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Disease Entity

Aging - is this a disease?

Our societal hard wired reverence of youth and beauty combined with advancing technologies and an increased understanding of the changes associated with aging has encouraged the development of fillers. Youthful beauty is characterized by full, smooth contours with a lack of surface irregularity.

Disease

Etiology

Facial expression through the repeated movement of the facial musculature, sun exposure, smoking and genetics predispose us to the manifestation of facial aging There can be hollowing in the area of the temples, droop of the brows, cheeks and lower eyelids, loss of skin elasticity, wrinkling, and contour changes. Unlike Botulinum toxin (Botox), which is useful for the treatment of dynamic wrinkles, fillers are useful for global and focal volume augmentation as well as the treatment of wrinkles or contour deficiencies at rest. Through the use of fillers an attempt is made to replace the matrix of collagen, volume of fat and hyaluronic substrate diminished in skin by age. Through a variety of techniques, deflated temples, brows, cheeks, lips, chins and rhytids can be rejuvenated. Additionally, several of the fillers may stimulate collagen synthesis, partially restoring dermal matrix components, balancing collagen production and degradation.

Risk Factors

No one can escape aging...unfortunately. There are however several factors that predispose to facial aging. These include sun exposure, ultra violet exposure (tanning booths), smoking, stress, poor nutrition and genetics. Though one cannot escape their genetics (currently), one can be proactive with sun avoidance, smoking cessation, nutrition and stress management.

Disciplined use of sun block with UVA and UVB coverage, a hat, umbrella, etc. will help to minimize sun induced melasma (dyschromia) and wrinkling. Avoidance of sun tanning booths and smoking are mandatory parts of a youthful skin maintenance regimen.

Additionally, the use of agents that increase collagen synthesis such as Retin-A and fillers may be part of a youthful skin maintenance program.

Primary prevention

Disciplined use of sun block with UVA and UVB coverage, a hat, umbrella, etc. will help to minimize sun induced melasma (dyschromia) and wrinkling. Avoidance of sun tanning booths and smoking are mandatory parts of a youthful skin maintenance regimen.

Additionally, the use of agents that increase collagen synthesis such as Retin-A and fillers may be part of a youthful skin maintenance program.

Diagnosis

Filler Classification

Fillers are manufactured by many companies in many forms, each attempting to optimize longevity, antigenicity, collagen stimulation, flow and fill characteristics. The field of injectable fillers is large with an ever increasing number of choices. The selection of filler generally is based on physician/patient preference and experience, location of injection, desired duration of fill, volume required, cost, and antigenicity.

The following is a list, classified by type, of the most widely known fillers in the United States, with key differentiating features:

Bovine Collagen

Zyderm, Zyplast

No longer available
Requires skin test (3% incidence allergy)
Lidocaine in syringe Lasts 3-5 months
Inamed

Artecoll, Artefill

Requires skin test
Incorporates PMMA micro spheres in a bovine collagen substrate (FDA approved 10/2006)
Artes Medical USA- Reports of antigenicity with granuloma formation. Difficult to resolve over corrections or irregularities.

Human Collagen

Cosmoderm, Cosmoplast

No skin test required
Lidocaine in syringe Lasts 2-6 months
Manufactured from cell culture of human foreskin Inamed

Porcine Collagen

Evolence

No longer available
No skin test required. Lasts 6 months OrthoNeutrogena, Colbar Lifesciences
FDA approved 06/2008
Pulled from market 2009

Hyaluronic Acid (HA - polysaccharide, hydrophilic, identical across species, no skin test required)

Restylane Restylane-L

Bacterial fermentation (20 mg HA/ml)
L contains 0.3% lidocaine (FDA approved January 29, 2010 Lasts up to 18 months with an interim injection
Medicis/ Inamed
FDA approved 12/2003

Perlane Perlane-L

Bacterial fermentation (streptococcus), cross linked (20 mg HA/ml)- more viscous than Restylane
L contains 0.3% lidocaine (FDA approved January 29, 2010 Lasts 6-9 months
Medicis
FDA approved 5/2007

Hylaform-Hylan B gel

Avian derived (rooster comb) Lasts 3-4 months
Genzyme, Inamed
FDA approved 04/2004

Captique

Bacterial fermentation (5 mg HA/ml) Lasts 4-6 months
Inamed

Juvederm

Juvederm XC

Bacterial fermentation (staphylococcus equi)
XC contains 0.3% lidocaine (FDA approved January 29, 2010 Lasts up to 12 months with an interim injection
Allergan
FDA approved 06/2006

