Joel L. Cohen

Understanding, avoiding, and managing dermal filler complications.

BACKGROUND Dermal fillers are increasingly being utilized for multiple cosmetic dermatology indications. The appeal of these products can be partly attributed to their strong safety profiles. Nevertheless, complications can sometimes occur. OBJECTIVE To summarize the complications associated with each available dermal filling agent, strategies to avoid them, and management options if they do arise. METHODS AND MATERIALS Complications with dermal fillers reported in peer-reviewed publications, prescribing information, and recent presentations at professional meetings were reviewed. Recommendations for avoiding and managing complications are provided, based on the literature review and the authors experience. RESULTS Inappropriate placement or superficial placement is one of the most frequent reasons for patient dissatisfaction. Due to the reversibility of hyaluronic acid, complications from these fillers can be easily corrected. Sensitivity to any of the currently approved FDA products is quite rare and can usually be managed with anti-inflammatory agents. Infection is quite uncommon as well and can usually be managed with either antibiotics or antivirals depending on the clinical features. The most concerning complication is cutaneous necrosis, and a protocol to treat the full spectrum of this process is reviewed. CONCLUSIONS Complications with dermal fillers are infrequent, and strategies to minimize their incidence and impact are easily deployed. Familiarity with each family of soft-tissue augmentation products, potential complications, and their management will optimize the use of these agents.

Etiology, prevention, and treatment of dermal filler complications.

The availability of dermal fillers for multiple cosmetic indications has led to a dramatic increase in their application. Although fillers are generally regarded as safe tools for soft tissue augmentation, complications can occur. Therefore, to describe and review the complications associated with the currently-available dermal filling agents, the authors conducted a literature review in peer-reviewed journals and present the reported complication rates. They also describe current strategies to avoid, diagnose, and manage complications if they do occur.

A validated lip fullness grading scale.

OBJECTIVES To develop the Lip Fullness Grading Scale for objective quantification of lip volume for a reliable assessment and to establish the reliability of this photonumeric scale for clinical research and practice. MATERIALS AND METHODS A 5-point photonumeric rating scale was developed to objectively quantify fullness of upper and lower lip separately. Nine experts rated photographs of 35 subjects, twice, separately for upper and lower lip. Inter- and intrarater variability was assessed by computing intraclass correlation coefficients. RESULTS Agreement between the experts was high. Bubble plots (bivariate scatter plots) demonstrated linearity in judgment by the experts. CONCLUSION The 5-point photonumeric scale generated spans the fullness of the upper and lower lip for which patients commonly seek correction. This scale is well stratified, with low intra- and interrater variability.

A validated grading scale for crow's feet.

OBJECTIVE To develop the Crows Feet Grading Scale for objective quantification of the severity of lateral canthal lines and to establish the reliability of this photonumeric scale for clinical research and practice. MATERIALS AND METHODS A 5-point photonumeric rating scale was developed to objectively quantify the severity of lateral canthal lines at rest and at maximum contracture of the orbicularis oculi. Nine experts rated photographs of 35 subjects, twice, with regard to the aspect crows feet in comparison with morphed images. Inter- and intrarater variability was assessed by computing intraclass correlation coefficients. RESULTS The agreement between the experts was significantly high. Furthermore, the test–retest correlation coefficients were high for each expert after an overnight interval, demonstrating low inter- and intraevaluator variability. CONCLUSION The 5-point photonumeric scale generated spans the severity of the type of crows feet for which patients most commonly seek correction. The scale is well stratified for consistent rating.

A validated grading scale for forehead lines.

BACKGROUND As with other facial wrinkles, the gradual loss and disorganization of collagen fibers and elastin, connective tissues that provide underlying support for skin, cause horizontal forehead rhytides in large part. OBJECTIVES To develop the Forehead Lines Grading Scale for objective quantification of horizontal forehead rhytides at rest and with expression and to establish the reliability of this photonumeric scale for clinical research and practice. MATERIALS AND METHODS The Forehead Lines Grading Scale is a 5-point photonumeric rating scale that was developed to objectively quantify resting (static) and hyperkinetic (dynamic) forehead lines. Inter- and intrarater variability was assessed by computing intraclass correlation coefficients. RESULTS The agreement between the experts was highly significant. Bubble plots (bivariate scatter plots) demonstrated linearity in judgment by the experts. CONCLUSION The 5-point photonumeric scale generated spans the severity of forehead lines for which patients commonly seek correction. The scale is well stratified for consistent rating.

