1. Botulinum toxin type A

• Botox
• Dysport
• Xeomin

2. Botulinum toxin type B

• Myobloc
• Relative potency ratios/dosage equivalences between neuromodulators is not well documented
  • Based on split-face studies:
    • 2.5-3 units Dysport = 1 unit Botox
• 1-1.3 units of Xeomin = 1 unit Botox
• BoNT onset of action: 3 days
• BoNT duration of action: 3 months (may vary between formulations)

• Glabellar Complex/Frown Lines
  • “Frown lines” are a result of the midline procerus muscle and paired corrugator supercilii muscles laterally
  • 3-5 units of Botox/Xeomin or Dysport equivalent injected at one or two sites along radix to target procerus
  • 6-10 units of Botox/Xeomin or Dysport equivalent at the medial ‘clubhead’ of the eyebrow and 2-3 units Botox/Xeomin or Dysport equivalent laterally to treat lateral fibers of corrugator

• Lateral Orbit 
  • Treatment of “crow’s feet” involves selective chemodenervation of orbicularis oculi muscle along the lateral orbital rim
  • The orbicularis oculi muscle acts as a sphincter; its superior and inferior bellies meet along lateral orbit to create horizontal vectors of force
    • “Crepey” lines or skin in the supraorbital and infraorbital region may be softened by treatment of these areas
  • Orbicularis oculi is important brow depressor ⇒ selective chemodenervation will result in reshaping of brow in addition to treating rhytids
  • Care must be taken to target injections outside orbital rim, within subcutaneous plane, to avoid effect on extraocular muscles or lid elevators
  • 10-20 units Botox/Xeomin or Dysport equivalent per side

• Forehead/Horizontal Wrinkles 
  • Frontalis = only brow elevator; responsible for forehead furrows
  • Over injection should be avoided as this may result in severe brow ptosis
  • Forehead should be injected with small even aliquots along uniform distributions so as not to alter brow position
  • 2-3 units Botox/Xeomin or Dysport equivalent at 4-5 evenly spaced injection sites on each side of the face

• Nasal Dorsum 
  • Paired nasalis muscle –intrinsic muscle of nasal dorsum in which vertical segment contributes to horizontal furrows or “bunny lines” along dorsum
  • 2-3 units of Botox/Xeomin or Dysport equivalent divided between both nasalis muscles

• Perioral Rhytids 
  • Filler and resurfacing techniques (e.g. chemical or laser) are the mainstay of treatment for this area
  • “Smoker’s lines” is misnomer; perioral lines are created from photoaging and repetitive contraction of orbicularis oris muscle
  • 4-6 total units Botox/Xeomin or Dysport equivalent injected in multiple small aliquots along vermillion border of upper/lower lip

• Depressor Anguli Oris (DAO)/ Marionette Lines
  • Depressor anguli oris muscle- arises from the mandible where it interdigitates with the platysma inferiorly and inserts with the orbicularis oris superiorly
  • Marionette lines, or melomental folds, form with persistent contraction of the DAO 
  • 3 units of Botox/Xeomin or Dysport equivalent injection of the DAO will help blunt these lines

• Mentalis Muscle/Chin Dimpling
  • Mentalis muscle– originates from the mandible, overlying the mentum, and inserts into the skin below the lower lip
  • 2-5 Unit of Botox/Xeomin or Dysport equivalent can be injected into multiple sites along the mentalis muscle 

• Aging Neck/Plastymal Banding
  • Proper patient selection is important in identifying individuals that will have optimal outcomes
    • Surgery remains the mainstay therapy for the aging neck, particularly in patients with excess skin and fat deposits
  • Injection sites and dosages vary
    • 6-40 units of Botox/Xeomin or Dysport equivalent per platysmal band distributed along 3-5 sites

• Chemical Browlift
  • Brow contouring can be achieved via neuromodulation of the medial and lateral brow
  • Injection of the lateral orbicularis oculi, can facilitate brow elevation
    • The lateral frontalis muscle will be left unopposed allowing for elevation
    • Asking the patient to squint will allow for identification of the lateral orbicularis oculi; injection should then be carried lateral to the lateral orbital rim
    • Medial brow elevation can be facilitated with treatment of the corrugators as described above
    • Inadvertent injection of the medial frontalis should be avoided to prevent “Spock-like” deformity

