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.

Bilateral ocular manifestations of Sturge-Weber syndrome: a rare case report.

The rare neurocutaneous condition known as Sturge-Weber syndrome (SWS) is characterized by leptomeninges, or angiomas affecting the face, eyes, and brain. We report a newly diagnosed case that came to our institute complaining of a diminution of vision BE that had been going on for the past 1 year. Upon examination, the patient exhibited bluish discoloration of the sclera, an increase in the size of the cornea, and the characteristic port wine stain (PWS) on the face. Intraocular pressure BE was 30 mmHg with an applanation tonometer. The cup disc ratio on fundoscopy was 0.9 RE and 0.8 LE with characteristic glaucomatous disc changes BE. The child was treated with antiglaucoma medications. Abbreviations: SWS = Sturge-Weber syndrome, PWS = Port wine stain, CNS = Central nervous system, CT = Computed Tomography, IOP = Intraocular pressure, OCT = Optical coherence tomography, RE = Right eye, LE = Left eye, BE = Both eyes, ASOCT = Anterior segment optical coherence tomography.

532-nm potassium titanyl-phosphate laser versus 595-nm pulsed dye laser for port-wine birthmarks: A prospective, randomized, split-side study.

BACKGROUND: Pulsed dye lasers (PDL) are currently the first-line treatment of port-wine birthmarks (PWB). Due to high maintenance costs and instable technology, alternative methods are needed. OBJECTIVES: To compare clinical outcomes of a variable-sequenced, long-pulsed 532-nm potassium titanyl-phosphate (KTP) laser and PDL on treating PWB. METHODS: A prospective, randomized, split-side study. Patients were treated with a KTP laser and PDL with 1 to 5 sessions at intervals of 6-8 weeks. A follow-up visit was scheduled 6 weeks post-treatment. Efficacy was evaluated through colorimetric analysis, area reduction measurements and clinical evaluations by two blinded investigators based on photo documentation. Subjects provided rating of pain intensity during treatment, post-treatment reactions and satisfaction. Safety was measured by adverse events. Maintenance issues of the laser systems were documented. RESULTS: A total of 35 patients (mean age 42.1 years) were enrolled. 63% were female. Patients received 2.4 (SD 1.4; 1-5) treatment sessions. Colorimetric analysis indicated a comparable clearance effect in PWB of both KTP laser and PDL. Independent investigators rated clinical appearance to be significantly improved compared to baseline. No significant difference was observed between both laser systems. Regarding post-treatment reactions, the KTP laser caused less swelling, purpura and crusts. 96% would recommend both treatment modalities. Patients were satisfied with both laser systems. During the study, PDL systems malfunctioned for 6.6 months in total. For the KTP laser, we did not observe any system failures. CONCLUSION: Our data indicate that the KTP laser of the latest generation with large-spot sizes, subpulse technology and cryogen cooling has a comparable efficacy to the PDL in treating PWB. In addition, KTP laser is associated with greater tolerability, fewer technical failures and lower repair costs. Further prospective studies are required to determine the true effectiveness of the KTP laser in PWB treatment. This study was preregistered in Clinicaltrials.gov (NCT05771298).

Large birth mark and unilateral swelling of the lower extremity in a young teenager.

We describe an early adolescent male who was diagnosed with vascular malformation associated with unilateral limb overgrowth based on the clinical findings of a persistent port-wine stain since birth and gradually progressing right lower limb oedema since early childhood. Clinicians should keep in mind to clinically evaluate such malformations in detail, as well as contemplate genetic testing in patients presenting with a large port-wine stain at birth, particularly if well demarcated and lateral in a lower extremity.

Weekly Pulsed Dye Laser Treatments for Port-Wine Birthmarks in Infants.

