Rosacea treatment with 532 nm KTP versus 595 nm pulsed dye laser—A prospective, controlled study

Pulsed‐dye lasers (PDL) are one of the standard therapies for rosacea, but alternatives are needed.

Due to the pronounced symptoms and relapsing nature, rosacea has a substantial negative impact on the quality of life for patients, prompting them to seek treatment. 4,5Therapeutic options vary depending on the severity of rosacea and can include topical agents, systemic pharmaceuticals, and laser treatments. 6Based on the principles of selective photothermolysis, vascular-specific lasers have been the mainstay in laser medicine for treating erythema and telangiectasia in rosacea. 7Among these lasers, the pulsed-dye laser (PDL) established as one of the standard treatment methods and has been proven to be an effective and safe option. 8tely, there has been a growing interest in alternatives to the conventional PDL due to its high financial implications associated with laser acquisition and maintenance. 9Recently, variablesequenced, large-spot KTP lasers have been introduced into dermatologic laser medicine.These lasers have a larger spot size, higher fluence settings, various pulse shapes, and an integrated cryogen cooling.
However, to date, the evidence on the effectiveness of the variable-sequenced, large-spot KTP on rosacea is limited.Therefore, the aim of this prospective, controlled study was to compare the efficacy, safety, and tolerability of the present 532 nm KTP with the 595 nm PDL in the treatment of rosacea.

| Study design
This study was designed as a prospective, controlled, investigator-

| Treatment protocol
A comprehensive medical history of previous treatments was obtained.Patients were assigned to either a 595 nm PDL (VBeam®, Candela Medical Cooperation, Marlborough, MA, USA; Cynergy™, Cynosure®, Langen, Germany; VascuStar® DYE, Asclepion Laser Technologies, Jena, Germany) or a variable-sequenced, large-spot 532 nm KTP (DermaV®, Lutronic Medical Systems®, Hamburg, Germany) in a 1:2 ratio.The choice of the PDL system used depended on their operational condition.Table 1 shows the treatment parameters.The integrated cryogen cooling device of the KTP and a PDL (VBeam®) as well as an air cooling (Cryo6®, Zimmer Aesthetics, Neu-Ulm, Germany) for the other PDL systems were used.After laser treatment, gel masks provided further cooling.A topical anesthesia prior to treatment was not needed.Parameters were adjusted according to the clinical end point.For the KTP, the end point was defined as transient fading of vessels, accompanied by a gentle purpuric or pink reaction, while avoiding persistent purpura.With the PDL systems, the end point was reached when the vessels vanished, or when purpuric discoloration was reached.Patients were advised to apply a hydrating cream (Moisturizing Cream, Cetaphil®, Galderma, Zug, Switzerland) at home and to refrain from using chemical peelings, serums, and photosensitizing medications.Additionally, they were instructed to avoid UV exposure, extensive sports activities, and sauna sessions post-treatment.

| Standardized photographic documentation
For each session, photographs were taken from the front and from a 45° plane from each side using a three-dimensional imaging system (Vectra®, Canfield Scientific inc., Bielefeld, Germany).For white balancing, a standardized color palette (SpyderCheckr®, Datacolor®, Marl, Germany) was applied.To ensure standardization, a neutral light background and an artificial light source were used while natural light was shielded.Patients were advised to remove decorative cosmetics and jewelry and gently pull back their hair.They were asked to have a relaxed facial expression.

| Efficacy assessments
Primary end point was the improvement of rosacea-associated erythema 6 weeks after last treatment session compared with TA B L E 1 Applied laser parameters of the KTP and pulsed-dye laser (PDL).For cooling for the KTP and one PDL system (VBeam®), the integrated cooling device was used.For the other two PDL devices, an air cooling system was applied.baseline.Here, erythema was quantified using the CIE L*a*b* color space model, a color organization system, which is standardized by the Commission Internationale de l'Éclairage (CIE).It is a three-dimensional color space and expresses the gray scale from 0 (black) to 100 (white), the red/green values from -a (green) to +a (red), and the yellow/blue axis from -b (blue) to +b (yellow). 10,11an a* of the lesional region was calculated and subtracted with mean a* of non-lesional regions to delete background erythema (Δa*). 12condary end points were assessed by two blinded independent board-certified dermatologists and included the improvement of the overall appearance using the Global Aesthetic Improvement Scale (GAIS; scale from 0-very much improved to 4-worse), and of erythema and telangiectasia using a 5-point scale (from 0-excellent improvement to 4-no response). 13,14In addition, patients were asked to evaluate their primary and secondary rosacea features on a 5-point scale ranging from 0 (none) to 4 (severe).