Enhancing the Growth of Natural Eyelashes: The Mechanism of Bimatoprost-Induced Eyelash Growth

BACKGROUND Many women desire prominent eyelashes. In December 2008, bimatoprost ophthalmic solution 0.03% was approved for the treatment of hypotrichosis of the eyelashes in the United States. OBJECTIVE To review eyelash physiology and the proposed mechanisms by which the topical pros‐tamide product bimatoprost enhances eyelash growth. METHODS AND MATERIALS Clinical and preclinical studies pertaining to the efficacy, safety, and mechanisms of action of bimatoprost are presented. RESULTS Treatment with bimatoprost increases the percentage of eyelash follicles in anagen at any one time. This probably accounts for its ability to lengthen lashes. Bimatoprost‐induced stimulation of melanogenesis appears to result in darker lashes and, at the same time, appears to increase the size of the dermal papilla and hair bulb, affecting lash thickness and fullness. Such effects, largely demonstrated in animal studies, are consistent with the results of a recent Food and Drug Administration phase III clinical trial. The favorable safety profile of bimatoprost in human subjects is probably secondary to the limited exposure of ocular tissues resulting from topical application at the base of the upper lashes. CONCLUSION By influencing the eyelash hair cycle and follicles, bimatoprost ophthalmic solution 0.03% is a safe and effective means of enhancing eyelash growth. Dr. Cohen has served as a consultant and clinical trial participant for Allergan, Inc.

A Validated Grading Scale for Marionette Lines

BACKGROUND Melomental folds, or marionette lines, are one of the consequences of facial aging. The curvilinear wrinkles formed because of facial movements and the aging process extend downward from the oral commissures. OBJECTIVES To develop the Marionette Lines Grading Scale for objective quantification of the severity of melomental folds and to establish the reliability of this photonumeric scale for clinical research and practice. MATERIALS AND METHODS A 5-point photonumeric rating scale was developed to objectively quantify the severity of melomental folds. Nine experts rated photographs of 35 subjects, twice, with regard to marionette lines in comparison with morphed images. Inter- and intrarater variability was assessed by computing intraclass correlation coefficients. RESULTS The agreement between the experts was high. Bubble plots (bivariate scatter plots) demonstrated linearity in judgment by the experts. CONCLUSION The 5-point photonumeric scale generated spans the severity of marionette lines for which patients commonly seek correction. The scale is well stratified for consistent rating.

Melanoma In Situ Treated Successfully Using Imiquimod After Nonclearance with Surgery: Review of the Literature

BACKGROUND The standard of care for melanoma in situ (MIS) is surgical removal by surgical excision with a 5‐mm margin or Mohs micrographic surgery, but as more and more MIS is diagnosed in the head and neck region, surgeries may not be an option for patients when the lesions are large or less well defined. In addition, when negative margins cannot be achieved without grossly disfiguring the patient or when patients have medical comorbidities that preclude a surgical option, other treatment modalities may be considered. Recently, topical treatment with an immunomodulator, imiquimod, has been proposed as an alternative treatment for MIS. OBJECTIVE We report a case of MIS successfully treated with topical imiquimod cream. In addition, because there has not been any comprehensive review of the use of topical imiquimod on melanoma and MIS, we conducted an extensive literature search and reviewed the topic in detail. MATERIALS AND METHODS Using the keywords “imiquimod,” “melanoma,” “melanoma‐in‐situ,” and “lentigo maligna,” we searched the literature using PubMed in an attempt to find all relevant articles on the use of imiquimod on MIS or melanoma. RESULTS There were 46 reports involving 264 patients on the use of imiquimod on MIS or lentigo maligna. Twenty‐three reports were published on the use of imiquimod on metastatic melanoma involving 55 patients, and two articles were on melanoma, with two patients in total. In addition, there were two articles on the use of imiquimod on dysplastic or atypical nevi with a total of 13 subjects. CONCLUSION Imiquimod appears to be beneficial in the treatment of MIS and melanoma metastases when surgical options are not feasible. Imiquimod should not be used for removal of dysplastic or atypical nevi. The treatment regimens varied from study to study, and there are no randomized controlled trials in the literature. More studies are needed to develop a reliable and reproducible treatment regimen, to fully elucidate the role of imiquimod in the treatment of MIS and melanoma, and to determine the prognostic predictors for favorable responses to imiquimod.

