1. Overview of Picosecond Laser

Picosecond laser refers to a laser with an output pulse width at the picosecond level, mainly including 755nm, 532nm and 1064nm 3 working wavelengths. Due to its extremely short pulse width, picosecond laser can achieve extremely high peak power in an instant, thus producing photoacoustic effect (or photomechanical effect) on the target chromophore, breaking up tattoo dye particles or melanin particles into smaller particles, making them easier to be cleared by chromophilic cells such as macrophages, and causing a lighter inflammatory reaction. Therefore, picosecond laser is more effective and has lighter adverse reactions than Q-switched laser in the treatment of tattoos and most pigmented diseases. In addition, through a honeycomb focusing lens or a holographic diffraction lens, picosecond laser can be focused into a dot matrix beam of uniform size and uniform spacing. Since each microbeam has an extremely high peak power, when it exceeds the photodecomposition threshold of the target chromophore (melanin or hemoglobin), the target chromophore absorbs energy nonlinearly to produce a photodecomposition effect and form a plasma. The plasma continues to efficiently absorb laser energy while expanding continuously, eventually producing an explosion phenomenon in the epidermis or dermis, leading to the formation of cavitation bubbles, which is laser-induced optical breakdown (LIOB) [1]. There is no damage to the tissues around LIOB, and the inflammatory reaction is also very mild. With the occurrence of LIOB, new collagen and elastic fibers may appear in the dermis [2,3]. The LIOB effect enables fractional picosecond laser to improve photoaging and acne pitting scars. Compared with ablative fractional laser and near-infrared non-ablative fractional laser, it has fewer adverse reactions and almost no downtime.

2. Indications, parameter selection and contraindications for picosecond laser application

2.1 Pigmented diseases

Picosecond laser can be used to treat a variety of epidermal and dermal pigmented diseases. It has ideal effects on freckles, solar lentigo, nevus of Ota and other diseases; it is effective for coffee spots, freckle-like nevus and other diseases, but there is still a certain recurrence rate; the efficacy of picosecond laser for pigmented hairy epidermal nevus and Reil's melanosis is still uncertain, and it can be used as one of the improvement methods.

Diseases with increased epidermal pigmentation, such as freckles, solar lentigo, and coffee spots, can be treated with 532nm Nd:YAG picosecond laser or 755nm alexandrite picosecond laser. Treatment parameters should be set according to the patient's skin type and skin lesion color, and generally mild white frost reaction is used as the treatment endpoint. In the treatment of freckles and solar lentigo, patients with Fitzpatrick type Ⅲ~Ⅳ skin, lesions with obvious contrast and clear boundaries with normal skin have better efficacy; while patients with lighter skin lesions and concurrent chloasma have a higher chance of post-inflammatory pigmentation than the former. For the treatment of coffee spots, freckles, etc., some patients can have significant effects, but the chance of recurrence is high.

For skin-dermal pigmentation diseases such as pigmented piloepidermal nevus and Reil's melanosis, 532nm Nd:YAG picosecond laser, 755nm alexandrite picosecond laser, and 1064nm Nd:YAG picosecond laser can be used as one of the treatment methods, but the efficacy is still uncertain.

For skin-dermal pigmentation diseases such as nevus of Ota and acquired nevus-like spots of Ota, 755nm alexandrite picosecond laser and 1064nm Nd:YAG picosecond laser can be used for treatment. The treatment interval is generally 3 to 6 months, and the treatment effect is ideal. Generally, recovery can be achieved after several treatments. The number of treatments required to achieve recovery of nevus of Ota in children is generally less than that in adults. In recent years, studies have confirmed that alexandrite picosecond laser treatment of Ota nevus[4] and acquired Ota nevus-like macules[5] has a higher skin lesion clearance rate than Q-switched alexandrite nanosecond laser single-session treatment, and requires fewer treatments to achieve complete recovery. The incidence of post-inflammatory pigmentation after treatment of acquired Ota nevus-like macules is high, and the treatment interval can be extended accordingly. For patchy blue nevus, treatment is effective in some patients, but the number of treatments is significantly increased. Occasionally, studies have reported that blue nevus can become malignant, and during treatment, attention should be paid to whether the skin lesions increase in size or ulcerate in a short period of time.

