Medical Applications of Picosecond Lasers for Removal of Non-Tattoo Skin Lesions—A Comprehensive Review

Abstract

Picosecond lasers are gaining increasing popularity in dermatology and aesthetic medicine due to their favorable safety profile and a wide range of therapeutic applications. While originally employed primarily for tattoo removal, their versatility has extended their use to the treatment of various aesthetic skin conditions, including hyperpigmentation, acne scars, stretch marks, and signs of photoaging. Owing to their ultra-short pulse duration, picosecond lasers effectively target pigment particles and stimulate dermal remodeling, offering patients a safe and effective solution to improve the appearance of their skin. The introduction of the picosecond laser into clinical dermatology practice marks a notable advancement in addressing a broad spectrum of skin problems.

1. Introduction

Technological advancements have significantly contributed to the development of laser therapy. A wide range of laser devices, which may be used for treating facial and body lesions, are currently available [1]. Among these, picosecond (PS) lasers, which emit pulses of short duration, have attracted particular attention of the researchers [2]. Based on the principles of selective photothermolysis, such ultra-short pulse durations make it possible to enhance the therapeutic effect at the target site, while minimizing the risk of damage to the neighboring tissues. Picosecond lasers have outperformed conventional nanosecond lasers in terms of treatment efficacy, safety and therapeutic outcomes, especially in patients with darker skin phototype [3]. Picosecond lasers were initially used to remove tattoos and were introduced to improve treatment efficacy and reduce the side effects linked with using nanosecond lasers during these procedures [4]. They are still widely utilized for this indication, as evidenced by the literature [5], but research has demonstrated that picosecond lasers yield promising results in treating other dermatological conditions, including pigmentation disorders, acne scars, striae distensae, and signs of aging [2,4,6].

2. The Mechanism of Action in Picosecond Laser Treatment

A picosecond laser interacts with various tissues through two primary mechanisms: photo-thermo-mechanical disruption (PTMD) and laser-induced optical breakdown (LIOB) [7]. The former relates to non-fractionated laser beams and is based on the principle that ultrafast temperature changes, which are induced by the picosecond pulses, generate intense acoustic shock waves within the targeted chromophores, creating tensile stress which exceeds the rupture threshold of a chromophore [2]. A significant photomechanical interaction occurs when the duration of the pulse is shorter than stress relaxation time [7].

This photomechanical (photoacoustic) effect is the main method of fragmenting subdermal ink particles (tattoo) and cellular melanosomes using picosecond laser irradiation, facilitating their clearance by macrophages and other phagocytic cells [2]. In tattoo removal with Q-switched nanosecond lasers, the duration of the laser pulse is shorter than the thermal relaxation time of the tattoo pigments, allowing for the achievement of a thermal confinement. At the same time, another important phenomenon, known as stress confinement, must be taken into account. Stress relaxation can be explained as follows—when a particle is heated, it undergoes thermal expansion. The expansion propagates to the surrounding tissue as a vibrational wave, a process which is called stress diffusion. If a particle is heated very briefly, the stress generated in the particle does not have enough time to dissipate, resulting in stress confinement. If the stress level exceeds a critical threshold, the particle will fracture. This mechanism is analogous to thermal confinement and rapid temperature rise described in the thermal relaxation theory, which posits that if a structure is heated to a certain temperature, thermal energy will spread to the surrounding tissues by thermal conduction. However, if a structure is heated over an extremely brief time period, the temperature rises rapidly because heat diffusion does not occur—this is known as thermal confinement. Once thermal confinement is achieved, selective photothermolysis of the target structure becomes possible. Achieving thermal confinement depends on the time threshold of the structure, defined as thermal relaxation time (TRT). TRT is determined by the absorption coefficient and the heat diffusion coefficient of the structure [8].

The energy of a picosecond laser may be fractionated using different optical lenses, which allows for the concentration of higher peak energies within the microbeams and the preservation of the adjacent tissues [2]. The commercially available fractional optical delivery technologies include diffractive lens arrays (DLA), micro-lens arrays (MLA), and holographic optical matrices. Distinct optical arrays, with varying spot sizes, have been used in different PS laser devices. DLA technology is used in the 755 nm alexandrite Picosure laser (Picosure TM, Cynosure, Westford, MA, USA). It consists of closely packed individual hexagonal lenses, with a 500 μm pitch. In turn, a neodymium-doped yttrium aluminum garnet (Nd:YAG) (532 nm and 1064 nm) picosecond laser PICOPLUS (PICOPLUS; Lutronic Corp., Goyang, Republic of Korea) employs the MLA technology with a 4-mm spot size to generate zones of high-intensity tissue damage, while the adjacent structures remain unaffected [9].

Closely packed microlenses divide the picosecond pulses into columns of high fluence, which irradiate only 10% of the target area, while the background receives laser pulses of lower fluence. The sites which receive high-fluence laser irradiation absorb approximately 20-fold more energy than the background regions exposed to low-fluence laser pulses. High-fluence fractionated laser emission promotes the synthesis of collagen and elastin through photothermal and photomechanical effects, without surface ablation [10].