Importance: Early treatment of port-wine birthmark (PWB) can be life-altering and is often associated with improved outcomes and quality of life. There is growing evidence that shorter treatment intervals may play a role in more rapid PWB clearance; however, the optimal treatment interval has not been established. Objective: To describe the outcomes of once-weekly pulsed dye laser (PDL) treatments for PWB in infants. Design, Setting, and Participants: This case series analyzed the medical records of patients with PWB who received once-weekly PDL treatments between January 1, 2022, and December 31, 2023, at the Laser & Skin Surgery Center of New York. These patients were younger than 6 months. Before-and-after treatment photographs were independently assessed and graded 2 months after initiation of treatment. Intervention: Once-weekly PDL treatments. Main Outcomes and Measures: The primary outcome was the percentage improvement of PWB, which was graded using the following scale: 0% (no improvement), 1% to 25% (mild improvement), 26% to 50% (moderate improvement), 51% to 75% (marked improvement), 76% to 95% (near-total clearance), and 96% to 100% (total clearance). Results: Of the 10 patients (6 males [60%]; median [range] age at first treatment, 4 [<1 to 20] weeks) included, 7 (70%) had experienced either near-total clearance (76%-95%) or total clearance (96%-100%) of their PWB with once-weekly PDL treatments after 2 months. The other 3 patients all saw marked improvement (51%-75%) and subsequently went on to achieve near-total clearance with additional treatments. The median (range) duration of treatment and number of treatments to achieve near-total or total clearance in all patients were 2 (0.2-5.1) months and 8 (2-20) treatments, respectively. No adverse events were noted. Conclusion and Relevance: This case series found that once-weekly PDL treatments for PWB in the first few months of life was associated with near-total or total clearance of PWB with no reported adverse events, suggesting improved outcomes can be achieved with shorter overall treatment duration. Further investigation into this novel decreased treatment interval of 1 week is warranted.

[Rapamycin and HPPH Co-Loaded Nanodrug Delivered via Dissolvable Microneedles to Treat Port-Wine Stains]. / å ±è½½é›·å¸•éœ‰ç´ å’Œå ‰å ‹æ´›çš„çº³ç±³è¯ç‰©å¤åˆå¯æº¶è§£å¾®é’ˆæ²»ç–—é²œçº¢æ–‘ç—£çš„å®žéªŒç ”ç©¶.

Objective: Port-wine stains are a kind of dermatological disease of congenital capillary malformation. Based on the biological characteristics of port-wine stains and the advantages of microneedle transdermal administration, we intend to construct a nanodrug co-loaded with rapamycin (RPM), an anti-angiogenesis drug, and photochlor (HPPH), a photosensitizer, and integrate the nanodrug with dissolvable microneedles (MN) to achieve anti-angiogenesis and photodynamic combination therapy for port-wine stains. Methods: First, RPM and HPPH co-loaded nanoparticles (RPM-HPPH NP) were prepared by the emulsification solvent-volatilization method, and its ability to generate reactive oxygen species (ROS) was investigated under 660 nm laser irradiation. Mouse hemangioendothelioma endothelial cells (EOMA) were used as the subjects of the study. The cellular uptake behaviors were examined by fluorescence microscopy and flow cytometry. The cytotoxicity effects of RPM-HPPH NP with or without 660 nm laser irradiation on EOMA cells were examined by MTT assays (with free RPM serving as the control). Then, hyaluronic acid (HA) dissolvable microneedles loaded with RPM-HPPH NP (RPM-HPPH NP@HA MN) were obtained by compounding the nanodrug with HA dissolvable microneedle system through the molding method. The morphological characteristics and mechanical properties of RPM-HPPH NP@HA MN were investigated by scanning electron microscope and electronic universal testing machine. The penetration ability of RPM-HPPH NP@HA MN on the skin of nude mice was evaluated by trypan blue staining and H&E staining experiment. Results: The RPM-HPPH NP prepared in the study had a particle size of 150 nm and generated large amounts of ROS under laser irradiation. At the cellular level, RPM-HPPH NP was taken up by EOMA cells in a time-dependent manner. The cytotoxicity of RPM-HPPH NP was higher than that of free RPM with or without laser irradiation. Under laser irradiation, RPM-HPPH NP exhibited stronger cytotoxic effects and the difference was statistically significant (P<0.05). The height of the needle tip of RPM-HPPH NP@HA MN was 600 µm and the mechanical property of a single needle was 0.75048 N. Trypan blue staining and HE staining showed that pressing on the microneedles could produce pores on the skin surface and penetration of the stratum corneum. Conclusion: RPM-HPPH NP@HA MN can deliver RPM-HPPH NP percutaneously to the lesion tissue and realize the synergistic treatment of port-wine stains with anti-angiogenic therapy and photodynamic therapy, providing a new strategy for the construction of nanodrug-loaded microneedle delivery system and the clinical treatment of port-wine stains.

Quantitative analysis of lesion images to evaluate the efficiency of vascular-targeted photodynamic therapy for port-wine stains: Four case reports.

