On The Front Lines: What’s New in Botox and Facial Fillers

Introduction

Since the advent of botulinum toxin and bovine collagen for injection in the 80s, the minimally invasive cosmetic surgery market has boomed. Newer, easier to use products have combined with a creative approach to rejuvenation to make these products more popular than ever, accounting for approximately $10 billion dollars in sales each year in the U.S.¹ Despite the recent economic downturn, the size and wealth of the aging baby boomer market continues to drive growth for aesthetic procedures, of which botulinum products and dermal fillers are key players.

Botox & Related Pharmacologicals

Although seven different types of botulinum neurotoxin are produced by the bacterium Clostridium botulinum, only types A and B have been prepared for commercial use. Botulinum toxin acts by blocking neuromuscular transmission causing temporary relaxation of nearby muscle tissue. This relaxation translates into a myriad of medical uses, both functional and cosmetic. First used clinically by Alan Scott, MD, in 1980 to treat strabismus, the cosmetic effects of botulinum toxin were soon described by a husband and wife team working in Vancouver, Doctors Alistair and Jean Carruthers (dermatology and ophthalmology, respectively). Approved by the FDA in 1989 for the treatment of strabismus, blepharospasm, and hemifacial spasm, Botox® (Botox® Cosmetic, Allergan, Inc. Irvine, CA) gained approval for cosmetic use in 2002 to temporarily improve the appearance of moderate-to-severe glabellar frown lines and most recently in 2010 for treatment of migraine.²

Although approved only for selected medical conditions, Botox and other purified botulinum toxins are used by physicians of almost every specialty for an array of off-label medical indications. On the face, Botox is commonly used to soften crow’s feet, forehead lines, and vertical lip lines. It can be used to temporarily lift brows, nasal tips, or downward mouth corners. It can widen eyes and smooth platysmal neck bands. Apart from cosmetic use, physicians utilize Botox for a variety of medical conditions including: pediatric incontinence, hyperhidrosis, overactive bladder, anal fissure, dysphonia, headache, underarm sweating and spastic disorders due to disease or injury of the central nervous system like trauma, stroke, multiple sclerosis, and Parkinson’s disease.³ The National Institute of Health currently has more than 79 Botox trials enrolling for medical diagnoses such as reduced lung function, thoracic outlet syndrome, psoriasis, achalasia, and back spasm.⁴ Other researchers report that Botox can be useful in facial scar improvement, non-surgical breast lift, diabetic foot pain, depression and chronic pelvic pain.^{5 6}

For six consecutive years, Botox Cosmetic has been the most common cosmetic procedure in the U.S. among surgical and non-surgical treatments.⁷ In 2007, 4.6 million procedures were performed in doctor’s offices across the nation according to the American Society for Aesthetic Plastic Surgeons.⁸ Largely due to direct consumer marketing, Botox is the most recognizable brand name of commercially prepared purified botulinum toxin. There are, however, additional botulinum products approved for use in the U.S. Myobloc (Solstice Neurosciences, Inc, Malvern, PA) is approved for cervical dystonia. It is used less commonly for cosmetic use because of injection pain as well as a shorter duration of effect. ⁹ The latest botulinum product to market, Dysport, (Medicis Pharmaceuticals, Scottsdale, AZ/Ipsen, Berkshire, UK) has been available for many years in Europe, but only recently approved by the FDA in May 2009 for cervical dystonia and cosmetically for glabellar lines. Dysport has been reported in some patient diaries to work more quickly than Botox Cosmetic, erasing creases in just two days compared to the three to seven days needed for Botox. Some doctors report that Dysport may last longer and have more “spread” or migration from injection sites than Botox. Additional training for Dysport injection is needed by even experienced Botox injectors as Dysport and Botox units are not interchangeable. Dysport is contraindicated in patients with cow’s milk protein allergy as the product may contain traces of that substance.¹⁰ PurTox (Mentor Corporation, Santa Barbara, CA) and Xeomin (Merz Pharmaceuticals, Frankfurt, Germany) are additional versions of botulinum type A currently being studied in FDA trials.

