Evidence-Based Clinical Practice Guidelines for Laser-Assisted Drug Delivery.

Importance: Laser-assisted drug delivery (LADD) is used for various medical and cosmetic applications. However, there is insufficient evidence-based guidance to assist clinicians performing LADD. Objective: To develop recommendations for the safe and effective use of LADD. Evidence Review: A systematic literature review of Cochrane Central Register of Controlled Trials, Embase, and MEDLINE was conducted in December 2019 to identify publications reporting research on LADD. A multidisciplinary panel was convened to draft recommendations informed by the systematic review; they were refined through 2 rounds of Delphi survey, 2 consensus meetings, and iterative review by all panelists until unanimous consensus was achieved. Findings: Of the 48 published studies of ablative fractional LADD that met inclusion criteria, 4 were cosmetic studies; 21, oncologic; and 23, medical (not cosmetic/oncologic), and 6 publications of nonablative fractional LADD were included at the request of the expert panel, producing a total of 54 studies. Thirty-four studies (63.0%) were deemed to have low risk of bias, 17 studies (31.5%) had moderate risk, and 3 (5.5%) had serious risk. The key findings that informed the guidelines developed by the expert panel were as follows: LADD is safe in adults and adolescents (≥12 years) with all Fitzpatrick skin types and in patients with immunosuppression; it is an effective treatment for actinic keratosis, cutaneous squamous cell carcinoma in situ, actinic cheilitis, hypertrophic scars, and keloids; it is useful for epidermal and dermal analgesia; drug delivery may be increased through the application of heat, pressure, or occlusion, or by using an aqueous drug solution; laser settings should be selected to ensure that channel diameter is greater than the delivered molecule; antibiotic prophylaxis is not recommended, except with impaired wound healing; antiviral prophylaxis is recommended when treating the face and genitalia; and antifungal prophylaxis is not recommended. The guideline's 15 recommendations address 5 areas of LADD use: (I) indications and contraindications; (II) parameters to report; (III) optimization of drug delivery; (IV) safety considerations; and (V) prophylaxis for bacterial, viral, and fungal infections. Conclusions and Relevance: This systematic review and Delphi consensus approach culminated in an evidence-based clinical practice guideline for safe and effective use of LADD in a variety of applications. Future research will further improve our understanding of this novel treatment technique.

Clinical and histologic evaluation of a fractional radiofrequency treatment of wrinkles and skin texture with novel 1-mm long ultra-thin electrode pins.

BACKGROUND: Fractional radiofrequency (RF) microneedling technologies have shown effectiveness in treating skin laxity and wrinkles. We report the first experience using a novel device with 1-mm long ultrathin electrodes that utilizes a smooth RF-assisted ablation mode. OBJECTIVE: To evaluate the safety and effectiveness of treatment with a fractional RF device using 1.0-mm long × 0.15-mm diameter ultrathin electrode tips for improvement of facial skin texture and wrinkles. METHODS AND MATERIALS: This was a prospective, open-label, intraindividual-controlled trial. Nine participants (mean age: 47.6, Fitzpatrick skin type II-IV, Fitzpatrick Elastosis Wrinkle Scale [FEWS] score: 3-6) underwent six treatment sessions with a fractional RF technology utilizing an array of 6 × 6 1-mm long ultrathin electrodes. Treatment effectiveness was assessed by FEWS and the Global Aesthetic Improvement Scale (GAIS). Safety and tolerance were evaluated. RESULTS: Three months after the sixth treatment session, blinded, investigator-assessed FEWS decreased from baseline 4.33 ± 0.67-3.33 ± 0.67 (p < 0.005); 88.9% of participants showed overall skin improvement using the physician-assessed GAIS, and all of the participants reported improvement in skin texture and wrinkles. Treatment was well tolerated, with no adverse events and no downtime. Histological analysis in a porcine model showed a fractional pattern of epidermal ablation and dermal coagulation with intervening zones of normal healthy tissue. These changes were followed by progressive epithelialization over a period of 13 days. CONCLUSION: The fractional RF technology with the novel 1.0 long × 0.15 mm ultrathin electrodes tips was effective in improving skin texture and wrinkles without impacting the participants' daily activities.

