Hematoporphyrin Monomethyl Ether Photodynamic Therapy Research Articles

Recent progress in hematoporphyrin monomethyl ether-photodynamic therapy for port-wine stains: updates and insights.

Port-wine stains (PWS) are congenital vascular malformations characterized by capillary malformations that persist and often darken over time. Traditional treatment methods, including laser therapy, have shown varying degrees of effectiveness and can be associated with significant side effects. Hematoporphyrin Monomethyl Ether-Photodynamic Therapy (HMME-PDT) has emerged as a promising alternative, offering targeted treatment with potentially fewer adverse effects. This paper aims to evaluate the clinical efficacy and potential of HMME-PDT as a treatment strategy for PWS. It provides a comprehensive review of the literature and clinical investigations to assess the application and outcomes of HMME-PDT in treating PWS. Briefly introduce the nature of PWS, innovations and challenges in treatment, the mechanism of HMME-PDT, clinical effectiveness and sonographic appearance, safety and long-term effects, and challenges and suggestions for optimizing treatment. The review highlights the mechanism by which HMME-PDT works, focusing on its ability to target abnormal blood vessels selectively. Clinical evaluations included clinical and sonographic assessments to determine the efficacy of the treatment. The findings revealed significant improvements in the clinical appearance and sonographic features of vascular lesions following HMME-PDT. The paper also discusses the utility of dermoscopy in HMME-PDT applications, factors affecting treatment efficacy, the impact of thermal assistance on the effectiveness of PDT, and the management of adverse reactions through proper nursing care. The review underscores the considerable potential of HMME-PDT as an effective treatment for PWS, noting its promising outcomes in clinical and sonographic assessments. However, it also emphasizes the need for further research to standardize treatment protocols and assess long-term outcomes.

Clinical efficacy and safety of two different hematoporphyrin monomethyl ether-mediated photodynamic therapy regimen in Chinese children with port-wine stain.

Hematoporphyrin monomethyl ether-photodynamic therapy (HMME-PDT) has achieved encouraging clinical outcomes in adult port-wine stain (PWS). Optimal treatment option for children with PWS was minimal. To compare whether the clinical effectiveness of HMME-PDT with the 5-min (fast) administration treatment regimen (FATR) was better than the 20-min (slow) administration treatment regimen (SATR) for PWS of children in vivo and in vitro. Thirty-four children with PWS were divided into two groups including FATR and SATR. The two groups received three times HMME-PDT, respectively. Treatment efficacy and safety were evaluated in vivo and in vitro. Erythema index (EI) was used to evaluate the clinical outcomes. Both FATR and SATR were effective and safe in children with PWS after HMME-PDT. There were significance differences between the two groups in reductions of EI after the second treatment (p < 0.001) and the third treatment (p < 0.001) with HMME-PDT. The serum HMME concentration reach the peak level at short time compare with SATR group. A significance increased superoxide levels were observed in FATR group compare to SATR groups in vitro (p < 0.05). Our study suggested that HMME-PDT was effective and safe for children with PWS, the therapy regimen with FATR was better in clinical efficacy than that of the SATR.

Hematoporphyrin Monomethyl Ether Photodynamic Therapy of Port Wine Stain: Narrative Review.

Port wine stain (PWS) is a congenital and progressive capillary malformation characterized by structural abnormalities of intradermal capillaries and postcapillary venules. The visible manifestation is often considered a disfigurement and the accompanying social stigma often causes serious emotional and physical impact. Hematoporphyrin monomethyl ether (HMME) is a newly authorized photosensitizer for treating PWS in China. Hematoporphyrin monomethyl ether photodynamic therapy (HMME-PDT) has successfully treated thousands of Chinese patients with PWS since 2017, and HMME-PDT may be one of the most promising strategies for the treatment of PWS. However, there are few reviews published about the clinical use of HMME-PDT. So in this article, we want to briefly review the mechanism, efficacy evaluation, effectiveness and influencing factors, and the common postoperative reactions and treatment suggestions of HMME-PDT in the treatment of PWS.

The Relationship Between the Effectiveness of HMME-PDT and the Dermoscopic Features of Port-wine Stains in Chinese Pediatric Patients: A Retrospective Study.

