Tretinoin cream 0.02% for the treatment of photodamaged facial skin: a review of 2 double-blind clinical studies

In extensive clinical studies and practical use since its US Food and Drug Administration approval in 1995, tretinoin emollient cream 0.05% has been shown to be safe and effective in the treatment of fine facial wrinkles, mottled hyperpigmentation, and skin roughness. To provide additional prescribing flexibility for various patient needs, a new lower concentration formulation, tretinoin cream 0.02% was chosen for further development. Two multicenter, randomized, double-blind, vehicle-controlled clinical., studies were conducted to evaluate the safety and efficacy of the lower concentration tretinoin formulation in the treatment of moderate-to-severe facial photodamage. Results indicate statistically significant improvement in fine wrinkling, coarse wrinkling, and yellowing with the use of tretinoin cream 0.02% at week-24 end point, compared with placebo. Therapy with tretinoin cream 0.02% was well tolerated overall and demonstrated a favorable safety profile. Both studies demonstrated that tretinoin cream 0.02% is safe and effective for the treatment of moderate-to-severe photodamaged facial skin.     

Loss of elastic fibers causes skin wrinkles in sun-damaged human skin

BACKGROUND: Although wrinkling is the most obvious sign of aged skin, the detailed pathomechanism of wrinkle development has not been elucidated. OBJECTIVES: In this study, we investigated the role of elastic fibers in the formation of skin wrinkles. METHODS: Loss of elastic fibers was measured quantitatively in the facial skins of subjects representing seven decades, and then compared with wrinkle severities. We also investigated whether topical retinoic acid treatment to photoaged human skin can restore destroyed elastic fiber, and the correlation between wrinkle improvement with increase in elastic fibers in RA-treated facial skin. RESULTS: We found a significant correlation between decreases in the length, width, number and total area of oxytalan fibers and wrinkle severity. Furthermore, we found that topical application of retinoic acid (0.025%) to chronically photodamaged skin regenerated and restored elastic fibers, and that there was a significant positive correlation between the amount of newly regenerated elastic fiber and the wrinkle improvement caused by retinoic acid. CONCLUSIONS: Our results provide an objective insight into the role of elastic fibers in skin wrinkle formation by providing a quantitative correlation between changes in oxytalan fibers and the severity of skin wrinkling.     

From skin microrelief to wrinkles. An area ripe for investigation

Skin microrelief alters progressively with age. Wrinkles do not result from these changes but are superimposed upon them. Wrinkles result from structural changes in the epidermis, dermis and hypodermis. Four types of wrinkles can be recognized. Type 1 wrinkles are atrophic. Type 2 wrinkles are elastotic. Type 3 wrinkles are expressional. Type 4 wrinkles are gravitational. Each type of wrinkle is characterized by distinct microanatomical changes and each type of wrinkle develops in specific skin regions. Each is likely to respond differently to treatment. Skin microrelief and skin folds can be identified on histological examination. By contrast, only minimal dermal changes are found beneath permanent or reducible wrinkles compared with immediately adjacent skin. A series of objective and non-invasive methods is available to quantify the severity of wrinkling.     

A novel treatment option for photoaged skin

Background DNA damage as a result of ultraviolet (UV) exposure plays an important role in the progression of cutaneous aging. Both folic acid and creatine have been linked to the process of DNA protection and repair. Aims This study aims to investigate the effects of a commercially available folic acid– and creatine‐containing formulation to fight the clinical signs of premature skin aging. Patients/methods Both in vitro and in vivo home‐in‐use studies using a folic acid– and creatine‐containing formulation were performed aiming to elucidate the efficacy in terms of improvement of skin regeneration, protection from UV‐induced DNA damage (Comet assay), reduction of wrinkle volume, and skin visco‐elasticity. Furthermore, clinical evaluation and photography were carried out to determine the improvement of clinically graded parameters after treatment. Results Cultured full‐thickness epidermal skin models supplemented with folic acid and creatine after epithelial perturbation showed an accelerated skin regeneration compared to untreated control models. Similarly, application of a folic acid– and creatine‐containing formulation significantly improved epidermal turnover in vivo as evidenced by smaller corneocytes derived from the treated sites relative to the vehicle‐treated sides. In addition, topical in vivo application of this formulation significantly protected from UV‐induced DNA lesions, increased skin firmness, and reduced wrinkle volume compared to untreated control areas. Expert grading confirmed a significant decrease of fine and coarse wrinkles in the periocular region as well as overall wrinkles, tactile roughness, and laxity. Conclusions Taken together, these results show that the combination of folic acid and creatine significantly accelerates epidermal skin regeneration in vitro and in vivo. Together with the finding of improved biomechanical skin properties, we conclude that the described topical formulation provides an effective treatment option for (photo)‐aged skin.     