2.2 Skin rejuvenation

Skin aging refers to the skin aging phenomenon caused by natural or non-natural factors, including endogenous and exogenous aspects. Skin aging is often accompanied by a series of pathological and physiological changes such as thinning of the epidermis, reduction of dermal collagen, decreased tightness of the epidermal junction, and atrophy or reduction of dermal papillae, capillaries, and skin appendages. The clinical manifestations are dry and rough skin, loose and lack of elasticity, increased wrinkles, dull color, large pores, spots and plaques, etc. Currently, 755nm and 1064nm picosecond lasers are mainly used for facial rejuvenation treatment. Weiss et al. [6] used 755nm Alexandrite picosecond laser honeycomb mode to improve patients' perioral and periorbital wrinkles. The study used a 6mm spot, 10HZ, 750ps pulse width, and 0.71J/cm2 treatment volume to treat 40 patients with Fitzpatrick wrinkle scores of 4 to 7. Six of the subjects underwent skin biopsy observations: One month after treatment, the basal keratinocytes were mildly vacuolated, the volume and density of dermal collagen increased, and the elastin fibers increased with mild inflammatory cell infiltration; three months after treatment, there was no inflammatory cell infiltration, the collagen structure continued to maintain an increasing trend in density, and the elastic fibers increased significantly; six months after treatment, histology showed a significant increase in dermal collagen, especially in the middle and lower dermis, and a significant increase in elastic fibers in the upper dermis. Two other clinical studies using picosecond lasers to improve wrinkles showed that picosecond lasers have a positive therapeutic effect on improving wrinkles and achieving facial rejuvenation [7,8].

2.3 Scars

Scars are tissues formed by the healing of human skin wounds. They can be divided into physiological scars and pathological scars. The latter can be divided into depressed scars, atrophic scars, hypertrophic scars and keloids. The application of photoelectric technology to treat pathological scars has always been one of the important clinical practices of scar treatment and has achieved satisfactory results [9]. Literature reports on the use of different wavelength picosecond pulse width lasers to treat pathological scars are mainly for acne depressed scars [10,11]. Bernstein et al. [12] used 1064nm or 532nm Nd:YAG picosecond lasers to treat facial acne depressed scars. 81% of the subjects believed that their condition had improved, and the degree of improvement could reach 60%. The subject satisfaction was as high as 85%. No complications such as pigmentation were observed. There was no significant difference in the treatment effect between the two wavelengths of picosecond lasers.

2.4 Melasma

Currently, both 1064nm Nd:YAG picosecond laser and 755nm alexandrite picosecond laser have been used to treat melasma. In clinical practice, some use non-fractional mode, some use fractional mode, and some use a combination of the two, but the number of cases in related studies is limited. Some studies have shown that the efficacy of Nd:YAG picosecond laser for melasma is slightly better than 2% or 4% hydroquinone cream for external use [13,14], while the efficacy of alexandrite picosecond laser is roughly equivalent to that of triple cream (0.01% fluocinolone acetonide, 4% hydroquinone, 0.05% retinoic acid) [15] and is better than large-spot, low-energy Q-switched Nd:YAG nanosecond laser [16], which removes pigments faster and more significantly. In the comparison of fractional mode and non-fractional mode in the treatment of melasma, a study showed that the alexandrite picosecond laser fractional mode had a higher improvement rate and a lower recurrence rate than the non-fractional mode (flat cap mode) [17]; however, the difference in the number of patients in the two groups in this study was significant, and the research results need to be verified. Therefore, there is no clear conclusion as to which of the two modes is better, non-fractional mode or fractional mode, and further research is needed.

There is no relatively unified treatment parameter and treatment plan for picosecond laser treatment of melasma. Most treatments are 3 to 6 times, with an interval of 1 to 4 weeks, and 4 weeks is more common. Like the large spot and low energy Q-switched Nd:YAG nanosecond laser, the energy of picosecond laser treatment of melasma should be low, and generally mild erythema, with or without edema, and no purpura are the treatment endpoints [13-17].

