Porphyrin biodistribution in UV-exposed murine skin after methyl- and hexyl-aminolevulinate incubation

Topical photodynamic therapy (PDT) with methyl-aminolevulinate (MAL) is a well-established treatment for precancerous skin lesions and non-melanoma skin cancer. Treatment outcomes are less effective for thick than for superficial lesions, which are presumed to be due to insufficient PpIX biodistribution in tumour tissue. Hexyl-aminolevulinate (HAL) is a more lipophilic photosensitizer precursor than MAL and may penetrate the skin to a greater depth and more homogeneously. We compared HAL- and MAL-induced PpIX accumulation in specific skin compartments using concentrations of 2%, 6% and 20% HAL and MAL on long-term UV-irradiated mouse skin. Furthermore, 20% HAL and 20% MAL were applied to non-irradiated skin. Porphyrin fluorescence was measured by fluorescence microscopy in selected skin regions: the epidermis, superficial dermis, deep dermis and sebaceous gland epithelium down to a depth of 1 mm. We found higher PpIX fluorescence intensities in epidermis and sebaceous gland epithelium from 2%, 6% and 20% HAL (median 72-104 au) than in corresponding concentrations of MAL (median 35-69 au) (P < 0.01). Fluorescence intensities in the superficial (35 au) and deep dermis (32 au) were similar for HAL and MAL (P = 0.51) and lower than epidermal fluorescence intensities (P < 0.001). Significantly, higher median PpIX fluorescence intensities (64 au) were found in 20% MAL-incubated skin irradiated with UV than in non-irradiated skin (48 au) (P < 0.001). HAL-induced fluorescence intensities did not depend on UV exposure (HAL 20%, UV: 72 au, non-UV: 70 au) (P = 0.87). In conclusion, HAL express high affinity for epidermis and sebaceous gland epithelium, and MAL for actinically damaged skin, which raises future perspectives for improved selectivity in PDT.     

Photodynamic therapy with topical methyl‐ and hexylaminolevulinate for prophylaxis and treatment of UV‐induced SCC in hairless mice

Please cite this paper as: Photodynamic therapy with topical methyl‐ and hexylaminolevulinate for prophylaxis and treatment of UV‐induced SCC in hairless mice. Experimental Dermatology 2010; 19 : e166–e172. Abstract Background: Hexyl aminolevulinate (HAL) is a long‐chained 5‐aminolevulinic acid‐ester that has been proposed as a novel photosensitizing agent to methyl aminolevulinate (MAL) in topical photodynamic therapy (PDT). The more lipophilic HAL, may improve treatment outcome for non‐melanoma skin cancer. Objective: To compare the prophylactic and therapeutic effects of HAL‐ and MAL‐PDT for ultraviolet‐induced squamous cell carcinomas (SCCs) in hairless mice. Methods: Mice (n = 249) were irradiated with solar UV‐radiation (UVR) until SCC occurred. Before any skin changes developed, two prophylactic PDT treatments were given, using creams of HAL (2%, 6%, 20%) or MAL (20%) followed by illumination (632 nm, Aktilite, Photocure). Two therapeutic PDT‐treatments were given by randomization to the first developed SCC of 1 mm. Primary end‐points were time to first SCC of 1 mm and complete SCC clearance. Secondary end‐points were time to SCC‐recurrence, PpIX fluorescence and skin reactions to PDT. Results: The median time to first SCC was significantly longer for mice treated with prophylactic HAL‐PDT (2%, 6% and 20% HAL, 264 days) and MAL‐PDT (20% MAL, 269 days) than mice exposed to UVR (186 days) and UVR + placebo‐PDT (199 days) (P < 0.0001). The therapeutic efficacy of HAL‐ and MAL‐PDT showed cure rates of 23–61.5% (P = 0.11). Similar PpIX fluorescence intensity and severity of clinical reactions were seen for HAL‐ and MAL‐groups, although mice developed more intense hyper‐pigmentation when treated with 20% MAL‐PDT compared with 2% HAL‐PDT. Conclusions: PDT with HAL (2%, 6% and 20%) and MAL (20%) is equally effective to prevent and treat UV‐induced SCC in hairless mice.     