IntroductionAlthough pulsed dye laser (PDL) remains the gold standard for the treatment of port-wine stains (PWS), hematoporphyrin monomethyl ether photodynamic therapy (HMME-PDT) is another treatment modality that has been shown to be effective in the treatment of PWS. This study aimed to observe the clinical efficacy and therapeutic response of HMME-PDT in the treatment of pediatric Chinese patients with PWS and to analyze the association between the efficacy of therapy and the dermoscopic features of PWS.MethodsPediatric patients with PWS and negative HMME skin test were enrolled between December 2017 and May 2021. Patients received an intravenous injection of 5 mg/kg HMME, and lesions were irradiated with 532-nm LED green light with a power density of 70–80 mW/cm2 for 20–25 min. Digital photographs and dermoscopic images were taken before and after two treatment sessions, and the clinical response was observed. The relationship between the efficacy of HMME-PDT and the dermoscopic features of PWS was retrospectively analyzed.ResultsA total of 216 pediatric patients (1–14 years) were recruited. Sixty-six patients had the pink type, while 150 had the purple type. After two HMME-PDT sessions, 55 patients showed excellent efficacy (25.46%), 77 patients showed good efficacy (35.65%), 69 patients showed fair efficacy (31.94%), and 15 patients showed no improvement (6.95%). Dotted and globular vessels were highly associated with excellent efficacy (41.82%); linear vessels were mainly associated with good efficacy (54.55%); reticular vessels were mainly associated with fair (55.07%) and mixed vessels were mainly associated with no improvement (26.66%).ConclusionHMME-PDT is an effective and safe treatment for pediatric patients with PWS. Dotted and globular vessels as well as linear vessels showed better efficacy compared to the other dermoscopic patterns in patients with PWS. Dermoscopy can provide useful clinical information about treatment outcomes.

The Efficacy of Hematoporphyrin Monomethyl Ether Photodynamic Therapy in Adult Patients with Port-Wine Stains: A Retrospective Study.

IntroductionHematoporphyrin monomethyl ether-photodynamic therapy (HMME-PDT) has been showing promising results in the treatment of port-wine stains (PWSs). We evaluated the clinical efficacy and treatment response of HMME-PDT in adult Chinese patients with PWSs.MethodsA single-center retrospective study recruited adult PWS patients with negative HMME skin test results from December 2017 to May 2020. Patients received an intravenous injection of 5 mg/kg HMME and the lesions were exposed to 532 nm LED green light with an irradiation power density of 85–95 mW/cm2 for 20–25 min. Digital photographs were taken before and after two therapy sessions and observed by three blinded dermatologists for clinical response.ResultsA total of 72 patients aged between 18 and 55 years were recruited. There were 65 patients of the flat purple type, 5 of the hypertrophic type, and 2 of the nodular thickening type. Of the 65 patients, 7 showed excellent efficacy (10.77%), 13 patients indicated good efficacy (20.00%), 47 patients showed fair efficacy (64.62%), while 3 cases displayed no improvement (4.62%). All five patients of the purple and hypertrophic type showed fair efficacy (100%), and no improvement was observed in patients of the nodular thickening type (100%). Pain, pruritus, and a burning sensation were observed during treatment. Edema was noted on the treated areas post-treatment. No other obvious systemic adverse reactions were observed. ConclusionHMME-PDT is an effective and safe treatment for adult patients with purple PWSs. Multiple HMME-PDT treatments can improve the response and cure rate.

Hematoporphyrin monomethyl ether photodynamic therapy for the treatment of Sturge-Weber syndrome and large segmental facial port-wine stain.

Hematoporphyrin monomethyl ether (HMME) is a newly authorized photosensitizer for the treatment of port-wine stain (PWS) in China. However, no research on its efficacy for treating PWS lesions of Sturge-Weber syndrome (SWS) has been made. To assess the efficacy and safety of HMME-photodynamic therapy (PDT) in the treatment of SWS and simple large segmental facial PWS. Medical records of patients with SWS and large segmental facial PWS were reviewed. Efficacy was evaluated according to color blanching and graded as excellent (≥75%), good (50%-74%), fair (25%-49%), and poor (≤24%). Adverse events were analyzed. Nineteen patients with SWS and 33 patients with large segmental facial PWS were analyzed. 52.6% SWS and 69.7% PWS patients (p> .05) achieved at least 25% improvement. Common adverse events included short-term pain, edema, pruritus, exudation, and scab. No severe adverse event occurred. HMME-PDT was effective and safe for SWS and large segmental facial PWS.