Juvederm Ultra

Juvederm Ultra XC

Bacterial fermentation ( 24 mg HA/ml), cross-linked
Injection into mid/deep dermis, nasojugal lines
XC contains 0.3% lidocaine (FDA approved January 29, 2010 Lasts up to 12 months with an interim injection
Allergan
FDA approved 07/2007

Juvederm Ultra Plus

Juvederm Ultra Plus XC

Bacterial fermentation( 24 mg HA/ml), cross-linked
Injection into mid/deep dermis, nasojugal lines
XC contains 0.3% lidocaine (FDA approved January 29, 2010 Lasts up to 12 months with an interim injection
Allergan
FDA approved 07/2007

Voluma, Volbella, Vollure

Voluma™, is prepared with a combination of low molecular weight (<1 mDa) and high molecular weight (>1 mDa) hyaluronic acid. There is a mobile fiber network, facilitating a high degree of covalent binding to the cross-linking agent: 1,4-butanediol, (Data on file, Allergan Inc, 2012). This cross-linking capacity influences both the rheological properties (eg, G′ values) and the swelling ratio of the filler, ie, the amount of water a filler is capable of retaining. Voluma™ has a high G′ and a low swelling ratio, facilitating high lift capacity, which is desirable for deeper injections, with little change in the volume of the implant following its deposition (Data on file, Allergan Inc, 2012). Voluma was FDA approved in 2014 for midface injection.

Belotero Balance

Belotero Balance was approved by the Food and Drug Administration in 2011. It is a monophasic double crosslinked HA gel based on Cohesive Polydensified Matrix (CPM) technology that creates a low-viscosity gel product with variable densities of crosslinking. These variable zones of crosslinking theorectically allowthe product to integrate into irregularities in the dermis and the subcutaneous layers. The elastic and cohesive properties of Belotero Balance allow for the gel to be injected evenly and spread homogeneously across the targeted area and into the surrounding tissues. Belotero Balance has been recommended for the treatment of fine superficial lines and rhytids, such as lipstick lines and crows feet. It is believed to fill the market niche previously occupied by Zyderm and Cosmoderm.

Hydrelle Elevess

Cross linked hyaluronic acid (28 mg/ml) and lidocaine Anika Therapeutics, Coapt Galderma
FDA approved 07/2007

Long Lasting - no skin test required

Sculptra Aesthetic

Poly-L-lactic acid (40-63 microns in carboxymethylcellulose gel)
Lasts 18-24+ months
Sanofi Aventis
FDA approved for HIV lipoatrophy 08/2004
FDA approval for cosmetic use 7/2009. Some initial concerns about granuloma formation. This has been improved with increased dilution recommendations.

Radiesse (Radiance)

Calcium hydroxyl apatite in polysaccharide gel Nasojugal lines, cheek augmentation, lasts 2 years
Bioform Medical
FDA approved 12/2006

Permanent

Silicone-Adatosil, Silikon No skin testing FDA approved for ophthalmic use. Use in skin off- label Fat Autogenous, requires second site for extraction, large donor supply May require repeat injection of frozen fat to sustain fill as a percentage of graft does not survive

History

A thorough medical history should be taken and fillers carefully selected or avoided in patients that manifest the following conditions:

Severe allergies marked by a history of anaphylactic shock
Allergy to cow collagen or eggs
Allergy to lidocaine
Inflamed or infected skin (i.e., Herpes)
Tendency to form keloids or hypertrophic scars
Active inflammatory conditions of the skin or infection

Patients are advised to avoid blood thinners prior to filler injection. The duration of blood thinner avoidance is dependent on the type of thinner taken (i.e., Coumadin, aspirin, etc.). The decision regarding blood thinner discontinuation may need to be made by the patient’s internist or cardiologist in the event the patient is at risk of stroke or cardiovascular disease. It is important to advise patients about the anticoagulant properties of herbs such as gingko, garlic, ginger and ginseng, certain Chinese herbal rememdies as well as vitamin E and the omega-3 fatty acid supplements.

If a patient has a tendency to perioral herpes simplex infection, the injector may wish to pretreat the patient with an oral antiviral prior to perioral injection.

Once consent is given, the patient is pretreated with numbing cream (i.e., topical lidocaine 4%, oral mucosal injections in a ring distribution, etc.). When adequate anesthesia has been achieved the site to be injected is wiped with alcohol, chlorhexidine or other antiseptic of choice and the injections initiated.

