Using an intense pulsed light (IPL) module for the treatment of pigmented lesions

Pigmented lesions are largely benign and may lead to extreme distress. Various light and lasers may be used to treat pigmentation, often Q‐switched lasers are considered the method of choice, while intense pulsed light (IPL) devices may offer a less invasive treatment with a shorter downtime.

in post-inflammatory hyperpigmentation (PIH), melasma, solar lentigines, ephelides, café au lait macules, 1,3 and post-inflammatory erythema (PIE), 4 results from excessive production, distribution, or transportation of the pigment. 3Regardless of the underlying etiology, and although usually harmless, pigmented lesions can cause significant distress, especially when they occur on visible areas such as the face. 1 Laser therapy has been the subject of extensive clinical research as a treatment modality for pigmented lesions, 1 yet it carries a high risk of PIH and recurrence. 5The goal of laser technology is to deliver energy to a particular target without causing damage to the surrounding tissue.This is achieved by ensuring that the wavelength is absorbed primarily by the target tissue and less by the adjacent structures. 6Intense pulsed light (IPL) is a noncoherent polychromatic flash lamp that emits a spectrum of wavelengths that range approximately from 400 to 1200 nm.Similar to lasers, it is based on the principle of selective absorption of wavelengths by chromophores in the tissue.Several studies have demonstrated that IPL significantly reduces benign pigmented lesions such as solar lentigines and freckles 7 and improves the appearance of melasma. 1 This may be due to the nature of IPL, which is primarily superficial and broad in its action, causing gradual and uniform damage to the epidermis while sparing the deeper layers.
The damage, which extends just beyond the targeted structure, facilitates a controlled coagulation process under a micro-crust. 8 a result, after IPL treatment, it is common to observe a darkening of the treated areas followed by shedding of the micro-crust as part of the natural turnover of the epidermis. 8,9 addition, the IPL source contains a near-infrared component that is absorbed by water.This absorption results in a mild coagulation, causing inflammation that stimulates fibroblasts and promotes collagen production.In several studies, histological analysis has shown that the dermal heat generated by IPL treatments induces new collagen production, potentially resulting in improved skin texture. 7,8By utilizing certain wavelengths, pulses, and fluences, numerous skin conditions can be effectively treated with IPL.The optimal wavelength varies depending on its penetration depth, tissue interactions, and the target chromophore.Choosing the most suitable wavelength range can be facilitated by the use of cutoff filters. 7,9,10Pulse width modification is a new advancement in lasers and IPL to improve energy distribution.Conventional pulse distribution delivers energy unevenly, while new technologies aim for uniform energy delivery. 10e purpose of this study is to evaluate the safety, efficacy, tolerability, and overall well-being of patients using an IPL module for the treatment of pigmented lesions on visible areas of the skin.

| Treatment
Treatments were administered with the Dye-SR IPL Module (Harmony XL PRO, Alma Lasers Ltd., Caesarea, Israel) designed to operate within a specific band wavelength of 550-650 nm and incorporating the Advanced Fluorescence Technology (AFT) whereby uniform energy with controlled peak power is delivered throughout the entire pulse.This minimizes the risk of adverse effects when patients are exposed to non-therapeutic energy densities and uncontrolled peaks.Parameters of the device included a spot size of 3cm 2 and a pulse width of 12 ms at a fluence of 1-4 J/cm 2 .A thin layer of cooling gel was applied to all treatment areas prior to IPL application.
Patients received a series of 1-3 treatments at 4-week intervals.
The number of treatments administered was determined based on achieving satisfactory reduction in pigmentation and based on patient satisfaction.A follow-up visit was scheduled 2 months following the last treatment.

| Efficacy evaluation
To ensure an unbiased and objective evaluation of treatment efficacy, an expert dermatologist independent of the investigator performed a comprehensive evaluation to determine treatment efficacy.The evaluation was blinded and included comparing clinical photographs taken before and after the procedure and rating the overall improvement in the appearance of the lesions after the treatment.The Global Aesthetic Improvement Scale (GAIS) was used, where 0 is indicating no improvement and a 10-score indicating maximal improvement.Furthermore, patients rated their satisfaction with the treatment's outcome during their follow-up visit on an 11-point Likert scale.This scale ranged from 0 indicating maximal dissatisfaction to 10 indicating maximal satisfaction.