| Safety and tolerability assessment
During treatment, patients were asked to rate the pain intensity on the Numeric Rating Scale (NRS) from 0 (no pain) to 10 (unbearable pain).Any adverse events, including edema, dyspigmentation, and scar formation, were documented and treated accordingly.

| Patient satisfaction assessment
Patient satisfaction was assessed using a 5-point rating scale ranging from 0 (very satisfied) to 4 (unsatisfied).Furthermore, patients were asked whether they would recommend the treatment to others.

| Maintenance of laser systems
Any system failures of the KTP and PDL systems as well as treatment postponements were documented.

| Statistical analysis
Statistical evaluation was performed using the Microsoft® Excel (Version 16.56, Microsoft Cooperation) and MATLAB software (Version 9.11, The Mathworks Inc.).If not stated otherwise, the unpaired t-test was used to determine the difference in mean between groups.p-values <0.05 were defined as significant.
Descriptive data were presented as means, standard deviations, and ranges.

| Investigators' assessment
Six weeks after last treatment session, improvements in overall appearance, erythema, and telangiectasia were noted by the blinded investigators (Table 3).There were no significant differences in the degree of improvement between the KTP (n = 23) and PDL treatments (n = 10).Figure 1 and Figure 2 demonstrate representative images of patients before and after treatment with the KTP and PDL.

| Patients' assessment
Patients who underwent KTP treatment reported a significant improvement in flushing and persistent erythema (n = 29; p < 0.001).
In the PDL group, patients also noted a reduction of persistent erythema (n = 13; p < 0.001), but no significant difference in flushing.Compared with the KTP group, PDL-treated patients rated secondary symptoms of rosacea to be significantly improved (Figure 3).

| Tolerability and safety
Within the KTP group (n = 29), patients rated their pain intensity at 2.5 ± 1.6 (0-6) on the NRS.In the PDL group (n = 13), the pain was reported as 4.1 ± 1.8 (2-7), indicating a significantly higher level of pain (p < 0.05).All patients treated with the KTP experienced post-treatment mild-to-moderate swelling and erythema.Approximately 20% of these patients also exhibited purpuric reactions, which lasted for 1.3 ± 2.7 days (0-11.5).All patients in the PDL group reported swelling and purpura after treatment, which lasted for an average of 6.9 ± 3.9 days (0-15).Additionally, around 35% developed crusts, which lasted for 2.2 ± 3.5 days (0-10).There were no reports of serious adverse effects, and no patients in either treatment group had to discontinue the study due to adverse events.

| Patient satisfaction
The majority of patients in the KTP group (n = 29; 78.3%) and PDL group (n = 13; 71.4%) indicated a 0 or 1 on the 5-point rating scale.
84.6% of patients treated with the KTP would recommend the treatment, compared to 78.6% in the PDL group.

| Maintenance of the laser systems
During the study, all three PDL systems had to go through maintenance work due to system failures or the lack of dye kits, leading to The Global Aesthetic Improvement Scale (GAIS) was applied, ranging from 0 (very much improved) to 4 (worse).
For erythema and telangiectasia a score was used ranging from 0 (excellent improvement) to 4 (no response).
treatment postponements of six patients up to 4 weeks.The KTP did not had maintenance issues for the period of study.

