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Summary

The purpose of this project is to effectively reduce the occurrence of adverse reactions such as erythema and pigmentation after non-ablative fractional laser treatment by combining 1565 non-ablative fractional laser with 30% super molecular salicylic acid, providing patients with a safer new method of facial rejuvenation treatment.

Abstract

The 1565 nm non-ablative fractional laser can effectively stimulate collagen regeneration, achieving the effect of skin rejuvenation and anti-aging. In recent years, it has been widely used in dermatology, especially in facial rejuvenation, treatment of stretch marks, and acne scar treatment, with significant results. However, after the 1565 nm non-ablative fractional laser treatment, patients may experience short-term erythema and edema. The inflammation after treatment may also cause pigmentation, making it difficult for some patients to accept. This article introduces a treatment method of 1565 nm non-ablative fractional laser combined with 30% super molecular salicylic acid for facial rejuvenation, effectively reducing posttreatment erythema and post-inflammatory pigmentation. The method includes specific treatment steps and the respective endpoint reactions of each step. The method starts by selecting appropriate energy parameters for the 1565 nm non-ablative fractional laser treatment, followed immediately by the application of 30% supramolecular salicylic acid. The treatment should be stopped when a frosty reaction occurs. The purpose of this project is to provide patients with a safer new method of facial rejuvenation treatment.

Introduction

Facial aging usually refers to the changes that occur after aging, such as bone shrinkage and deformation, soft tissue relaxation and sagging, increased skin pigmentation, and wrinkles, among which the aging of the skin is the most obvious¹. The causes of facial aging are divided into exogenous and endogenous factors. Exogenous aging is caused by gravity, UV radiation, air pollution, smoking, excessive alcohol consumption, and malnutrition, among other factors². Endogenous aging is mainly an inevitable aging process caused by genetics and age. With the pursuit of a beautiful image by those seeking beauty, various technologies and treatment concepts have emerged. Among them, photonic beauty treatments have developed rapidly in the treatment of facial aging in recent years. According to statistics from the International Society of Aesthetic Plastic Surgery, the number of patients undergoing photonic beauty treatments in the United States in 2020 increased by 15.2% compared to 2019³.

Currently, there are various laser devices available for treating skin aging. These lasers are primarily used to reduce wrinkles and improve enlarged pores and can be categorized as ablative or non-ablative lasers. Non-ablative lasers, such as different wavelengths of erbium-doped glass (Er:Glass) lasers (1540 nm, 1550 nm, 1565 nm), are representative instruments for this purpose, with the ResurFX fiber optic laser being the most commonly used. The 1565 nm laser emitted by ResurFX can stimulate dermal collagen remodeling while maintaining the integrity of the epidermis. It has shown good efficacy and high safety for the treatment of periorbital wrinkles⁴. A prospective study has confirmed that non-ablative fractional lasers can improve various facial skin concerns, such as laxity, wrinkles, and coarse pores, among Asian patients, and the patients were satisfied with the treatment outcomes⁵. However, posttreatment complications such as pain, erythema, edema, crust formation, inflammatory hyperpigmentation, and acne eruptions were reported in 100% of cases treated with non-ablative fractional lasers. Currently, in order to alleviate the adverse reactions during and after non-ablative fractional laser treatment, methods include a topical anesthetic ointment that can be applied before treatment to improve treatment tolerance, and an adequate cold compress after laser treatment can shorten the duration of erythema and edema⁶. However, these treatments have limited effects in reducing pain and erythema edema and still cannot make all patients accept non-ablative fractional laser treatment.

Salicylic acid (SA) is a β-hydroxy acid extracted from willow bark, etc.⁷, with a concentration of 2% ~ 30%. SA can remove lipids between cells, reduce the adhesion of keratin-forming cells, and cause these cells to loosen and subsequently separate⁸. In addition, it has antibacterial, antifungal, and some anesthetic effects⁹. However, SA has poor solubility in water and easily precipitates in low-pH alcohol solutions and irritating solvents to the skin. To solve these limitations, supramolecular SA (SSA) was introduced. It forms water-soluble supramolecular entities in the form of intermolecular complexes through reversible non-covalent bonding and releases slowly during use, reaching maximum efficacy under low-pH conditions and reducing skin irritation¹⁰. Zhang et al.⁹. measured skin hydration, transepidermal water loss (TEWL), pH value of skin barrier-related parameters. After four treatments, TEWL decreased, while skin hydration and pH values increased. These results suggested that 30% of SSA peels did not damage the skin barrier function but improved instead.