Comparing HMME-PDT and Cynergy dual-wavelength laser in the treatment of facial PWS

BackgroundPulsed dye laser (PDL) is the gold-standard therapy for port-wine stains (PWSs), but the therapeutic efficacies vary widely with each individual. Recent studies suggest that hematoporphyrin monomethyl ether-photodynamic therapy (HMME-PDT) is an effective alternative in the treatment of PWS. This retrospective study aimed to compare the effects of HMME-PDT and Cynergy dual-wavelength laser on red and purple color types of PWS MethodsThis retrospective study included 38 PWS patients who received Cynergy dual-wavelength laser treatment (PDL group) and 39 PWS patients who received HMME-PDT treatment (HMME-PDT group). Patients in each group received two treatments. The curative effect of purple or red PWS in two groups was analyzed. ResultsAfter the first treatment, the total significant response rate and the total response rate of the HMME-PDT group were 43.59% and 74.36%, which were significantly higher than those of the PDL group (5.26% and 47.36%) (P < 0.05). After the second treatment, the total significant response rate and the total response rate of the HMME-PDT group were 69.23% and 100%, which were obviously higher than those of the PDL group (34.21% and 68.42%) (P < 0.05). For both groups, the total significant response rate of purple-type PWS was remarkably higher than that of red-type PWS (the HMME-PDT group: P = 0.004; the PDL group: P = 0.048). There was no obvious difference in terms of patient age and PWS location between the HMME-PDT and PDL groups. Furthermore, there was no considerable difference in the incidence of adverse reactions between the two groups (P > 0.05). ConclusionThe single-center retrospective study suggested that HMME-PDT might have better efficacies on purple and red PWS than PDL treatment. The total treatment efficacy was greater in purple-type PWS than in red-type PWS.

Hematoporphyrin monomethyl ether photodynamic therapy for the treatment of facial port-wine stains resistant to pulsed dye laser.

Pulsed dye laser is the first treatment choice for port-wine stains. However, as some facial port-wine stains are resistant to this modality, we evaluated the efficacy and safety of hematoporphyrin monomethyl ether (hemoporfin) photodynamic therapy for the treatment of such resistant port-wine stains. Patients were treated with two sessions of hemoporfin photodynamic therapy in our department. Patients received an intravenous injection of hematoporphyrin monomethyl ether (5 mg/kg) followed by 532 nm LED green light therapy. Three physicians graded the improvement in the port-wine stain, using a 4-level scale. Patients' satisfaction, reaction to treatment, and adverse effects were evaluated. Thirty-one patients (mean age, 23.9 ± 11.9 years, range, 3-48 years) were enrolled in this study. Hypertrophic lesions accounted for 48.4% of port-wine stain, with 80.6% of lesions being larger than 40 cm2. With regard to location, 41.9% were located on the central face and 32.3% involved a mix of the central and peripheral face. After one session, a treatment response was identified in 87.1% of cases, with the response deemed 'significant' in 29.0%. After two sessions, these rates increased to 100.0% and 61.3%, respectively. The clinical effect after two sessions was significantly greater than that after one session. Treatment reactions and adverse effects were well tolerated, and included pruritus, burning sensation, pain, edema, purpura-like change, blister, crust, and hyperpigmentation. Hemoporfin photodynamic therapy is a promising treatment for port-wine stains resistant to pulsed dye laser therapy.

Efficacy and related factors analysis in HMME-PDT in the treatment of port wine stains.

To observe the efficiency and safety of hematoporphyrin mono-methylether photodynamic therapy (HMME-PDT) in treating port-wine stains (PWS) with Chinese patients, and to evaluate the advantage of photograph,VISIA Complexion Analysis System, and dermoscopy in efficacy evaluation.Analyzing changes of pain during treatment and related adverse reactions. 62 patients were treated in our department during2017-2019 with HMME-PDT, among which, 20 cases were pink type, 32 cases were purple type and remain 11 cases were nodular thickening type. Initially, all patients received an intravenous injection of 5 mg/kg HMME, and then the lesion areas of the patients were exposed to 532 nm LED green light after 10 min. The irradiation power density was range between 80-100 mW/cm2. By utilization of photograph,VISIA system, and dermoscopy to evaluate the clearance after treatments, and then informing the patients to value the pain level during the treatment via visual analogue scale(VAS), and recording the adverse reactions. After 2 times treatments, 11 of the 62 cases were cured (17.74 %), 17 cases showed a good efficacy (27.42 %), 20 cases indicated alleviation (32.26 %), while 14 cases displayed no efficacy (22.58 %).By observation, The VISIA system combined with image analysis software is an excellent technique in assessing efficacy. Dermoscopy helps to classify PWS types.It showed that the pain level each patient could endure was distinct, and it's remarkable that when receiving consecutive 12.09 ± 3.74 min of treatment, most of patients have showed severe pain.Patients with severe pain except young children who couldn't value the pain, had better efficacy.The side effects after treatment mainly displayed with edema, crust, hyperpigmentation. No recurrence within 2 years. It shows that after treating with HMME-PDTt efficacy is remarkable, with advantage of safety and fewer side effects. HMME_PDT should undergo further research and promotion. VISIA system combined with image analysis software and dermoscopy are excellent techniques for evaluating efficacy.