| Safety evaluation
At the follow-up visit, patients were asked to rate the pain level associated with their treatment, using a scale of low, moderate, or high.The study closely monitored and recorded the incidence and severity of any adverse events throughout the study and follow-up period.

| Statistical analysis
Data analysis was performed using descriptive statistics, including minimum, maximum, mean values, and percentages as appropriate.
In addition, the Pearson correlation coefficient was used to measure the strength and direction of the linear relationship between patient satisfaction and physician ratings.A two-sample t-test was carried out to find significant differences between the ratings.Additionally, chi-squared tests were performed to analyze the impact of the number of treatments on treatment outcomes, as indicated by GAIS scores and satisfaction scores.As chi-squared tests are appropriate for categorical data, we categorized the continuous data of GAIS scores and patient satisfaction scores into two groups: scores above and below a threshold, which is the nearest integer above the mean.This allowed to use the chi-squared test to determine if there is a significant association between the number of treatments and the outcomes categorized below or above the mean.Microsoft Excel data analysis tool was used to perform these analyses with a significance level of α = 0.05.

| RE SULTS
Retrospective analysis was conducted on records of 20 patients treated for pigmented lesions between February 2022 and January 2023, of which nine had freckles, five had melasma, one had solar lentigo, three presented with PIH, and two with post-inflammatory erythema (PIE).Superficial hyperpigmentation generally required only one or two sessions, while melasma, solar lentigo, PIH, and PIE necessitated multiple sessions to achieve satisfactory hyperpigmentation reduction and patient satisfaction.
There were no cases of loss to follow-up, and outcome data were available for all patients.Patients' demographics are presented in Table 1 and 2. At the 2-month follow-up visit, the physician noted significant improvements, as evidenced by a mean GAIS score of 7.55 ± 1.15 (mean ± SD).In addition, the majority of patients were satisfied with their treatment results, as evidenced by a mean satisfaction score of 7.3 ± 1.26 (mean ± SD).Examples for this improvement are presented in Figures 1 and 2.
Additionally, there was a strong positive correlation between GAIS and patient satisfaction scores, with a Pearson correlation coefficient of 0.83.The t-test performed to compare the means of the GAIS and satisfaction scores yielded a p-value of 0.516, which significantly exceeds the selected alpha level of 0.05, indicating no significant statistical difference between the mean GAIS score and the mean satisfaction score.The chi-squared test was used to examine the relationship between the number of treatments and two critical outcomes-GAIS and patient satisfaction scores.For this analysis, continuous scores for both GAIS and satisfaction were converted to binary categories using a threshold of 8 to classify scores as either above average or below average.The chi-squared test for GAIS yielded a statistic of 2.019 with a p-value of 0.364, and the chisquared test for patient satisfaction yielded a statistic of 4.146 with a p-value of 0.126, both calculations with 2 degrees of freedom.The chi-square statistics of 2.019 and 4.146 are lower than the critical chi-square values at the 0.05 significance level.In addition, the pvalues for both tests exceed the chosen significance level of 0.05.This combination of results suggests that in this study the number of treatments did not have a statistically significant effect on whether GAIS or patient satisfaction scores were above or below the threshold of 8.
During the procedures, all patients reported low levels of pain, and there were no adverse events throughout the study and follow-up period.
Throughout the course of the study, additional positive outcomes that were not originally anticipated were identified.We believe their inclusion will provide valuable insights that can contribute to future research and decision making.At the follow-up visit, a no-

TA B L E 2 Treatment results.
validated, a positive relationship between the degree of pigmented lesions in patients and the degree of improvement in skin rejuvenation was observed.