• Masseter Muscle
  • The masseter originates from the zygomatic arch and maxilla inserting on the ramus inferiorly and coronoid
  • Masseter hypertrophy – may result from bruxism or chewing with resultant widening and prominence of the mandibular angle
  • 20-40 unit of Botox/Xeomin or Dysport equivalent may be injected into each masseter

• Facial Asymmetry
  • The paralytic effects secondary to use of neuromodulators may be beneficial in the treatment of facial symmetry from either hyper- or hypo-function of musculature such as in facial synkinesis

References:

1. Attenello, NH, Sheu, MC, Maas, CS.  Neuromodulators in Facial Aesthetics  In: Papel ID, Frodel JL, Holt GR Larrabee WF, Nachlas NE, Park SS, Sykes JM, Toriumi DM, eds. Facial Plastic and Reconstructive Surgery. 4th ed. New York: Thieme; 2016.
2. Petrus GM, Lewis D, Maas CS. Anatomic considerations for treatment with botulinum toxin. Facial Plast Surg Clin North Am 2007;15:1–9.
3. Maas CS, Kim EJ. Temporal brow lift using botulinum toxin A: an update. Plast Reconstr Surg 2003;112:109S–112S; discussion 113S–114S.
4. Ahn MS, Catten M, Maas CS. Temporal brow lift using botulinum toxin A. Plast Reconstr Surg 2000;105:1129–1135; discussion 1136–1139.
5. Carruthers J, Fagien S, Matarasso SL. Consensus recommendations on the use of botulinum toxin type a in facial aesthetics. Plast Reconstr Surg 2004;14:1S–22S.
6. Matarasso SL. Complications of botulinum A exotoxin for hyperfunctional lines. Dermatol Surg 1998;24:1249–1254.
7. Bikhazi NB, Maas CS. Refinement in the rehabilitation of the paralyzed face using botulinum toxin. Otolaryngol Head Neck Surg 1997;117:303–307.

• Understanding common side effects will facilitate management of potential complications
• Overall, safety profile of fillers is reassuring and adverse effects continue to decrease as new formulations with improved purification processes are developed
  • Data suggests similar safety profile across all skin types (Fitzpatrick I-VI is similar)
• Common side effects localized to site of injection include:
  • Bruising
  • Swelling
  • Tenderness
  • Itching
  • Erythema
• Slow injection rates (less than 0.3cc/min) may help reduce localized effects
• Hypersensitivity although rare may result in angioedema or anaphylaxis
• Specific adverse effects that may require intervention are discussed below

Tyndall Effect (“Rayleigh Scattering”)

• Discoloration of the skin, often described as a blue hue, at an injection site caused by superficial injection of HA fillers
  • Result of filler being directly visible through the skin
• The product itself is clear; however superficial injection results in scattering of light, refraction, with an underlying blue effect
• Most common site at risk = eyelid skin
  • Eyelid skin is the thinnest and therefore injection may be more apparent here
• Initial observation may be appropriate
  • If effect persists or worsens ⇒ Hyaluronidase can be used to help degrade product and reverse this complication

Lumps, Nodules, and Granuloma

• Irregularities may result from aggregation of products
  • Typically develop within 1st month post injection
  • Lips are at highest risk of nodularity and lump formation
  • Intramuscular injection within the orbicularis oris is associated with nodularity
• Granulomas are much rarer and present later than nodules
  • 6-24 months following injection

• All facial filler products are subject to biofilm formation; this may increase the risk of inflammatory infection such as infections and resultant granuloma formation despite appropriate identification and treatment
• Granuloma treatment – high dose intralesional steroid injection
• Other agents that have shown anecdotal utility in granuloma treatment 
  • 5-flurouracil (5-FU) 
  • Tacrolimus
  • Imiquimod
  • Bleomycin