Comparison of Two Generation Photosensitizers of PsD-007 and Hematoporphyrin Monomethyl Ether Photodynamic Therapy for Treatment of Port-Wine Stain: A Retrospective Study

Objective: To compare the efficacy and safety of the two generation photosensitizers, PsD-007 and hematoporphyrin monomethyl ether (HMME), for photodynamic therapy (PDT) of port-wine stain (PWS). Background: Vascular-targeted PDT has shown potentially beneficial results in treating PWS; however, the efficacy and safety of various photosensitizers have not been fully investigated. Materials and methods: We retrospectively analyzed 38 patients with PWS, who were treated with one session of PsD-007-mediated (n = 21) or HMME-mediated (n = 17) PDT. Clinical efficacy was assessed by a chromameter and visual assessment of color blanching of the PWS lesion. Adverse events were evaluated. Results: Neither visual nor chromameter optical evaluations showed significant differences between the PsD-007 and HMME groups (p = 0.337 and p = 0.191, respectively). The total response rate was 76.2% (n = 16) in the PsD-007 group and 88.2% (n = 15) in the HMME group. Good or excellent clearance was achieved in 42.9% patients in the PsD-007 group and 29.4% patients in the HMME group. The average ΔE (color expressed change or improvement) and mean blanching rate measured optically were higher in the PsD-007 group than in the HMME group without statistical differences (8.51 vs. 7.39, p = 0.649; 0.37 vs. 0.29, p = 0.191). Incidences of swelling, pruritus, scab formation, and other adverse reactions were similar for the two groups. There were no blisters, scarring, or hypopigmentation in either group. Conclusions: Both PsD-007- and HMME-mediated PDTs are effective and safe for treatment of PWS. However, HMME has a shorter photosensitivity period than does PsD-007, which might be more recommended.

Application of different noninvasive diagnostic techniques used in HMME-PDT in the treatment of port wine stains.

Hematoporphyrin monomethyl ether photodynamic therapy (HMME-PDT) is an effective method for treating port wine stains (PWS). However, methods to evaluate the treatment of HMME-PDT for PWS effectively and objectively are lacking. This study aimed to describe the different noninvasive diagnostic techniques used in the evaluation of treatment response to HMME-PDT for PWS. Thirty-one lesions of 22 patients with PWS were treated with HMME-PDT. Four noninvasive diagnostic techniques including VISIA-CR™ system, dermoscopy, high-frequency ultrasound (HFUS), and laser speckle contrast imaging (LSCI) were used to obtain standard radiographic data on skin color, skin thickness, blood vessel morphology, blood vessel distribution, and blood perfusion from lesions and surrounding normal skin before and after HMME-PDT. The standard image pattern of VISIA-CR™ system showed color change in the lesions of PWS after HMME-PDT. RBX red image of VISIA-CR™ system showed that erythema was highly aggregated even in invisible lesions at baseline but decreased after HMME-PDT. The erythema index reduced value d was related to the efficacy rating (γ = 0.631, P < 0.05). Dermoscopy showed that the number of spot-like and irregular linear vessels increased, which was correlated with the increase in clinical classification. After HMME-PDT, vascular rupture was observed by dermoscopy. The response rate of lesions with vascular rupture was 100.00% (20/20). Moreover, the response rate of lesions without vascular rupture was 63.64% (7/11). Vascular rupture sign was correlated with better efficacy (P < 0.05). HFUS showed that the dermis of PWS thickened and was arranged loosely with scattered linear hypoechoic signal. After HMME-PDT, the dermal layer of the lesions became thinner with a decreased linear hypoechoic signal. The response rate of the lesions with linear hypoechoic signal was 76.92% (10/13), and that without linear hypoechoic signal was 94.44% (17/18). The lesions without linear hypoechoic signal in the dermis showed better efficacy (P < 0.05). In some lesions, LSCI showed high blood perfusion signal in PWS lesions and blood perfusion reduction after HMME-PDT. VISIA-CR™ system can be used to observe not only visible but also invisible lesions of PWS. Moreover, lesions fading after HMME-PDT can be described objectively by VISIA-CR™ system. Dermoscopy played an important role in the clinical classification of PWS, including assessing vascular injury after HMME-PDT, guiding the adjustment of therapeutic dose, and selecting the end point of treatment. Both HFUS and LSCI can be used to assist treatment response evaluation of HMME-PDT.