The tissue effects of fractional PS lasers depend on chromophore-assisted ionized plasma formation, known as laser-induced optical breakdown (LIOB) [2]. LIOB is initiated with the generation of accelerated seed electrons, which collide with the surrounding molecules and release more free electrons. This process, which is referred to as ionization or electron avalanche, leads to the formation of a collection of free electrons, i.e., plasma. Plasma absorbs the incoming electromagnetic radiation, causing optical failure or optical breakdown and the subsequent tissue ablation. Following LIOB, a mechanical response occurs in the skin due to the rapid expansion of plasma, leading to photodisruption. Photodisruptive effects may manifest as shockwave emission, formation of cavitation bubbles, or shockwave recoil following bubble collapse, which also may contribute to tissue ablation. The findings of histological studies demonstrated that melanin and hemoglobin serve as primary chromophores for LIOB after fractional PS laser irradiation [7]. The photomechanical stress generated by fractional PS lasers permeates into the dermis, and stimulates fibroblast proliferation, collagen regeneration, and skin remodeling [11].

3. Types of Picosecond Lasers

It was not until the late 1990s that picosecond lasers became available in clinical practice [4]. Currently, devices utilizing picosecond pulses with wavelengths of 532, 670, 730, 755, 785, and 1064 nm have been developed. They differ not only in the length of the emitted wave but also in pulse duration and peak power [12]. Additionally, these lasers can be equipped with specialized lenses which may fractionate the emitted energy. Depending on the type of the lens, PS lasers can be classified into those with diffractive lens arrays, microlenses, and holographic optical matrices [13]. The choice of the laser for the treatment depends on the characteristics of the lesions and patient skin type [14]. The Fitzpatrick skin phototype scale is presented in

Table 1. The Fitzpatrick Skin Phototype Scale.

Fitzpatrick Skin Phototypes	Reaction to Sun Exposure	Complexion
	always burns, never tans	very fair
	burns easily, burns develop into a light tan	fair to light
	burns a moderate amount, burns develop into a light tan	light to medium
	burns a minimal amount, develops a moderate tan	moderately dark
	does not burn, develops dark tan	dark
	does not burn or change in appearance	very dark

[15].

Tanghetti and Jennings [16] compared the effects of a PS alexandrite laser (755 nm), with a diffractive lens system, and an Nd:YAG laser (532 nm/1064 nm), with a holographic optical system, in patients with Fitzpatrick skin types I–VI, using the energy ranges recommended by the manufacturers. Photos of the target area were taken (at 15 min. and 24 h post-procedure), and a histopathological examination of the skin samples biopsied 24 h after the procedure was performed. Their findings indicated that skin exposure to the PS Nd:YAG laser (532 nm/1064 nm) with a holographic optical system induced immediate erythema and small, scattered petechial hemorrhages, which in many cases persisted after 24 h post-procedure. In contrast, the alexandrite laser (755 nm) with a diffractive lens system also caused immediate erythema, which largely resolved within the next 24 h. Furthermore, the use of the fractional PS Nd:YAG laser (532 nm/1064 nm) with a holographic optical system was associated with focal areas of cutaneous and intraepidermal hemorrhage, together with vascular damage in some patients. Both lasers were shown to generate vacuoles within the skin, which were most likely associated with LIOB. Among the patients with Fitzpatrick skin types II–IV, these authors observed diffuse hemorrhagic areas in the skin due to vascular injury at 532 nm and 1064 nm wavelength, but not at 755 nm wavelength [16].

4. Clinical Indications

Initially, the application of picosecond lasers in dermatology focused on optimizing the removal of unwanted tattoos. Over time, technological advancements have broadened the scope of the clinical indications for laser treatment of various dermatological conditions, e.g., hyperpigmentation, photoaging, melasma, or scars [2].

4.1. Post-Acne Scarring

Acne vulgaris is a chronic skin condition, which is characterized by the presence of different types of skin lesions, including open and closed comedones, pustules, papules, and cysts, depending on the course of the disease. Inadequate treatment or severe forms of acne may lead to scarring [17], which is an undesirable and long-term consequence of the disease, negatively impacting the body image and self-esteem [18,19]. Atrophic scarring, the pathophysiology of which is associated with an excessive and prolonged inflammatory response, loss of collagen in the skin, and damage to the sebaceous glands, represents the most common type of acne scars. Several treatment methods which effectively address the issue of acne scarring are available, and these include ablative lasers, radiofrequency, and microneedling. However, they often require a prolonged period of recovery, are associated with significant pain, and may carry the risk of post-inflammatory hyperpigmentation (PIH). Contemporary dermatology and cosmetology offer various procedures which are linked with minimal risk of side effects, allowing the affected patients to return to daily activities shortly after the treatment [11,17]. Among others, the fractional PS laser, whose mechanism of action is based on fractional photothermolysis, is an example of such modern modality. In 2014, fractional photothermolysis was approved by the Food and Drug Administration (FDA) for the treatment of atrophic acne scars [6,20]. Compared to the nanosecond lasers, picosecond lasers deliver energy fluence at a shorter pulse duration, allowing for an adequate photoacoustic effect while lowering nonspecific photothermal damage. As a result, the safety of the treatment has considerably increased, with reduced risk for PIH. Recently, numerous studies have demonstrated the efficacy of fractional PS lasers for treating acne scarring, with minimal side effects [21].