Long‐pulsed dye laser vs. intense pulsed light for the treatment of facial telangiectasias: a randomized controlled trial

Objective This study aims to compare the efficacy and adverse effects of long‐pulsed dye laser (LPDL) and intense pulsed light (IPL) in the treatment of facial telangiectasias. Methods We used intra‐individual, randomized, controlled trial with split‐face treatments and single‐blind outcome evaluations in this study. Forty patients with symmetrically located facial telangiectasias received a series of three LPDL (V‐beam, 595 nm, Candela Laser Corp.) and three IPL treatments (Ellipse Flex, PR and VL2 applicators, Danish Dermatologic Development) at 6‐week intervals. Patients were evaluated 3 months after the final treatment. Outcome measures were clinical efficacy (five‐point ordinal scale), pain (10‐point numerical scale), adverse effects, patient satisfaction (10‐point numerical scale) and preferred treatment. Results Thirty‐nine of 40 patients completed the study. All but 2 patients obtained a reduction in facial telangiectasias from both IPL and LPDL treatments. Both treatments were effective with good or excellent response in 30 of 39 patients. The LPDL was superior in the overall reduction of telangiectasias by blinded photographic evaluations: Excellent clearance (75% to 100% vessel clearance) was found in 18 patients treated with LPDL (46%) and in 11 patients treated with IPL (28%) (P = 0.01). Patients experienced less pain from LPDL [4 (2–6)] than IPL treatments [7 (3–9)] (P < 0.001). No adverse effects (hypo‐/hyperpigmentation or scarring) were seen from any of the treatments. Patients were satisfied with both LPDL [8 (2–10)] and IPL treatments [7 (2–10)] (P = 0.05). Twenty‐five patients preferred the LPDL (64%), 8 patients preferred IPL (21%) and 6 patients had no preference (15%) (P < 0.001). Conclusion This study was based on two specific types of laser and IPL equipment, which effectively clear telangiectasias; however, the most beneficial outcome was from the LPDL.     

Intense pulsed light vs. long-pulsed dye laser treatment of telangiectasia after radiotherapy for breast cancer: a randomized split-lesion trial of two different treatments

Background Chronic radiodermatitis is a common sequela of treatment for breast cancer and potentially a psychologically distressing factor for the affected women. Objectives To evaluate the efficacy and adverse effects of treatments with a long‐pulsed dye laser (LPDL) vs. intense pulsed light (IPL) in a randomized split‐lesion trial. Methods Thirteen female volunteers with radiodermatitis and Fitzpatrick skin types II–III were included in the study. Subjects received a series of three treatments at 6‐week intervals with half‐lesion LPDL (V‐beam Perfecta, 595 nm) and half‐lesion IPL (Ellipse Flex); the interventions were randomly assigned to left/right or upper/lower halves. Primary end‐points were reduction in telangiectasia, patient satisfaction and preferred treatment. Secondary end‐points were pain and adverse effects. Efficacy was registered by blinded photographic evaluations 3 months after the final treatment. Results Eleven patients completed the study. Telangiectasia cleared with both treatments but the efficacy of LPDL was superior. Blinded photographic evaluations showed median vessel clearances of 90% (LPDL) and 50% (IPL) (P = 0·01). LPDL treatments were associated with lower pain scores than IPL treatments [median visual analogue scale (VAS) score 4·3 and 6·0, respectively, P < 0·01]. Patients were slightly more satisfied with LPDL (median VAS score 8) than IPL treatments (median VAS score 7; P < 0·05) and more preferred LPDL (n = 9) to IPL (n = 2) (P < 0·01). Two patients withdrew from the study because of hypopigmentation of the IPL treated areas, which slowly repigmented within 1 year. Conclusions This study was based on two specific laser and IPL devices, and found the LPDL treatment to be advantageous compared with IPL due to superior vessel clearance and less pain.     

