Largest comparative analysis: Novel large spot size 595 nm, high-energy, pulsed dye laser reduces number of treatments for improvement of adult and pediatric port wine birthmarks.

OBJECTIVE: Port wine birthmarks (PWBs) are vascular malformations affecting 0.3%-0.5% of newborns with the tendency to persist into adulthood without adequate treatment of the heterogenous ectatic vessels. This study compares treatment outcomes and parameters of the prior generation pulsed dye laser (PPDL) and the larger spot novel generation pulsed dye laser (NPDL) to establish whether a larger spot size laser provides greater clearance with fewer treatments. METHODS: One hundred and sixty patients were treated with either the PPDL (80 patients) and NPDL (80 patients) with retrospective review of age, body site, laser treatment parameters, number of treatments, and improvement following laser therapy. RESULTS: Patients treated with PPDL were older on average than patients treated with NPDL (mean 24.8 ± 19.7 vs. mean 17.1± 19.3 years, p < 0.05). The majority of lesions treated with PPDL were located on the face and neck, whereas truncal and extremity sites were more frequently treated with the NPDL. Use of NPDL was associated with a mean maximum spot size of 13.1 mm and mean maximum fluence of 7.3 J/cm2 with pulse durations of 0.45-3 ms, whereas use of the PPDL was associated with a mean spot size of 10.8 mm and mean maximum fluence of 8.8 J/cm2 with pulse durations of 0.45-6 ms. Fifty percent improvement was seen with 8.8 PPDL treatments compared to 4.3 NPDL treatments (p ≤ 0.01) with no significant difference in overall mean improvement between both devices at the chosen parameters. Multiple regression analysis showed that device type, not age or lesion location, was the only statistically significant independent variable to affect the endpoint of at least 50% improvement of the lesion. CONCLUSIONS: Use of the larger spot NPDL is associated with achieving 50% improvement with fewer treatments.

Good response to pulsed dye laser in patients with capillary malformation-arteriovenous malformation syndrome (CM-AVM).

Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is an autosomal dominant disorder caused by heterozygous mutations in RASA1 and EPHB4. Capillary stains in CM-AVM are compatible with Schöbinger's phase I AVMs. Vascular laser has been classically contraindicated for the treatment of AVMs, as there is a fear of accelerating their progression. In this study, we have treated capillary stains in five CM-AVM patients with pulsed dye laser, with improvement and without worsening or recurrence of the lesions after 1 year of clinical and ultrasound follow-up.

Double Pass 595 nm Pulsed Dye Laser Does Not Enhance the Efficacy of Port Wine Stains Compared with Single Pass: A Randomized Comparison with Histological Examination.

OBJECTIVE: To compare the efficacy and safety of double-pass pulsed dye laser (DWL) and single-pass PDL (SWL) in treating virgin port wine stain (PWS). BACKGROUND: The increase in the extent of vascular damage attributed to the use of double-pass techniques for PWS remains inconclusive. A prospective, side-by-side comparison with a histological study for virgin PWS is still lacking. MATERIALS AND METHODS: Twenty-one patients (11 flat PWS, 10 hypertrophic PWS) with untreated PWS underwent 3 treatments at 2-month intervals. Each PWS was divided into three treatment sites: SWL, DWL, and untreated control. Chromametric and visual evaluation of the efficacy and evaluation of side effects were conducted 3 months after final treatment. Biopsies were taken at the treated sites immediately posttreatment. RESULTS: Chromametric and visual evaluation suggested that DWL sites showed no significant improvement compared with SWL (p > 0.05) in treating PWS. The mean depth of photothermal damage to the vessels was limited to a maximum of 0.36-0.41 mm in both SWL and DWL sides. Permanent side effects were not observed in any patients. CONCLUSIONS: Double-pass PDL does not enhance PWS clearance. To improve the clearance of PWS lesions, either the depth of laser penetration should be increased or greater photothermal damage to vessels should be generated.

Port-Wine Stains: A Focused Review on Their Management.