The results of using diffractive lens array mode of a picosecond pulsed alexandrite laser (755 nm) for the reduction of scarring are particularly promising [3]. Brauer et al. [22], were the first to confirm the potential of a 755-nm alexandrite PS pulse duration laser with diffractive lens array in their cohort of 20 patients (15 women, 5 men) with acne scarring and I–V skin types. Their patients underwent six treatment sessions with a picosecond laser every 4–8 weeks. Three months after the final session, scar imaging and histopathological evaluation were performed. Mean reduction of the scar volume was 27%, and microscopic analysis revealed an increase in the number of elastic and collagen fibers in the dermis. The patients reported to be ‘satisfied’ or ‘highly satisfied’ with the overall appearance and texture of their skin during the final treatment session and at 1 and 3 months of follow-up. They also reported transient erythema and edema, both of which resolved within a few hours (max. two days) after the procedure [22].

Lin et al. [23] conducted a comparative study to assess the efficacy of a non-ablative fractional laser (1550 nm) and a picosecond laser (755 nm) with DLA for the treatment of atrophic facial acne scars among Asian patients. The non-ablative laser demonstrated superior efficacy, although the picosecond laser treatment proved to be less painful, induced only transient erythema, and did not result in PIH or exacerbation of the acne lesions [23].

Huang et al. [24], reported excellent, long-lasting efficacy of the 755 nm PS laser with a diffractive lens in treating atrophic acne scars. These authors also emphasized the suitability of this laser for Asian skin types, without the risk of PIH. Their study included three cases with the longest clinical follow-up after treatment with the 755 nm PS laser and diffractive lens. The effectiveness of the treatment was evaluated using photographic documentation. Each patient underwent 4–6 treatment sessions. All participants exhibited mild to moderate improvement in scar texture after an average of 4.28 sessions, with a mean follow-up period of 7.3 weeks. In light of the relative novelty of this technology, the long-term effectiveness of PS lasers remains to be determined. That study provided valuable insight into the sustainability of therapeutic efficacy, which was visible at least six months post-treatment and remained significant until 28 months after treatment completion [24]. Studies showing the effects of using picosecond lasers to treat acne scars are presented in

Table 2. Studies showing the effects of using picosecond lasers to treat acne scars.

Authors	Type of Study	Number of Patients	Type and Location of the Lesions	Skin PHOTOTYPES	Type of Picosecond Laser	Number of Procedures	Treatment Parameters	Results
Brauer et al. [22]	clinical trial	20	rolling-type acne scars, boxcar scars, icepick scars; face	I–V	alexandrite (755 nm) with diffractive lens array	6	spot size 6 mm; fluence 0.71 J/cm2; repetition rate 5 Hz; pulse width 750 ps	significant improvement in skin texture; high patient satisfaction; increase in collagen and elastin fibers in the skin
Lin et al. [23]	a prospective randomized split-face clinical study	23	rolling-type acne scars, boxcar scars, icepick scars; face	III–IV	alexandrite (755 nm) with diffractive lens array	3	spot size 6 mm; fluence 0.71 J/cm2; pulse width 750 ps; repetition rate 10 Hz	improvement in skin texture of 1–25%; no side effects: very low pain level
Huang et al. [24]	case report	3	rolling-type acne scars, boxcar scars, icepick scars; face	III–IV	alexandrite (755 nm) with diffractive lens array lens array	4–6	no data	significant improvement in skin texture several months after the last session

.

4.2. Striae Distensae

Striae distensae (stretch marks) are visible linear scars which develop in areas where the dermis has been damaged due to excessive stretching [25]. Anatomically, these lesions predominantly appear on the buttocks, lower back, thighs, calves, breasts/chest, abdomen, upper arms, and knees [26]. Striae are twice as prevalent in females as compared to males, mainly among individuals aged 5–50 years [25]. The clinical presentation depends on their maturation stage. In the early stage, they manifest as erythematous, raised, linear lesions, which may be accompanied by mild pruritus. These are commonly referred to as the red striae. With further maturation, they undergo atrophy and depigmentation, eventually evolving into hypopigmented, atrophic scars known as the white striae [27]. The pathogenesis of striae distensae remains to be elucidated, although the prevailing theories suggest that it is associated with the alterations in the components of the extracellular matrix: fibrillin, elastin, and collagen. These structures ensure that the skin possesses tensile strength and elasticity. Elevated concentrations of glycosaminoglycans and a significantly reduced number of vertical fibrillin fibers beneath the dermo-epidermal junction and within the elastic dermis are found in patients with striae as compared to individuals with normal skin. The orientation of the elastin and the fibrillin fibers in the deeper dermis is disrupted. In the early stages of striae formation, the elastic fiber network is markedly disorganized, and the newly synthesized fibrils, rich in tropoelastin, are thin and structurally disorganized. Furthermore, as the collagen fibers become significantly separated during this period, the newly disorganized collagen fibrils are not able to repair the damaged collagen fibers due to excessive stretching of the skin, ultimately leading to the formation of the atrophic striae [28].