Herpes Simplex Virus (HSV) – associated skin lesions

• Patients with prior history of herpes simplex virus should be treated with prophylaxis using oral antiviral medication
• Antiviral medication should be used 2-3 days prior to injection and treatment should continue 1 week post injection
• In those with a herpetic outbreak – oral antiviral medication should be started promptly
  • Acyclovir 800mg five times per day for 7-10 days
  • Valacyclovir 1g three times per day for 7-10 days
• Antiviral prophylaxis should be specifically considered in patients undergoing lip injections
  • Filler use within the perioral region is associated with increased rates of herpetic reactivation
    • Disruption of the dermal layer is suspected to result in viral reactivation

Skin Necrosis

• Multiple mechanisms may result in skin necrosis following filler injection
  • Vascular micro-embolism
  • Direct vascular injury
  • Vessel compression from surrounding injection
• Intravascular injection may present with following symptoms
  • Pain
  • Blanching
  • Duskiness
  • Diffuse ecchymosis
• Delayed compression with resultant vascular compromise may present without initial signs or symptoms
  • Soft tissue loss with ulceration and eschar formation develops within 1 week
  • Most common sites of vascular compromise
    • Nose; nasal tip in particular
    • Glabella
  • Nasal skin necrosis – associated with direct injection or injection of nasolabial folds
• Vessels (end-arteries) most at risk for compromise from embolization or mechanical compression
  • Labial
  • Angular
  • Supra-orbital
• Suspected vascular compromise during injection ⇒ abort injection immediately with application of warm compress
  • Nitropaste 
  • Hyaluronidase 
  • Removal of filler with puncture and local expression may be performed as a last resort
• Prevention of skin necrosis may be facilitated by the below
  • Knowledge of regional vascular anatomy
  • Use of small caliber needles – theoretically may decrease speed of injection
  • Avoidance of repeated, excessive volume, injection within one area
  • Aspiration prior to injection to avoid intravascular administration
  • Avoidance of excessive pressure or force applied to local tissues during injection and massage

Vision Loss

• Rare yet extremely devastating complication following filler injection and embolism to ophthalmic vasculature
• Vision loss occurs within minutes following injection and is frequently associated with ocular pain within the affected eye
• Has been described following injection to the following areas
  • Glabella
  • Nasal dorsum
  • Periocular 
  • Initial treatment
    • Ocular massage
    • Timolol drops
  • Other less proven but potentially useful treatments include
    • Diuretics (mannitol)
    • Corticosteroids
    • Calcium channel blockers
    • Anticoagulation
    • Needle decompression of the anterior chamber
    • Intraorbital hyaluronidase
  • This complication constitutes an immediate emergency with poor prognosis
• Preventative measures include use of blunt cannulas within the periocular region

References

1. Loyo, M Lee LN, Kontis, TC.  Injectable Fillers of the Face In: Papel ID, Frodel JL, Holt GR Larrabee WF, Nachlas NE, Park SS, Sykes JM, Toriumi DM, eds. Facial Plastic and Reconstructive Surgery. 4th ed. New York: Thieme; 2016.
2. Ozturk CN, Li Y, Tung R, Parker L, Piliang MP, Zins JE. Complications following injection of soft-tissue fillers. Aesthet Surg J 2013;33(6):862–877.
3. Daines SM, Williams EF. Complications associated with injectable soft-tissue fillers: a 5-year retrospective review. JAMA Facial Plast Surg 2013;15(3):226–231.
4. Cox SE, Adigun CG. Complications of injectable fillers and neurotoxins. Dermatol Ther 2011;24(6):524–536.
5. Kim DW, Yoon ES, Ji YH, Park SH, Lee BI, Dhong ES. Vascular complications of hyaluronic acid fillers and the role of hyaluronidase in management. J Plast Reconstr Aesthet Surg 2011;64(12): 1590–1595.
6. Sung MS, Kim HG, Woo KI, Kim YD. Ocular ischemia and ischemic oculomotor nerve palsy after vascular embolization of injectable calcium hydroxylapatite filler. Ophthal Plast Reconstr Surg 2010;26(4):289–291.