Physical examination

Examination of the patient includes an assessment of facial volume deficiency with attention to the temples, brows, upper eyelid, brow, tear trough, inframalar hollow, cheeks, nasojugal lines, marionette lines and lip contour.

Noted as well should be the patient’s Fitzpatrick Skin Type as well as documentation of aging changes including wrinkling and pigmentary changes.

Diagnostic procedures

The hyalurons are an excellent choice for both the novice injector and the novice patient. That the hyaluronic based filler can be dissolved with the use of hyaluronidase ( Hylenex, Vitrase,

Amphadase, etc.) offers a distinct advantage over other fillers. The ability to dissolve the filler not only reassures the patient and injector that over corrections or unwanted contours can be removed, but in the event of a vascular occlusive event, the hyaluronidase is a useful adjunct to therapy to clear an occlusion and area of potential necrosis.

There is a growing body of literature on the interaction between various hyaluronic acid fillers and the various versions of the enzume hyaluronidase. The article by Paap and Silkiss referenced below. provides a comprehensive review of these interactions.

Management

When a patient is referred for filler consultation, it is useful to assess the patient’s concerns with mirror in hand. A careful assessment of the areas of potential treatment combined with a frank discussion of the benefits and limitations of fillers should be undertaken. It is important that patient expectations be managed in a tactful way with full disclosure.General treatment

Injection techniques

There are a variety of injection techniques. Technique is crucial as injections placed too superficially may cause the appearance of irregularities, lumps or bumps. Injections that are placed too deeply may simply be ineffective for the volume of filler injected.

Additionally, different fillers have entirely different conceptual filling techniques. For instance, the hyalurons are used to fill a depression, plump a lip or decrease the contour disparity between the “mountain of fat herniation and the valley of the descended suborbicularis oculi fat pad”. Radiesse may be used to provide volume augmentation of the cheek in an effort to rejuvenate the midface and have a secondary lift effect in the nasojugal region.

Sculptra is designed to provide global volume restoration. Sculptra is a suspension of particles that are placed widely in an area of volume deficiency. The initial volume delivered disappears within 24- 48 hours. Over the course of the next several months, collagen deposition is stimulated resulting in an overall appearance of rejuvenation. Sculptra may be injected in several sessions separated by 4-6 weeks depending on volume deficiency and desired effect.

For hyaluronic fillers there are several standard techniques that are utilized for filling a fold or depression. A linear threading technique may be used along the length of the rhytids in areas such as the nasojugal fold, marionette lines or procerus furrow. A multipoint “droplet” technique along the length of the rhytids or contour may be used in the tear trough region or nasojugal fold. Techniques also involve the placement of numerous threads of material horizontally across the fold. This in effect causes a rhytid subcision with use of the filler as a temporary spacer. A linear threading technique with lying down of a significant volume of material may be used for augmentation and lift in the midface.

Filler may also be used to augment the sub brow region. Lip augmentation is useful to restore the youthful Cupid’s bow and philtrum. Lip augmentation may also be used to treat the fine vertical “lipstick’ lines and restore the fullness of the lip lost with age. Here not only can the individual lines be treated but the material injected broadly over the upper lip rhytids to encourage possible collagenesis. Overcorrection of the lips however, may lead to a simian-like elongated distance from the base of the nose to the upper lip or an artificial, over enhanced appearance. This appearance is neither beautiful nor youthful. Rather, it makes individuals look lost in time.

Complications

With many of these therapies, common side effects may include erythema, induration, and some bruising in the immediate post injection period. Granuloma formation may occur in some patients, and abscess may occur rarely. There are reported cases of local necrosis and sloughing from injection secondary to vascular occlusion. the incidence of vascular occlusion leading to blindness and even cerebral infarction, though rare- perhaps 1:10,000 occur most commonly with injections performed in the area of the dorsal root of the nose the medial upper eyelid. Fat injections appear to place the patient at greater risk. The mechanism of occlusion is thought to be retrograde injection of the particles into the supraorbital, supratrochlear or nasal dorsal artery with retrograde occlusion of the ophthalmic artery. With the release of pressure, forward migration of the particulates into the central retinal artery, posterior communicating arteries or external carotid artery may occur. The use of flash back observation, cannulas, low pressure and fat injection avoidance in these areas have been recommended. In fact, given the elaborate interconnection between the internal and external carotid artery system, vascular occlusion leading to blindness can occur from an injection in any part of the face. The use of retrobulbar hyaluronidase as rescue therapy is unsubstantiated to date. ^[1]

More commonly there may be concerns regarding overcorrection. Fillers that are hyaluronic acid based may be “dissolved” with hyaluronidase if needed. Ovine hyaluronidase is known as Amphadase or Vitrase. Hylenex has been pulled from the US market. These substances can be injected directly into the area of overfill to help diminish a contour irregularity or area of overfill quickly.