Retinal injury thresholds for 532, 578, and 630 nm lasers in connection to photodynamic therapy for choroidal neovascularization

The purpose of this study was to explore the retinal injury thresholds in rabbits and evaluate the influence of retinal pigmentation on threshold irradiance at laser wavelengths of 532, 578, and 630 nm which might be involved in hypocrellin B (HB) and hematoporphyrin monomethyl ether (HMME) photodynamic therapy (PDT) for choroidal neovascularization (CNV). The eyes of pigmented and non-pigmented rabbits were exposed to 532, 578, and 630 nm lasers coupled to a slit lamp biological microscope. The exposure duration was 100 seconds and the retinal spot size was 2 mm throughout the experiment. The minimum visible lesions were detected by funduscopy at 1 and 24 hours post exposure. Bliss probit analysis was performed to determine the ED50 thresholds, fiducial limits and probit slope. In pigmented rabbits, the 24-hour retinal threshold irradiances at 532, 578, and 630 nm were 1,003, 1,475, and 1,720 mW/cm(2) , respectively. In non-pigmented rabbits, the 24-hour threshold irradiances were 1,657, 1,865, and 15,360 mW/cm(2) , respectively. The ED50 for 24-hour observation differed very little from the ED50 for 1-hour observation. The non-pigmented rabbits required a ninefold increase in threshold irradiance at 630 nm comparing to the pigmented rabbits. This study will contribute to the knowledge base for the limits of laser irradiance in application of HB or HMME PDT for CNV.

Antibacterial efficacy of HMME-PDT on Enterococcus faecalis within infected simulated lateral canals in vitro model with different energy

Objective The purpose of this study was to assess the antibacterial effects of hematoporphyrin monomethylether-photodynamic therapy (HMME-PDT) on Enterococcus faecalis within infected simulated lateral canals in vitro with different energy.Methods Simulated lateral canals were prepared on extracted teeth.The specimens were infected with Enterococcus faecalis and then were randomly divided into eight groups.Group A was considered as negative control,its specimens were irrigated with physiological saline.Group B was the positive control,they were irrigated with 5.25％ NaClO.Other groups were incubated with HMME at concentration of 40 μg/ml for 5 min,followed by exposure to light at 532 nm for 120 s with different powers in a spiral pattern.Groups were named C-H,in corresponding with the power 50,60,70,80,90,100 mW.Microbial samples (the dentin chips from simulated lateral canals) were taken before and after the treatments.The survival fractions in each simulated lateral canal was calculated by counting colony-forming units(CFUs).Results 1.The HMME-PDT-treated groups resulted in a significant reduction in the number of E.faecalis in simulated lateral canals compared with the negative controls(P＜0.05).2.The antibacterial effects of group D、E、F、G、H were higher than the NaCl0-irrigated group(P＜0.05).3.The difference of antibacterial effects between the F、G、H groups was in significant(P＞0.05).Conclusion HMME-PDT had significant inhibitive efficacy on Enterococcus faecalis within infected simulated lateral canals and the efficacy was power-depended.It can play the best effect with the power of 80 mW. Key words: Hematoporphyrin monomethylether; Photodynamic therapy; Enterococcus faecalis; Lateral canals

Effects of Photodynamic Therapy Using Hematoporphyrin Monomethyl Ether on Experimental Choroidal Neovascularization

Hematoporphyrin monomethyl ether (HMME) is a novel and promising second-generation porphyrin-related photosensitizer for photodynamic therapy (PDT). To study the effects of HMME PDT on choroidal neovascularization (CNV) in rats, the PDT was performed 20 min after HMME bolus injection, which was investigated prior to the PDT by fluorescence microscopy with laser-induced CNV, and delivered at an irradiance of 400, 600 and 1000 mW cm(-2) corresponding to a fluence of 36, 54, 90 J cm(-2) in PDT plan I (15 mg kg(-1) HMME). In PDT plan II (30 mg kg(-1) HMME), the laser had a constant irradiance of 600 mW cm(-2), which was delivered for 60, 90 or 150 s, to also achieve total energy doses of 36, 54 or 90 J cm(-2). CNV closure rates assessed by fluorescein angiography and histologic damage to treated areas of choroid and retina varied as a function of the dose of HMME and of the activating light energy fluence. Endothelial cell labeled by platelet/endothelial cell adhesion molecule-1 presented treated CNV lesions that were significantly reduced in size (P < 0.01). It can be concluded that PDT using HMME can effectively occlude CNV. HMME is a potentially useful photosensitizer for the reduction in CNV size of irradiated areas.