| DISCUSS ION
Currently, lasers and energy-based devices play a major role in the treatment of pigmented lesions. 5The tissue effect is achieved from laser energy heating a chromophore and from a secondary spread of heat to the adjacent tissues.The extent of tissue damage is determined by the temperature and the exposure time.The thermal relaxation time (TRT) refers to the time it takes for heated tissue to reduce its temperature to half of its maximum value.To successfully damage the target tissue, the fluence must be high enough to deliver sufficient thermal energy while the pulse duration, which determines the exposure time, must be shorter than the TRT of the target tissue.Exceeding the tissue TRT may result in non-specific thermal damage caused by heat diffusion to the surrounding tissues. 6When targeting melanin in pigmented lesions, the TRT of the melanosome is relatively short.Therefore, lasers with shorter pulse durations and minimal absorption by hemoglobin and water are typically preferred. 1Q-switched lasers are often considered the method of choice for pigmented lesions, because they emit pulses that are shorter than the TRT of melanosomes, resulting in minimal damage to surrounding tissue. 1,8,9ile IPL pulses exceed the TRT of the melanosomes, potentially causing more damage to the surrounding tissue, the damage is limited by the relatively low fluences of IPL technology.In addition, IPL offers a noninvasive procedure with shorter downtime than laser treatment. 8Results of a 22-subject randomized study comparing Q-switched laser and IPL for the treatment of axillary hyperpigmentation showed no significant difference in results between the two treatments.However, pain scores were lower with the IPL. 11While the broad wavelength range of IPL is an advantage in some respects, this versatility comes at the expense of selectivity, as the broad spectral range may not be optimal for targeting specific chromophores. 9However, by narrowing the wavelength range, IPL treatments can achieve greater selectivity in targeting tissue chromophores that have higher absorption coefficients within the specific wavelength range.This increased selectivity can significantly improve the efficacy and precision of IPL treatments. 7,12,13 this study, treatment of pigmented lesions with the IPL module in the wavelength spectrum of 550-650 nm was found to be safe and effective for freckles, melasma, solar lentigo, PIH, and PIE.
Similarly in a systematic review it was found that IPL was consistently effective in the treatment of lentigines and ephelides and was found to improve melasma although efficacy depended also on other factors. 14We found a strong positive correlation between treatment outcomes and patient satisfaction, and no statistically significant difference was observed between them.Both findings suggest that clinical assessment and patient satisfaction are consistent and reflect treatment effectiveness from a clinical and patient perspective.In our study, the number of treatments did not significantly affect the outcomes or patient satisfaction.In addition, the use of the AFT technique yielded superior results for superficial lesions.AFT offers an additional advantage by converting wasted wavelengths into the usable spectrum, which has also been demonstrated in other studies. 15,16e results of this study align with previous research on the use of IPL platforms for various skin conditions.For instance, a review suggested that the use of an IPL module emitting primarily between 500 and 600 nm is fast, simple and safe for the treatment of ecchymoses which are common side effects of filler injections and appear as discoloration of the skin. 13In another study, a group of 65 patients with refractory melasma were treated with a combination of topical application and IPL in the wavelength range of 570 nm to 950 nm.At the 12-week follow-up, both independent observers and the patients themselves reported a positive outcome with good to excellent response.In addition, no significant adverse effects were observed during the course of treatment. 16rthermore, a split-face study of 20 participants treated for photodamage compared the efficacy of narrowband IPL using a wavelength range of 500-600 nm with dual-band IPL using a broader spectral output of 500-670 nm and 870-1200 nm.The results showed that treatment with narrowband IPL produced comparable or even superior results compared to the broader spectral output technology. 12 our study, the primary focus of IPL treatment was the treatment of pigmented lesions on the skin.However, during the course of our observations, we noted several additional positive outcomes, including pore reduction, skin tightening, and an overall reduction in wrinkles.Interestingly, we observed a positive relationship between the extent of pigmented lesions present in patients and the degree of improvement in skin rejuvenation.This suggests that the absorption of IPL light in chromophores and subsequent heat release from IPL treatment may stimulate neocollagenesis, contributing to these additional beneficial effects.
While the lack of histological and physiological data precludes a direct link to collagenesis, we hypothesize that the effects of the IPL light band extend beyond interactions with the targeted chromophores.Specifically, we suggest that the observed beneficial effects on the skin are not only a result of the interaction with chromophores but may also be due to the influence of scattered photons on fibroblast synthesis.Approximately 4%-7% of the radiation reaching the skin is reflected, while the remaining 93%-96% is either scattered or absorbed.Scattering, resulting from skin inhomogeneities, is a type of elastic interaction between a photon and matter that changes the direction of the photon. 17search on the efficacy of IPL devices for skin rejuvenation has yielded inconsistent results but the potential for collagen stimulation as an additional benefit of using an IPL device has been suggested by some, 18 with histologic evidence of increased type 1 and type 3 collagen after IPL therapy. 9L targets melanin, oxyhemoglobin/deoxyhemoglobin, and water, which allows it to treat pigmented lesions, vascular lesions, and stimulate collagen remodeling. 19While water absorption is significant only in the near-infrared (NIR) and mid-infrared (MIR) portions of the spectrum, the possibility of collagen stimulation by IPL may be indirect through tissue heating, causing controlled injury responses. 20After injury, a complex sequence of events stimulates fibroblasts and leads to collagen production. 21One study showed that a specific IPL device focused on the narrow region of 550-680 nm was able to induce fibroblast activation and increase collagen formation leading to dermal remodeling. 22Collagen remodeling in the skin involves not only the proliferation of new collagen but also the degradation of denatured collagen.Collagen degradation is triggered by both matrix metalloproteinase (MMP) secretion and transforming growth factor-beta (TGF-beta) inhibition.Mitogen-activated protein kinases (MAPKs) are involved in MMP and TGFβ secretion processes in response to stress stimuli.In an additional study, IPL irradiation at different fluences was found to inhibit the secretion of TGF-β1 and increase the secretion of MMP-1; in addition, the phosphorylation of MAPKs was inhibited in a fluence-dependent manner, diametrically opposite to the effect of UV exposure, strongly suggesting that it is a potential signal transduction to reverse skin aging. 23rther statistical analysis is required to definitively determine the significance of our observations.Nevertheless, the preliminary results are encouraging and provide insight into the additional benefits of this treatment that may be the focus of future research.

