Noncoherent Red Light Research Articles

Pulsed Dye Laser Does Not Seem as Effective as Red Light in Basal Cell Carcinoma Mal-Pdt: A Small Pilot Study

Multiple light sources can be used for photodynamic therapy (PDT) with good results, but there are few comparative studies. This study compares the efficacy of treatment of basal cell carcinoma with PDT and two light sources, the non-coherent red light and pulsed dye laser 595 nm. In this small pilot study red light is more effective, but many more studies are needed to draw definitive conclusions.

Photodynamic therapy for a hypertrophic scarring: a promising choice

The case we report is about a female patient, 69 years old, who had a hypertrophic scarring on the right cheek because of a bite by her dog. She had attempted many types of topical and intralesional treatments but without success. The patient underwent photodynamic therapy (PDT), employing a methyl ester of 5-aminolevulinic acid (MAL) as topical photosensitizer and a non-coherent red light at a wavelength of 632 nm. This session was then repeated three more times at 2-week intervals. A month after the last session, the scarred area significantly softened, becoming more flexible, less erythematous, smoother and reduced in volume. The patient was greatly satisfied with the clinical and cosmetic result, she had no more than rough scarring on the cheek, and her skin in the area around the lesion was very smooth, wrinkle-free. She did not show any recurrence of her hypertrophic scarring after 1 year of follow-up. PDT revealed to be the most effective approach if compared with previous therapeutic options received by the patient, but further studies are necessary to evaluate protocols to be used for the best results in this kind of application.

The effect of noncoherent red light irradiation on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells

Mesenchymal stem cells (MSCs) are promising for use in regenerative medicine. Low-level light irradiation (LLLI) has been shown to modulate various processes in different biological systems. The aim of our study was to investigate the effect of red light emitted from a light-emitting diode (LED) on bone marrow MSCs with or without osteogenic supplements. MSCs both with and without osteogenic supplements were divided into four groups, and each group was irradiated at doses of 0, 1, 2 and 4J/cm(2). Cellular proliferation was evaluated using WST-8 and 5-ethynyl-2'-deoxyuridine (EdU) fluorescence staining. The alkaline phosphatase activity, mineralization, and expression of osteoblast master genes (Col1α1, Alpl, Bglap and Runx2) were monitored as indicators of MSC differentiation towards osteoblasts. In groups without osteogenic supplements, red light at all doses significantly stimulated cellular proliferation, whereas the osteogenic phenotype of the MSCs was not enhanced. In groups with osteogenic supplements, red light increased alkaline phosphatase activity and mineralized nodule formation, and stimulated the expression of Bglap and Runx2, but decreased cellular proliferation. In conclusion, nonconherent red light can promote proliferation but cannot induce osteogenic differentiation of MSCs in normal media, while it enhances osteogenic differentiation and decreases proliferation of MSCs in media with osteogenic supplements.

The effects of 620nm noncoherent red light irradiation on proliferation and osteogenic differentiation of rat osteoblasts

Objective To investigate the effects of 620nm noncoherent red light emitted from light-emitting diode (LED) on proliferation and osteogenic differentiation of rat osteoblasts.Methods Osteoblasts were isolated from SD rat and cultured in vitro.The LED was placed at 2cm above the cell layer.Cells were divided into four groups and each group was irradiated for 0s, 150s, 300s and 600s at energy dose of 0, 1, 2, and 4J/cm2, respectively.Cells were irradiated once every day.Cellular proliferation activities were evaluated by using cell counting kit-8 ( CCK-8 ) at 2nd and 4th d.The alkaline phosphatase (ALP) ratio activity was evaluated by alkaline phosphatase activity kit at the 9th d, and expressions of osteoblast master genes ( Collα1, Bglap and Runx2) were monitored as indicators of osteoblast differentiation by reverse transcription-polymerase chain reaction (RT-PCR) technique.Results In the group irradiated with 1 and 2 J/cm2 proliferation activities of osteoblasts enhanced significantly compared with the control group at the 4th d ( P < 0.05 ).In the group irradiated with 4 J/cm2 ALP ratio activity elevated significantly compared with the control group at the 9th d ( P <0.05 ).In the group of red light irradiation expressions of Bglap and Runx2 enhanced significantly.Conclusion The 620nm nonconherent red light emitted from LED can promote proliferation of osteoblasts and enhance osteogenic differentiation significantly. Key words: Osteoblast; Proliferation; Differentiation; Photobiomodulation