Treatment of facial and non-facial lentigines with a 730 nm picosecond titanium: Sapphire laser is safe and effective.

OBJECTIVE: A 730 nm picosecond-domain laser was developed to improve the clearance of pigmented lesion and reduce adverse events. This study assessed the safety and efficacy of this system for the clearance of lentigines and explores how the short picosecond pulses interact with tissue via histology. STUDY DESIGN AND METHODS: Twenty subjects with Fitzpatrick skin types II-IV were enrolled in this prospective, IRB-approved study. Four treatments were administered using a 730 nm picosecond-domain laser. Pre- and posttreatment photos were assessed by blinded reviewers at 4- and 12-week follow-up visits, using a 5-point clearance scale. Subject satisfaction was measured using a 5-point scale. Investigator Global Improvement Score (IGIS) was performed at the 4- and 12-week follow-up visits, using an 11-point clearance scale. Subject pain level was measured using an 11-point scale (no pain [0], extreme pain [10]). Histology of 730 and 532 nm picosecond pulses was compared with 755 and 532 nm nanosecond pulses. RESULTS: Sixteen subjects with a total of 118 discontinuous treatment areas, each comprised of 1-20 lesions, completed all study visits. Thirty body regions were studied, including arms (6), hands (16), scalp (1), forehead (2), face (3), and back (2). Spot sizes ranging from 2 to 5 mm diameters were used with fluences ranging from 0.8 to 4.0 J/cm2 . Mean pain score was 3.6 of 10 for all four treatments. Ninety-nine percent of randomly paired 4-week posttreatment images and 100% of 12-week posttreatment images were correctly identified from their respective baseline images by three blinded reviewers. Mean IGIS demonstrated scores of 6.7 and 7.0 at 4- and 12-week follow-up visits, respectively. At the 4- and 12-week follow-up visits, 76% and 73% of subjects, respectively, were satisfied to highly satisfied. The mean clearance score for all 118 treatment areas was 3 of 4 in follow-up visits. At 12-week follow-up, 36% of 118 treatment areas had a clearance score of 4, and 38% had a clearance score of 3. Post treatment, there was typical erythema, edema, dryness, crusting, and itching but negligible purpura, no pinpoint bleeding, blistering or scarring, and no significant hyperpigmentation or hypopigmentation. Histology showed diffuse, focal epidermal vacuolization ~5-10 µm in diameter and mild extravasation of erythrocytes with 730 nm picosecond pulses, while diffuse epidermal vacuolization was observed with coalescence of vacuoles (~20-100 µm), junctional clefting and mild extravasation of erythrocytes with 755 nm nanosecond pulses. Picosecond pulses of the wavelength of 532 nm produced diffuse, focal epidermal vacuolization and larger dermal vacuoles to depths of 500 µm, while 532 nm nanosecond pulses produced diffuse epidermal vacuolization with coalescence of vacuoles and marked dermal hemorrhage. CONCLUSION: This study demonstrated the potential of a new 730 nm picosecond-domain laser for the clearance of lentigines. The results showed good clearance with no adverse events and good subject satisfaction in patients with skin type II-III. Additional studies need to be conducted on darker skin types. The histopathologic findings demonstrate that the picosecond 730 nm laser produces excellent selectivity for pigment with minimal disruption of the dermal-epidermal junction and may therefore reduce healing times and the risk of adverse events.

Treatment of periorbital wrinkles using thermo-mechanical fractional injury therapy versus fractional non-ablative 1565 nm laser: A comparative prospective, randomized, double-arm, controlled study.