Hair removal in hirsute women with normal testosterone levels: a randomized controlled trial of long‐pulsed diode laser vs. intense pulsed light

Background Hirsutism is a common disorder in women of reproductive age, and androgen disturbances may aggravate the condition. Limited evidence exists regarding efficacy of hair removal in this specific population and no data are available for patients with verified normal testosterone levels. Objectives To compare efficacy and safety of intense pulsed light (IPL) vs. long‐pulsed diode laser (LPDL) in a well‐defined group of hirsute women with normal testosterone levels. Methods Thirty‐one hirsute women received six allocated split‐face treatments with IPL (525–1200 nm; Palomar Starlux IPL system) and LPDL (810 nm; Asclepion MeDioStar XT diode laser). Testosterone levels were measured three times during the study period. Patients with intrinsically normal or medically normalized testosterone levels throughout the study were included in efficacy assessments (n = 23). Endpoints were reduction in hair counts assessed by blinded photoevaluations at baseline and 1, 3 and 6 months after final treatment, patient‐evaluated reduction in hairiness, patient satisfaction, treatment‐related pain and adverse effects. Results IPL and LPDL reduced hair counts significantly, with median reductions from baseline of 77%, 53% and 40% for IPL and 68%, 60% and 34% for LDPL at 1, 3 and 6 months, respectively. At 6 months follow‐up, there was no significant difference between treatments in terms of hair reduction (P = 0·427), patient assessment of hairiness (P = 0·250) and patient satisfaction (P = 0·125). Pain scores were consistently higher for IPL [median 6, interquartile range (IQR) 4–7] than LPDL (median 3, IQR 2–5) (P < 0·001). Conclusion Hirsute women with normal or medically normalized testosterone levels responded equally well to IPL and LPDL treatments of facial hairiness, but the efficacy declined over 6 months.     

Comparison of protoporphyrin IX accumulation and destruction during methylaminolevulinate photodynamic therapy of skin tumours located at acral and nonacral sites

Background Topical photodynamic therapy (PDT) is successful in the treatment of nonmelanoma skin cancers and associated precancers, but efficacy is significantly reduced in actinic keratosis lesions not located on the face or scalp. Objectives To compare the changes in protoporphyrin IX (PpIX) fluorescence in lesions undergoing routine methylaminolevulinate (MAL) PDT and the clinical outcome observed 3 months after treatment in lesions located at acral and nonacral sites. Methods This study was a noninterventional, nonrandomized, observational study, which monitored changes in PpIX fluorescence in 200 lesions during standard dermatological MAL‐PDT. These data were subsequently analysed in terms of lesions located at acral and nonacral sites. Results Clinical clearance was significantly reduced (P < 0·01) in acral skin lesions when compared with lesions located at nonacral sites. The accumulation and destruction of PpIX fluorescence was significantly reduced in these acral lesions (P < 0·05 and P < 0·001, respectively). Specifically, lesion location at acral sites significantly reduced changes in PpIX fluorescence in actinic keratosis lesions during MAL‐PDT (P < 0·01 and P < 0·05). Conclusions These data suggest that reduced PpIX accumulation and the subsequent reduction in PpIX photobleaching within acral lesions result in the reduced responsiveness of these lesions to MAL‐PDT. Future work should therefore aim to improve photosensitizer accumulation/photobleaching within lesions located at acral sites.     

Topical polyphenolic antioxidants reduce the adverse effects of intense pulsed light therapy

Background: Intense pulsed light therapy (IPL) has been associated with erythema and increased lipid peroxidation. Polyphenolic antioxidants have been shown to decrease inflammation and reduce oxidative stress in irradiated skin. Objective: To determine whether the topical application of polyphenolic antioxidants to IPL‐treated skin reduced the adverse effects of IPL exposure. Methods: In a split‐face study, 10 volunteers underwent three full‐face IPL treatments (16 J/cm², 10ms, 560nm filter) spaced 3 weeks apart. A polyphenolic antioxidant solution was pneumatically applied to the left side of the face, beginning immediately before the first IPL treatment then weekly for six treatments. The lipid peroxide concentration, skin antioxidant level and skin moisture content were obtained before and after the study. Results: Skin treated with IPL alone contained a significantly higher concentration of lipid peroxides when compared to skin treated with IPL plus polyphenolic antioxidants (p<0.05). Skin treated with IPL alone contained a significantly lower level of polyphenolic antioxidants and had a significantly lower moisture content (p<0.05). Conclusions: In this study, the concurrent pneumatic topical application of polyphenolic antioxidants reduced lipid peroxidation and skin dehydration in IPL‐treated skin. Polyphenolic antioxidants may confer a protective effect on facial skin and enhance the effects of IPL therapy.     