SIGNIFICANCE: Vascular-targeted photodynamic therapy (V-PDT) is a clinically approved therapeutic approach for treating vascular-related diseases, such as port-wine stains (PWS). For accurate treatment, varying light irradiance is required for different lesions due to the irregularity of vascular size, shape and degree of disease, which commonly alters during different stages of V-PDT. This makes quantitative analysis of the treatment efficiency urgently needed. APPROACH: Lesion images pre- and post- V-PDT treatment of patients with PWS were used to construct a quantitative method to evaluate the differences among lesions. Image analysis techniques were applied to evaluate the V-PDT efficiency for PWS by determining the Euclidean distances and two-dimensional correlation coefficients. RESULTS: According to the image analysis, V-PDT with good treatment efficiency resulted in a larger Euclidean distance and a smaller correlation coefficient compared with the case having lower V-PDT efficiency. CONCLUSIONS: A new method to quantify the Euclidean distances and correlation coefficients has been proposed, which is promising for the quantitative analysis of V-PDT efficiency for PWS.

Simulating PDT of port-wine stains in the in vivo chicken wattle model using Hemoporfin and radiation at 532 nm: Comparison of a LED and a laser source.

Port-wine stain (PWS) birthmarks are congenital capillary malformations occurring in 0.3 %∼0.5 % of newborns. Hemoporfin-mediated vascular-acting photodynamic therapy (Hemoporfin PDT) is an emerging option for treating PWS. This in vivo study aimed to compare laser and light-emitting diodes (LED) as light source for Hemoporfin PDT. Chicken wattles were used as the animal model. Color and histopathological changes were evaluated after combining Hemoporfin with KTP laser or LED light source of 532 nm at the same doses. Both PDT approaches could induce significant vascular injury and color bleaching. Although the use of the laser resulted in a greater vascular clearance, the LED showed more uniform distribution both in the beam profiles and tissue reaction and exhibited better safety. This in vivo study suggests that the LED is a favorable choice for larger PWS lesion.

Hematoporphyrin monomethyl ether-mediated photodynamic therapy for acquired port-wine stain at lower extremity: Two case reports.

Two cases of acquired port-wine stain (APWS) at lower extremity were treated with hematoporphyrin monomethyl ether (HMME) and 532 nm LED green light-mediated photodynamic therapy (HMME-PDT). No serious adverse reactions were observed during or post-treatment period. Five-month follow-up showed significant reduction of red patches after a single HMME-PDT treatment in both cases.

Current clinical evidence is insufficient to support HMME-PDT as the first choice of treatment for young children with port wine birthmarks.

BACKGROUND: Port wine birthmark (PWB) is a congenital vascular malformation of the skin. Pulsed dye laser (PDL) is the "gold standard" for the treatment of PWB globally. Hematoporphyrin monomethyl ether (HMME or hemoporfin)-mediated photodynamic therapy (HMME-PDT) has emerged as the first choice for PWB treatment, particularly for young children, in many major hospitals in China during the past several decades. AIM: To evaluate whether HMME-PDT is superior to PDL by comparing the clinical efficacies of both modalities. METHOD: PubMed records were searched for all relevant studies of PWB treatment using PDL (1988-2023) or HMME-PDT (2007-2023). Patient characteristics and clinical efficacies were extracted. Studies with a quartile percentage clearance or similar scale were included. A mean color clearance index (CI) per study was calculated and compared among groups. An overall CI (C0), with data weighted by cohort size, was used to evaluate the final efficacy for each modality. RESULT: A total of 18 HMME-PDT studies with 3910 patients in China were eligible for inclusion in this analysis. Similarly, 40 PDL studies with 5094 patients from nine different countries were eligible for inclusion in this analysis. Over 58% of patients in the HMME-PDT studies were minors (<18 years old). A significant portion (21.3%) were young children (<3 years old). Similarly, 33.2% of patients in the PDL studies were minors. A small proportion (9.3%) was young children. The overall clearance rates for PDL were slightly, but not significantly, higher than those for HMME-PDT in cohorts with patients of all ages (C0, 0.54 vs. 0.48, p = 0.733), subpopulations with only minors (C0, 0.54 vs. 0.46, p = 0.714), and young children (C0, 0.67 vs. 0.50, p = 0.081). Regrettably, there was a lack of long-term data on follow-up evaluations for efficacy and impact of HMME-PDT on young children in general, and central nervous system development in particular, because their blood-brain barriers have a greater permeability as compared to adults. CONCLUSION: PDL shows overall albeit insignificantly higher clearance rates than HMME-PDT in patients of all ages; particularly statistical significance is nearly achieved in young children. Collectively, current evidence is insufficient to support HMME-PDT as the first choice of treatment of PWBs in young children given: (1) overall inferior efficacy as compared to PDL; (2) risk of off-target exposure to meningeal vasculature during the procedure; (3) administration of steriods for mitigation of side effects; -and (4) lack of long-term data on the potential impact of HMME on central nervous system development in young children.

Klippel-Trenaunay syndrome or not? An exploration of atypical presentations.

