DR MICHELE KOO, MD, FACS, BOARD CERTIFIED PLASTIC SURGEON, ST LOUIS, MISSOURI wants you to know that JUVEDERM and BOTOX are an extremely safe, economical way with no down time to soften your face in a significant way by smoothing and filling in the facial wrinkles that make you look tired and older than you are. Why always be asked if you are mad or tired? Take charge of your life and in 30 minutes in Dr Koo’s office rejuvenate your face with JUVEDERM AND BOTOX to lift up the frowns around your mouth, ever so subtlely plump your lips, and fill in those deep nasolabial folds.

Dr Koo wants you to know that JUVEDERM AND BOTOX are extremely safe and has been FDA approved for facial use to fill creases and smooth the dynamic lines of your face around the eyes and forehead.

The following is a continuation of an article by Dr Mary Lupo, published in the Plastic & Reconstructive Journal, January 2008. Dr Koo hopes that this is helpful information to let you understand the fillers that are available and to realize that the fillers are very safe.

One small open-label study in France treated 49 subjects with Juvéderm 30 in either one or two of four possible injection sites, the nasolabial folds (59 percent), upper lip (37 percent), glabella (16 percent), and bitterness folds (10 percent).4 Most subjects had a touch-up at 1 to 2 months after treatment, with a mean of 0.6 ml administered at each session. Wrinkle severity improvement of approximately 50 percent on a five-point scale remained stable up to 11 months after initial treatment.
Interestingly, in our study, the nasolabial folds initially treated with Zyplast returned almost to baseline after the initial 24-week period, but subsequent treatment with Juvéderm Ultra Plus resulted in the same duration of clinically significant improvement as seen in the nasolabial folds originally treated with Juvéderm Ultra Plus.

The most significant finding from our studies is the extended duration of correction for Juvéderm Ultra Plus, in particular, for severe folds. Other resorbable fillers (collagens and hyaluronic acids) have not been proven to last beyond 6 months. The most comparable product, Perlane, was developed to treat deeper folds in that it is indicated for injection into the deep dermis and has larger hyaluronic acid gel particles than its sister product Restylane, both from Medicis Aesthetics (Scottsdale, Ariz.).5 Juvéderm has a different manufacturing process that creates a homogenous gel without a granular consistency.

In a split-face study comparing Perlane to Zyplast in 68 subjects with a range of different wrinkle severities from mild to extreme, 26 percent were classified as having severe nasolabial folds before treatment, although results were not stratified by baseline nasolabial fold severity.6 At 6 months after optimal correction, 59 percent of all Perlane-treated folds maintained correction, as opposed to the 96 percent noted in the Juvéderm Ultra Plus severe folds study. Moreover, at 9 months, only 49 percent of the Perlane folds were rated as superior to Zyplast, with 37 percent showing equivalency between Perlane and Zyplast and 14 percent showing Zyplast to be superior to Perlane.

Given that Juvéderm Ultra Plus outlasts the temporary dermal fillers, perhaps it should be compared with the semipermanent fillers Radiesse (BioForm Medical, San Mateo, Calif.) and Sculptra (Dermik Aesthetics, Berwyn, Pa.). Radiesse consists of synthetic calcium hydroxylapatite microspheres suspended in a gel of glycerin, water, and sodium carboxymethylcellulose.7 Following injection, the gel dissipates, collagen production is stimulated for volumizing, and phagocytosis gradually breaks down and eliminates the microspheres.

In December of 2006, the U.S. Food and Drug Administration approved Radiesse for correction of moderate to severe facial wrinkles and folds such as nasolabial folds and for facial lipoatrophy in people with human immunodeficiency virus,8 although the product had earlier been approved for other uses such as vocal cord augmentation and was used off-label, particularly for deep creases such as severe nasolabial folds.9 The pivotal trial involved 117 subjects treated with Radiesse in one nasolabial fold and human collagen in the other nasolabial fold with up to two touch-ups allowed at 2-week intervals to attain optimal correction (mean Radiesse injection volume, 1.2 ml).8 Rated on a six-point scale using blinded photographic assessments, the mean improvement in wrinkle severity at 6 months was 1.3 (compared with 1.7 on a five-point scale for Juvéderm Ultra Plus at the same time point), and no long-term data were provided.

In a small open-label study, patient self-reports showed duration of nasolabial fold correction of 10 to 12 months for four of 18 subjects and greater than 12 months for 14 of 18 subjects.10 Another open-label study was based on surveys sent to 609 subjects who had received Radiesse injections to the nasolabial folds or other facial areas.11 Responses to the 6-month survey were received from 155 subjects, and responses to an additional survey sent between 12 and 24 months after initial treatment were received from 112 subjects. Average subject satisfaction at 6 months was 3.9 on a five-point scale (with 5 being most satisfied). In the 12- to 24-month survey, 69 percent reported satisfaction, although the most common comment was thought it would last longer. Importantly, 84 percent of subjects (n = 512) required repeated treatments to achieve or maintain optimal correction. Of those, 63 percent had touch-ups at 4 to 6 weeks and 53 percent at 5 to 9 months.

Sculptra is an injectable poly-L-lactic acid indicated for correction of lipoatrophy though, like Radiesse, it is used off-label for cosmetic wrinkle correction and volumizing. The product must be reconstituted with water at least 2 hours before injection, and the correction fades within 1 week as the fluid is absorbed. The mechanism of action is the stimulation of collagen production, which requires several injections at intervals of at least 2 weeks to generate cosmetic improvement.12 Clinical studies on Sculptra have focused on human immunodeficiency virus-positive subjects with facial lipoatrophy13; thus, the longevity of correction in facial wrinkles is unknown.

