A feasible way to explore real blood vessels thermal responses to laser irradiation by combing optical clearing and the reflectance spectra measurements: animal experiment study.

Laser therapy has been widely used to treat port-wine stains (PWS) and other cutaneous vascular lesions via selective photothermolysis. Animal models are a valuable tool for investigating thermal responses beneath the skin. However, in previous animal experiments, such as the dorsal skin chamber model, one side of the skin was removed, resulting in the loss of mechanical support for the target blood vessel. In this study, the optical clearing technique was applied to the dorsal skin, allowing direct observation of real thermal responses within the tissue without removing the covering skin. The target blood vessels were irradiated with a pulsed 1064 nm Nd: YAG laser. The corresponding thermal responses were recorded using a CCD camera. Additionally, variations in skin reflectance spectra were measured before and after laser irradiation. Due to the optical clearing and reflectance spectra measurement, vessel responses such as contraction, reperfusion, and full occlusion were correlated with specific variation patterns in reflectance spectral signals.

Assessment of the efficacy of 595 nm pulsed dye laser in the management of facial flat angiomas. Results of a case series.

BACKGROUND: Studies on pulsed dye laser (PDL) have shown the best efficacy and safety data for treating vascular anomalies among the various lasers used and the 595-nm PDL has been used to treat cutaneous vascular anomalies for about 30 years. The purpose of this study was to assess the efficacy of 595 nm Pulsed Dye Laser in the management of facial flat angiomas present in the form of Port-Wine Stain. MATERIALS AND METHODS: Seven cases of PWS in Fitzpatrick skin type ranged from I to III and colour ranging from pink to purple, were treated with 595 nm pulse Dye Laser. Patients underwent to 6-8 laser sessions at 20-30 days intervals. Results obtained were judged by dermatologist, by comparing pre-treatment and post-treatment photographs, 6 months after the last session and a quartile scale of lesion clearance (4-point Investigator Global Assessment scale): 1 = no or low results (0%-25% of the lesion area improved), 2 = slight improvement (25%-50% of the lesion area cleared), 3 = moderate-good improvement (50%-75%), and 4 = excellent improvement (75%-100%) was used. Possible side effects such as blisters, hyper/hypopigmentation, and scarring were monitored. RESULTS: All patients observed global improvements. 71% of patients achieved excellent clearance and 29% patients achieved good-moderate clearance of their angioma. Patients were asked for a subjective evaluation of the results: 57% of patients were very satisfied, 29% were satisfied, and 14% patients were not very satisfied with the results. No patients were dissatisfied. No significant side effects were noted. CONCLUSION: This research confirms the efficacy of the 595 nm PDL for flat angioma management, without considerable side effects.

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.

Time interval between pulse dye laser treatments of port-wine stains: 30 years of experience.

Port-wine stains (PWS) are frequently refractory to laser treatments. The aim of this study is to evaluate the role of treatment interval time. From 1990, 216 patients underwent Pulsed Dye Laser sessions. The laser sessions were scheduled at a minimum interval of 4 weeks to a maximum of 48 weeks. Clinical outcomes were assessed 8 weeks after the last laser session. Better results were obtained with 8 weeks interval time between therapy session, and high efficacies were also found for intervals of 4, 6 and 10 weeks. For greater interval instead, the effectiveness is significantly lower.

Complication rates and safety of pulsed dye laser treatment for port-wine stain: a systematic review and meta-analysis.

Pulsed dye laser (PDL) is the most commonly used method for port-wine stain (PWS); however, no studies have reported the safety of PDL. This review aimed to collect and summarize complications reported in relevant literature, assess complication rates in treating PWS with PDL, and explore the relevant influencing factors. A systematic review and meta-analysis were conducted to search for related studies in PubMed, Embase, and the Cochrane Library until August 2022. Two reviewers independently evaluated the risk of bias of included studies. Stata Software version 17.0 was used for the analysis. All complications reported in the literature are divided into acute phase complications and long-term complications. Overall pooled purpura, edema, crusting, blistering, hyperpigmentation, hypopigmentation, and scarring rates were 98.3%, 97.6%, 21.5%, 8.7%, 12.8%, 0.9%, and 0.2%, respectively. Although the acute adverse reactions were found to be common, the long-term permanent complications clearly have a lower frequency, and the occurrence of scarring is much lower than that initially thought. This indicates that effective protective measures after treatment are very important for preventing scar formation. Overall, PDL treatment for PWS shows a high level of safety and low chances of causing long-term complications.

Can 595-nm Pulsed Dye Laser in Conjunction With an Optical Clearing Agent Improve the Treatment of Port-Wine Stains?