BACKGROUND: Non-ablative fractional laser is an effective modality for the treatment of periorbital wrinkling, one of the earliest signs of skin aging. Thermo-mechanical fractional injury (TMFI) therapy (Tixel®, Novoxel®, Israel) is an innovative technology that is now being used for facial skin rejuvenation. Our study compares the clinical results, side effects, and downtime profile between TMFI treatment and non-ablative fractional 1565 nm laser (ResurFX®, Lumenis, Israel). METHODS: This was a prospective study of 68 patients (64 women, 4 men) with skin types I-VI in two medical centers (34 from Israel, 34 from the USA) that were randomized to receive either TMFI or NAFL treatment for periorbital wrinkling. Patients received 3-5 treatments, 3-5 weeks apart. Six months after the last treatment, the change in Fitzpatrick Wrinkling Classification System (FWCS) was calculated by three non-involved physicians and compared to pretreatment results. Side effects and downtime profiles were assessed in each group (including VAS pain assessment, time required to refrain from work and social activity, and time required for the resolution of redness, edema, and crusts.) RESULTS: A moderate improvement in periorbital wrinkling was demonstrated in both groups, with an average improvement of 1.6 ± 0.6 in FWCS in the TMFI group and an average improvement of 1.7 ± 0.8 in the NAFL group (p < 0.001). Postprocedural VAS score was 5.86 ± 2.3 in the NAFL group and 4.01 ± 2.6 in the Tixel® group. Approximately 80% of subjects returned to both work and social activities two days postprocedure. Crusts were reported by 52% of patients in the TMFI group, compared to 16% of patients in the NAFL group more than 48 hours postprocedure (p < 0.05). There were no statistically significant differences in the other parameters between the two groups. CONCLUSION: TMFI is an effective and safe modality for the treatment of periorbital wrinkling, with comparable results to the 1565 nm NAFL.

Efficacy and Safety of High-Intensity, High-Frequency, Parallel Ultrasound Beams for Fine Lines and Wrinkles.

BACKGROUND: Ultrasound energy has been used for cutaneous rejuvenation, including treatment of fine lines and wrinkles. Ultrasound waves of high intensity can induce thermal injury in the dermis, which causes tissue coagulation and remodeling. OBJECTIVE: To examine the safety and utility of a novel ultrasound device that uses high-intensity, high-frequency, parallel ultrasound beams to improve fine lines and wrinkles of the face and neck. MATERIALS AND METHODS: A prospective, multicenter, clinical study investigated the utility of this novel ultrasound device to improve fine lines and wrinkles. Sixty subjects were enrolled for single treatment to the face and neck. RESULTS: Fifty-eight subjects completed the study. The mean age was 58 years, and 87.9% were women. Fitzpatrick skin Types I to VI were represented. Assessments compared 12-week follow-up with baseline. Two blinded reviewers agreed in identifying pretreatment and post-treatment photographs for 78% of subjects. There was significant improvement of 1 to 3 Fitzpatrick Wrinkle and Elastosis Scale units in 86% of subjects. For investigator global improvement scores, 88% of subjects had improvement. Overall, 72% of subjects noted improvement, and the majority were satisfied. There were no device-related adverse events. CONCLUSION: Treatment with a novel ultrasound device that uses high-intensity, high-frequency, parallel ultrasound beams safely improved the clinical appearance of fine lines and wrinkles of the face and neck.

Laser Therapy of Traumatic and Surgical Scars and an Algorithm for Their Treatment.

BACKGROUND AND OBJECTIVES: This paper describes the laser techniques available for the treatment of surgical and trauma scars and develops recommendations for an algorithmic-based treatment approach based on extensive clinical experience and published data. STUDY DESIGN/MATERIALS AND METHODS: We reviewed the literature regarding laser treatment of surgical and traumatic scars and incorporated the clinical experience of the authors to develop an algorithm for the treatment of surgical and trauma scars. RESULTS: In order to develop treatment recommendations, scars were differentiated based on their clinical characteristics. Specific scar characteristics aid in determining the appropriate treatment strategy for different types of complex surgical and trauma scars. CONCLUSION: Laser therapy is first-line therapy for traumatic and surgical scars. The treatment approach should be guided by scar characteristics (e.g., anatomic location, type of injury, color, thickness, tension, scar age, and activity) and involves choosing the appropriate laser type and determining the benefit of combination therapy with surgical and nonsurgical treatment modalities to optimize treatment responses. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Quantitative evaluation of skin shrinkage associated with non-invasive skin tightening: a simple method for reproducible linear measurement using microtattoos.