One salient point about the semipermanent fillers is that they are generally injected through larger needles than used with collagen or hyaluronic acid-based fillers to prevent the particles in the product from clogging the needle. A 25-gauge needle is preferred for Sculptra,14 and a 25- to 27-gauge needle is recommended for Radiesse,15 with a larger needle having greater propensity to generate tissue trauma and pain on injection. In contrast, Juvéderm Ultra Plus is injected through a smaller 27-gauge needle.2 Moreover, Radiesse and Sculptra are intended for placement only in the deep dermis or dermal-subcutaneous junction and do not have the flexibility to treat finer wrinkles and folds, as can Juvéderm Ultra Plus.

CONCLUSIONS
Juvéderm Ultra Plus represents an excellent combination of attributes for a dermal filler. Permanent products bear some long-term risk if the initial correction is excessive or misapplied and can result in an unnatural appearance as aging tissues shrink and make the filler visible.16 Semipermanent fillers, in contrast, are prone to the problems endemic to the particulate nature of these products, may require larger needle sizes, and have limited utility in superficial defects or wrinkles. Juvéderm Ultra Plus may have found the sweet spot of an ideal duration for wrinkle correction with a good safety profile.

DR MICHELE KOO, MD, FACS, BOARD CERTIFIED PLASTIC SURGEON, ST LOUIS, MISSOURI wants you to have to latest information of the research on BOTOX AND JUVEDERM. This is the continuation of the article by Dr Mary Lupo published in Plastic and Reconstructive Surgery Journal, January 2008.

Dr Koo stays ahead of the learning curve and constantly re-evaluates the products available to you as well as her own results to give you the best and newest most optimal treatments. Furthermore, she performs all of the treatments herself and follows you very closely so as to tailor all future treatments for you so they will be as perfect as possible for your skin and face. Dr Koo believes in custom tailoring your treatment. She is respecful of your budget and time and will discuss all the options available to you for smoothing the wrinkles on your face and softening the years away with filler.

This continues the article on Juvederm by Dr Mary Lupo as published in Plastic & Reconstructive Surgery January 2008.

Subjects in the subset with severe nasolabial folds (Wrinkle Assessment Scale grade 3) were included if they had fully visible bilateral nasolabial folds that were severe at the deepest part (as assessed by the evaluating investigator) and were approximately symmetrical and of equal severity on each facial side. Exclusion criteria included hypersensitivity to bovine collagen or hyaluronic acid; history of atopy, anaphylaxis, multiple severe allergies, or allergy to meat or lidocaine; current immune therapy or history of autoimmune disease; tendency to develop hypertrophic scarring; use of oral retinoids or, in the nasolabial fold area, over-the-counter or prescription antiwrinkle treatments, microdermabrasion, or chemical peels in the 4 weeks before randomization; and any cosmetic procedure or tissue augmentation at the nasolabial folds in the 6 months before study entry.

Subjects were eligible to enroll in the repeated treatment study if they completed the initial 24-week period, indicated at the final visit that the Juvéderm-treated side was preferred, and the repeated treatment was performed between 24 and 36 weeks (±14 days) after initial optimal correction was achieved in the pivotal study. The main exclusion criteria included facial hair that would interfere with the visual assessments of nasolabial fold severity and having undergone or having plans to undergo any tissue augmentation with temporary, permanent, or semipermanent dermal fillers; botulinum toxin injection; laser resurfacing; dermabrasion; chemical peel; or face lift in the lower two-thirds of the face less than 30 days before the repeated treatment or at any time thereafter through the end of the extended follow-up period. Eligible subjects underwent their repeated treatment to both nasolabial folds on the same day with the same Juvéderm formulation that was used during the pivotal study treatment.

Statistical analysis was performed on the intent-to-treat population for effectiveness data and on the as-treated population for safety data. A value of p < 0.05 was used to determine statistical significance. The improvements in nasolabial fold severity score were compared with baseline using a signed rank test, and the proportion of nasolabial folds with a clinically significant improvement (one or more point decrease on the five-point scale compared with baseline) was evaluated using a McNemar test. Mean nasolabial fold severity scores were compared against the control by means of generalized estimating equations analyses.

RESULTS
Subjects
The initial study enrolled 439 subjects through 11 investigational sites across the United States. A total of 87 subjects with severe nasolabial folds (both nasolabial folds rated as a 3 on the five-point scale) were randomized to treatment with Juvéderm Ultra Plus in one nasolabial fold and Zyplast in the opposite nasolabial fold. Nearly all [n = 82 (94 percent)] of the subjects completed the 24-week follow-up period and most [n = 70 (81 percent)] of the subjects returned for the complimentary repeated treatment. Because of varying circumstances (e.g., scheduling issues, Hurricane Katrina), a small number of subjects (n = 16) had effectiveness evaluations 1 year or more after their last study treatment (before any repeated treatment). These subjects were statistically similar to the other study subjects in terms of injection volume and nasolabial fold severity at 6 months. Thus, these subjects’ long-term results (i.e., effectiveness at 1 year or more) can be extrapolated to the overall population.

Demographic data revealed that most subjects were female Caucasians with a mean age of 49 years (range, 26 to 74 years). The full range of Fitzpatrick skin types was represented, and 36 percent of subjects had darker skin types (Fitzpatrick types IV through VI).

Five of the original 11 sites participated in the repeated treatment study, enrolling 17 subjects from the Juvéderm Ultra Plus severe fold baseline cohort, all of whom completed the originally planned 24-week follow-up period after repeated treatment. Although the 48-week time point had already passed for a number of these subjects before the protocol amendment extending the study, eight subjects enrolled and received an effectiveness assessment at 48 weeks. Demographic details for those subjects participating in the repeated treatment study were similar to the original study.

Continued on Next Blog