Fluorescence induction of protoporphyrin IX by a new 5‐aminolevulinic acid nanoemulsion used for photodynamic therapy in a full‐thickness ex vivo skin model

Please cite this paper as: Fluorescence induction of protoporphyrin IX by a new 5‐aminolevulinic acid nanoemulsion used for photodynamic therapy in a full‐thickness ex vivo skin model. Experimental Dermatology 2010; 19 : e302–e305. Abstract: An ex vivo porcine skin model was utilized to analyse the penetration of 5‐aminolevulinic acid (5‐ALA) contained in a nanoemulsion‐based formulation BF‐200 ALA (10% 5‐ALA‐hydrochloride) versus 16% aminolevulinate methyl ester‐hydrochloride in a commercially cream (MAL cream) by fluorescence microscopy of their common metabolite protoporphyrin IX (PpIX) after 3, 5, 8 and 12 h. Fluorescence signals of PpIX in pig skin treated with BF‐200 ALA were stronger than those for MAL cream. At 8 and 12 h, the PpIX fluorescence signals were 4.8‐ and 5.0‐fold higher than those measured after MAL cream application. Fluorescence signals of PpIX after application of BF‐200 ALA were detected in deeper tissue layers of the epidermis than after application of MAL cream (97.2 ± 5.7 μm for BF‐200 ALA vs 42.0 ± 4.2 μm for MAL cream). These data implicate that BF‐200 ALA in photodynamic therapy might lead to a superior therapeutically effect of intraepidermal (in situ) squamous cell carcinomas.     

Topical antioxidant application augments the effects of intense pulsed light therapy

Background There has been great interest in improving the efficacy of nonablative technologies by combining them during facial skin rejuvenation. The purpose of this study was to determine whether the addition of topical polyphenolic antioxidants to an intense pulsed light (IPL) treatment regimen augmented the effects of facial IPL treatments. Methods Thirty female volunteers, ages 34–52, with skin phototypes 1–3 were randomly assigned into three groups: group A (n = 10) received three full‐face IPL treatments spaced 3 weeks apart; group B (n = 10) underwent 6‐weekly full‐face treatments of a pneumatically applied topical polyphenolic antioxidant solution; group C (n = 10) received the combination of the three full‐face IPL treatments and the six full‐face topical antioxidant applications. Skin biopsies, skin polyphenolic antioxidant levels, and skin moisture content levels were obtained and clinical efficacy variables were noted prior to and following the treatment period. Results Compared to group A, group C demonstrated significantly greater epidermal and papillary dermal thickness, decreased lipid peroxide concentration, increased skin moisture content, and increased polyphenolic antioxidants levels (P < 0.05). There was qualitative improvement in hydration, texture, and pore size. Compared to group B, group C demonstrated significantly greater papillary dermal thickness (P < 0.05), and qualitative improvement in reduction of fine lines, reduction of hyperpigmentation, and skin dullness. group B and group C had equivalent polyphenolic antioxidant levels, lipid peroxide concentration, and epidermal thickness. Conclusion The addition of polyphenolic antioxidants to an IPL regimen improved the clinical, biochemical, and histological changes seen following IPL treatment alone. These data support the use of multimodal therapy to create synergy and to optimize clinical outcomes in nonablative facial skin rejuvenation.     