| Limitation
The study has several limitations that should be acknowledged.
First, the study was conducted in a retrospective manner.In addition, the study was performed at a single center, and the sample size of the study was relatively small.Another limitation is the lack of diversity in skin types among the participants.To strengthen the level of evidence, a multicenter clinical trial involving multiple regions and ethnic groups should be conducted.In addition, large controlled and blinded comparative studies with longer follow-up periods are needed.
The IPL module has demonstrated safety and efficacy in targeting pigmented lesions on the face, neck, and décolleté.Furthermore, it appears to have the potential to stimulate collagen production, suggesting a range of possible beneficial effects.

FU N D I N G I N FO R M ATI O N
This research received no external funding.

CO N FLI C T O F I NTE R E S T S TATE M E NT
There are no conflicts of interest that are relevant to this work.

DATA AVA I L A B I L I T Y S TAT E M E N T
All data are contained within the article only.No supplementary material exists.

E TH I C S S TATEM ENT
This is a retrospective collection of anonymized data from previously recorded routine assessments and does not present risk of exposure of personal data of patients.The study was approved by the Ethic Committee of Alma Mater Europaea College of Medical Sciences "Rezonanca" number AD-3392/23.

D ECL A R ATI O N S
This publication is original, contains independent, unpublished work that has not been submitted for publication elsewhere.

R E FE R E N C E S
phototherapy, immunosuppression, current use of retinoids or photosensitizing agents, and a history of radiotherapy in the area treated.

F I G U R E 1
A 25-year-old patient before (left) and 2 months following (right) three treatment sessions demonstrating a profound clearance of facial pigmented lesions and erythema.F I G U R E 2 A 45-year-old patient before (Left) and 2 months following (right) two treatment sessions demonstrating a significant clearance of freckles in forehead, cheeks, and perioral area.

table reduction
Patients' demographics.
a Standard deviation.a Standard deviation.b Scale 0-10.