contour deformities,
and superficial beading. The MD Codes approach aims to minimize these variables by providing
detailed recommendations for product choice, placement and delivery.
Although most filler-related complications are minor and transient, it is important to discuss the full
spectrum of possible adverse events with patients, including allergic reactions, infection,
intravascular complications and late-onset events. It is advisable to obtain upfront informed consent
for both the procedure and management of potential complications. Serious filler complications are
rare but can include anaphylactic reactions, skin necrosis, and blindness.42,43
While utilizing the MD Codes approach for this study, complications were typically minor and
transient, largely involving bruising or soft-tissue edema. This aligns with previous data
Post-injection pain is common and can be reduced by injecting small quantities at a low speed.
Injectables typically contain small amounts of lidocaine as part of their injection carrier, obviating the
need for local anesthesia and nerve blocks, which may distort anatomy.44
The risk of bleeding increases when injecting into highly vascular areas, such as the lip or the
periorbital region. Slow speed and deep-plane injection are key to decreasing bleeding,45 and
reducing the risk of bruising, hematoma and asymmetry – and hence of patient complaints.
Infectious complications are rare, but patients with susceptibility to infection or a history of herpes
simplex infection may require prophylactic antiviral/antibacterial treatment.45 Although no routine
prophylactic antibiotics were administered in the present study, and despite high treatment
volumes, only one patient developed an infection. This was successfully managed with ciprofloxacin
500 mg twice daily for 10 days.
Delayed-onset events are generally defined as presenting ≥ 4 weeks after HA filler treatment, with
the documented time of onset varying from 1 to 6 weeks post-injection.45,46 The most common
clinical signs are swelling, induration, and nodulation, but may include erythema, discoloration,
persistent intermittent-delayed edema, scars, telangiectasia, foreign-body granuloma, filler
migration, and neovascularization.47 Despite a low incidence of around 1% per patient according to
recent studies,48,49 delayed-onset reactions currently pose an increasing concern worldwide.
Recommended best practices for the prevention of delayed-onset adverse reactions include patient-
related factors, preventive aseptic procedures, and injection technique and volume considerations,
with most consensus recommendations agreeing that larger bolus volumes of HA may increase the
risk of foreign-body reactions, granulomatous reactions and other complications.50 However, despite
the larger volumes utilized in the present study, no patients developed late-onset nodules during the
follow-up period lasting ≤ 24 months.
All dermal fillers can potentially induce histological reactions, which may be of particular concern if
they persist and lead to a more chronic inflammatory process.3 Severe granulomatous reactions may
rarely occur and should be managed according to current treatment algorithms.45 Patients with a
CONCLUSIONS
Injectable HA dermal fillers and BoNTA are excellent options for the treatment of facial aging and
contour deficiencies, as they offer a viable non-surgical alternative in patients seeking a safe,
minimally invasive, and affordable youthful appearance. It is imperative that injectors have a
thorough knowledge of all available products and their properties, as this enables optimal product
pairing to specific indications, with consequent maximal efficacy and patient satisfaction.41 Injectable
procedures may be effectively combined with laser or light-source therapies52 for synergistic
treatment of wrinkles, folds, age-related skin laxity and photodamage. It should be noted that a
severely ptotic face may often require a combination of tissue suspension and volume augmentation
to achieve optimal long-term patient satisfaction.53,54
The MD Codes approach used in this study represents a universal language and methodology for
obtaining and documenting consistent results. The present study – performed in a large patient
cohort – demonstrates that full facial rejuvenation based on the MD Codes approach delivers
clinically relevant, reproducible aesthetic improvement, with high patient satisfaction. In the hands
of an experienced injector, there were no major safety issues during treatment or follow up despite
high volume delivery.
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