Evaluation of procollagen I deposition after intense pulsed light treatments at varying parameters in a porcine model

Several lasers and light sources have been reported to induce dermal collagen remodeling without damaging the epidermis. The intense pulsed light (IPL) system, which emits polychromatic light of wavelengths between 560 and 1200?nm belongs to this group of increasingly popular non‐ablative skin rejuvenation devices. Various IPL treatment parameters can be adjusted to achieve optimal dermal remodeling and clinical improvement. The aim of this study was to evaluate variations in IPL treatment parameters and the effect on procollagen I deposition. Marked areas of a live Yorkshire pig's flank skin were irradiated with a single or double pass of an IPL source using a fluence of 30 or 40?J/cm² and a cut‐off wavelength filter of 590?nm. Skin biopsies were performed on postoperative days 1, 7, 14, 21, and 42. A statistically significant increase in procollagen I in treated versus untreated sites was found on postoperative days 21 and 42, but not earlier. There was a uniformly significant increase in procollagen I on day 42 using the 590?nm filter at both 30 and 40?J/cm² with either a single or double pass. The increase in procollagen was greater with a fluence of 40?J/cm² compared with 30?J/cm².     

Objective and non‐invasive evaluation of photorejuvenation effect with intense pulsed light treatment in Asian skin

Background Intense pulsed light (IPL) has been widely used for photorejuvenation. Although previous literature has shown clinical effectiveness of IPL treatments on cutaneous photoaging, the associated changes in the biophysical properties of the skin following IPL treatments have not been fully elucidated. Objective The aim of this study was to evaluate changes in skin biophysical properties in patients with photoaging after IPL treatments, using non‐invasive, objective skin measuring devices. Patients and methods A total of 26 Korean women with facial dyschromias underwent three sessions of IPL treatment at 4‐week intervals. Outcome assessments included standardized photography, global evaluation by blinded investigators, patients’ self‐assessment and objective measurements of colour (Mexameter MX18, Chromatometer), elasticity (Cutometer), roughness (Visiometer), sebum (Sebumeter) and skin hydration (Corneometer). Results Intense pulsed light treatments produced a 15% decrease in the size of representative pigmented lesions (P < 0.05). Patients’ self‐assessment revealed that 84% and 58% of subjects considered their pigmented lesions and wrinkles were improved respectively. Objective colorimetric measurement demonstrated significant improvements following IPL treatments that were most remarkable after one session of IPL. Moreover, skin elasticity showed significant improvements at the end of the study. Skin wrinkles as measured using Visiometer showed a mild improvement without statistical significance. Sebum secretion and water content of skin remained unchanged. Conclusions Intense pulsed light provided significant improvement in the appearance of facial pigmented lesions in Korean patients. These effects appeared to be more remarkable in improving pigmentation, skin tone and elasticity.     

Use of light-emitting diode photomodulation to reduce erythema and discomfort after intense pulsed light treatment of photodamage

Objectives This study evaluates the use of light‐emitting diode (LED) photomodulation therapy to accelerate resolution of post–intense pulsed light (IPL) erythema. Methods In this split‐face study, 15 subjects were randomized to receive LED treatment to one side of the face as determined by computer‐generated randomization numbers. All 15 subjects received a single IPL treatment for facial photodamage. Immediately after IPL treatment, one side of the face was treated for 35 s with the LED device. The other side was not treated. Subjects returned 24 h later for a second LED treatment on the same side of the face. Posttreatment erythema was rated on both sides of the face by the blinded investigator and by subjects immediately after IPL treatment, 24 h later, and 1 week later on a scale of 0% (no erythema) to 100% (severe erythema). Patients commented on posttreatment discomfort immediately after IPL treatment. Results Mean erythema scores on the first visit were significantly higher (P = 0.0054) on the side not treated with LED (52.7 ± 24.6) than on the LED‐treated side (43.3 ± 21.9). Visit 2 data showed a similar trend (P = 0.0281). The subjects reported similar findings with mean erythema scores on the first visit on the LED‐treated side (46.7 ± 25.3) compared with the untreated side (60.0 ± 23.3); the difference was significant (P = 0.0382). On the second visit, the mean erythema scores trended lower on the LED‐treated side (24.3 ± 22.1) than on the untreated side (27.9 ± 25.8), but the difference did not reach statistical significance (P = 0.1365). Erythema scores on both facial sides were 0 for all subjects 1 week after IPL treatment. Four patients commented that posttreatment discomfort was considerably less on the LED‐treated side immediately after treatment. Conclusion LED photomodulation treatment may accelerate the resolution of erythema and reduce posttreatment discomfort in IPL‐treated patients with photodamage.     