Non-invasive skin-tightening devices can induce thermal denaturation and skin shrinkage via externally applied radiofrequency emissions or high-frequency ultrasound. Therefore, the purpose of this study is to develop and test a method for measurement of skin reduction associated with application of such energy devices. Twenty-five healthy participants with mild to moderate skin laxity of the arms were enrolled. Pinpoint microtattoos were placed at each of the treatment sites to delineate two 6 × 12 cm rectangles per subject. A non-stretchable filament, tape and marking pen apparatus was used to measure the size of each rectangle before treatment and at follow-up visit by two blinded investigators. After randomization, one side received a single pass with a radiofrequency device (6.78 MHz), while the contralateral side received multiple passes. Participants underwent two treatment sessions to each side 2 weeks apart, and returned for follow-up 4 weeks after the second treatment. Length and area measurement were analyzed to assess precision and accuracy of measurements and to compare efficacy of treatment between pre- and post-treatment. Concordance correlation coefficients (CCC) demonstrated substantial inter-investigator reliability and precision in length measurements (CCC, 0.94 to 0.98 in pre-treatment; 0.95 to 0.98 in post-treatment). Measurements at the 6-week post-treatment follow-up demonstrated a statistically significant skin reduction in all six of the measured parameters. A simple skin measurement method requiring minimal instrumentation can quantitatively evaluate skin shrinkage associated with non-invasive skin-tightening devices.

Laser Treatment of Professional Tattoos With a 1064/532-nm Dual-Wavelength Picosecond Laser.

BACKGROUND: Picosecond-domain laser pulses improve the photomechanical disruption of tattoos. OBJECTIVE: This study evaluates the efficacy and safety of a novel, dual-wavelength, 1,064/532-nm, picosecond-domain laser for tattoo clearance. MATERIALS AND METHODS: This was a prospective, self-controlled, clinical study of 34 subjects with 39 tattoos treated at 2 sites with an interval of 4.8 ± 1.6 weeks and up to 10 treatments (mean, 7.5). Blinded evaluation and investigator assessment of serial digital images was performed to evaluate treatment efficacy in the 36 tattoos that received at least 3 treatments. Investigators also assessed efficacy before each treatment visit up to 10 treatments. Safety and tolerability was evaluated for all 39 tattoos that underwent at least 1 treatment. RESULTS: Blinded evaluation demonstrated that lightening of tattoos was achieved in all subjects, with 86% (31 of 36 tattoos) showing at least a 50% clearance after 3 treatments. Adverse events were few and transient in nature. Patient satisfaction and treatment tolerability were high. CONCLUSION: Treatment of single-colored and multicolored tattoos with this novel 1,064/532-nm picosecond laser is highly safe and effective.

Treatment of facial photodamage and rhytides using a novel 1,565 nm non-ablative fractional erbium-doped fiber laser.

BACKGROUND AND OBJECTIVE: Non-ablative fractional lasers (NAFL) generate microscopic non-contiguous columns of thermal injury in the dermis, resulting in collagen remodeling. This manuscript details our experience with a novel 1,565 nm scanned, erbium-doped fiber NAFL for the treatment of facial photodamage. STUDY DESIGN/MATERIALS AND METHODS: A prospective, open-label clinical trial was conducted at two clinical sites in the United States on 16 female subjects with a mean age of 49.6 years, Fitzpatrick skin types II to IV, and a baseline Fitzpatrick-Goldman Wrinkle and Elastosis Score (FGWES) of 3-6. Each subject received three treatments at 4-5 week intervals with follow-up assessments at 1, 3, and 6 months after the last treatment. RESULTS: The mean FGWES demonstrated a statistically significant decrease from baseline both at 3 months (-0.58 ± 0.23, P = 0.02) and 6 months (-0.66 ± 0.22, P = 0.008) after the last treatment. Fifty percent (95%CI [24.21%, 68.49%]) of subjects showed a significant (at least 1 grade) improvement in FGWES from baseline at 3-month follow-up. At least 72% of subjects perceived the results as "moderate" to "very good" at 3 months post-treatment, with comparable satisfaction rates. Treatments were not associated with a high level of pain or discomfort and typical downtime was less than 2 days. No unexpected adverse events or serious adverse events were reported. CONCLUSION: The 1,565 nm erbium-doped scanned NAFL is an effective treatment for facial wrinkles with a favorable recovery and side effect profile.