Therefore, some scholars advocate the use of non-ablative fractional laser combined with SSA chemical peel treatment to improve problems such as large pores and acne¹¹. However, according to the author’s experience, the immediate use of SSA chemical peel treatment after 1565 nm non-ablative fractional laser treatment has not been fully utilized in clinical practice, which may be due to different treatment sequences in previous clinical practice. This article introduces a new treatment method to improve the adverse reactions after 1565 nm non-ablative fractional laser treatment, combined with relevant visual aids, in order to help more patients receive 1565 nm non-ablative fractional laser treatment for facial rejuvenation.

Protocol

All procedures carried out in research involving human participants were in accordance with the approval of the Ethics Review Committee of the First Affiliated Hospital of Chongqing Medical University (Research Ethics in 2023 [2023-119]). Informed consent was obtained from the patients before undergoing the procedure.

1. Pretreatment preparation

1. Lesion selection and clinical indications
   1. Patient selection
      1. Select female patients with Fitzpatrick skin type III-IV¹² and clinical symptom quantitative score of facial aging > 9 points¹³.
      2. Exclude patients who fall into any of these categories: pregnant and breastfeeding women; patients with a history of allergy to lidocaine and/or salicylic acid; patients with malignant tumors, scars, diabetes, neuromuscular diseases, bleeding tendency, anticoagulants, glucocorticoids or immunosuppressive drugs; patients who have received laser or other treatments within the past 6 months.
   2. Patient preparation
      1. After cleaning the patient's face, use the skin detector to perform a skin test.
      2. Then, apply the compound lidocaine cream externally to the treatment area and leave it for 40 min. Afterward, wash the entire face with water and dry it with sterile gauze.
2. 1565 nm non-ablative fractional laser device parameter settings.
   1. Choose the 1565 nm non-ablative fractional laser device (ResurFX mode) (as shown in Figure 1) for comprehensive facial treatment on the patient.
   2. Set the energy level using the Energy Setting key, usually between 30-40 mJ, with the desired endpoint reaction being erythema and mild edema, which generally appear tens of seconds after treatment and, in rare cases, occur minutes later.
   3. Adjust the treatment density using the Density Setting key, usually between 200-300 spots/cm², with the desired endpoint reaction being erythema and mild edema.
3. Have the patient lie comfortably on the treatment bed, with the doctor sitting at the head end of the bed. Disinfect the entire treatment area with iodophor, remove the iodine with sterile saline, and then dry the area with sterile gauze.
4. Disinfect the treatment head of the device with a 75% alcohol pad.
   NOTE: Both the doctor and the patient should wear specific protective goggles in preparation for the treatment.

2. Treatment

1. Enter the treatment interface and select the ResurFX mode (as shown in Figure 2).
   1. Choose the appropriate spot size and shape, and click Ready on the instrument interface (Figure 3). Gently place the treatment head on the skin surface of the treatment area and press the Trigger button on the treatment instrument to start the treatment.
   2. After the treatment prompt sound stops, release the Trigger button, lift the handle, and select the next treatment area for treatment. Ensure that the treatment spots do not overlap. Treat the entire face for 1 time.
   3. Keep the skin area dry during the treatment process. During each energy emission process, firmly adhere the treatment head to the skin surface.
   4. Test the spot at the lower jaw or in front of the ear first, with the endpoint reaction being redness and slight edema, before performing a large-area treatment. During the entire treatment process, cover the patient's eyes with an eye mask (provided by the instrument manufacturer) to protect the patient's eyes.
2. Perform non-ablative fractional laser treatment of the face with 1565 nm energy.
   1. Minimize overlap between each spot. Different parts require different suitable parameters. For example, patients with Fitzpatrick III/IV generally require a treatment energy of 30-35 mJ and a density of 200-250 spots/cm² for the forehead.
   2. Set the treatment energy for the cheek area to 35-40 mJ and the density to 200-250 spots/cm². Set the treatment energy for the nose to 35-40 mJ and the density to 250-300 spots/cm².
   3. After the entire face is treated, click Standby on the instrument treatment interface to place the instrument in standby mode.
3. Apply 30% supramolecular salicylic acid immediately after the whole-face laser treatment.
   NOTE: The application order is generally forehead, nose, chin, cheeks, and temples.
4. Gently massage for 5-10 min.
   1. After evenly applying SSA to the entire face, gently massage in a circular motion with fingers wearing latex gloves to promote absorption.
      NOTE: The specific reaction time depends on the appearance of the endpoint reaction, which is facial redness or white frost reaction.
   2. Rinse off with water immediately when the endpoint reaction appears. If the reaction time has reached 10 min but the end point reaction does not appear, rinse off with water immediately.