Oxygen saturation and perfusion changes during dermatological methylaminolaevulinate photodynamic therapy

Background Methylaminolaevulinate (MAL)‐photodynamic therapy (PDT) is a successful topical treatment for a number of (pre)cancerous dermatological conditions. In combination, light of the appropriate wavelength, the photosensitizer protoporphyrin IX (PpIX) and tissue oxygen result in the production of singlet oxygen and reactive oxygen species inducing cell death. Objectives This study investigates real‐time changes in localized tissue blood oxygen saturation and perfusion in conjunction with PpIX fluorescence monitoring for the first time during dermatological MAL‐PDT. Methods Oxygen saturation, perfusion and PpIX fluorescence were monitored noninvasively utilizing optical reflectance spectroscopy, laser Doppler perfusion imaging and a fluorescence imaging system, respectively. Patients attending for standard dermatological MAL‐PDT were recruited to this ethically approved study and monitored prior to, during and after light irradiation. Results Significant reductions in mean blood oxygen saturation (P < 0·005) and PpIX fluorescence (P < 0·001) were observed within the first minute of irradiation (4·75 J cm^?2) while, in contrast, perfusion was observed to increase significantly (P < 0·01) during treatment. The changes in oxygen saturation and PpIX fluorescence were positively correlated during the initial phase of treatment (r² = 0·766). Conclusions Rapid reductions in the localized blood oxygen saturation have been observed for the first time to occur clinically within the initial minutes of light irradiation and positively correlate with the concurrent PpIX photobleaching. Furthermore, perfusion increases, suggesting that the microvasculature compensates for the PDT‐induced oxygen depletion.     

Topical application of 5-aminolaevulinic acid, methyl 5-aminolaevulinate and hexyl 5-aminolaevulinate on normal human skin

BACKGROUND: 5-Aminolaevulinic acid (ALA) and its ester derivatives are used in photodynamic therapy. Despite extensive investigations, the differences in biodistribution and pharmacokinetics of protoporphyrin IX (PpIX) induced by ALA and its derivatives are still not well understood, notably for humans. OBJECTIVES: To study porphyrin accumulation after topical application of ALA and two of its ester derivatives in normal human skin. METHODS: Creams containing 0.2%, 2% and 20% (w/w) of ALA, methyl 5-aminolaevulinate (MAL) and hexyl 5-aminolaevulinate (HAL) were applied on normal human skin of six volunteers. The amount and distribution of porphyrins formed in the skin was investigated noninvasively by means of fluorescence spectroscopy. RESULTS: Fluorescence emission and excitation spectra exhibited similar spectral shapes for the all drugs, indicating that mainly PpIX was formed. Low concentrations (0.2% and 2%) of MAL induced considerably less PpIX in normal human skin than similar concentrations of ALA and HAL. A high concentration (20%) of ALA gave higher PpIX fluorescence in normal human skin than was found for MAL and HAL. CONCLUSIONS: The concentrations inducing half of the maximal PpIX fluorescence are around 2% for ALA, 8% for MAL and 1% for HAL.     