High-Intensity Focused Ultrasound for the Treatment of Wrinkles and Skin Laxity in Seven Different Facial Areas

BackgroundHigh-intensity focused ultrasound (HIFU) treatment has recently emerged in response to the increasing demand for noninvasive procedures for skin lifting and tightening.ObjectiveThis study was aimed at evaluating the clinical efficacy of and patient satisfaction with HIFU treatment for wrinkles and laxity in seven different areas of the face in Asian skin.MethodsTwenty Korean patients with facial wrinkle and laxity were analyzed after a single session of HIFU treatment. Two independent, blinded clinicians evaluated the clinical improvement in seven areas of the face by comparison of standardized photographs obtained before, and at 3 and 6 months after treatment. Assessment of subjective satisfaction and adverse effects of treatment were done by using questionnaires.ResultsThe physicians'' evaluation and patients'' satisfaction with the clinical effects of HIFU in each area were similar regardless of the number of treatment shots. The jawline, cheek, and perioral areas were the sites where HIFU was most effective, in decreasing order. The adverse effects included erythema and swelling in six cases, and purpura and bruising in two cases. However, the adverse effects were mild and transient.ConclusionHIFU could be a safe, effective, and noninvasive procedure that can be used to improve facial wrinkles and skin laxity in Asian skin. It is particularly effective for clinical improvement in the jawline, cheek, and perioral areas.     

The anatomy and pathogenesis of wrinkles

The anatomy of linear wrinkles ("crow's feet' and temporal frown lines), fine criss-cross wrinkles of the face and wrinkling of the general body surface of elderly persons, was studied by light and scanning electron microscopy. No histological features distinguished the various wrinkles from surrounding skin. It was concluded that the wrinkle is a configuration change, like the grooves worn into an old glove, without specific structural alterations at the histological level. As regards pathogenesis, the common setting was found to be deterioration of the elastic tissue network. The skin becomes looser, excessive, and loses the ability to snap back to its original state after being deformed.     

Hyaluronic acid microneedle patch for the improvement of crow's feet wrinkles

Hyaluronic acid (HA) has an immediate volumizing effect, due to its strong water‐binding potential, and stimulates fibroblasts, causing collagen synthesis, with short‐ and long‐term effects on wrinkle improvement. We investigated the efficacy and safety of HA microneedle patches for crow's feet wrinkles. Using a randomized spilt‐face design, we compared microneedle patches with a topical application containing the same active ingredients. We enrolled 34 Korean female subjects with mild to moderate crow's feet wrinkles. The wrinkle on each side of the subject's face was randomly assigned to a HA microneedle patch or HA essence application twice a week for 8 weeks. Efficacy was evaluated at weeks 2, 4, and 8. Skin wrinkles were measured as average roughness using replica and PRIMOS. Skin elasticity was assessed using a cutometer. Two independent blinded dermatologists evaluated the changes after treatment using the global visual wrinkle assessment score. Subjects assessed wrinkles using the subject global assessment score. Skin wrinkles were significantly reduced and skin elasticity significantly increased in both groups, although improvement was greater in the patch group at week 8 after treatment. In the primary and cumulative skin irritation tests, the HA microneedle patch did not induce any skin irritation. The HA microneedle patch is more effective than the HA essence for wrinkle improvement and is a safe and convenient without skin irritation.     

Electro-optical synergy (ELOS™) technology for nonablative skin rejuvenation: a preliminary prospective study

BACKGROUND AND OBJECTIVES: In this preliminary prospective study, we evaluated the efficacy and safety of nonablative wrinkle treatment using combined radiofrequency (RF) and optical energy (Polaris). The dual energy technology of Polaris, called ELOS, which stands for electro-optical synergy, uses synchronous pulses of bipolar RF current and pulsed visible light (diode laser) delivered in the same pulse. MATERIALS AND METHODS: Twenty-four subjects with periorbital and perioral wrinkles received six treatments at 4-week intervals with the Polaris WR (Syneron, Inc., Israel, 900 nm, max. RF energy 100 J/cm(3), max. laser energy 50 J/cm(2)). Each treatment consisted of two passes over the treatment area using pulsed optical and RF parameters that were determined by the patient's skin phenotype and distribution of target chromophores. The follow-up period was 3 months after the last treatment. RESULTS: Independent scoring of blinded photographs showed a wrinkle score improvement of at least 1 (0 = no improvement, 1 = medium, 2 = good, 3 = excellent improvement) 3 months after the last of six treatment sessions. There was no difference between periorbital and perioral wrinkle reduction. Fifty-eight per cent (14/24) of the subjects reported a notable wrinkle reduction; 16% noted mild to moderate oedema and erythema lasting for no more than 1 day. Scarring or pigmentary changes were not detected. The average pain score was 0.6 (0 = no pain, 5 = intolerable pain). CONCLUSION: Multiple treatments with the Polaris WR produced objective and subjective reduction of periorbital and perioral wrinkles. The occurrence of side-effects and pain was very low. The clinical effect may be caused by matrix coagulation of the deep dermis by the RF and selective thermolysis of blood vessels with the 900 nm diode laser.     