Typically, striae distensae develop during puberty, pregnancy, periods of rapid weight fluctuations (both loss and gain), and may arise as a consequence of various systemic diseases or pharmacotherapy [29]. Striae constitute a common aesthetic concern which significantly affects the quality of patient life, especially young women [30]. Currently, a whole range of treatment modalities may be used to reduce their visibility, with laser therapy proving to be highly effective [31]. The eCO₂ laser (10 600 nm) and the Er:YAG (erbium-doped yttrium aluminum garnet) laser (2940 nm) are among the commonly employed ablative fractional lasers to treat striae. These lasers yield promising therapeutic results but their application is associated with a risk of complications such as prolonged post-inflammatory hyperpigmentation, especially in case of the eCO2 laser, with higher energy settings, and in patients with darker skin phototypes [28]. Non-ablative lasers, such as the erbium-glass (Er:Glass 1540 nm) and the Nd:YAG 1064 nm, have also proven to be effective in striae therapy. They offer an alternative to the ablative lasers as they are associated with reduced invasiveness and shorter recovery time. The picosecond laser, which induces microscopic tissue damage, is the most recent non-ablative fractional laser with a diffractive lens array or holographic fractional technology [32,33].

Currently, the picosecond laser, which induces microscopic tissue damage, represents the most recent development in non-ablative fractional lasers utilizing a diffractive lens array or holographic fractional technology [34]. Fusano et al. [35] used a fractional PS Nd:YAG laser (1064 nm) to reduce mature, atrophic striae located on the breasts, abdomen, and buttocks of Caucasian women, who underwent four treatment sessions at monthly intervals. The Global Aesthetic Improvement Scale (GAIS) and optical evaluation of the skin structure via 3D imaging, at baseline and 6 months post-treatment, were used to assess the efficacy of the therapy. Additionally, reflectance confocal microscopy was employed to evaluate microscopic changes in the skin after the therapy. An overall improvement (GAIS) was reported by 81.4% of the physicians and 66% of the patients. The findings of 3D imaging revealed significant improvement in skin texture and striae depth. These results were corroborated by confocal microscopy, which indicated collagen remodeling and formation of new dermal papillae. That confirms that the fractional picosecond laser facilitates collagen neogenesis and dermal repair through microinjury-induced remodeling [35].

Kaewkes et al. [36] investigated long-term efficacy and safety of the fractional PS Nd:YAG laser (1064 nm) for treating mature striae in individuals with darker skin phototypes (IV–V). Similar to Fusano et al., these authors performed four treatment sessions at monthly intervals and assessed treatment efficacy using 3D imaging. However, in their study, skin texture was evaluated more frequently, i.e., not only at 6 months post-treatment, but also at 1 month after the second session, and at 1 and 3 months after the final session. These authors observed a progressive improvement in skin texture, up until the last follow-up visit. A moderate to significant improvement in striae appearance was found in 90% of the participants. That study confirmed the efficacy, tolerability, and, most importantly, safety of using the 1064 nm fractional PS laser for treating mature striae in individuals with darker skin tones [36].

Zaleski-Larsen et al. [37] compared the outcomes of treating mature abdominal striae using two non-ablative laser modalities: the erbium-glass (1565 nm) laser and the 1064/532 nm fractional PS Nd:YAG laser. The therapeutic outcomes were similar in terms of improvement of the skin texture and reduction of the depth of the striae, while the participants reported less pain and shorter recovery period in the PS laser group [37]. Studies reporting the effects of using picosecond lasers to treat stretch marks are presented in

Table 3. Studies reporting the effects of using picosecond lasers to treat stretch marks.

Authors	Type of Study	Number of Patients	Type and Location of the Lesions	Skin PHOTOTYPES	Type of Picosecond Laser	Number of Procedures	Treatment Parameters	Results
Fusano et al. [35]	clinical report	27	striae albae; breasts, abdomen, buttocks	II–III	fractional Nd:YAG laser with frequency-double wave (1064/532 nm)	4	Spot size 8 mm; fluence 0.6 ± 0.2 J/cm2; laser pulse duration 450 ps,	significant improvement in skin texture and marked reduction in stretch marks (PGAIS * 81.4%, SGAIS ** 66.6%); high patient satisfaction, collagen remodeling and presence of new dermal papillae as determined by confocal microscopy
Kaewkes et al. [36]	clinical report	20	striae albae; abdomen	IV–V	fractional Nd:YAG (1064 nm)	4	spot size 8 mm; fluence 0.6 J/cm2; repetition rate 10 Hz; pulse duration 750 ps;	significant improvement in skin texture at 1 month post-treatment increasing over time; moderate to marked improvement in appearance of stretch marks in 90% of subjects; high tolerability and safety with skin phototypes IV–V
Zaleski-Larsen et al. [37]	split body double-blinded trial	20	striae alba; abdomen	no data	fractional Nd:YAG laser with frequency-double wave (1064/532 nm)	3	1064 nm (spot size 6 mm; fluence 1.3 mJ/µbeam; 4 passes) 532 nm (spot size 6 mm; fluence 0.4 mJ/µbeam; 2 passes)	improvement in skin texture by 30%; improvement in stretch mark atrophy by 35%; overall improvement in skin condition by 48%; low pain and short recovery

* PGAIS—Physician Global Aesthetic Improvement Scale, ** SGAIS—Subject Global Aesthetic Improvement Scale.

.