3. Posttreatment care

1. Apply cold saline gauze for 30 min immediately after treatment.
2. Do not clean the face for 3 days after the treatment. Apply moisturizing and repairing products externally and pay attention to sun protection.
   NOTE: After the treatment, there may be slight scabbing on the face. It is not recommended to use sunscreen and facial makeup before the scabs fall off. Items for physical sun protection, such as a mask, hat, or parasol, can be chosen. Patients must not wash their face for 3 days but could gently wipe it with normal saline.

Representative Results

The 1565 nm non-ablative fractional laser can improve facial aging, such as pores, texture, and brown spots. However, the combination of a 1565 nm non-ablative fractional laser with SSA can effectively reduce adverse reactions such as erythema and pigmentation while improving facial aging. The right side of the patient's face was treated with a 1565 nm non-ablative fractional laser, while the left side was treated with a 1565 nm non-ablative fractional laser combined with 30% supramolecular salicylic acid. At 14 days posttreatment, the erythema on the left side faded faster than on the right side. At 30 days posttreatment, the brown spots, which represent the pigmentation of the face, on the left side were better improved than the right side of the face. In addition, we conducted a randomized, double-blind, half-face controlled trial with 16 patients. The observation found that both treatment methods significantly improved pores and wrinkles compared to baseline (p < 0.05). However, the combination of 1565 nm non-ablative fractional laser with 30% supramolecular salicylic acid had better effects on redness and brown spots, with significant improvement from the baseline (p < 0.05), compared to 1565 nm non-ablative fractional laser alone, especially for facial redness. At day 30 after the treatment, the redness in the combined therapy group was significantly lower than in the laser alone (Figure 4). Besides, the combination therapy improved faster than the 1565 nm non-ablative fractional laser alone in all four parameters. Furthermore, the female facial aging clinical symptom quantitative score¹³ showed that both treatment methods had significant effects on improving facial aging. However, the combination of 1565 nm non-ablative fractional laser with SSA had better effects than using 1565 nm non-ablative fractional laser alone (p < 0.05) (as shown in Figure 5). The details of the scoring method are included in Table 1. Representative images of a patient's face taken at different time points during the treatment are shown in Figure 6. Note that the significance of the treatment is not clear in Figure 6.

During each follow-up, the patient is subjected to a skin detection test using a skin detector, and the values obtained from the detector are used for statistical analysis. All the statistical analyses were performed by using GraphPad Prism 9.00 (GraphPad Software). The quantitative data are presented as medians with interquartile ranges, and the differences were compared by the Mann-Whitney test. The differences between different times and groups were compared using two-way ANOVA of repeated measures methods. Two-sided P < 0.05 was considered statistically significant.

Figure 1: M22 intense pulsed light device. The left treatment handpiece is for intense pulsed light therapy, and the right treatment handpiece is for 1565 nm non-ablative fractional laser therapy. Please click here to view a larger version of this figure.

Figure 2: Selecting the 1565 nm non-ablative fractional laser mode (red rectangle). Please click here to view a larger version of this figure.

Figure 3: 1565 nm non-ablative fractional laser parameter adjustment interface. Select the spot shape (red arrow), spot size (yellow arrow), spot density size (blue arrow), and laser energy (green arrow). Please click here to view a larger version of this figure.