Klippel-Trenaunay syndrome (KTS) is a rare, congenital disorder typically emerging in early infancy or childhood. The classic presentation of KTS is distinguished by a triad of clinical features: a port-wine stain, early-onset varicosities and limb overgrowth. However, a notable variant of KTS has been documented, characterised by limb shortening rather than lengthening, occasionally referred to as 'inverse KTS'. This report details two cases that display this unusual presentation-both patients had classical features of port-wine stain and varicose veins but both experienced shortening of the affected limb. Whether these cases represent a variant of KTS or a new clinical syndrome altogether is uncertain. They however offer valuable insights into the nuances and breadth of clinical manifestations associated with this syndrome.

Lesion segmentation using 3D scan and deep learning for the evaluation of facial portwine stain birthmarks.

BACKGROUND: Portwine stain (PWS) birthmarks are congenital vascular malformations. The quantification of PWS area is an important step in lesion classification and treatment evaluation. AIMS: The aim of this study was to evaluate the combination of 3D scan with deep learning for automated PWS area quantization. MATERIALS AND METHODS: PWS color was measured using a portable spectrophotometer. PWS patches (29.26-45.82 cm2) of different color and shape were generated for 2D and 3D PWS model. 3D images were acquired by a handheld 3D scanner to create texture maps. For semantic segmentation, an improved DeepLabV3+ network was developed for PWS lesion extraction from texture mapping of 3D images. In order to achieve accurate extraction of lesion regions, the convolutional block attention module (CBAM) and DENSE were introduced and the network was trained under Ranger optimizer. The performance of different backbone networks for PWS lesion extraction were also compared. RESULTS: IDeepLabV3+ (Xception) showed the best results in PWS lesion extraction and area quantification. Its mean Intersection over Union (MIou) was 0.9797, Mean Pixel Accuracy (MPA) 0.9908, Accuracy 0.9989, Recall 0.9886 and F1-score 0.9897, respectively. In PWS area quantization, the mean value of the area error rate of this scheme was 2.61 ± 2.33. CONCLUSIONS: The new 3D method developed in this study was able to achieve accurate quantification of PWS lesion area and has potentials for clinical applications.

Macrocheilia as an Atypical Clinical Presentation of Capillary Malformation-Arteriovenous Malformation Type 2.

This case report describes a 53-year-old man with multiple erythematous macules and papules diffusely distributed on the frontal area, cheeks, eyelids, nose, and supralabial skin.

Pulsed dye laser and adjuvant topical therapies for the treatment of port-wine stains: A systematic review.

OBJECTIVES: The current gold standard treatment for port-wine stains (PWS) is pulsed dye laser (PDL). However, multiple treatment sessions may be necessary and complete resolution is often not achieved. Neoangiogenesis can occur soon after treatment and is thought to be a major factor contributing to treatment failure. Adjuvant antiangiogenic topical therapies may therefore improve the efficacy of pulsed dye laser treatment of port-wine stains. MATERIAL AND METHODS: Following PRISMA guidelines, we searched PubMed, Embase, Web of Science, and clinicaltrials.gov using "port-wine stain," "nevus flammeus," "capillary malformation," "sturge weber," and "pulsed dye laser" as keywords and medical subject heading (MeSH) terms. Articles were included if they (1) were a randomized controlled trial (RCT); (2) studied patients with PWS; and (3) investigated topical adjuvant therapies with PDL. Bias was assessed using the Critical Appraisal Skills Programme (CASP) Randomized Controlled Trial Standard Checklist. RESULTS: 1835 studies were identified, with six studies meeting inclusion criteria. The total number of patients studied was 103 (range: 9-23), with 8-36 week follow-up. The average age ranged from 11 to 33.5 years old. Three studies examined adjuvant topical sirolimus (n = 52), two examined timolol (n = 29), and one studied imiquimod (n = 22). Two of three RCTs reported no improvement through colorimetric analysis with topical sirolimus; however, one of these studies did show a significant improvement through Investigator Global Assessment (IGA) score. The last sirolimus study showed significant improvement through digital photographic image scoring (DPIA). Studies examining topical timolol reported no change in PWS appearance compared to placebo. The addition of 5% adjuvant imiquimod cream did lead to significant improvement. A variety of outcome measures were used. Imiquimod and sirolimus led to mild cutaneous adverse events, while timolol caused no side effects. None of the adverse events led to treatment discontinuation. Study quality was moderate in three, high in two, and low in one. CONCLUSION: The efficacy of adjuvant topical therapy was unclear. Limitations included variation in concentration and duration of adjuvant therapies, differences in follow-up time, and inconsistent outcome measure reporting. Given their potential clinical promise, larger prospective studies examining topical adjuvant therapies should be considered.