Photodynamic therapy: New treatment for recalcitrant Malassezia folliculitis

Malassezia folliculitis commonly has been treated with oral antifungal medications. However, it has many therapeutic weaknesses such as infection relapse, drug resistance, or adverse effects like hepatotoxicity and gastrointestinal discomfort. Hence, there remains an ongoing need for alternative treatments for recalcitrant Malassezia folliculitis. Recently, many dermatologists suggest photodynamic therapy (PDT) as an alternative therapeutic option for its antimicrobial effect. To investigate the efficacy of methyl 5-aminolevulinic acid (MAL)-PDT for the treatment of recalcitrant Malassezia folliculitis. Six Korean patients aged 23-47 years with recalcitrant Malassezia folliculitis were enrolled in this study. The patients enrolled in this study either refused oral medication or were unable to take oral antifungal agents due to hepatotoxicity concerns. Thus, we offered these patients MAL-PDT as an alternative treatment option. For all patients, photographs of the lesion(s) were taken prior to initiating treatment. MAL cream (Metvix, Galderma, France) was applied to each lesion (located on the patients' trunks) and covered with an adhesive occlusive dressing polyurethane film (Tegaderm, 3M Healthcare, St. Paul, MN). After 3 hours, the cream was wiped off and illumination was performed immediately thereafter with non-coherent red light using light-emitting diodes (Aktilite lamp, PhotoCure, Oslo, Norway, average wavelength 630 nm, light dose 37 J/cm(2)). Illumination was performed for 7.5 minutes. Patients underwent totally three sessions of MAL-PDT at 2-week intervals. One month after the last PDT treatment, patients returned to the hospital and lesions were photographed. After three sessions of MAL-PDT, inflammatory lesions had decreased and improved obviously in four patients, had improved slightly in one patient, and had not improved in one patient. MAL-PDT may be an effective treatment option for patients with recalcitrant Malassezia folliculitis. However, the data on MAL-PDT are still limited, and additional controlled trials including multiple patients will be necessary to verify the results of this pilot study.

Photodynamic therapy for methicillin‐resistant Staphylococcus aureus infection in a mouse skin abrasion model

Methicillin-resistant Staphylococcus aureus (MRSA) skin infections are now known to be a common and important problem in the Unites States. The objective of this study was to investigate the efficacy of photodynamic therapy (PDT) for the treatment of MRSA infection in skin abrasion wounds using a mouse model. A mouse model of skin abrasion wound infected with MRSA was developed. Bioluminescent strain of MRSA, a derivative of ATCC 33591, was used to allow the real-time monitoring of the extent of infection in mouse wounds. PDT was performed with the combination of a polyethylenimine (PEI)-ce6 photosensitizer (PS) and non-coherent red light. In vivo fluorescence imaging was carried out to evaluate the effect of photobleaching of PS during PDT. In vivo fluorescence imaging of conjugate PEI-ce6 applied in mice indicated the photobleaching effect of the PS during PDT. PDT induced on average 2.7 log(10) of inactivation of MRSA as judged by loss of bioluminescence in mouse skin abrasion wounds and accelerated the wound healing on average by 8.6 days in comparison to the untreated infected wounds. Photobleaching of PS in the wound was overcome by adding the PS solution in aliquots. PDT may represent an alternative approach for the treatment of MRSA skin infections.