Port-wine stain (PWS) is the second most common congenital vascular malformation characterized as ectatic capillaries and venules in the dermis that clinically appears as a deep red to purple patch on the skin. Typically, PWS progressively darken and may become hypertrophic or nodular without treatment. There are several treatment options available for PWS from topical antiangiogenic agents to laser therapies. Vascular-specific lasers are the gold standard in treating PWS and classically pulsed dye lasers are usually the treatment of choice. However, some patients with PWS are recalcitrant to PDL and may require a combination of treatment methods. Nonetheless, even with the advancements in laser therapies utilized today, it is can be difficult to achieve complete clearance of the PWS. Thus, new innovations for treating recalcitrant PWS are underway in order to improve overall patient treatment outcomes.

J Drugs Dermatol. 2017;16(11):1145-1151.

Nd:YAG laser-induced morphology change and photothermal conversion of gold nanorods with potential application in the treatment of port-wine stain.

Based on the principle of selective photothermolysis, 1064 nm Nd:YAG laser has great potential for the treatment of deeper and larger PWS. However, the clinical effectiveness is limited because of the weak absorption of blood to Nd:YAG laser. The aim of this study is to obtain the optimal irradiation conditions to effectively destroy vascular lesions with the assistance of PEG-modified gold NRs to enhance blood absorption of Nd:YAG laser. In our study, PEG-modified gold NRs were prepared by the seeded growth method. Gold NRs after exposure to Nd:YAG laser were characterized using absorption spectra and transmission electron microscope images. The tissue-like phantom containing a glass capillary with blood was prepared and exposed to Nd:YAG laser to investigate the laser energy density and pulse number required for blood coagulation before and after the addition of gold NRs in blood. The results show that the millisecond Nd:YAG laser irradiation does not result in the shape change of gold NRs. After injection of gold NRs into the bloodstream (4.60 mg/kg), the absorbance of blood at 1064 nm increased 3.9 times. The threshold energy density for the treatment of PWS decreased by 33% (from 30 to 20 J/cm2). Our findings provide an experimental guide for choosing laser parameters and gold NRs concentration for the treatment of deeper and larger PWS with the assistance of PEG-modified gold NRs in vivo in the future.

A randomized side-by-side study comparing alexandrite laser at different pulse durations for port wine stains.

BACKGROUND AND OBJECTIVES: Pulsed dye laser (PDL) represents the gold-standard treatment for port wine stains (PWS). However, approximately 20% of patients are poor responders and yield unsatisfactory end-results. The Alexandrite (Alex) laser may be a therapeutic alternative for selected PWS subgroups, but optimal laser parameters are not known. The aim of this study was to assess clinical PWS clearance and safety of Alex laser at a range of pulse durations. MATERIALS AND METHODS: Sixteen individuals (14 previously PDL-treated) with deep red (n = 4), purple macular (n = 5) and purple hypertrophic (n = 7) PWS were included. Four side-by-side test areas were marked within each lesion. Three test areas were randomized to Alex laser at pulse durations of 3, 5, or 10 ms (8 mm spot, DCD 60/40), while the fourth was untreated. The lowest effective fluence to create purpura within the entire test spot was titrated and applied to intervention areas. Standardized clinical photographs were taken prior to, immediately after laser exposure and at 6-8 weeks follow up. Clinical PWS clearance and laser-related side effects were assessed using clinical photos. RESULTS: Alex laser at 3, 5, and 10 ms pulse durations demonstrated significant clearance compared to untreated controls (P < 0.001). Three milli second pulse duration exhibited improved clearance versus 5 ms (P = 0.016) and 10 ms (P = 0.004), while no difference between five and 10 ms was shown (P = 0.063). Though not significant, good responders (>50% clearance) were more likely to have purple hypertrophic PWS (5/7) compared to purple macular (2/5) and deep red lesions (1/4). Eight laser-exposed test areas (17%) developed hypopigmented atrophic scarring. Side effects tended to be more frequently observed with 5 ms (n = 4) and 10 ms (n = 3) versus 3 ms pulse duration (n = 1). Correspondingly, 3 ms was associated with a superior (n = 6) or comparable (n = 10) overall cosmetic appearance for all individuals. CONCLUSION: Alex laser at 3 ms pulse duration offers superior clinical clearance and safety compared to 5 and 10 ms, and seems best suited for purple hypertrophic PWS. Treatment should be restricted to experienced personnel due to a particularly narrow therapeutic window. Lasers Surg. Med. 49:97-103, 2017. © 2016 Wiley Periodicals, Inc.

Treatment of port wine stains using Pulsed Dye Laser, Erbium YAG Laser, and topical rapamycin (sirolimus)-A randomized controlled trial.

