Wrinkle treatment for the new millennium

Two new filler agents are gels that are hyaluronic acid derivatives, which are identical across species and across tissue types, and thus are highly biocompatible.

Issue: September 1, 2000

ByJerome R. Klein, MD, FACS

Multiple remedies for the alleviation of facial wrinkles have been advocated. Laser resurfacing, micro dermabrasion, Botox injections, and collagen, all have been and are used, and all have some shortcomings. There is no one perfect treatment and the ophthalmic surgeon who treats this problem will be pleased to know there are other types of preparations — hyaluronic acid derivatives — that are effective and yield good results. These new uses of viscoelastic materials, although not Food and Drug Administration approved, are one of many examples of how ophthalmic technology has been utilized elsewhere in the body. Both general ophthalmologists as well as trained oculoplastic surgeons will find this article educational and perhaps start utilizing these new agents in their own practices. Dr. Jerome Klein is an expert in the field of cosmetic surgery.

Stephen M. Soll, MD, FACS

The new European “collagens” are coming, and to borrow a phrase used by New York Sun Editor Francis Church on Sep. 21 in an editorial reply to reader Virginia O’Hanlon in 1897, “Yes Virginia, there is life for Healon after cataract surgery.” I have referred to this new material as European collagen, as most cosmetic patients are knowledgeable about collagen and can relate to the fact that a new type of filler agent is available in Europe.

(Editor’s note: The Food and Drug Administration has not approved the use of Healon for this procedure. Healon only is indicated for use in anterior segment surgery.)

These agents are essentially a more cross-linked form of Healon (sodium hyaluronate; Pharmacia Corporation). Most ophthalmologists have a long history of the intraocular use of Healon or other viscoelastic gels and are very comfortable with the material. Thus, it is not a big leap of faith for a physician to use a more cross-linked version in the skin.

Patients, especially international patients, have been coming into the office for the past 6 months asking for them. They have already made their way into the U.S. lay magazines, which have been alerting the readers to their imminent arrival, not to mention our international colleagues’ Web sites, which have the hyaluronic acids (HAs) listed in great detail for wrinkle treatment.

Botox for facial wrinkles

I was one of the first physicians in the United States to announce the benefits of Botox (botulinum toxin type A; Allergan) for facial wrinkles at the American Academy of Facial Plastic & Reconstructive Surgery 1992 spring meeting in Palm Desert, Calif., in a presentation entitled “Botulinum Toxin for Facial Use.” This was subsequently published in the Ocular Surgery News Oct. 15, 1992 issue (“Botulinum toxin use for facial wrinkles,” page 166) through the foresight of Dr. David Soll.

If you think Botox is a miracle for wrinkle treatment, then you are going to love these new Hylaform (Biomatrix Inc., Ridgefield, N.J.) and Restylane (Q-Med AB, Uppsala, Sweden) gels. In fact, these new filler agents are gels that are HA derivatives that are identical across species and across tissue types, and thus are highly biocompatible. They are naturally integrated into the tissue. With time, they undergo isovolemic degradation. It should be noted that 56% of hyaluronic acid in the body is found in skin and 35% is found in the musculoskeletal system.

---Male patient with deep nasal labial folds shown prior to Restylane injection.

Although Mark Twain maintained that wrinkles should merely indicate where smiles have been, wrinkle treatment is in the mainstream now that the American population is in an aging epidemic. In 25 years, 50% of the population will be over 50 years of age. Furthermore, psychological pain is much better understood and some dermatologists believe that beautiful people tend to be more successful, happier and adapt better to life. Dr. Glogau has developed a photodynamic classification. These agents are best used in: type 2 wrinkles — in motion, “kinetic,” wrinkling as skin moves, slight lines near the eyes and mouth, age in the mid-30s; and type 3 wrinkles — at rest, “static,” visible wrinkles all the time, noticeable decolorations, age in the 40s to 50s. Thus these HA gels are ideal for the augmentation of soft tissues or for the contour correction of cutaneous skin insufficiencies by means of injection into the dermis for your average cosmetic patient.

Hylaform and Restylane

---Deep nasal labial folds immediately following 0.35 cc Restylane injection in each side.

There are two versions of this viscoelastic hylan gel: Hylaform and Restylane. Hylaform comes as a single type of injectable viscoelastic hylan gel, while Restylane is available in three different viscosities depending on the type of correction of facial wrinkles, that is, fine lines around the mouth, nasal labial folds or general injection of papillary dermis wrinkles and depressed scars or acne pitting of the deep dermis/reticular layer. Hyaluronic acid is a polysaccharide present in the intercellular matrix of most human tissue hyaluronan and is identical across species and across tissue types. Hylaform, like Healon, is derived from an avian source (rooster combs) and contains 5 to 30 µg/mL of avian protein closely bound. Restylane is produced from non-animal stabilized HA (NASHA) through a bacterial fermentation of streptococci.