4.3. Pigmentation Disorders

The picosecond laser is an advanced technology which proved to be beneficial in treating benign pigmentation disorders, including freckles, solar lentigines, melasma, Hori’s nevus, Ota’s nevus, and post-inflammatory hyperpigmentation [38]. These skin lesions constitute a common aesthetic concern and can negatively impact the well-being and self-esteem of the affected individuals [39]. The treatment of pigmentation disorders poses a challenge, especially in individuals with higher skin types (III–IV) as compared to those with lighter skin tones [40]. Apart from genetically determined skin phototype, the depth of the pigmentary lesions plays a crucial role as far as the success of laser therapy is concerned. Dermal pigmentation disorders, in contrast to epidermal lesions, are more resistant to medical interventions, tend to be chronic in nature, are associated with a higher risk of PIH, and usually require a higher number of treatment sessions [41]. Extensive photothermal damage, which may be induced by lasers, is a common cause of complications in patients with darker skin types. That fact contributed to the development of PS laser technology, which relies on photoacoustic destruction rather than photothermolysis [6]. PS lasers, emitting wavelengths of 532 nm, 755 nm, and 1064 nm, which effectively fragment pigment clusters into smaller particles with minimal thermal effects, thus reducing the risk of inflammation and PIH, are used [42,43].

Melasma, which manifests as irregular, light-to-dark brown patches on the face, is one of the most prevalent and recurrent pigmentation disorders in women [44]. The Nd:YAG (1064 nm) PS laser is often used for treating melasma. Bernstein et al. [45], conducted a study using this laser, equipped with a fractional handpiece with microlens array, among 20 adult individuals of both sexes (Fitzpatrick I–IV) with facial melasma. The participants underwent a series of four monthly treatments. Skin reaction was assessed immediately after the session, and therapy efficacy was evaluated by dermatologists through photographic analysis at 3 and 8 months after treatment completion using the Modified Melasma Area and Severity Index (mMASI). Also, the patients rated their discomfort and satisfaction level after each session. Significant improvement of the skin condition and less visible melasma was found at 3 and 8 months post-treatment, which was consistent with the patient-reported outcomes. All treatments were well-tolerated by the patients, with only mild and transient side effects (erythema and edema), and low pain scores (mean: 3.8 ± 2.3 on an 11-point scale) [45].

Chan et al. [46] also used a fractional Nd:YAG (1064 nm) PS laser in Asian women with Fitzpatrick skin types III–IV and facial melasma. The participants underwent nine treatment sessions every 4–6 weeks. The efficacy of the therapy was assessed using the mMASI score, based on photographs taken at 6 and 12 weeks post-treatment. The total mMASI score decreased by 75% at 6 weeks and by 66.7% at 12 weeks after therapy completion. Furthermore, 75% of the women reported visible skin improvement as compared to baseline within 6 weeks of treatment, which was consistent with high levels of satisfaction with the outcome. The main objective of that study was not only to evaluate the efficacy of fractional Nd:YAG PS laser therapy for melasma, but also to assess its safety for darker skin types. Mild erythema (84.4%) and edema (1.1%), both of which resolved within one week, were the most common adverse events. No cases of hypo- or hyperpigmentation were observed, and the procedure was described as ‘minimally painful’ by the participants. These findings suggest that the fractional Nd:YAG PS laser is an effective, well-tolerated, and, most importantly, safe treatment option for treating melasma in Asian skin types [46].

The literature offers a report about a combination laser therapy using a 1064 nm PS laser and a 1927 nm thulium laser for melasma reduction in a 44-year-old female [47]. During the procedure, both lasers were used simultaneously, first the pigmented lesions were treated with a non-ablative PS laser (1064 nm), and next, the thulium laser, which generates a dense network of microthermal injury zones, followed by pigment migration from the deeper dermis and epidermis, while stimulating controlled healing and dermal remodeling. Erythema, persisting for 3 days, developed immediately after the procedure. The patient also reported transient darkening of the lesions for about 7 days, followed by gradual fading over the course of the next 3–4 weeks. At 4 weeks of follow-up, a noticeable lightening of the pigmentation lesions was observed, indicating the effectiveness of the combined laser approach [47].

Promising results of treating melasma with 755 nm PS lasers have also been reported. Manuskiatti et al. [48], compared the efficacy and safety of using the 755 nm PS laser in melasma treatment by applying a fractionated beam (diffractive lens array) on one side and a full beam (flat optics) on the other side of the face. The study included 18 women with Fitzpatrick skin types IV and V and mixed-type melasma. All participants underwent five treatment sessions at monthly intervals. Treatment efficacy was assessed through comparative analysis of the photographs taken at baseline and after therapy completion, as well as at 1, 3, and 6 months post-treatment, and by measuring melanin concentration and size of the melasma-affected area. The physicians observed a 25% reduction in melasma severity with both lasers, which correlated with the improvement reported by the patients. The measurements of melanin concentration and area with melasma revealed a tendency toward improvement on both sides of the face. No statistically significant differences between the results of applying the two laser modalities were observed during the follow-up visits. Objective assessments of melasma severity aligned with the clinical evaluation. However, the full beam (flat optics) treatment was associated with a lower PIH incidence as compared to the fractionated beam [48].