BACKGROUND AND OBJECTIVE: Pulsed Dye Laser (PDL) is currently the gold standard treatment for port wine stains (PWS), although the degree of lesion blanching is variable and often unpredictable. This appears to be due to reformation and reperfusion of blood vessels. Rapamycin has shown potential as an antiangiogenic agent and may prevent the revascularization after PDL treatment. The objective of this study was to evaluate the efficacy of adjuvant use of (commercially available) topical rapamycin after PDL treatment in patients with PWS. MATERIALS AND METHODS: We conducted a prospective, intra-patient, randomized controlled trial. Four treatment areas of 1 cm2 were created in each PWS. PDL-only treatment was compared to the following three treatments: PDL + rapamycin, PDL + Erbium YAG laser ablation of the stratum corneum + rapamycin, and rapamycin monotherapy. We also compared PDL + Erbium YAG + rapamycin with PDL + rapamycin. The primary endpoint was the percentage clearance assessed colorimetrically at 6 months follow-up. Secondary outcomes were photographic evaluation by an expert panel, patient satisfaction, treatment related pain, and safety. RESULTS: Fourteen patients completed the treatment protocol. The highest percentage clearance was achieved with PDL-only treatment (mean [SD] 16% [34]), but there were no statistically significant differences between treatments. The best photographic evaluation and highest patient satisfaction were also achieved with PDL-only treatment, but only the difference between PDL-only and rapamycin monotherapy was statistically significant. The treatment related pain was well tolerated. Application-site pruritus was a frequent occurring adverse event. Allergic contact dermatitis to rapamycin occurred in one patient. There were no serious adverse events. CONCLUSION: Topical application of the commercially available solution of rapamycin (Rapamune® 0.1%) as an adjuvant to PDL treatment does not appear to improve PWS blanching. Lasers Surg. Med. 49:104-109, 2017. © 2016 Wiley Periodicals, Inc.

Hemoporfin Photodynamic Therapy for Port-Wine Stain: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) has shown potentially beneficial results in treating port-wine stain, but its benefit-risk profile remains undefined. This study aimed to evaluate the efficacy and safety of PDT conducted with hemoporfin and a 532 nm continuous wave laser to treat port-wine stain clinically. PATIENTS AND METHODS: This randomized clinical trial was conducted in eight hospitals in China. Participants were adolescent and adult patients (age range: 14-65 years old) with port-wine stain. During stage 1 (day 1 to week 8) all patients were randomized at a 3:1 ratio to treatment (532 nm laser irradiation (96-120 J/cm2) with hemoporfin (5mg/kg; PDT-hemoporfin, n = 330)) or placebo groups (irradiation with placebo (PDT-placebo, n = 110)); during stage 2 (week 8 to 16) patients in both groups were offered treatment. Clinician-evaluators, who were blind to the study, classified each case on the following four-level scale according to assessment of before and after standardized pictures of the lesion area: no improvement: <20%; some improvement: 20-59%; great improvement: 60-89%; or nearly completely resolved: ≥90%. The primary efficacy endpoint was proportion of patients achieving at least some improvement at week 8. The secondary efficacy endpoints were proportion of patients achieving nearly completely resolved or at least great improvement at week 8, proportion of patients achieving early completely resolved, at least great improvement, or at least some improvement at week 16, and the corresponding satisfaction of the investigators and the patients (designated as 'excellent', 'good', 'moderate', or 'ineffective') at weeks 8 and 16. RESULTS: Compared to the PDT-placebo group, the PDT-hemoporfin group showed a significantly higher proportion of patients that achieved at least some improvement (89.7% [n = 295; 95% CI, 85.9%-92.5%] vs. 24.5% [n = 27; 95% CI, 17.4%-33.3%]) at week 8 (P < 0.0001) and higher improvements for all secondary efficacy endpoints. Treatment reactions occurred in 99.5% (n = 731; 95% CI, 98.7%-99.8%) of the PDT-hemoporfin treatments (n = 735). Hyperpigmentation occurred in 22.9 per 100 patient-treatments (n = 168; 95% CI, 20.0-26.0) in the PDT-hemoporfin treated patients. CONCLUSIONS: Hemoporfin-mediated PDT is an effective and safe treatment option for adolescent and adult patients with port-wine stain. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-08000213.