Long-term safety of repeated administrations of a new formulation of botulinum toxin type A in the treatment of glabellar lines: Interim analysis from an open-label extension study

BACKGROUND A new formulation of botulinum toxin type A (BoNT-A) (Dysport) has recently been approved in the United States for the treatment of glabellar lines. OBJECTIVE We sought to evaluate the long-term safety of repeated administrations of this BoNT-A formulation. METHODS In all, 768 individuals (1500 planned) from phase III clinical trials received as many as 6 repeated treatments of open-label BoNT-A (50 U) over 17 months, with a minimum of 85 days between treatments. Participants received a telephone call at day 7 postinjection to check for adverse event (AE), with clinical evaluations on days 14 and 30, and monthly until retreatment, study completion, or early termination. Safety end points were AEs, changes in vital signs, and assessment of serum-neutralizing antibodies to BoNT-A. RESULTS Of the 285 participants reporting at least one treatment-emergent AE at the interim analysis cutoff, only 74 (26%) reported at least one possibly or probably related event after 2259 treatments with BoNT-A. The incidence of treatment-emergent AEs around the injection sites and eyes was low (< or = 3%). Ten participants (1%) experienced 10 instances of ptosis. No participants developed neutralizing antibodies to BoNT-A or clinically significant changes in vital signs. LIMITATIONS This is an interim analysis of a larger multicenter extension study. CONCLUSIONS Multiple treatments with BoNT-A (50 U) over 17 months were well tolerated.

Adverse Events Associated With Mohs Micrographic Surgery Multicenter Prospective Cohort Study of 20 821 Cases at 23 Centers

IMPORTANCE Detailed information regarding perioperative risk and adverse events associated with Mohs micrographic surgery (MMS) can guide clinical management. Much of the data regarding complications of MMS are anecdotal or report findings from single centers or single events. OBJECTIVES To quantify adverse events associated with MMS and detect differences relevant to safety. DESIGN, SETTING, AND PARTICIPANTS Multicenter prospective inception cohort study of 21 private and 2 institutional US ambulatory referral centers for MMS. Participants were a consecutive sample of patients presenting with MMS for 35 weeks at each center, with staggered start times. EXPOSURE Mohs micrographic surgery. MAIN OUTCOMES AND MEASURES Intraoperative and postoperative minor and serious adverse events. RESULTS Among 20 821 MMS procedures, 149 adverse events (0.72%), including 4 serious events (0.02%), and no deaths were reported. Common adverse events reported were infections (61.1%), dehiscence and partial or full necrosis (20.1%), and bleeding and hematoma (15.4%). Most bleeding and wound-healing complications occurred in patients receiving anticoagulation therapy. Use of some antiseptics and antibiotics and sterile gloves during MMS were associated with modest reduction of risk for adverse events. CONCLUSIONS AND RELEVANCE Mohs micrographic surgery is safe, with a very low rate of adverse events, an exceedingly low rate of serious adverse events, and an undetectable mortality rate. Common complications include infections, followed by impaired wound healing and bleeding. Bleeding and wound-healing issues are often associated with preexisting anticoagulation therapy, which is nonetheless managed safely during MMS. We are not certain whether the small effects seen with the use of sterile gloves and antiseptics and antibiotics are clinically significant and whether wide-scale practice changes would be cost-effective given the small risk reductions.