Techniques for injection of filler are location dependent. In order to avoid unhappy patients, novice injectors are wise to use Hyalurons as their longevity is limited as well as reversible with hyaluronidase. Additionally the Hyalurons are can be used on all parts of the face- even the lips or those areas with thin skin such as the tear trough. Tear trough injection is especially technique dependent as the filler may be evident through the thin eyelid skin either visually via a bluish Tyndall effect or palpably with a contour abnormality.

Fillers that are not manufactured with lidocaine can be combined with a local anesthetic by using a two way stop cock. Generally 0.2 cc of Lidocaine (1or 2%) with or without epinephrine per 1 cc of filler is admixed.

Prognosis

The use of fillers can be gratifying for both the patient and doctor. The ability to artfully and skillfully reduce age related changes and enhance an individual’s appearance and well-being is a worthy endeavor. Filler rejuvenation is likely to become more widespread and effective in the future, as the technology continues to advance.

Additional Resources

The American Society of Ophthalmic Plastic and Reconstructive Surgery. Botulinum Toxin and Facial Fillers. https://www.asoprs.org/index.php?option=com_content&view=article&id=90:botulinum-and-facial-fillers&catid=20:site-content Accessed March 06, 2023.

References

↑ Paap, MK, Milman, T, Ugradar, S, Goldberg, R, Silkiss, RZ, Examining the Role of Retrobulbar Hyaluronidase in Reversing Filer Induced Blindness, Ophthalmic Plast Reconstr Surg. 2020 May/Jun;36(3):231-238.

Silkiss, RZ, Curbside Consults in Ophthalmic Plastic Surgery, Ed. Kersten R, McCulley, T, Slack 2010.
Dayan, SH, Bassichis BA Facial dermal fillers: selection of appropriate products and techniques Aesthet Surg J. 2008 May-Jun; 28(3):335-47.
Lupo, MP, Natural look in volume restoration J Drugs Dermatol. 2008 Sep; 7(9):833-9
Carruthers JD, Glogau, RG, et al, Advances in facial rejuvenation: Botulinum toxin type A, hyaluronic acid dermal fillers, and combination therapies-consensus recommendations Plast Reconstr Surg.2008 May; 121(Suppl):5S-30S
Buck, DW, Alam M, Kim JY, Injectable fillers for facial rejuvenation: a review J Plast Reconstr Aesthet Surg. 2009 Jan; 62(1):11-8
Tezel A, Fredrickson GH, The science of hyaluronic acid and dermal fillers J Cosmet Laser Ther. 2008 Mar; 10(1):35-42
Rao V, Chi S, Woodward J.Reversing facial fillers: interactions between hyaluronidase and commercially available hyaluronic-acid based fillers, J Drugs Dermatol. 2014 Sep;13(9):1053-6.
Lowe NJ, Maxwell CA, Patnaik R, Adverse reactions to dermal fillers: review Dermatol Surg. 2005 Nov; 31(11 pt 2):1616-25
Carle MV, Roe R, Novack R, Boyer DS., Cosmetic facial fillers and severe vision loss, JAMA Ophthalmol. 2014 May;132(5):637-9.
Paap MK, Silkiss RZ, The interaction between hyaluronidase and hyaluronic acid gel fillers - a review of the literature and comparative analysis Plast Aesthet Res 2020;7:36. 12 Jul 2020

12.Paap MK, Milman T, Ugradar S, Silkiss RZ. Assessing Retrobulbar Hyaluronidase as a Treatment for Filler-Induced Blindness in a Cadaver Model. Plast Recon Surg. 
2019 Aug;144(2):315-320

[1] Paap, MK, Milman, T, Ugradar, S, Goldberg, R, Silkiss, RZ, Examining the Role of Retrobulbar Hyaluronidase in Reversing Filer Induced Blindness, Ophthalmic Plast Reconstr Surg. 2020 May/Jun;36(3):231-238.

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Skin Fillers

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