Liang et al. [49] compared the efficacy and safety of three melasma treatment modalities: a non-fractional PS Nd:YAG laser (1064 nm), a non-fractional PS alexandrite laser (755 nm), and a 2% hydroquinone cream among 60 patients with Fitzpatrick skin types III–IV. The participants were randomized into three groups. The laser groups underwent three treatment sessions at 4-week intervals, while the third group applied hydroquinone cream twice daily for 12 weeks. All groups demonstrated a significant decrease in MASI scores from week 4 to week 24 as compared to baseline. The lowest MASI values were observed in the Nd:YAG laser group, while the MASI scores in the alexandrite laser (755 nm) group and the hydroquinone cream group were comparable. At the same time, patient satisfaction scores were highest in the Nd:YAG laser group, followed by the alexandrite laser group, with the hydroquinone group reporting the lowest satisfaction levels. Melasma recurrence was reported in only four patients (6.8%). Other adverse events were transient, resolving within 1 week to 6 months. These findings suggest that the non-fractional PS Nd:YAG laser is more effective in the reduction of melasma than the non-fractional PS alexandrite laser, whose efficacy was comparable to that of 2% hydroquinone cream therapy [49].

Apart from melasma, other common hyperpigmentation disorders include freckles, lentigines, and post-inflammatory hyperpigmentation. Ren et al. [50] investigated the long-term efficacy of the 755 nm PS alexandrite laser in reducing PIH. They analyzed two cases of post-traumatic PIH in individuals with Fitzpatrick skin type III, treated with a combination of the 755 nm PS alexandrite laser and either a diffractive lens array or a zoom handpiece. Based on photographic documentation, the efficacy of the treatment was independently evaluated by two plastic surgery specialists, blinded to the clinical data. After 2–3 treatment cycles, significant or complete improvement was observed in both cases. There were no signs of recurrence during the three-year follow-up period, which suggests that the 755 nm PS alexandrite laser, in combination with a diffractive lens array or zoom handpiece, offers an effective, long-term, and safe treatment option for treating PIH [50].

Qilei Che et al. [43], evaluated the clinical efficacy of a 730 nm PS laser for treating freckles and solar lentigines. This laser operates with an ultrashort pulse duration and it allows for an efficient fragmentation of pigment within the target tissues. The study included 50 patients with Fitzpatrick skin types III–IV, who underwent two sessions with the 730 nm picosecond laser at one-month intervals. The rates of lesion clearance after one and two sessions were 53.1% and 78.4%, respectively, while the clearance rates at 1 and 6 months post-treatment were 78.7% and 78.4%, respectively. As many as 90% of the patients reported ≥ 95% lesion reduction at six months of follow up, with the overall satisfaction rate of 86.0%. PIH was observed in only two patients with Fitzpatrick type IV, and no lesion recurrence was reported. These findings emphasize the superiority of the 730 nm PS laser in treating freckles and lentigines [43].

Kauvar et al. [51], in their study involving 20 patients with Fitzpatrick skin types II–IV who underwent treatment for lentigines, reported comparable results. In addition to assessing the safety and efficacy of the 730 nm PS laser, these authors performed histopathological analyses to evaluate the impact of short laser pulses on the skin as compared to the effects of 532 nm PS pulses and 532 nm and 755 nm NS pulses. The 730 nm PS laser demonstrated high efficacy in reducing lentigines, with no adverse events and high patient satisfaction. Histological analysis revealed dispersed, focal vacuolization (5–10 µm in diameter) of the epidermis and mild erythrocyte extravasation following 730 nm PS pulses, whereas the 755 nm nanosecond pulses led to diffuse epidermal vacuolization with vacuole coalescence (20–100 µm), junctional separation, and mild erythrocyte extravasation. The 532 nm PS pulses resulted in dispersed, focal epidermal vacuolization with larger dermal vacuoles, extending to the depth of 500 µm, while the 532 nm nanosecond pulses induced diffuse epidermal vacuolization, with vacuole coalescence and prominent dermal hemorrhage. These histological findings indicate that the 730 nm PS laser is a superior pigment-selective modality, with minimal disruption to the dermo-epidermal junction, which suggests that it may reduce healing time and minimize the risk of adverse events [51]. Studies showing the effects of using picosecond lasers to reduce hyperpigmentation are presented in

Table 4. Studies showing the effects of using picosecond lasers to reduce hyperpigmentation.