Currently, the quality of clinical studies on the treatment of melasma with picosecond laser varies, the follow-up time is short, the research design is flawed, and some clinical research results show limited efficacy. Therefore, it is currently believed that picosecond laser can be used as an auxiliary means of treating melasma, but not as a means of maintenance treatment. The complexity of the factors and causes of melasma also determines that picosecond laser is not suitable as a single treatment method. In-depth research and discussion are still needed in terms of the selection of fractional and non-fractional modes of picosecond laser, the setting of optimal treatment parameters, the risk of recurrence, and the combined use with other treatment methods.

2.5 Tattoos

The evidence level for the treatment of tattoos with picosecond laser is 1a, which is the highest level of evidence among all its indications and is also the gold standard for the treatment of tattoos [18,19]. Picosecond laser has a good effect on tattoo removal of almost all colors, and many observations have shown that the treatment effect of picosecond laser tattoo is better than that of Q-switched nanosecond laser, and the number of treatments is less, the energy density is lower, and the adverse reactions are less.

The reason why picosecond laser is effective in tattoo removal may be related to the fact that the tattoo dye particles of different sizes, 40~300nm, just correspond to the thermal relaxation time of picosecond laser (about 12~1060ps). A computer simulation study believes that picosecond laser can generate a high temperature of 900℃, resulting in a strong pressure wave. This strong mechanical effect can cause carbon particles to break, which is also one of the mechanisms of high efficiency of picosecond laser treatment. Picosecond laser can also change the optical properties of tattoo dye and reduce the visibility of dye [20-22].

2.5.1 Indications 

Tattoos can be divided into decorative tattoos, cosmetic tattoos and traumatic tattoos. Decorative tattoos can be divided into professional tattoos and amateur tattoos[23]. These tattoos can all be removed with picosecond lasers. There is no research comparing the efficacy of picosecond lasers of various wavelengths, but according to the theory of selective photothermal therapy, researchers usually use 755nm and 1064nm lasers to treat black, blue, and green tattoos. One to two treatments can remove about 75% of tattoos[24]. 532nm picosecond lasers are used to treat purple, red, yellow, and orange tattoos. Yellow tattoos are usually difficult to remove with Q-switched lasers, but 532nm picosecond lasers have good effects, which may be related to the mechanical effect of picosecond lasers[25].

The following points need to be considered in the evaluation of tattoo efficacy: Professional tattoos are less effective than amateur tattoos because the former have a higher dye density and are located deeper. It is also necessary to understand the scar condition because scars can cause laser scattering and immune disorders, thereby affecting the effect[26]. The location of the tattoo is also a factor that affects the efficacy. The head and neck have rich regional lymph nodes and blood vessels, which are helpful for pigment removal, while the distal limbs are just the opposite.

2.5.2 Parameter selection 

Picosecond laser treatment parameters include spot diameter, pulse frequency and energy density, which vary from device to device. At the same time, it is also necessary to select according to the color, location, type of the tattoo, and the patient's age and skin type. Due to the large differences in literature reports, the following parameters are for reference only. The recommended parameters for Nd:YAG 532nm picosecond laser are: energy density 1.1~1.4 J/cm2, spot diameter 2.5~3.3mm, pulse width 450~500ps, and treatment interval of 6~8 weeks[25]. The recommended parameters for the frequency-doubled picosecond laser (PicoWay®) are: 1064nm energy density is 1.6~2.5J/cm2, 532nm energy density is 0.5~0.8J/cm2, spot diameter is 3~5mm, and pulse width is 350~450ps[27]. The reference settings for the 755nm alexandrite laser (Cynosure®, PicoSure) are: energy density 2.0~2.83J/cm2, pulse time 500~750ps, spot diameter 3.0~2.6mm[24]. During treatment, the handle should be kept vertical, and the spot overlap should be less than 10%. The endpoint of treatment is the immediate gray-white color of the skin at the tattoo site. If obvious epidermal damage occurs, the laser treatment energy should be reduced. Since the remaining pigment is less and the location is deeper, in principle, the energy required for each subsequent treatment should be higher than the previous one.