积雪苷治疗35例鱼尾纹12周疗效观察

目的 评估积雪苷治疗鱼尾纹的临床疗效及安全性.方法 采用12周随机、双盲、赋形剂自身对照试验,通过第0、4、8、12周研究者盲法评价皱纹程度、受试者盲法自评、仪器测量3个方面评价试验用药侧与对照侧鱼尾纹的改善情况.结果 完成试验的35名受试者的双侧鱼尾纹程度根据研究者盲法评估,在使用第4周,治疗组与对照组的皱纹变化有统计学意义(P＜0.05).在第8、12周试验用药侧的皱纹程度的减轻优于对照侧,皱纹评分具有统计学意义(P＜0.05).采用Visioscan VC98定量测量双侧鱼尾纹SEw值结果显示,试验用药侧随时间的变化SEw的值增大,即皱纹程度减轻,与对照侧相比,差异有统计学意义.受试者评估显示,双侧药物在使用过程中刺激性及粗皱纹的改善情况无差异,外眦部位肌肤纹理改善方面治疗侧优于对照侧(P＜0.05).结论 积雪苷霜软膏每日3次局部外用改善鱼尾纹有一定疗效,无不良反应.     

Tazarotene 0.1% cream versus tretinoin 0.05% emollient cream in the treatment of photodamaged facial skin: a multicenter, double-blind, randomized, parallel-group study.

OBJECTIVES: To compare the efficacy and tolerability of tazarotene 0.1% cream and tretinoin 0.05% emollient cream in the treatment of photodamaged facial skin. METHODS: Subjects were eligible to enroll in this multicenter, double-blind, randomized, parallel-group study if they had at least mild levels of facial fine wrinkling and mottled hyperpigmentation, and at least moderate levels of one of these. Subjects were randomly assigned to apply either tazarotene cream or tretinoin emollient cream to their faces once each evening for 24 weeks. RESULTS: A total of 173 subjects were enrolled, of whom 157 completed. All significant between-group differences in efficacy measures were in favor of tazarotene - for fine wrinkling at the study endpoint and, at earlier timepoints, for treatment success (> or =50% global improvement), and the overall integrated assessment of photodamage, mottled hyperpigmentation, and coarse wrinkling. Both products were comparable in terms of cosmetic acceptability and tolerability except that tazarotene was associated with a transiently higher incidence of a burning sensation on the skin (in the first week of treatment but not thereafter). CONCLUSIONS: Tazarotene 0.1% cream can offer superior efficacy over tretinoin 0.05% emollient cream in the treatment of facial photodamage, particularly with respect to the speed of improvement.     

Tazarotene 0.1% cream versus tretinoin 0.05% emollient cream in the treatment of photodamaged facial skin: a multicenter,double‐blind,randomized, parallel‐group study

OBJECTIVES: To compare the efficacy and tolerability of tazarotene 0.1% cream and tretinoin 0.05% emollient cream in the treatment of photodamaged facial skin.

METHODS: Subjects were eligible to enroll in this multicenter, double‐blind, randomized, parallel‐group study if they had at least mild levels of facial fine wrinkling and mottled hyperpigmentation, and at least moderate levels of one of these. Subjects were randomly assigned to apply either tazarotene cream or tretinoin emollient cream to their faces once each evening for 24 weeks.

RESULTS: A total of 173 subjects were enrolled, of whom 157 completed. All significant between‐group differences in efficacy measures were in favor of tazarotene – for fine wrinkling at the study endpoint and, at earlier timepoints, for treatment success (≥50% global improvement), and the overall integrated assessment of photodamage, mottled hyperpigmentation, and coarse wrinkling. Both products were comparable in terms of cosmetic acceptability and tolerability except that tazarotene was associated with a transiently higher incidence of a burning sensation on the skin (in the first week of treatment but not thereafter).

CONCLUSIONS: Tazarotene 0.1% cream can offer superior efficacy over tretinoin 0.05% emollient cream in the treatment of facial photodamage, particularly with respect to the speed of improvement.     