Hylaform and Restylane are approved throughout Europe, Israel, Canada and Australia. Neither agent requires a pre-injection skin test or refrigeration — a big plus over collagen. These agents are very similar to collagen in that they are filler agents. Thus, the area injected may feel full or swollen. There may be areas that feel lumpy and may need to be massaged post-injection. Thin areas of skin such as the nasal dorsum are to be avoided because of the risk of overlying necrosis. These agents are dissimilar from collagen in that they are clear gels, no allergy testing is required, no refrigeration is necessary and injected sites should not be overcorrected (overfilled). In addition, they also differ from Cymetra (micronized alloderm tissue) as there is no need for testing for any viruses such as HIV, or Hepatitis B and C, Human T Lympotrophic virus, etc.

Both HAs are reported to have no known contraindications to their use when used as recommended. They are reported to be nonantigenic — they do not cause inflammatory, toxic or foreign body reactions. However, Synvisc (Biomatrix Inc.), an HA that has been approved for intra-articular use for the treatment of osteoarthritis, is contraindicated in patients allergic to avian proteins, feathers and/or egg products. They should not be used with disinfectants containing quaternary ammonium salts for skin preparation because hyaluronan can precipitate out. I also would not personally use them in patients who are pregnant or breast feeding.

Restylane’s insert states that “it should not be used in patients with unattainable expectations. Not for use in or near sites with active skin disease. Do not use concomitantly with peels/laser treatments as there is a theoretical risk of eliciting an inflammatory reaction at implant site. Side effects: injection related 1 to 7 days: erythema, swelling, pain, itching, discoloration, tenderness. Adverse hypersensitivity reactions in 1/ 2000. PT’s range from swelling, induration locally and peripherally, erythema, tenderness, and acneform papules and are either after injection or delayed 2 to 4 weeks.” These reactions may be mild to moderate, self limiting and can last 2 weeks. Occasionally a patient may need steroids. Obviously these patients should not be re-treated. Also, the material could be injected into dermal blood vessels with subsequent occlusion.

The technique depends on the location being addressed. One can either layer or thread it versus serial puncture. The material in the nasal labial folds should be placed in multiple tissue planes as one does with fat and should be massaged in. You also may elect to augment the area with Botox to allow the material to fixate and not be worked out by the dynamically contracting muscles of facial expression. It is very important to use the needle hold with Hylaform, as the needle can act as a projectile since the syringe does not have a Luer lock. Restylane has a Luer lock syringe so it does not have this concern. Both come with a 30-gauge needle but often a 27-gauge needle will work better. Although it is mentioned that you should not overfill as you do with collagen, I feel that, depending on the clinical presentation, you may not use this as a firm rule.

The approximate physician cost is $200 for 1cc of Hylaform and 0.7cc of Restylane.

Female patient with vertical smokers’ creases and lines at angle of mouth.	Deep nasal labial folds immediately following 0.35 cc Restylane injection in each side.
Female patient with vertical smokers’ creases and lines at angle of mouth.	Immediately post Hylaform injection of 0.5 cc. Needle puncture sites present.

For Your Information:

Jerome R. Klein, MD, FACS, can be reached at Trump Tower, 16th Floor, 725 Fifth Ave., New York, NY 10022; (212) 371-7373; and at 9454 Wilshire Blvd., Beverly Hills, CA 90212; (310) 550-7006; e-mail: plastic-surgeon@prodigy.net. Dr. Klein has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Stephen M. Soll, MD, FACS, is associate clinical professor of surgery/ophthalmology, University of Medicine and Dentistry, Robert Wood Johnson Medical School, Camden, NJ. He can be reached at Soll Eye Associates, 5001 Frankford Ave., Philadelphia, PA 19124; (215) 288-5000; Fax: (215) 288-5601.

Allergan Inc. can be reached at 2525 Dupont Drive, Irvine, CA 92612; (800) 366-6554; fax: (800) 752-7006.

Biomatrix Inc. can be reached at 65 Railroad Ave., Ridgefield, NJ 07657; (201) 945-9550; fax: (201) 945-0363.

Pharmacia Corporation can be reached at 100 Route 206 N, Peapack, NJ 07977; (908) 901-8000; fax: (908) 901-8379.

Q-Med AB can be reached at Seminariegatan 21, 75228, Uppsala, Sweden; (46) 18-474-90-00; fax: (46) 18-474-90-01.

References:

Hallen L, Johansson C, Laurent C. Cross-linked hyaluronan (Hylan B gel): a new injectable remedy for treatment of vocal fold insufficiency—an animal study. Acta Otolaryngol. 1999;119(1):107-111.

Manna F, Dentini M, Desideri P, De Pita O, Mortilla E, Maras B. Comparative chemical evaluation of two commercially available derivatives of hyaluronic acid (Hylaform from rooster combs and Restylane from streptococcus) used for soft tissue augmentation. J Eur Acad Dermatol Venereol. 1999;13(3):183-192.

Cantisano B. Hyaluronic Acid Gel Injection for Facial Rejuvenation: 3 Years Experience Operative Techniques in Oculoplastic, Orbital & Reconstructive Sx. 1999.