Topical Methyl Aminolevulinate Photodynamic Therapy Using Red Light-Emitting Diode Light for Multiple Actinic Keratoses

Photodynamic therapy (PDT) is an effective treatment for actinic keratoses (AKs). Light-emitting diodes (LEDs) offer practical advantages when treating multiple lesions. To evaluate the efficacy and tolerability of PDT using a LED and topical methyl aminolevulinate (MAL) for treatment of multiple AKs. One hundred thirty-one patients with four to 10 non-pigmented, previously untreated thin or moderately thick AKs on the face or scalp were enrolled in this multicenter, double-blind, randomized, placebo-controlled study. MAL or matching placebo cream was applied to the débrided lesion surface for 3 hours before illumination with noncoherent red light (630 nm, light dose 37 J/cm(2)). Treatment was repeated 1 week later. Efficacy was evaluated in 57 patients with 418 lesions treated with MAL PDT and 58 with 414 lesions treated with placebo PDT. Sixteen patients were excluded as protocol violators (not randomized). MAL PDT was superior (p< .001) to placebo PDT in lesion complete response rates (83.3%, 95% confidence interval (CI)=79.3-86.7%, vs 28.7%, 95% CI=24.4-33.4%) and patient complete response rates (all lesions showing complete response; 68.4%, 95% CI=54.8-80.1% vs 6.9%, 95% CI=1.9-16.7%). Topical MAL PDT using a LED is an effective treatment for multiple AKs.

Photodynamic Therapy With Methyl Aminolevulinate for Prevention of New Skin Lesions in Transplant Recipients: A Randomized Study

Organ transplant recipients on long-term immunosuppressive therapy are at increased risk of non-melanoma skin lesions. Repeated field photodynamic therapy using topical methyl aminolevulinate (MAL) may have potential as a preventive treatment. This open randomized, intrapatient, comparative, multicenter study included 81 transplant recipients with 889 lesions (90% actinic keratoses (AK)]. In each patient, the study treatment was initially administered to one 50 cm area on the face, scalp, neck, trunk, or extremities (n=476 lesions) twice (1 week apart), with additional single treatments at 3, 9, and 15 months. On each occasion, the area was debrided gently and MAL cream (160 mg/g) applied for 3 hr, before illumination with noncoherent red light (630 nm, 37 J/cm2). The control, 50 cm2 area (n=413 lesions) received lesion-specific treatment (83% cryotherapy) at baseline and 3, 9, and 15 months. Additionally, all visible lesions were given lesion-specific treatment 21 and 27 months in both treatment and control areas. At 3 months, MAL photodynamic therapy significantly reduced the occurrence of new lesions (65 vs. 103 lesions in the control area; P=0.01), mainly AK (46% reduction; 43 vs. 80; P=0.006). This effect was not significant at 27 months (253 vs. 312; P=0.06). Hypopigmentation, as assessed by the investigator, was less evident in the treatment than control areas (16% vs. 51% of patients; P<0.001) at 27 months. Our results suggest that repeated field photodynamic therapy using topical MAL may prevent new AK in transplant recipients although further studies are needed.

Genital Warts Treated By Photodynamic Therapy

The patient, a 30-year-old man with numerous genital condylomata acuminata (CA), has had unsuccessful treatment with liquid nitrogen, 20% podophyllin, and repeated 0.5% podophyllotoxin solution with 5% imiquimod (Figure 1). Before the appearance of CA, he experienced acute orchiepididimitis and a Candida infection. The patient was immunologically examined, and the lower level of lymphocytes, slightly reduced level of IgM, and C4 complement were revealed. Results from a human immunodeficiency virus examination were negative. After the therapeutic failure mentioned above, photodynamic therapy (PDT) was initiated using 20% aminolevulinic acid (5-ALA) in a gel. The photosensitizer was applied to lesions and 10 mm of surrounding skin in a 1-mm-thick layer under occlusive dressing for 3 hours and then removed with saline and nonwoven gauze. The site was immediately irradiated with noncoherent red light with an emission spectrum of 580 to 680 nm wavelength (Medeikonos PDT-Model 200, Medeikonos AB, Sweden). The total light dose was 50 J/cm(2); light intensity ranged from 70 to 90 mW/cm(2). Because of persistent fluorescence during photodynamic therapy, the treatment was repeated 10 times in 2-week intervals with a follow-up of 1, 3, and 6 months after its completion. After the last PDT treatment, the persistent fluorescence disappeared completely. The absence of fluorescence corresponded with a healed clinical finding without scarring and pigmentation (Figure 2). The period from the initiation of PDT to the consolidation of CA was 22 weeks. During PDT treatment, the patient felt only mild burning, which disappeared after the illumination stopped. Six months after the therapy, there were no signs of recurrent disease.