Authors	Type of Study	Number of Patients	Type and Location of the Lesions	Skin Phototypes	Type of Picosecond Laser	Number of Procedures	Treatment Parameters	Results
Bernstein et al. [45]	clinical report	20	melasma; face	I–IV	fractional Nd:YAG (1064 nm)	4	spot size 6 mm; fluence 1.7−2.9 mJ/µbeam; repetition rate 6–8 Hz; pulse duration 450 ps; 2 passes	significant improvement in skin condition and reduction in the appearance of melasma (according to Mmasi *); high patient satisfaction; high treatment tolerance
Chan et al. [46]	clinical report	20	melasma, face	III–IV	fractional Nd:YAG (1064 nm)	up to 9	spot size—6 mm; fluence range −1.3–1.9 mJ/µbeam; repetition rate 5–10 Hz; pulse duration 450 ps; 4 passes	statistically significant improvement in mMASI, high patient satisfaction; no serious side effects; no post-treatment hypo-/hyperpigmentation; low procedure pain (VAS **—1.92/10)
Kozińska, Gras-Ozimek [47]	case report	1	melasma; face	no data	Nd:YAG (1064 nm) + thulium laser (1927 nm)	1	no data	visible brightening of melasma, low pain of the procedure, short recovery period
Manuskiatti et al. [48]	randomized controlled trial	18	melasma; face	IV–V	alexandrite (755 nm) with and without diffractive lens array	5	spot size 8 mm; average fluence 0.4 J/cm2; frequency 2.5 Hz; 2 passes	reduction of melasma by 25% for both lasers, lower incidence of post-inflammatory hyperpigmentation for the unfractionated beam
Liang et al. [49]	clinical trial	60	melasma; face	III–IV	non-fractional Nd:YAG (1064 nm) vs. non-fractional alexandrite (755 nm) vs. topical hydroquinone	3	Nd:YAG (spot size 7 mm; fluence 0.75–0.90; repetition 8 Hz; 2 passes; pulse duration 450 ps) alexandrite (spot size 6–8 mm; fluence 0.40–0.71; repetition 10 Hz; 2 passes; pulse duration 750 ps)	greatest reduction of MASI score for Nd:YAG; comparable MASI improvement for alexandrite laser and topical hydroquinone, highest patient assessment score for Nd:YAG laser treatment
Ren et al. [50]	case reports	2	PIH ***; face	III	alexandrite (755 nm) with diffractive lens array	2–4	first case (pulse width 750 ps; frequency 10 Hz, spot size 8 mm, energy density 0.4 J/cm2)second case (pulse width 750 ps; frequency 1 Hz; spot size 3.2 mm; energy density 2.49 J/cm2)	significant or complete improvement after treatment in both cases; no recurrence during 3 years of follow-up
Qilei Che et al. [43]	retrospective analysis	50	solar lentigines, freckles; face	III–IV	730 nm picosecond laser	2	Pulse width 250 ps; frequency 1 Hz, energy density 1.5–1.8 J/cm2	significant lightening of hyperpigmentation after one and six months of treatment; high satisfaction with treatment results; no recurrence of lesions; short downtime
Kauvar et al. [51]	clinical trial	20	solar lentigines; arms, hands, scalp, forehead, face, back	II–III	730 nm picosecond laser vs. 532 nm picosecond laser vs. 532 and 755 nm nanosecond pulses lasers	up to 4	mean fluence 2.2–3.9 J/cm2; mean spot size 2.0–2.9 mm;	significant reduction of lentigines; no adverse events; high patient satisfaction; high selectivity of the 730 nm laser to melanin, proven by histological analysis

* mMASI—modified Melasma Area and Severity Index, ** VAS—Numerical Visual Analog Scale, *** PHI—Post-inflammatory hyperpigmentation.

.

4.4. Skin Aging

Skin aging is a physiological process which occurs with progressing time. The primary clinical manifestations of skin aging include pigmentary changes, telangiectasia, loss of firmness, and formation of wrinkles, which is associated with cellular aging, reduced synthesis of the collagen, and increased cell degradation. Skin aging is influenced by two types of factors: intrinsic and extrinsic. Intrinsic factors primarily include the cumulative effects of time and the effect of the related physiological characteristics, whereas extrinsic factors include ultraviolet radiation, smoking, exposure to wind and to harmful chemicals. These stimuli, especially the extrinsic factors, cause macromolecular structural damage and the related functional changes in skin cells, leading to accelerated aging of the skin [52,53]. Non-invasive aesthetic procedures, e.g., laser therapy, are employed to improve the appearance of the aging skin. Laser technology provides a variety of skin rejuvenation options, including ablative, non-ablative, and fractional laser treatments, and the choice of the method depends on the condition of the skin [54,55]. Fractional ablative lasers, such as the CO₂ laser (10,600 nm) and the Er:YAG laser (2940 nm), are considered to be the gold standard for skin rejuvenation. They offer the chance of significant clinical improvement but they are associated with lengthy recovery periods and marked adverse effects, including edema and persistent crusting. Non-ablative lasers, which stimulate regenerative processes within the skin while preserving the integrity of the epidermis, offer an interesting alternative [56]. Among others, picosecond lasers with fractional modes belong to that category. The high fluence pulses emitted by these lasers induce the synthesis of collagen and elastin through photomechanical effects, without surface ablation [9]. Due to their favorable safety profile, particularly in individuals with higher Fitzpatrick skin phototypes, non-ablative PS lasers have become a popular method of achieving skin rejuvenation among Asian patients [57].

Wardhani et al. [57], used a 755 nm PS alexandrite laser with a diffractive lens array to assess its efficacy and safety in facial skin rejuvenation among the Indonesian population. The study included 20 participants, aged 36–55 years, with clinical signs of photoaging (Fitzpatrick III–V). Each patient underwent two treatment sessions, with a four-week interval. Identical treatment parameters were applied to all patients (6 mm, 0.71 J/cm², 10 Hz), with a minimum of 3–4 passes until mild erythema was achieved. The condition of the skin was evaluated at baseline and four weeks after treatment completion, based on the standardized photographs of the affected area. Wrinkle count, pigmentation, and skin texture were taken into consideration. One month after treatment completion, moderate improvement (25–50% reduction in skin changes) was observed in 40% of the participants, while good improvement (50–75% reduction in skin changes) was confirmed in 60% of the patients. Mild erythema and transient swelling, which are typical after skin procedures, were present in all participants. Additionally, five patients developed solar urticaria, and two (Fitzpatrick III) developed petechiae. All adverse effects resolved within a few days and no cases of post-inflammatory hyperpigmentation or hypopigmentation were observed. These findings suggest that the 755 nm PS laser is an effective and safe modality for facial skin rejuvenation in Indonesian patients [57].