BACKGROUND: Studies have demonstrated that glycerol can act as an optical clearing agent (OCA) to increase the light penetration through the skin and laser deposition to the target chromophore, thus potentially increasing the efficacy of laser treatment. OBJECTIVE: To evaluate whether a pulsed dye laser (PDL) in combination with an OCA can increase the efficacy in treating port-wine stains (PWSs). METHODS: Thirteen patients with untreated PWSs underwent 3 treatment sessions at 6-week intervals. Each PWS was divided into OCA + PDL sites (PDL treatment after topical use of 0.5 mL hydrous glycerol for 5 minutes), PDL sites, and untreated sites. The chromametric evaluation and visual evaluation (VAS) of the efficacy and the assessment of side effects were conducted 3 months after the final treatment. RESULTS: Visual evaluation was 2.69 versus 2.07 (p = .025) and 3.38 versus 3.07 (p = .04) for OCA + PDL and PDL-only sites after the first and second sessions. After the third session, the chromameter and VAS indicated no significant difference between the 2 sites. Permanent side effects were not observed. CONCLUSION: Greater efficacy was observed after the first 2 treatments on the OCA + PDL sites. Although after multiple sessions, the OCA + PDL treatment did not improve efficacy over just PDL alone.

Triple pass laser therapy for recalcitrant facial port wine stains.

Patients with recalcitrant facial port wine stains (rfPWS) can be challenging to manage, often leaving the clinician with difficult decisions for treatment options. 'Triple therapy' consists of using three different laser wavelengths at each treatment setting. The evidence on outcomes is limited as this treatment approach has not been previously reported to the best of our knowledge. Children who received triple therapy at least once for rfPWS, and for whom SIAscopy readings had been taken, were retrospectively identified. SIAscope readings were compared before the first triple therapy treatment and at final the most recent clinical follow-up. The clinical appearance was also assessed using a Visual Analogue Scale comparing clinical photographs taken before triple therapy to those taken at the most recent clinical follow-up. A total of 47 children were identified and included in our review. The SIAscope readings showed an overall significant (p < 0.001) lightening with 39 (83%) showing lightening and 8 (17%) patients showing a darkening. Scores using the VAS also showed improvement with 55% experiencing an improvement in their clinical appearance, 38% showing no visible change and 6% appearing to have worsened. Triple therapy can offer improvement of rfPWS which have failed to respond to single wavelength laser therapy. SIAscopy and VAS scores correlate well in assessing clinical response; however, the added clinical benefit of SIAscopy in vascular laser clinics remains uncertain.

Wavelength optimization for the laser treatment of port wine stains.

Based on the well-known principle of selective photothermolysis, laser has been a promising way for the treatment of port wine stains (PWSs). The laser wavelengths used for PWS's clinical treatment include but are not limited to pulsed dye laser (PDL) in 585-600 nm, long-pulse 755-nm alexandrite, and 1064-nm Nd:YAG lasers. The objective of this study was to investigate the optimal wavelength for PWS's laser treatment. A two-scale mathematic model was constructed to simultaneously quantify macroscale laser energy attenuation in two-layered bulk skin and microscale local energy absorption on target blood vessels within Krogh unit. The effects of morphological parameters, including epidermal melanin content, epidermal thickness, dermal blood content, blood vessel depth, and diameter on laser energy deposition within target blood vessels, were investigated from the visible to near-infrared bands (500-1100 nm). The energy deposition ratio of target blood vessel to epidermal surface was proposed to determine the optimal laser wavelength for PWS with different skin morphological parameters. The bioheat transfer modeling and animal experiment are also conducted to prove our wavelength optimization. The optimal wavelengths for lightly pigmented skin with small and shallow target blood vessels are 580-610 nm in the visible band. This wavelength coincides with commercially used PDL. The optimal wavelength shifts to 940 nm as the epidermal pigmentation increases or the size and blood vessel depth increases. The optimal wavelength changes to 1005 nm as the epidermal pigmentation or the size and burying depth of target blood vessel further increases. Nine hundred forty nanometers can be selected as a general wavelength in PWS treatment to meet the need in most widely morphological structure. Lasers with wavelengths in the 580-610, 940, and 1005 nm regions are effective for treating PWS because of their high optical selectivity in blood over the epidermis.

Current Practices in Pediatric Dermatology Laser Therapy: An International Survey.