Figure 4: Skin testing results of a half-face control test on 16 female patients with facial aging. Compared to the baseline, both treatments significantly improved pores and wrinkles (p < 0.05), with no significant difference between the two treatments (P > 0.05). Compared to the baseline, the 1565 nm non-ablative fractional laser combined with 30% super-molecular salicylic acid treatment significantly improved the red and brown areas (p < 0.05), while the 1565 nm non-ablative fractional laser alone showed no significant difference compared to the baseline (p > 0.05). Please click here to view a larger version of this figure.

Figure 5: Quantitative clinical symptom scores for female facial aging before and after treatment in a half-face controlled trial of 16 female patients with facial aging. Compared to baseline, both treatments effectively improved the clinical symptoms of facial aging, but the combination of 1565 nm non-ablative fractional laser with 30% supramolecular salicylic acid was superior to the 1565 nm non-ablative fractional laser alone (p < 0.05). Please click here to view a larger version of this figure.

Figure 6: 1565 nm non-ablative fractional laser combined with 30% super molecular salicylic acid improves facial rejuvenation. The patient's left face(L) was treated with 30% ultramolecular salicylic acid immediately after the 1565 nm non-ablative fractional laser treatment, while the right face(R) was treated with 1565 nm non-ablative fractional laser treatment alone. (A1, A2, A3) Before treatment. (B1, B2, B3) 1 day after treatment. (C1, C2, C3) 14 days after treatment. (D1, D2, D3) 30 days after treatment. Please click here to view a larger version of this figure.

Roughness and Dryness of Facial Skin			Score
Roughness or dryness felt in one area of the cheeks, forehead, or mouth area			1
Roughness or dryness felt in two areas or roughness with scaling in one area			2
Roughness felt in all areas or roughness with scaling in more than one area			3
Fine Wrinkles on the Face			Score
Faint crow's feet at the corners of the eyes and superficial wrinkles on the forehead			1
Coarse crow's feet at the corners of the eyes, forehead, and cheeks			2
Prominent wrinkles at the corners of the eyes, forehead, cheeks, mouth area, and neck			3
Irregular Pigmentation Changes on the Face			Score
Patches mainly on the cheeks, covering less than 30% of the face, with a light brown color and scattered distribution			1
Yellow-brown patches on both cheeks and forehead, covering more than 50% of the face, with a darker brown color and fused patches			2
Scattered dark brown patches on the forehead, cheeks, nose sides, and lips, covering over 70% of the face			3
Pallor of the Face			Score
Yellowish complexion with skin radiance			1
Yellowish complexion without skin radiance			2
A dry and dull yellowish complexion with no skin radiance			3
Elasticity of Facial Skin			Score
Decent elasticity, with skin recovering quickly after pressing but leaving more wrinkles around the pressed area			1
Poor elasticity, with skin recovering within 1-2 seconds after pressing			2
Very poor elasticity, with skin taking more than 2 seconds to recover after pressing			3
Redness and Burning Sensation of Facial Skin			Score
Skin prone to redness and burning sensation, occurring 2-4 times per year			1
Skin frequently experiencing redness and burning sensation, triggered by seasonal changes or changes in skincare products			2
Total Score

Table 1: The scoring method used in this study.

Discussion

1565 nm non-ablative fractional laser can effectively stimulate collagen rearrangement, achieving the effect of rejuvenation and anti-aging. It is used in the treatment of facial rejuvenation, stretch marks, and acne scars¹⁴. However, after 1565 nm non-ablative fractional laser treatment, there may be obvious pain and redness immediately, and posttreatment inflammation pigmentation easily occurs, which makes it difficult for some patients to accept. In this article, we described an effective method to alleviate posttreatment erythema and reduce inflammatory pigmentation by combining a 1565 nm non-ablative fractional laser with 30% super molecular salicylic acid. This method showed that 1565 nm non-ablative fractional laser combined with 30% super molecular salicylic acid has a significant effect on improving facial rejuvenation. Posttreatment transient redness disappears faster, and the pigmentation improvement effect is more significant. It is of great significance for the application of non-ablative fractional lasers in facial rejuvenation treatment.