Ross et al. [58] investigated the efficacy of a fractional PS laser (1064/532 nm) in reducing pigmentation irregularities and fine wrinkles on the face, which are typical signs of photoaging. The study included 18 patients (Fitzpatrick I–III), with 10 completing the full treatment protocol. Each participant underwent three laser sessions, with 4-week intervals. Assessment of the skin was performed by analyzing photographs taken at baseline and at 1, 3, and 6 months of follow-up after treatment completion. During each visit, patient satisfaction and treatment-related discomfort were also documented for both wavelengths (532 nm and 1064 nm). The treatment utilized only fractional optics, with the handpiece configured to deliver 100 microbeams per hexagonal area with a 10-mm diameter. The micro-spot sizes were 700 μm for the 532 nm wavelength and 400 μm for the 1064 nm wavelength. A maximum of six passes were performed for each wavelength, first for 1064 nm, followed by 532 nm. These results indicate that the laser used in that study was well tolerated by the patients (minimal pain, mild side effects), and resulted in mild-to-moderate improvement in wrinkle reduction and pigmentation correction, with pigmentary improvements being more pronounced than wrinkle reduction. This effect was most likely attributable to the use of the 532 nm wavelength. Additionally, the 532 nm wavelength was also linked with more intense erythema and greater discomfort immediately after the treatment [58].

Lim et al. [59] investigated the possibility of skin rejuvenation using a fractional PS Nd:YAG laser (1064 nm). They conducted an in vivo study on the skin of old and young female hairless mice, performing topographical assessments, histological analyses, and electron microscopy of the treated area. The first part of the study was supposed to confirm the efficacy of the PS Nd:YAG laser, while the second attempted to elucidate its mechanism of action. The study included sixty-week-old and twenty-week-old mice. Older mice underwent three treatments, with a 10-day interval between the sessions, while the younger mice received only a single treatment. Each treatment involved five passes of the laser beam using the following parameters: spot size—10 × 10 mm, fluence—0.24 J/cm², pulse frequency—3 Hz. Histological and molecular analyses were conducted at 1 and 6 h after the laser treatment. A significant improvement in skin topography was observed in the older mice on the surfaces which were treated with the laser. The skin surface became noticeably smoother. Histological images of the skin samples from the treated areas in older mice revealed higher dermal thickness, with a higher content of collagen, elastin, and key extracellular matrix components. Additionally, an increase in epidermal thickness was observed in the laser-treated area. In contrast, histological images of the skin of the younger mice showed no distinct microthermal damage but localized epidermal erosion and focal condensation of the collagen, accompanied by extravasation of red blood cells, one-hour post-treatment. No significant perivascular inflammatory cell infiltration was detected, either 1 or 6 h post-treatment. These authors also found elevated levels of heat shock proteins, growth factors, and platelet-activating factors in the laser-treated area as compared to the control group. These findings suggest that the mechanism of action of the fractional PS Nd:YAG laser (1064 nm) is associated with partial disruption of the collagen fibrils and capillaries through photomechanical and photothermal effects, which induces a mild inflammatory response, leakage of plasma and red blood cells, and increased expression of the growth factors involved in dermal regeneration [59]. Studies showing the effects of using picosecond lasers to reduce signs of skin aging are presented in

Table 5. Studies showing the effects of using picosecond lasers to reduce signs of skin aging.

Authors	Type of Study	Number of Patients	Type and Location of the Lesions	Skin Phototypes	Type of Picosecond Laser	Number of Procedures	Treatment Parameters	Results
Wardhani et al. [57]	retrospective study	20	photoaging; face	III–V	alexandrite (755 nm) with diffractive lens array	2	spot size 6 mm; fluence 0.71 J/cm2; frequency 10 Hz; 3 to 4 passes	significant improvement in skin pigmentation, texture, and wrinkle depth; mild side effects (short-term erythema and swelling); high safety for dark skins (no hypo/hyperpigmentation)
Ross et al. [58]	clinical trial	18	photoaging; face	I–III	fractional Nd:YAG laser with frequency-double wave (1064/532 nm)	3	pulse duration 800 ps; spot size 10 mm; total pulse energy −350 mJ for 1064 nm and 250 mJ for 532 nm	moderate improvement in pigmentation and fine wrinkles in 93% of patients at 532 nm and in 79% at 1064 nm according to GAI *, only mild post-treatment erythema
Lim et al. [59]	preclinical reports	5 (2 old and 3 young mice)	in vivo study on the skin of old (60-week-old) and young (20-week-old) female mice	-	fractional Nd:YAG (1064 nm)	older mice −3; younger mice 1	spot size 10 mm; fluence 0.24 J/cm2; frequency 3 Hz; 5 passes	significant improvement in skin topography of older mice (marked smoothing of the skin); increase in dermal thickness on histological examination, increase in collagen synthesis markers and inflammatory cytokines

* GAI—Global Aesthetic Improvement.

.

5. Summary

The presented data indicate the multidirectional applications of picosecond lasers. These devices may be helpful when addressing various aesthetic concerns and across different skin types, with minimal risk of adverse effects.