BACKGROUND AND OBJECTIVES: To date, there are no well-established guidelines regarding laser therapy for the treatment of cutaneous lesions in pediatric patients. We aim to ascertain the types of lasers commonly used, types of lesions treated, and factors that affect the selection of specific laser modalities in pediatric patients. STUDY DESIGN/MATERIALS AND METHODS: An anonymous online survey was distributed to healthcare providers who treat children with lasers through listservs of four major national and international dermatology and laser organizations. RESULTS: Outpatient office-based procedure rooms are the most common clinical setting for laser procedures (74.4%), and pulsed dye laser is the most commonly used laser (95.4%). Conditions routinely treated with lasers included port wine stains (95.4%), infantile hemangiomas (81.5%), other vascular lesions (81.5%), scars (77.7%), and hair (60.8%). 84.4% of respondents expressed concern about general anesthesia in patients <2 years old. Nevi of Ota is treated with laser more frequently (52.3%) than other pigmented lesions. LIMITATIONS: Limited generalizability of case examples to general conditions. CONCLUSIONS: Vascular lesions are the most common lesions treated with lasers in pediatric dermatology patients, and most providers are using these devices in the outpatient setting. Many providers are concerned about the effects of repeated general anesthesia in infants, and there appears to be a trend toward providing laser therapy in the outpatient setting without general anesthesia. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Adjuncts to pulsed dye laser for treatment of port wine stains: a literature review.

Noninvasive pulsed dye laser is the current gold standard for the treatment of port wine stains. However, most port wine stains are not completely cleared after pulsed dye laser therapy, owing to insufficient photocoagulation and laser-induced vascular regeneration and reperfusion. Several studies have explored approaches designed to improve treatment efficacy. This integrative literature review summarizes the results of clinical and animal studies published between 2004 and 2021. Pulsed dye laser has been administered in combination with photoelectric devices (the neodymium: yttrium-aluminum-garnet lasers, dual-wavelength 1064-/595-nm laser irradiation, fiberoptic Nd-YAG laser, photodynamic therapy, and radio frequency), and drugs (rapamycin, imiquimod, timolol, axitinib, endothelin receptor antagonist, artificial red blood cells and oxymetazoline). The initial results suggest that combination therapy is a direction worth exploring in the future. Further large prospective, blinded and controlled multicenter clinical trials with longer follow-up period are required to obtain more robust evidence.

Does interval time between pulsed dye laser treatments for port-wine stains influence outcome? A systematic review and meta-analysis.

The pulsed dye laser (PDL) is the standard treatment for port-wine stains (PWS). Maximal improvement occurs after multiple treatment sessions; however, the optimal treatment interval has yet to be determined. The aim of this study was to review whether there is an association between PDL treatment interval and outcome of PWS. Six databases were searched by three reviewers for publications investigating treatment of PWS with PDL. The 75% improvement rates (75IR) were extracted for quantitative analysis. Meta-regression was used to investigate the association between treatment intervals and 75IR. The systematic review included 1 RCT and 33 cohort studies (7 prospective cohorts and 26 retrospective cohorts), with a total of 3777 patients. The pooled 75IR was 37% (95% CI 29-45%; I2 = 95%). Light Fitzpatrick skin type (p = 0.04), facial anatomic location (p = 0.01), and young age (p = 0.008) were associated with 75IR. In an unadjusted (p = 0.42) and multivariable adjusted (p = 0.98) meta-regression, no association was found between time interval between treatments and 75IR. These results persisted in a sensitivity analysis of studies with a mean patient age of ≤ 1. The majority of included studies were heterogeneous and retrospective. Based on cohort studies of low-to-moderate quality, time intervals between PDL treatments are not associated with PWS outcome.

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.

Laser treatment of vascular dermatological diseases using a pulsed dye laser (595 nm) in combination with a Neodym:YAG-laser (1064 nm).

There are many vascular anomalies which are often a diagnostic and therapeutic challenge. They are classified in vascular tumors (e.g. infantile hemangioma) or vascular malformations (e.g. port-wine-stain). Moreover there are several other and rare vascular disregulations and diseases in the field of dermatology. Many laser systems focus on the therapy of vascular pathologies. We use a pulsed dye laser (595 nm) on its own or in combination with a Neodym:YAG-laser (1064 nm) to treat those vascular diseases. This paper points out the advantages and side effects of these two laser systems and describes the limitations of those.

Treatment of port wine stains with 595-nm pulsed dye laser in 27 pediatric patients: A prospective study in the Iranian population.

Port wine stain (PWS) is a congenital vascular malformation, which is visible at the birth as the red patches, mostly on the face and neck. Previous studies have shown good efficacy and safety of 595-nm pulsed dye laser (PDL). Here, we have conducted a prospective study to assess the efficacy and safety profile of pediatrics with PWS, treated with 595-nm PDL. Twenty-seven patients (10 males and 17 females) with the mean age of 5.7 ± 2.8 (range 1-13) years old were included in the study. Following 6.2 (range 4-10) sessions of treatment, 70.74 ± 18.5% of improvement was detected three months after the final session. Fourteen (51.8%) patients achieved a higher than 75% of improvement; nine (33.4%) patients experienced 50%-75% improvement; four (14.8%) patients experienced a less than 50% improvement. V1 involvement and a marked improvement within the first five sessions found to be good prognostic factors. Regarding age, sex, skin type, color and size of the PWS, no significant association with therapeutic response were detected. Blister and crust, atrophic macules, and hyperpigmentation were noted in six (22.2%), one (3.7%), and one (3.7%), respectively. In conclusion, 595-nm PDL looks an effective and relatively safe therapeutic approach in the treatment of Iranian pediatric PWS patients.