The adverse reactions during and after the treatment with 1565 nm non-ablative fractional laser are more obvious. Before treatment, topical anesthetic ointment can be applied to improve the treatment tolerance. Before performing the full-face treatment with a 1565 nm non-ablative fractional laser, a spot test can be performed on the skin in the preauricular area to determine the appropriate energy parameters. Chan et al.¹⁵ reported that 12.4% to 20.2% of patients experienced pigmentation after the treatment with a 1565 nm non-ablative fractional laser. The occurrence of pigmentation may be related to the larger spot density and energy density. By reducing the energy and spot density, the incidence of pigmentation can be effectively reduced.

In our method, instead of using saline gauze for cold compress after the 1565 nm non-ablative fractional laser treatment, we immediately apply the super-molecular salicylic acid (SSA) treatment. Using the anti-inflammatory and skin barrier repair effects of SSA, we can quickly fade redness and effectively prevent post-inflammatory hyperpigmentation. After the SSA treatment, we use saline gauze as a cold compress.

Applying SSA immediately after 1565 nm non-ablative fractional laser treatment may lead to a faster appearance of the end point response of SSA topical application, namely the appearance of a white frost reaction. During the procedure, it is important to observe the local slight white frost reaction, which does not affect subsequent procedures and does not require immediate cleaning. Most patients can wash it off after 5-10 min.

The parameter setting of the 1565 nm non-ablative fractional laser is crucial. The parameter settings for different areas are different. Generally, the energy and spot density of the forehead and periocular areas are lower than those of the mid-face. The ideal parameters are to cause endpoint reactions such as erythema, slight edema, and no bleeding. Next, apply SSA on the face and massage it with the hands to promote absorption of SSA and react with the skin. Observe the endpoint reaction to achieve the best results. The ideal endpoint reaction of the SSA application is the appearance of white frost. The time for the appearance of true white frost is generally 5-10 min. Once a white frost appears, wash it off with water immediately. Finally, treatment providers should be aware that when patients have inflammatory skin lesions, such as acne, the endpoint reaction will appear faster. This requires the treatment providers to strictly control the specific manifestations of the endpoint reaction and terminate the reaction of SSA in time, i.e., rinse it off with water.

1565 nm non-ablative fractional laser utilizes fractional technology to deliver laser energy to the dermal tissue while preserving the epidermis, producing strong photothermal effects that stimulate collagen regeneration to achieve the purpose of tendering skin and removing wrinkles¹⁶. However, posttreatment pain, redness, edema, even scab formation, post-inflammatory pigmentation, acne outbreak, etc., occur after non-ablative fractional laser treatment, which makes some patients refuse non-ablative fractional laser for facial rejuvenation. Salicylic acid peeling is a mature, safe, and simple treatment for acne. Its mechanism of treating acne includes inhibiting the activated protein kinase/sterol regulatory element binding transcription factor 1 pathway in sebocytes to reduce sebum production and inhibiting nuclear factor κB (NF-κB) activity to control inflammation¹⁷. Therefore, we recommend a new method of combining the two treatments. This method effectively reduces the inflammatory response after 1565 nm non-ablative fractional laser treatment, reducing posttreatment redness edema and other adverse reactions such as inflammatory pigmentation.

Materials

ResurFX fiber optic laser	Lumenis, Yokneam, Israel	M22 system	1565 nm non-ablative fractional laser
ISEMECO skin detector	Isomeco Biomedical Technology Co., Ltd.,Shanghai, China	MC-2600	Skin testing can be conducted under 5 types of spectrum
Compound lidocaine cream	Beijing Unigroup Pharmaceutical Co., Ltd., China	Guo Yao Quan Zi H20063466	This product is a compound preparation, consisting of prilocaine and lidocaine. Each gram of this product contains 25 mg of prilocaine and 25 mg of lidocaine.
30% supramolecular salicylic acid	BRODA, Shanghai Ruizhi Medical Technology Co., Ltd., China	N/A	It can be used for anti-inflammatory and repairing the skin barrier.