Penetration enhancement of two topical 5‐aminolaevulinic acid formulations for photodynamic therapy by erbium:YAG laser ablation of the stratum corneum: continuous versus fractional ablation

Please cite this paper as: Penetration enhancement of two topical 5‐aminolaevulinic acid formulations for photodynamic therapy by erbium:YAG laser ablation of the stratum corneum: continuous versus fractional ablation. Experimental Dermatology 2010; 19 : 806–812. Abstract: 5‐Aminolaevulinic acid (ALA) is used in photodynamic therapy (PDT). Response rates of PDT vary widely, which may be because of the limited uptake of topically applied photosensitisers. We investigated skin penetration and fluorescence induction of protoporphyrin IX (PpIX) after applying either 20% ALA cream or 20% aminolaevulinic acid solution on laser‐stripped stratum corneum (SC) in an ex vivo full‐thickness porcine skin model. Both formulations are used in clinical practice. To enhance the skin penetration of ALA, we used two different 2940‐nm erbium:yttrium–aluminium–garnet (Er:YAG) laser systems to partially ablate the SC: continuous and fractional ablation. Different fluences were applied ranging from 0.5 to 1.5 J/cm² (continuous ablation) and from 4 to 24 J/cm² (fractional ablation). Fluorescence microscopy was used for detecting PpIX‐induced fluorescence. Compared to skin without laser pretreatment, mean fluorescence intensity (MFI) of PpIX was enhanced 13.8‐fold after continuous ablation with 1.0 J/cm² and 7.3‐fold after fractional ablation with 4 J/cm²; each laser procedure was followed by 4‐h incubation with lipophilic ALA cream. Optimal parameters for continuous ablation without damage to the epidermis were 1 J/cm² for both formulations, fractional ablation was best with 4 J/cm². Histological evaluations of laser‐treated skin showed necrosis and apoptosis, depending on light dose. In laser‐stripped skin, PpIX fluorescence was detected earlier and reached deeper epidermal layers than in untreated skin. Continuous laser ablation induced higher PpIX fluorescence levels than fractional ablation. This method offers a promising new tool for enhancing ALA penetration in PDT without damaging the underlying tissue.     

Effectiveness of low-fluence and short-pulse intense pulsed light in the treatment of melasma: A randomized study

Background: Various treatment protocols for melasma have been suggested in the literature, but the efficacy and safety of treatment varies according to the report. Objective: To investigate the selective photothermolytic effect of fluence-dependent intense pulsed light (IPL) in the treatment of melasma. Methods: Twenty Korean adults with melasma were enrolled, randomly assigned to two groups and treated at fluences of 10 or 13 J/cm² of IPL weekly over 6 weeks. Subjects were evaluated at baseline and weekly during the 6 weeks of treatment and at 3 weeks following the final treatment. Melanin and erythema indices were scored using a spectrophotometer. Results: The modified Melasma Area Severity Index (MASI) score of 20 patients at inclusion was 11.6 (± 0.9). Both 10J and 13J IPL treatment groups had decreased modified MASI scores from 2 weeks onward at statistically significant levels. Both 10J and 13J IPL treatment groups showed decreased melanin indices with statistically significant differences from 3 weeks onward. The effect of IPL on melasma was slightly greater in patients treated with 13J of IPL than in those treated with 10J over the entire duration of the study. The erythema index was transiently increased in weeks 1–3, but after 4 weeks it decreased to sub-baseline levels. Conclusion: We suggest that a low-fluence IPL protocol could provide more effective treatment for melasma with minimal side effects in Asian skin.     

Ultrastructural changes seen after ALA‐IPL photorejuvenation: A pilot study

Background. Intense pulse light (IPL) treatment currently represents one of the most popular non‐ablative photodamage skin treatments. Recent anecdotal evidence suggests that aminolevulonic acid (ALA) photodynamic therapy using IPL as a light source is superior to IPL alone for photorejuvenation.

Methods. Seven adult subjects (six women, one man) with minimal photodamage were treated with full face IPL treatment. Half of the face was pre‐treated with topical ALA. Pre‐and post‐treatment biopsies were analyzed for changes in collagen by electron microscopic ultrastructural analysis.

Results. An increase in type I collagen fibers was seen after treatment in all subjects. There was a greater increase in type I collagen formation in those subjects who were pre‐treated with topical ALA.

Conclusion. This small pilot study is the first to focus on the ultrastructural changes seen after ALA‐IPL photorejuvenation. We found a greater shift toward type I collagen synthesis in the ALA‐IPL group compared to the IPL group. The addition of ALA to IPL treatment for photorejuvenation may be superior to IPL alone.     