2.5.3 Precautions[23]  

For tattoos suspected of containing titanium dioxide or iron oxide dyes (white, tan, brown or rust color in the tattoo), there is a risk of darkening after pulsed laser treatment. For patients with dark skin, lower energy density and/or longer laser wavelength (e.g., 1064nm) should be used to reduce the risk of hypopigmentation. Traumatic tattoos caused by gunpowder should be treated with caution using Q-switched or picosecond lasers, as laser shock can cause micro-explosion of implanted particles, resulting in depression and atrophic scars. Patients with active inflammation, infection or other systemic diseases may experience slow postoperative healing and possible scarring. Patients with photosensitive skin and pregnant and lactating women should avoid picosecond laser treatment.

3. Picosecond laser operation process and precautions

Operation process: ① Clean the patient's face; ② Take photos and keep them for archiving before treatment; ③ Doctors and patients wear protective glasses; ④ According to the indications, choose hand tools, energy, frequency, spot size, and treatment; ⑤ Pay attention to observe the intraoperative spot reaction and treatment endpoint reaction (the appearance of erythema or white film, etc.); ⑥ Apply cold compress after surgery; ⑦ Explain the postoperative precautions and skin moisturizing care measures.

Precautions: ① Avoid sun exposure for 1 month before and after picosecond laser treatment. It is recommended to continue to use sunscreen after the treatment; ② The skin of the treatment area must be thoroughly cleaned before surgery; ③ Cold compress or cold spray is recommended after surgery to relieve reactions such as erythema; ④ Pay attention to moisturizing after surgery and avoid using irritating skin care products; ⑤ For some indications, postoperative scabs are normal and can generally fall off on their own in about 7 days. Do not forcibly remove scabs; ⑥ For different indications, perform the next treatment according to the interval period explained by the doctor.

4. Adverse reactions and prevention strategies of picosecond laser treatment

There are three pulse output modes of picosecond lasers, which have both similarities and differences in the adverse reactions and their prevention and treatment. Small spot high-energy tissue blasting is mainly used for tattoo removal and the treatment of hyperpigmented skin diseases; large spot low-energy scanning irradiation is mainly used for the improvement of skin color and skin quality; dot-matrix spot scanning irradiation is mainly used for superficial wrinkle improvement, pore reduction and other skin rejuvenation treatments, and can improve scars and treat capillary dilation.

The characteristics of picosecond lasers are that the photoacoustic effect is greater than the photothermal effect, and the tissue thermal damage is significantly less than that of Q-switched lasers. Therefore, adverse reactions rarely occur after surgery [28,29]. However, due to their extremely high instantaneous power, erythema, purpura, edema, blisters, pigmentation and even scars may still occur locally after the above-mentioned modes, especially after small-spot high-energy blasting treatment, the above-mentioned reactions are more likely to occur locally. The most common adverse reaction is post-inflammatory pigmentation, which is most common after the treatment of melasma. Some patients are sensitive to pain during treatment.

The cause of adverse reactions is related to excessive energy and repeated irradiation of too many spots on the same part. Preventive measures include: fully understanding the patient's skin condition, understanding the equipment condition, and selecting appropriate treatment parameters. For darker skin, the irradiation energy should be reduced, especially the number of irradiated spots. Take necessary repair measures after surgery and strictly protect against the sun.

For intraoperative pain, local anesthetics can be applied locally before surgery or a mask containing local anesthetics can be applied externally; for large-area blasting treatment, general anesthesia can be performed if necessary. Postoperative erythema and edema are generally mild, and cold spray and cold compress mask can be used. Ice compress can be used if necessary. No special treatment is required for individual small blisters. Larger blisters should be drained of blister fluid, the wound surface should be protected, and external repair products such as epidermal growth factor should be used. If there is scab, the scab should be protected as much as possible, and repair treatment should be continued after the scab falls off. For post-inflammatory pigmentation, repair, anti-inflammatory and depigmentation treatment can be given according to the degree of pigmentation.