| DISCUSS ION
The present study establishes the first prospective, controlled trial to compare the efficacy, safety, tolerability, and patient satisfaction of a variable-sequenced, large-spot 532 nm KTP to the conventional 595 nm PDL in the treatment of rosacea.The data demonstrated that the present KTP performs comparable efficacy to the PDL in treating rosacea-associated symptoms, while also demonstrating a favorable safety profile.
The study findings indicate that both the KTP and PDL are similarly effective in treating rosacea-associated persistent erythema and telangiectasia.Notably, the KTP appears to have a positive impact on flushing, which could not be proven with the PDL.However, secondary symptoms of rosacea, such as burning sensation, edema, and dry sensitivity, seem to respond more favorable to PDL treatments.It is important to note that the degree of treatment response varied among the subjects, potentially influenced by the relapsing nature of the disease and patients' lifestyle.Although not measured in a structured manner, PDL seem to be more effective on larger vessels.Regarding adverse events, common post-laser reactions were observed in both laser systems.Severe adverse events did not occur.6][17] These studies consistently demonstrated similar efficacy and safety outcomes with sub-purpuric parameters.However, given that some studies suggested increased effectiveness with purpuric passes in treating rosacea and following the recommendations of the German guideline, we opted for purpura-inducing parameters. 8,18,19We chose these parameters to maximize the effectiveness of the applied PDL systems and to ensure a valid comparison with the efficacy of the variable-sequenced, large-spot KTP.To further ensure comparability, we used similar pulse lengths for both KTP and PDL systems.Although these settings could potentially induce purpura in both systems, we only observed a significant purpuric reaction in the applied PDL systems.As we attempted purpuric reactions with the PDL, a meaningful comparison regarding downtime and AEs might be compromised in the present study.
In Germany, the challenges related to acquiring and maintaining PDL systems have led to treatment postponements and limitations in health care of patients with rosacea and other vascular lesions.
A national survey revealed that a substantial number of laser physicians would not invest in a PDL for their practices anymore due to the associated financial burden. 9Given that we encountered no system-related issues with the KTP in our study, we propose that the variable-sequenced, large-spot KTP might serve as a promising alternative to PDL, particularly when considering the absence of consumables for its acquisition.
This study has some limitations.First, we did not exclude the influence of patients' lifestyle habits such as diet and UV exposure, which could potentially be influencing variables in our analysis.
Second, the relatively short interval to follow-up might miss recurrences of rosacea symptoms.In addition, the optimal parameters for the KTP remain undefined due to its recent introduction.These parameters may adapt over time to effectively target larger vessels.
Given that the PDL is a well-established and extensively studied system, we opted for a larger cohort pool for the KTP.However, it is important to note that the smaller case number might impact the validity of the PDL data.Furthermore, using three different PDL laser systems might limit the interpretation of the results.Due to the unpredictable operational status of the systems, we tried to compromise this incidence by using similar settings and end points.
We conclude by objective analysis of erythema, blinded outcome evaluation, and patients' assessment that the variable-sequenced, large-spot KTP is an effective and safe method to treat rosaceaassociated flushing, erythema, and telangiectasia.Secondary symptoms of rosacea seem to respond better after PDL then after KTP treatment.By providing lower downtime and fewer adverse events, this laser suggests a superiority to the conventional PDL.Further studies are warranted to evaluate its long-term efficacy and safety and analyze the recurrence rates of rosacea after treatment with both KTP and PDL.
blinded trial.It was approved by the local ethics committee (2022-100 910-BO-ff), preregistered on Clini caltr ials.gov (NCT05771298) and conducted in accordance with the Good Clinical Practice guidelines and the Declaration of Helsinki.Patients were recruited from the dermatological Laser Department of the University Medical-Center Hamburg-Eppendorf, Germany.Male and female patients from the age of 18 with rosacea were included.Exclusion criteria were pregnancy, open wounds in the area to treat, history of topical pharmaceutical treatment in the last 2 weeks, and history of systematic treatment for rosacea in the last 4 weeks.Further contraindications were medications causing photosensitization, excessive UV exposure within 4 weeks prior to treatment, and Fitzpatrick skin types V and VI.After informed consent, patients received up to three treatment sessions at intervals of 6-8 weeks.A follow-up visit was scheduled on Week 6 post-treatment.

F I G U R E 1 3
A 46-year-old patient (A) before and (B) after three KTP laser treatment sessions observed a substantial improvement of erythema and telangiectasia.Assessment of the improvement of the overall appearance, erythema, and telangiectasia in rosacea patients treated with either a KTP or pulsed-dye laser (PDL) at Week 6 posttreatment by two blinded investigators.
seems to be superior to PDL regarding downtime and tolerability due to the lack of transient purpuragenic discoloration.Additionally, patients reported significantly less pain during KTP treatments.Patients in the PDL group who would not recommend the treatment indicate the long downtime or the insufficient clinical outcome as a reason.Patients who did not recommend KTP treatment mainly cited a lack of substantial improvement as their reason.FI G U R E 2 A 74-years old patient (A) before and (B) after three pulsed-dye laser treatment sessions.Significant decrease in erythema could be determined.F I G U R E 3 Patients' assessment of rosacea symptoms at baseline and follow-up visit (6 weeks after last treatment session).Scale from 0none to 4-severe.ns: not significant; *p < 0.05; **p < 0.01.The PDL is considered as one of the standard treatments of various vascular lesions.Conventional KTPs were primarily assigned to small telangiectasias due to their small spot size and low fluence, which restricted their depth of laser penetration.Moreover, the 532 nm wavelength falls relatively high on the melanin absorption spectrum, which limited the utility of conventional KTPs for deeper vascular lesions.However, with the advancements such as a larger spot size and integrated controlled cryogen cooling, deeper laser penetration was made possible while still protecting the epidermis from excessive heat.