Inflammatory morphea mimicking an acquired port-wine stain initially treated with pulsed-dye laser.

The early inflammatory lesions of morphea may present with erythema or violaceous patches and plaques before evolving into areas of sclerosis. They have been misdiagnosed as acquired port-wine stains (PWSs). We report a previously well 7-year-old Chinese girl presenting with early facial morphea mimicking an acquired PWS with unusual histologic features of perineural inflammation. The presence of cutaneous perineural inflammation may be seen in a small percentage of cases of morphea and appears to be a feature of early inflammatory morphea. We report this case to highlight the importance in recognizing this entity and summarize the reported cases of inflammatory morphea mimicking acquired PWSs.

Comparison of pulsed dye laser (PDL) and photodynamic therapy (PDT) for treatment of facial port-wine stain (PWS) birthmarks in pediatric patients.

BACKGROUND: Vascular-acting photodynamic therapy (PDT) might be an alternative approach for treating port wine stain (PWS) birthmarks, but the usefulness of PDT for pediatric patients has not been fully investigated. STUDY DESIGN: Medical records of pediatric patients (3-10 years old) with red and purple facial PWS were analyzed. Clinical outcomes after one session of PDL (585 nm, 4.8-6.5 J/cm(2)) and PDT (Hemoporfin - 3.5mg/kg, copper vapour laser - 120 J/cm(2)) were compared. RESULTS: The rate of excellent response in PDT group was significantly higher than that in PDL group (25.0% vs 10.9%). For red lesions there was no significant difference in overall response between PDL and PDT group, but for purple lesions the overall response rate of PDT group was significantly higher than that of PDL group (93.0% vs 75.6%). Lesions located at the forehead, cheek and jaw regions showed better responses to PDT. Incidences of pigmentation and scar formation in PDT group were significantly lower than PDL group (8.3% vs 21.1%). CONCLUSION: This study suggests that PDT is safe and effective for treating facial PWS of childhood patients.

[Potential and limitations of dye laser therapy for capillary malformations]. / Möglichkeiten und Grenzen der Farbstofflasertherapie bei kapillären Malformationen.

Capillary malformations (port-wine stains) are observed in less than 1 % of neonates and may occur coincidentally with other vascular and nonvascular malformations. Two thirds of lesions occur in the head and neck area and may have important cosmetic and psychological implications for the patients. Treatment with flashlamp-pumped pulsed dye lasers is still the therapy of choice for capillary malformations and can be applied to infants. If the laser device is used appropriately, the rate of persistent side effects is low. Although laser treatment achieves good clearance in the majority of patients with capillary malformations, complete clearance is rare. New therapeutic options are thus urgently required.

Simulating light transport through skin for color prediction of port wine stain lesions: a review.

A survey of the literature is presented regarding the simulation of port wine stain (PWS) skin color. Knowledge of PWS features, such as the depths and diameters of affected vessels, is essential for informing laser treatment. These may be determined through the inverse application of a skin model. The techniques which have been applied to achieve this are analyzed in detail. Radiative transfer (RT) is found to be the preferred method of simulation. By far the most common approximations to RT are the diffusion approximations, which have been applied successfully in the past and Monte Carlo techniques, which are now the methods of choice. As the requirements for improvement of laser treatment on an individual basis continues, the needs for further work towards accurate estimations of individual optical coefficients and robust, flexible simulation techniques are identified.

Port-wine stain laser treatments and novel approaches.

BACKGROUND AND OBJECTIVES: Port-wine stains (PWSs) are capillary vascular malformations that are commonly resistant to treatment. Currently, the pulsed dye laser (PDL) is the treatment of choice. Multiple treatments are required and complete blanching after laser irradiation is rarely achieved. We review current therapeutic modalities for PWSs and recent developments for enhanced clearance. STUDY DESIGN/MATERIALS AND METHODS: Relevant literature was reviewed including PDL modifications for improved efficacy, alternative laser devices for treatment-resistant PWSs, and the addition of agents to modulate the wound-healing response after laser irradiation. RESULTS: Although PDL is the treatment of choice for PWSs, increased understanding of interactions between PWSs and PDL has led to improvements in therapeutic outcome in terms of lesion blanching. CONCLUSIONS: Preliminary evidence of combination therapy using antiangiogenic agents after laser irradiation appears promising and could lead to the development of a new standard of care for PWSs.