The application of 595-nm pulsed dye laser for vascular anomalies in a Chinese population: a 10-year experience.

BACKGROUND: The 595-nm pulsed dye laser (PDL) has been used to treat vascular anomalies for about 30 years; however, there are insufficient data in Chinese patients concerning therapeutic efficacy, optimized parameters, and procedure techniques. OBJECTIVE: To study the efficacy and relevant factors in PDL therapy for vascular anomalies in Chinese patients. METHOD: We enrolled 431 patients with 8 different vascular anomalies and no previous treatment in this retrospective study. A detailed classification of vascular anomalies and various parameters and techniques of PDL were studied. The clinical outcomes were analysed using the Investigator Global Assessment. RESULTS: Improvements were significantly correlated with infantile haemangioma (IH) subtypes (p < 0.05). A significant correlation between efficacy and lesion colour, anatomical sites, and hypertrophic-type port-wine stain (PWS) was found (p < 0.05). There was no significant correlation between efficacy and age or sex (p > 0.05). CONCLUSION: PDL is an effective and safe therapeutic modality for managing vascular anomalies in Chinese patients. We determined that differentiating and identifying IH subtypes prior to treatment could be a useful parameter for predicting therapeutic results.  Lesion colour, sites, and hypertrophic changes in PWS are relevant therapeutic factors. PDL parameters and techniques differ according to the various vascular anomalies to achieve optimal results.

Prospective analysis of the port-wine stain patient population in the Netherlands in light of novel treatment modalities.

BACKGROUND: Pulsed dye laser is the gold standard for port-wine stain (PWS) treatment. However, pulsed dye lasers achieve suboptimal clinical results in a majority of patients. Patient demand for novel therapies and willingness to participate in clinical studies is currently unknown, yet, imperative for steering R&D activity. The objective of this study was to evaluate these two factors in relation to PWS patient demographics. METHODS: A questionnaire was used to assess patient and PWS characteristics, treatment history, efficacy, and satisfaction, stress level, willingness to travel and pay for an effective treatment, participation in clinical studies, and amenability to intravenous drug administration. Descriptive statistics and correlation analysis were performed. RESULTS: Of the respondents (N = 108), 65% would participate in clinical studies and 49% would accept intravenous drugs. For an effective treatment, 58% was prepared to pay over €2,000 and 48% would travel more than 6 h. Travel time was inversely correlated with age, clearance rate, and satisfaction. Facial PWS patients had undergone more treatments, were less satisfied, and less willing to participate in studies or accept intravenous drugs. Stress levels were higher in females. CONCLUSION: There is considerable demand for new PWS therapies, and a substantial proportion of patients are willing to participate in clinical studies.

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.

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.

Combined pulsed dye laser and fiberoptic Nd-YAG laser for the treatment of hypertrophic port wine stain.

The hypertrophic Port Wine Stain (PWS) is only partially and superficially treated with the Pulsed dye laser (PDL) because of its limited depth of penetration. We used combined PDL and fiberoptic 1444-nm Nd-YAG laser to treat a case with hypertrophic PWS. METHOD: After tumescent anesthesia, few holes were made by a 16-gauge needle on different sides of the lesion. The fiberoptic tip of 1444-nm Nd-YAG laser was inserted within the holes and was pushed forward while triggering. In a fan pattern and by a back and forth movement, the subcutaneous and deep dermal areas were coagulated. The skin and outer mucosal surfaces were then treated by PDL. The fiberoptic system used was Accusculpt 1444-nm Nd-YAG laser (Lutronic lasers, South Korea), and the PDL used was 585 nm Nlite system (Chromogenex UK). The parameters used for PDL were fluence = 9 Joules/cm2 and the spot size was 5 mm. The parameters used for fiberoptic 1444-nm Nd-YAG laser were: Pulse rate = 30 Hz, pulse energy = 300 mJ, power = 6 W, and the total energy = 4000 J for the whole face and mucosa. RESULT: Little sign of regression and moderate purpura were detected immediately after combined fiberoptic Nd-YAG and PDL therapy. The lesion gradually regressed within 4 months with satisfactory color and volume change. CONCLUSION: Combined fiberoptic Nd-YAG laser and PDL can be used for the treatment of deeper and superficial layers of hypertrophic PWS.