Consensus for Nonmelanoma Skin Cancer Treatment, Part II: Squamous Cell Carcinoma, Including a Cost Analysis of Treatment Methods.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in the United States. Cutaneous squamous cell carcinoma has an estimated incidence of more than 700,000 new cases per year and a 5% risk of metastasis. OBJECTIVE: To provide clinicians with guidelines for the management of cSCC based on evidence from a comprehensive literature review and consensus among the authors. MATERIALS AND METHODS: The authors conducted an extensive review of the medical literature on treatment methods for cSCC, taking into consideration cure rates, recurrence and metastatic rates, aesthetic and functional outcomes, and cost effectiveness of the procedures. RESULTS: Surgical treatments provide the best outcomes for cSCC. Mohs micrographic surgery is a cost-effective procedure that affords the highest cure rate, maximal tissue preservation, and superior cosmetic outcomes. Nonsurgical methods may be used as a primary treatment for low-risk squamous cell carcinomas, but the cure rates are lower. CONCLUSION: The cure rate remains the most important consideration in choosing the treatment method, but additional factors, such as the patient's general medical condition, psychosocial circumstances, the location of the tumor and cost effectiveness of the therapy should be considered. Mohs micrographic surgery remains the preferred treatment for high-risk tumors and tumors located in cosmetically sensitive areas.

Consensus for nonmelanoma skin cancer treatment: basal cell carcinoma, including a cost analysis of treatment methods.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in the US population affecting approximately 2.8 million people per year. Basal cell carcinomas are usually slow-growing and rarely metastasize, but they do cause localized tissue destruction, compromised function, and cosmetic disfigurement. OBJECTIVE: To provide clinicians with guidelines for the management of BCC based on evidence from a comprehensive literature review, and consensus among the authors. MATERIALS AND METHODS: An extensive review of the medical literature was conducted to evaluate the optimal treatment methods for cutaneous BCC, taking into consideration cure rates, recurrence rates, aesthetic and functional outcomes, and cost-effectiveness of the procedures. RESULTS: Surgical approaches provide the best outcomes for BCCs. Mohs micrographic surgery provides the highest cure rates while maximizing tissue preservation, maintenance of function, and cosmesis. CONCLUSION: Mohs micrographic surgery is an efficient and cost-effective procedure and remains the treatment of choice for high-risk BCCs and for those in cosmetically sensitive locations. Nonsurgical modalities may be used for low-risk BCCs when surgery is contraindicated or impractical, but the cure rates are lower.

Ultrasonic delivery of silica-gold nanoshells for photothermolysis of sebaceous glands in humans: Nanotechnology from the bench to clinic.

Recent advances in nanotechnology have provided numerous opportunities to transform medical therapies for the treatment of diseases including cancer, atherosclerosis, and thrombosis. Here, we report, through in vitro studies and in vivo human pilot clinical studies, the use of inert, inorganic silica-gold nanoshells for the treatment of a widely prevalent and researched, yet poorly treated disease of acne. We use ~150nm silica-gold nanoshells, tuned to absorb near-IR light and near-IR laser irradiation to thermally disrupt overactive sebaceous glands in the skin which define the etiology of acne-related problems. Low-frequency ultrasound was used to facilitate deep glandular penetration of the nanoshells. Upon delivery of the nanoshells into the follicles and glands, followed by wiping of superficial nanoshells from skin surface and exposure of skin to near-infrared laser, nanoshells localized in the follicles absorb light, get heated, and induce focal thermolysis of sebaceous glands. Pilot human clinical studies confirmed the efficacy of ultrasonically-delivered silica-gold nanoshells in inducing photothermal disruption of sebaceous glands without damaging collateral skin.

Acne Treatment Based on Selective Photothermolysis of Sebaceous Follicles with Topically Delivered Light-Absorbing Gold Microparticles.