Recent advances in characterizing biological mechanisms underlying UV-induced wrinkles: a pivotal role of fibrobrast-derived elastase

In clinical studies, the formation of facial wrinkles has been closely linked to the loss of elastic properties of the skin. Cumulative irradiation with ultraviolet (UV) B at suberythemal doses significantly reduces the elastic properties of the skin, resulting in the formation of wrinkles. In in vitro studies, we identified a paracrine pathway between keratinocytes and fibroblasts, which leads to wrinkle formation via the up-regulation of fibroblast elastases that degrade elastic fibers. UVB irradiation stimulates the activity of fibroblast elastases in animal skin. Scanning electron microscopy revealed that cumulative UVB irradiation elicits a marked alteration in the three-dimensional structure of elastic fibers, which is closely associated with the subsequent reduction in the elastic properties of the skin, resulting in wrinkle formation. Studies using anti-wrinkle treatments suggest a close relationship between the recovery of wrinkles and an improvement in the linearity of elastic fibers. Those studies also suggest a close correlation between the recovery in the linearity of elastic fibers and the improvement in skin elasticity. In a study using ovariectomized animals, we characterized the important role of elastase in their high vulnerability to UV-induced wrinkle formation. A synthetic inhibitor specific for fibroblast elastases significantly prevents wrinkle formation without reducing the elastic properties of the skin, accompanied by minor damage in elastic fibers. Finally, we identified an effective extract of Zingiber officinale (L.) Rose from a screen of many herb extracts, which has a safe and potent inhibitory activity against fibroblast elastases. Animal studies using the L. Rose extract revealed that it has significant preventive effects against UVB-induced wrinkle formation, which occur in concert with beneficial effects on skin elasticity. A 1-year clinical study on human facial skin to determine the efficacy of the L. Rose extract demonstrated that it inhibits the UV-induced decrease in skin elasticity and prevents or improves wrinkle formation in skin around the corner of the eye without changing the water content of the stratum corneum. Our long-term studies support our hypothesis for a mechanism of wrinkle formation in which cytokine expression is activated by UV irradiation and triggers dermal fibroblasts to increase the expression of elastase. That increase in elastase results in the deterioration of the three-dimensional architecture of elastic fibers, reducing skin elasticity and finally leading to the formation of wrinkles.     

Photodamage pilot study: a double-blind, vehicle-controlled study to assess the efficacy and safety of tazarotene 0.1% gel

BACKGROUND: Tazarotene, a potent acetylenic retinoid for topical use, might be expected to benefit photodamaged skin, including improving the classical signs of fine wrinkles, mottled hyperpigmentation, and roughness. OBJECTIVE: Our purpose was to determine the efficacy and safety of tazarotene 0.1% gel in the treatment of photodamaged dorsal forearm skin. METHODS: Ten healthy female volunteers, aged 45 to 65 years, with moderately photodamaged forearm skin applied tazarotene 0.1% gel to one arm and vehicle gel to the other once daily for 12 weeks. The study was a double-blind, randomized, paired-comparison evaluation conducted at a single site. RESULTS: Tazarotene showed beneficial effects for several efficacy variables. It was more efficacious than vehicle in reducing skin roughness and fine wrinkling based on objective measurements. Tazarotene also corrected epidermal atrophy and atypia and improved skin hydration properties. CONCLUSION: In this 12-week pilot study tazarotene redressed abnormalities associated with photo-damaged skin.     

A clinical study on the usefulness of autologous plasma filler in the treatment of nasolabial fold wrinkles

Background: Recently, the efficacy of autologous plasma filler for the reduction of facial wrinkles has been demonstrated. Objective: The aim of our study is to validate the efficacy and safety of autologous plasma filler in treating nasolabial fold wrinkles. Material and methods: Twenty Korean patients with moderate-to-severe nasolabial fold wrinkles were enrolled. The patients were treated with one session of autologous plasma filler. The wrinkle improvement effects were evaluated at 1-week, 4-week, 8-week, and 12-week after the treatment. Three assessment methods were applied. First, two independent dermatologists assessed cosmetic results using a 5-point wrinkle assessment scale. Second, global aesthetic improvement score was used for assessment of the final cosmetic results. Third, patient satisfaction was surveyed. Also, the adverse effects associated to treatment were observed. Results: Mean age of the patients was 44.5 years. The average 5-point wrinkle assessment scale score was significantly improved at 1, 4, 8, and 12 weeks after treatment, comparing to before treatment (p < 0.01). The patients’ average global aesthetic improvement score also indicated better cosmetic outcomes. Conclusion: The clinical improvement with sufficient patients’ satisfaction and no significant adverse events demonstrated that novel autologous plasma filler could be considered as efficient and safety treatment option for nasolabial fold wrinkles.     