Spatial frequency domain imaging of port wine stain biochemical composition in response to laser therapy: a pilot study.

BACKGROUND AND OBJECTIVE: Objective methods to assess port wine stain (PWS) response to laser treatment have been the subject of various research efforts for several years. Herein, we present a pilot study using a newly developed, light emitting diode (LED) based spatial frequency domain imaging (SFDI) device to record quantitatively biochemical compositional changes in PWS after laser therapy. STUDY DESIGN/PATIENTS AND METHODS: A SFDI system was used to image before, and after, five PWS treatment sessions [n = 4 subjects (one subject was imaged before and after two consecutive laser treatments)]. SFDI derived wide-field optical properties (absorption and scattering) and tissue chromophore concentrations including oxy-hemoglobin (ctO(2) Hb), deoxy-hemoglobin (ctHHb), total hemoglobin (ctTHb), and tissue oxygen saturation (stO(2) ) are presented for skin imaged prior to and immediately after laser treatment. The SFDI derived images were analyzed by comparing the above measurements in PWS to those of normal skin and tracking changes immediately after laser exposure. RESULTS: Elevated oxy-hemoglobin (>20%) and tissue oxygen saturation (>5%) were measured in all PWS lesions and compared to values for normal skin prior to treatment. Laser treatment resulted in an increase in deoxy-hemoglobin (>100%), decrease in tissue oxygen saturation (>10%), and reduced scattering (>15%) in all PWS lesions. One subject was followed before and after two consecutive laser treatments and the overall improvement in PWS lesion blanching was quantitatively assessed by measuring a 45% decrease in dermal blood volume. CONCLUSION: SFDI is a rapid non-contact wide-field optical technique that shows potential as an imaging device that can be used to quantify biochemical compositional changes in PWS after laser therapy. Future work will investigate the potential of SFDI to provide intra-operative guidance for laser therapy of PWS lesions on an individual patient basis.

Contact and contactless diffuse reflectance spectroscopy: potential for recovery monitoring of vascular lesions after intense pulsed light treatment.

Optical fiber contact probe diffuse reflectance spectroscopy and remote multispectral imaging methods in the spectral range of 400 to 1100 nm were used for skin vascular malformation assessment and recovery tracing after treatment by intense pulsed light. The results confirmed that oxy-hemoglobin relative changes and the optical density difference between lesion and healthy skin in the spectral region 500 to 600 nm may be successfully used for objective appraisal of the therapy effect. Color redness parameter a* = 2 is suggested as a diagnostic border to distinguish healthy skin and vascular lesions, and as the indicator of phototreatment efficiency. Valuable diagnostic information on large area (>5 mm) lesions and lesions with uncertain borders can be proved by the multispectral imaging method.

Laser and IPL treatment of port-wine stains: therapy options, limitations, and practical aspects.

Port-wine stains (PWS) are congenital, progressive vascular malformations of the dermis that are often disfiguring, particularly when located in a cosmetically relevant area. Thus, the successful clearance of PWS is of highest medical relevance, and laser therapy is the treatment of choice for this indication. Numerous trials have shown the effectiveness of both lasers and incoherent light sources. Laser or IPL treatments achieve good clearance in the majority of PWS, but complete clearance is rare. Thus, new therapeutic options are urgently required. Photodynamic therapy is a relatively new approach in the treatment of PWS. Our review aims to summarize therapy options of port-wine stains, depending on treatment area, patient age, and vessel architecture. Recent developments in this field and new insights into the pathogenesis of PWS are discussed. The review also highlights practical aspects, complications that can occur, and how to prevent them.

Fast and robust extraction of optical and morphological properties of human skin using a hybrid stochastic-deterministic algorithm: Monte-Carlo simulation study.

A hybrid deterministic-stochastic algorithm combining the simplex method (SM) and a genetic algorithm (GA) was applied to the problem of extracting the optical and morphological properties of human skin (HSOMPs) from visual reflectance spectroscopy data. The results using the GA-SM hybrid algorithm adopting tournament selection and selecting new sets of HSOMPs were compared with those using other conventional optimization algorithms that have generally been used for the extraction of HSOMPs. Monte-Carlo simulation showed that the suggested GA-SM hybrid algorithm enhanced the stability of the inverse solutions and computational efficiency.