Topical photodynamic therapy for prevention of new skin lesions in renal transplant recipients

Preclinical data suggest that topical methyl aminolevulinate photodynamic therapy may have potential in preventing new skin lesions in transplant recipients. An open intra-patient randomized study investigated the prevention potential of this treatment in 27 renal transplant patients with actinic keratoses and other skin lesions in two circular contralateral areas (5 cm diameter). The treatment area surface was debrided and methyl aminolevulinate cream (160 mg/g) was applied for 3 h prior to illumination by non-coherent red light (570-670 nm, light dose 75 J/cm2). The control area was not treated. The mean time to occurrence of the first new lesion was significantly longer in treated than control areas (9.6 vs 6.8 months, treatment difference 2.9 [95% confidence interval 0.2 to 5.5] months, p = 0.034). Over 12 months, 62% (16/26) of treated areas were free from new lesions compared with 35% (9/26) in control areas. These findings indicate that topical methyl aminolevulinate photodynamic therapy is a promising preventive treatment against new skin lesions in immunosuppressed patients.

Photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: Results of a prospective randomized multicenter trial

Background: Photodynamic therapy (PDT) is a promising new treatment modality for actinic keratoses. Methyl aminolevulinate (MAL) (Metvix, PhotoCure, Oslo, Norway) leads to selective accumulation of photoactive porphyrins in premalignant skin lesions and makes the lesions susceptible to phototoxic effects on illumination with red light. Objective: This multicenter, randomized, double-blind study compared complete response rates, cosmetic outcome, and patient satisfaction for PDT with cream containing 160 mg/g MAL or placebo cream in the treatment of actinic keratoses. Methods: After application of the cream under occlusion for 3 hours, the lesions were illuminated by noncoherent red light (570-670 nm, light dose 75 J/cm 2). Treatment was repeated after 1 week and response was assessed 3 months later. A total of 80 patients were randomized into the study, 42 in the active and 38 in the placebo group. Results: Complete lesion response rate was higher after MAL PDT than placebo, 89% versus 38% per protocol analysis ( P = .001). An excellent or good cosmetic outcome was reported in more than 90% of patients treated with MAL. Conclusion: In this small study, PDT using topical MAL was a safe and effective treatment for actinic keratoses with excellent cosmetic outcome. It is a promising treatment that could benefit from further study. (J Am Acad Dermatol 2003;48:227-32.)

Porphyrin-sensitized phototreatment as a conservative therapy in gynaecological oncology

Three patients having neoplastic lesions of the lower genital tract were treated by photodynamic therapy, using haematoporphyrin IX hydrochloride as sensitizer and a non-coherent red light. Irradiations were performed at 12, 24, 48 and 72 h from dye injection for 15 min at a fluence of 0.6 W/cm2. The successful outcome of the therapy and the prospects for photodynamic therapy in gynaecological oncology are discussed.

Hematoporphyrin Derivative Photochemotherapy of Experimental Bladder Tumors

Recent studies have shown that disruption of tumor blood flow is a major consequence of hematoporphyrin derivative photochemotherapy. A series of experiments was undertaken on the transplantable N-(4-(5-nitro-2-furyl)-2-thiazolyl)-formamide induced urothelial tumor in Fischer 344 rats to determine a dose response for both hematoporphyrin derivative and light. Tumor blood flow was used as the biologic criteria of response. Hematoporphyrin derivative doses of 10μg./gm. body weight or above were necessary to cause a significant decrease in tumor blood flow when the tumors were illuminated with 360joules/cm.2 of noncoherent red light (>590nm.). With a constant hematoporphyrin derivative dose of 20μg./gm. body weight, significantly lower tumor blood flows were observed with fluences of 240joules/cm.2 and above.In order to correlate dose response to tumor regression, experiments were done in which tumor dry weights were determined 3 weeks after completion of photochemotherapy (360joules/cm.2). Hematoporphyrin derivative doses of 10μg./gm. body weight or above were necessary to induce tumor regression. These studies support the hypothesis that disruption of tumor blood flow is a tumoricidal mechanism of hematoporphyrin derivative photochemotherapy.