Treatment of facial telangiectasia with a small spot of intense pulsed light: A case series of three patients

Intense pulsed light (IPL) technology has long been used in the treatment of facial telangiectasia. While the large spot size of traditional IPL devices offers rapid coverage, it has limitations in terms of visibility and uniform contact with the skin in contoured areas of the face. The novel IPL used in this study had a small spot size (6.35 mm) and shorter wavelength (500–635 nm), allowing the use of high fluence without burning the normal epidermal tissue surrounding the lesion, thus providing better efficacy. Treatment of facial telangiectasia using small‐spot IPL is effective with a low risk of dermatological damage, and its uses for medical care are expected to diversify.     

Mexametric and cutometric assessment of the signs of aging of the skin area around the eyes after the use of non‐ablative fractional laser,non‐ablative radiofrequency and intense pulsed light

The assessment of the signs of aging within eyes area in cutometric (skin elasticity) and mexametric (discoloration and severity of erythema) examination after the treatment with: non‐ablative fractional laser, non‐ablative radiofrequency (RF) and intense light source (IPL). This study included 71 patients, aged 33–63 years (the average age was 45.81) with Fitzpatrick skin type II and III. 24 patients received 5 successive treatment sessions with a 1,410‐nm non‐ablative fractional laser in two‐week intervals, 23 patients received 5 successive treatment sessions with a non‐ablative RF in one‐week intervals and 24 patients received 5 successive treatment sessions with an IPL in two‐week intervals. The treatment was performed for the skin in the eye area. The Cutometer and Mexameter (Courage + Khazaka electronic) reference test was used as an objective method for the assessment of skin properties: elasticity, skin pigmentation and erythema. Measurements of skin elasticity were made in three or four sites within eye area. The results of cutometric measurements for R7 showed the improvement in skin elasticity in case of all treatment methods. The largest statistically significant improvement (p < .0001) was observed in case of laser and RF, during treatment sessions, at sites at upper and lower eyelid. The smallest change in skin elasticity for the laser, RF and IPL – p = .017, p = .003 and p = .001, respectively—was observed in a site within the outer corner of the eye. In all sites of measurements and for all methods, the greatest improvement in skin elasticity was demonstrated between the first and second measurement (after 3rd procedures). The majority of the results of mexametric measurements—MEX (melanin level) and ERYT (the severity of erythema) are statistically insignificant. Fractional, non‐ablative laser, non‐ablation RF and intense light source can be considered as methods significantly affecting elasticity and to a lesser extent erythema and skin pigmentation around the eyes. Fractional non‐ablative laser is a method which, in comparison to other methods, has the greatest impact on skin viscoelasticity. These procedures are well tolerated and are associated with a low risk of side effects.     

Long‐term clinical results of IPL photorejuvenation

BACKGROUND: Non‐ablative photorejuvenation is characterized by the reduction of intrinsic and extrinsic changes in photodamaged skin. Only short‐term improvement has been documented previously.

OBJECTIVE: To evaluate quantitatively the short‐term and long‐term clinical effectiveness of multiple full‐face IPL treatments for non‐ablative facial photorejuvenation.

METHODS: A total of 47 patients with varying degrees of photodamaged skin and rosaceal dermatitis underwent a series of four to five IPL treatments with a Vasculight (Lumenis Corp). Treatments were conducted every 3–4 weeks. Photographs were taken at baseline and after the treatment series was completed at both 6 weeks and 6 months. Adverse effects and clinical improvement were documented. A patient satisfaction questionnaire was completed and reviewed at the 6‐month evaluation period.

RESULTS: Standardized evaluation of rhytids showed a statistically significant improvement in wrinkles at both evaluation endpoints. Some degradation occurred over time. Facial vascularity, dyschromia, and large pore size progressively improved from the 6‐week measurement to the 6‐month measurement.

CONCLUSION: This clinical study demonstrates that non‐ablative facial rejuvenation is associated with long‐term clinical improvement of facial rhytids, abnormal vascularity and pigmentary disorders with minimal risks and side effects to the patient.