The pathophysiology of acne vulgaris depends on active sebaceous glands, implying that selective destruction of sebaceous glands could be an effective treatment. We hypothesized that light-absorbing microparticles could be delivered into sebaceous glands, enabling local injury by optical pulses. A suspension of topically applied gold-coated silica microparticles exhibiting plasmon resonance with strong absorption at 800 nm was delivered into human pre-auricular and swine sebaceous glands in vivo, using mechanical vibration. After exposure to 10-50 J cm(-2), 30 milliseconds, 800 nm diode laser pulses, microscopy revealed preferential thermal injury to sebaceous follicles and glands, consistent with predictions from a computational model. Inflammation was mild; gold particles were not retained in swine skin 1 month after treatment, and uptake in other organs was negligible. Two independent prospective randomized controlled clinical trials were performed for treatment of moderate-to-severe facial acne, using unblinded and blinded assessments of disease severity. Each trial showed clinically and statistically significant improvement of inflammatory acne following three treatments given 1-2 weeks apart. In Trial 2, inflammatory lesions were significantly reduced at 12 weeks (P=0.015) and 16 weeks (P=0.04) compared with sham treatments. Optical microparticles enable selective photothermolysis of sebaceous glands. This appears to be a well-tolerated, effective treatment for acne vulgaris.

Fractional nonablative laser resurfacing: is there a skin tightening effect?

BACKGROUND: Fractional photothermolysis, an approach to laser skin resurfacing that creates microscopic thermal wounds in skin separated by islands of spared tissue, was developed to overcome the high incidence of adverse events and prolonged healing times associated with full coverage ablative laser procedures. OBJECTIVE: To examine whether fractional nonablative laser resurfacing induces skin tightening. MATERIALS AND METHODS: A literature review was performed to evaluate the clinical and histologic effects of fractional nonablative laser resurfacing and full coverage ablative resurfacing procedures. RESULTS: Fractional nonablative lasers produce excellent outcomes with minimal risk and morbidity for a variety of clinical conditions, including photodamaged skin, atrophic scars, surgical and burn scars. Efforts to induce robust fibroplasia in histologic specimens and skin tightening in the clinical setting have yielded inconsistent results. CONCLUSION: A better understanding of the histology of fractional laser resurfacing will help to optimize clinical outcomes.

Current status of surgery in dermatology.

An article titled "Current issues in dermatologic office-based surgery" was published in the JAAD in October 1999 (volume 41, issue 4, pp. 624-634). The article was developed by the Joint American Academy of Dermatology/American Society for Dermatologic Surgery Liaison Committee. A number of subjects were addressed in the article including surgical training program requirements for dermatology residents and selected advances in dermatologic surgery that had been pioneered by dermatologists. The article concluded with sections on credentialing, privileging, and accreditation of office-based surgical facilities. Much has changed since 1999, including more stringent requirements for surgical training during dermatology residency, and the establishment of 57 accredited Procedural Dermatology Fellowship Training Programs. All of these changes have been overseen and approved by the Residency Review Committee for Dermatology and the Accreditation Committee for Graduate Medical Education. The fertile academic environment of academic training programs with interaction between established dermatologic surgeons and fellows, as well as the inquisitive nature of many of our colleagues, has led to the numerous major advances in dermatologic surgery, which are described herein.

The evolution of melasma therapy: targeting melanosomes using low-fluence Q-switched neodymium-doped yttrium aluminium garnet lasers.

Melasma is an acquired disorder of pigmentation that commonly affects women with phototypes III-V, and it has a negative impact on the quality of life in affected individuals. It presents clinically as symmetric tan or brown patches on the face, most often involving the forehead, cheeks, perioral region, and periorbital region. On histologic examination, there is increased melanin in the epidermis and/or an increased number of melanosomes in the dermis, with a normal number of highly melanized and dendritic melanocytes. The mainstay of treatment is the use of sunscreen along with topical medications that suppress melanogenesis. Clearance is usually incomplete and recurrences or exacerbations are frequent, probably because of the poor efficacy in clearing dermal melanosomes. Treatment with high-energy pigment-specific lasers, ablative resurfacing lasers, and fractional lasers results in an unacceptably high rate of postinflammatory hyper- and hypopigmentation and rebound melasma. Recently, promising results have been achieved with low-fluence Q-switched neodymium-doped yttrium aluminium garnet laser treatment, which can selectively target dermal melanosomes without producing inflammation or epidermal damage, in all skin phototypes. This article reviews the current treatment modalities for melasma, the rationale for using and the clinical results of combination therapy with low-fluence Q-switched neodymium-doped yttrium aluminium garnet lasers.