Botox costs an average of $300–$600 dollars per injection site. Because the effects last three to six months, patients are required to return at regular intervals for ongoing treatments. Botox is most effective on dynamic wrinkles, ones that are noticeable with muscle movement. See Figure 1. Because Botox limits the action of a hyperactive muscle, it not only smoothes the face but also theoretically prevents wrinkles from deepening from additional facial creasing. See Figure 2.

Figures 1.

Figure 2.

How the Clostridium botulinum works on nerve endings.

Ideal Botox candidates are non-pregnant 18- to 65-year-olds with reasonable expectations who have stopped over the counter medicines, herbal remedies, aspirin and ibuprofen at least two weeks prior to injection. Patients who should not receive Botox injections include patients with neurological disorders like ALS, Lambert-Eaton syndrome or myasthenia gravis. The most commonly reported side effects include headache, respiratory infection, flu, temporary eyelid droop, and nausea.¹¹

Although most side effects from botulinum injections are mild and self-limited, some patients have experienced more severe side effects related to the spread of botulinum systemically which have resulted in hospitalization and in some cases, death. Because of these concerns, the FDA has placed a black box warning on botulinum products alerting them of the risk of muscle weakness, breathing difficulties, loss of bladder control and pneumonia. Most of the life-threatening cases have involved children with concurrent health problems given high doses of botulinum for spasticity. Officials speculate that many of the problems occurred when one botulinum product was substituted for another without appropriate dose adjustments. No life-threatening cases involved cosmetic or dermatologic procedures. Use of illegal or unauthorized Botox can have serious consequences.

Recently, the FDA approved changes to the established generic drug names of three botulinum products to “reinforce individual potencies and prevent medication errors.”¹² Botox/Botox Cosmetic will now be called onabotulinumtoxinA, Dysport is abobotulinumA, and Myobloc is now called rimabotulinumtoxinB. ¹³

Like Botox, dermal fillers also play a significant role in the arsenal of wrinkle-fighting, with more than five million procedures performed worldwide last year. ¹⁴ Hyaluronic acid fillers have long been used for intra-articular joint injections and in ophthalmic procedures such as cataract surgery, but only recently have technologic advances made them safer, more predictable and longer lasting for cosmetic use. Additionally, surgeons have recognized the value of volume enhancement in facial rejuvenation. Experts predict explosive growth over the coming years as women become more familiar with the products and their benefits. Experts estimate that of the 25 million American women age 30 and up that earn enough to afford filler treatments, only three percent are currently receiving them. According to these predictions, the filler market is poised for strong growth.¹⁵

Filler Products & Procedures

Often referred to as “liquid facelifts,” facial fillers differ from Botox in that they are approved for filling nasolabial lines and offer immediate results. Facial fillers fall into three main categories: collagen, hyaluronic acid and neocollagenic materials.

Collagen, the naturally occurring skin protein responsible for skin strength and elasticity, has been used less frequently in recent years because of short lived results and higher potential for allergic reactions. Approved for cosmetic use in 1981, older collagen fillers, like Zyderm or Zyplast (Inamed/Allergan, Irvine, CA), made from bovine sources require allergy testing one month prior to use. Newer collagen fillers like Cosmoplast and Cosmoderm (Inamed/Allergan), are derived from human skin and do not require skin testing. These fillers are reported to last three to four months. The newest collagen-based product, Evolence (Ortho-McNeil-Janssen Pharmaceuticals, Inc, Titusville, NJ), does not require skin testing. Evolence reported to last up to one year, has been removed from the market.