5. Combination treatment with picosecond laser

Due to the characteristics of small treatment damage and fast recovery, picosecond laser can be combined with other methods in the treatment of melasma, tattoos, photoaging, facial rejuvenation, acne scars, etc. Specific combined projects include intense pulsed light, laser, radio frequency, mesotherapy, microneedle, chemical peel, botulinum toxin injection, etc. The recommended treatment sequence is to first perform non-invasive or minimally invasive treatment, followed by invasive treatment. The treatment interval is usually 1 to 2 weeks depending on the specific project.

Picosecond laser combined with LED blue light can treat freckles, and combined with biophoton treatment can further enhance skin repair. The light modulation effect of biophotons combined with picosecond laser has a strong anti-inflammatory effect and can promote the production of collagen, restore skin health and vitality, and is not restricted by seasons. Even in summer, it will not cause photosensitivity reactions [30]. Picosecond laser combined with CO2 fractional laser to treat tattoos can significantly reduce the incidence of blisters caused by picosecond laser [31]. Picosecond laser can also be combined with pulsed dye laser to treat melasma and skin photoaging, combined with intense pulsed light for facial rejuvenation, and combined with mesotherapy to treat melasma and facial rejuvenation [33].

6. Outlook

For full-face treatment, stability between pulse width and wavelength is essential. The LIOB effect produced by picosecond laser activates the healing mechanism and leads to the formation of new collagen, mucin and elastic tissue, remodeling the skin, and continuously improves the skin texture and fine wrinkles of the subject over time, thereby rejuvenating the skin. Low energy density is conducive to balancing the photoacoustic and photothermal effects [32]. The 755nm wavelength and extremely short pulse duration act on the target chromophore in the skin, producing a photomechanical effect, which can safely and effectively remove tattoo particles and benign pigmented lesions. The 755nm wavelength can be used for both superficial pigmented lesions and dermal pigmentation, and is one of the treatment methods suitable for Asians. By adding a honeycomb focusing diffraction lens to the original picosecond laser beam, the energy density can be magnified 20 times to penetrate deep into the skin to decompose pigments, thereby achieving the effect of lightening spots, while stimulating the production of collagen and elastic fibers, reshaping the skin, and achieving full facial rejuvenation. PicoWay® has also applied the 532 Resolve Fusion handpiece in the United States and other countries. Its principle is to convert laser energy into a ring distribution by using a Resolve Fusion lens with a conical surface. The high-power area in the center produces a high photomechanical effect without causing bleeding points, and the wider peripheral low-power area produces a moderate photomechanical effect, which can also increase the coverage area during treatment. The 730nm wavelength handpiece uses a patented non-degradable titanium sapphire crystal and is suitable for the treatment of benign pigmented lesions in Asians (type II to IV skin), especially superficial pigmented lesions, which have a large absorption ratio of melanin and hemoglobin, and will cause fewer inflammatory pigmentation than the 532nm wavelength. It is currently believed that the 730nm wavelength can achieve satisfactory improvement in the treatment of freckles, solar lentigo, black papules, chloasma, and Ota nevus [33-35]. The 730nm wavelength can also be used to remove various blue and green tattoo dyes. The short pulse duration and high peak power of picosecond lasers can maximize the photoacoustic effect [18] and minimize the risk of inflammatory pigmentation [36]. Some studies have envisioned that further shortening the pulse width can increase the absorption rate of local drugs [37] or identify melanoma from the surrounding skin [38].

After decades of development, picosecond laser technology has achieved remarkable results. Compared with nanosecond laser technology, picosecond laser technology has shown its special advantages. In the future, picosecond laser technology still has great potential to be tapped, such as using picosecond lasers with shorter pulse widths and using titanium sapphire gain-switched lasers to generate 730nm picosecond lasers with higher electro-optical conversion efficiency and better stability. In particular, as the price of lasers decreases, the popularity of picosecond laser technology will increase rapidly, which will greatly promote the development of picosecond laser technology in the field of medical beauty and dermatology.

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