Many of the newer fillers, Restylane (Medicis), Juvederm/Juvederm Plus (Allergan), and Perlane (Medicis) are made of hyaluronic acid, a naturally occurring sugar in the human body. Hyaluronic acids work by attracting water, adding new volume under the surface of sagging skin, and by binding to collagen and elastin to move additional nutrients into the skin. ¹⁶ Researchers have found that injectable materials stretch fibroblasts stimulating the production of new collagen, further enhancing the reduction of facial wrinkles. Hyaluronic acid injections are also reported to slow the breakdown of existing collagen.¹⁷ Length of effect for these products can be six to nine months or longer. The more highly cross-linked products prolong the effect by resisting the body’s natural efforts to break them down. Older hyaluronic acid fillers like Hylaform and Hylaform Plus (Inamed) were animal based and required allergy testing, but the newer synthetic products (Restylane, Juvederm, Perlane) are non-animal based, eliminating the need for pre-testing. While some doctors mix lidocaine into filler products in their offices to enhance comfort, Prevelle Silk (Ortho McNeil Janssen) and Elevess (Artes Medical, Inc., San Diego, CA) and now Juvederm XC (Allergan, Irvine, CA) are hyaluronic acid-based fillers that incorporate pre-mixed lidocaine

Neocollagenic materials in the U.S. include Radiesse (Bioform Medical, Inc., San Mateo, CA), Artefill (Suneva Medical, Inc., San Diego, CA), and Sculptra (Sanofi-Aventis, Bridgewater, NF). Neocollagenic materials incite the body to produce new collagen in the injected area. Radiesse is a synthetic product that contains calcium hydroxyapatite, a mineral naturally found in human teeth and bone. Small microspheres of hydroxyapatite are suspended in gel to be used for moderate to deep wrinkles. Radiesse is generally used in deeper areas of the skin to minimize visible irregularities. Radiesse lasts 12–24 months, requires no skin test and is a radiologically visible material.¹⁸ Sculptra (poly-L-lactic acid) approved by the FDA in 2004 for the treatment of facial lipoatrophy in HIV, was recently approved for the correction of shallow to deep nasolabial folds and other facial wrinkles. Poly-L-lactic acid is a polysaccharide compound similar to resorbable suture material. Sculptra can be pre-mixed with lidocaine for enhanced comfort. Results can last up to two years.¹⁹ Although approved primarily for nasolabial folds, doctors have used facial fillers off-label for a variety of cosmetic indications. Lips, tear troughs, depressed scars, temples and static wrinkles have all been plumped with fillers. Fillers have been used to heighten brow bones, cheekbones, jaws and to reshape noses, chins, hands and buttocks. Some doctors have utilized fillers as a way to enhance the appearance of droopy earlobes and also to plump foot pads for more comfortable stiletto wear.

Facial fillers are generally administered to patients of a wide variety of ages, both male and female. Patients with significant allergies or sensitivities to any known filler compound should avoid filler injections. Patients on aspirin or any medication that could affect blood clotting should discuss risks of hematoma, bruising or bleeding complications. Other potential risks and side effects of fillers include temporary redness, pain, bleeding and tenderness at the site of injection as well as permanent blindness in some cases; paralysis of the face, lip, and eye has been reported. Necrosis can occur if materials are injected intravascularly or if stiffer materials compromise capillary beds. Asymmetry, under-or overcorrection is also possible. For under correction, additional filler can be added once the initial swelling has subsided. Overcorrection can usually be spontaneously corrected given time. Occasionally excess material can be expressed through a small needle puncture in the affected area. Hyaluronidase can be injected to dissolve excess hyaluronic acid fillers. More serious side effects can include immune system reactions, granulomas, and anaphylaxis. ²⁰

Conclusion

The availability of commercial botulinum toxin and injectable facial fillers has considerably broadened the scope and practice of minimally invasive cosmetic surgery. The use of these products has expanded from their original indications to encompass hypermobility, age-related volume loss and contouring to result in a multi-dimensional approach to facial aging. With a variety of price points, little down time, and clear benefits, these products have provided increased options to both doctors and patients, helping to restore a more natural youthful look to patients and enhancing the practice of minimally invasive cosmetic medicine.

Figure 3.

The newest collagen-based product, Evolence, does not require skin testing and is reported to last up to one year and may bruise less than other fillers.

Biography

Melissa Morrison Cable MD, MSMA member since 1999, practices ophthalmology in Kansas City, Missouri.

Contact: mcable@discovervision.com