A randomized, prospective study using the LPG technique in treating radiation-induced skin fibrosis: clinical and profilometric analysis

BACKGROUND/PURPOSE: Cutaneous fibrosis is the quite mandatory sequela after a breast cancer treated by radiotherapy and it induces more or less important functional troubles. The LPG technique is a technique of mechanical massage that allows skin mobilization by folding/unfolding. The aim of this study was to evaluate the changes on irradiated skin before and after LPG treatment by clinical and skin replica analysis. METHODS: Twenty women, 43-55 years old, who had been treated from 6 to 16 months before, for breast cancer with a conservative surgery and radiotherapy, had been enrolled in the trial. They were divided into two groups after randomization: the first group was LPG treated three times a week for 1 month; the second group was only placed under medical supervision. The clinical criteria studied were systematically studied before (T0), at the end of treatment (T1) and 1 month after the end of treatment (T2): pain, itching, skin dryness, erythema, skin infiltration, feeling of tightness and of induration of the skin. Softening of the skin was assessed at T1 and T2. Cutaneous replica was performed on the internal upper 1/4 of each breast with silicone material before, after and 1 month later after the end of the treatment. After polymerization, the replica was stored and then blindly analyzed by image analysis software. The following parameters were systematically measured: average skin roughness, average of wrinkles' depth and residual length, wrinkle number and the space between them. RESULTS: Clinically, the LPG treatment induced a decrease of erythema (10% of the patients vs. 40% before treatment), a decrease of pain and pruritus (10% vs. 20% and 40%, respectively) and a decrease of the feeling of induration of the skin (10% of the patients vs. 70% before treatment). Furthermore, a skin-softening sensation was noted by seven patients vs. one in the control group. Replica shows an increase of roughness and of furrow depth without any change in the residual length and an increase in the space between the wrinkles, whose number decreases. CONCLUSION: This study confirms the impact of the clinical sequelae induced on skin after radiotherapy and shows improvement of the clinical signs after treatment by the LPG technique. The latter induces changes of micro relief, suggesting a softening effect on the skin. These preliminary results have to be confirmed on a more important group of patients.     

In the shadow of the wrinkle: experimental models

Research on aging has run for decades, and knowledge on the biologic process of skin chronological and photoaging is still increasing thanks to read across results generated between human, animal, and in vitro studies. However, wrinkles should not be considered to result only from the aging process. There are few reports on specific wrinkle histological features compared to the surrounding skin, and there is thus a need in really wrinkling skin animal and in vitro models. UV-irradiated Hr mouse is a good model because it develops wrinkles. Nevertheless, as mouse skin is somehow different from human skin, the innovative model of wrinkling human skin xenograft on SCID mice seems to be really promising. Concerning in vitro and ex vivo models, although there have been considerable advances in reconstructing realistic aged skins, there is still a lack of in vitro wrinkling skin model, and unfortunately, this gap will probably be difficult to fill.     

Finite element modelling of forearm skin wrinkling

Background/purpose: Human skin is a complex multilayered material. Although there are many numerical models of skin in existence, which accurately simulate several of its complex mechanical characteristics, there are very few models that simulate wrinkling – a phenomenon common to all human skin. The purpose of this study was to develop a multilayer model of skin, which could simulate wrinkling more realistically than the existing models in the literature. Method: The skin on the volar forearm was wrinkled by displacing two tabs, which were attached to the skin surface towards each other. Eight volunteers were used in the experiment. The profiles of the wrinkles were measured using a customised laser profilometer system. The maximum range and average roughness of the wrinkle profiles were calculated. The multilayer model of skin consisted of the stratum corneum, dermis and underlying hypodermis. The constitutive equations for each layer were implemented into a finite element model and the wrinkling experiments were simulated. The results of the model were compared with the results of the experiments. Results: The size of the wrinkles predicted by the model fell within the range of the wrinkle sizes measured in the experiments. The maximum range and average roughness differed by 34% and 43% from the corresponding mean experimental results, respectively. The results show that the proposed three‐layer skin model simulates wrinkling more realistically than either a single or a two‐layer model. Conclusion: A three‐layer model of skin has been developed and validated under the harsh conditions of wrinkling. It has been shown that a three‐layer model better simulates the wrinkling of skin as compared with models of fewer layers. The model has several applications, including simulating skin aging and the design of more realistic artificial skin. The model can also be used to study the interaction of surgical scalpels or razors with human skin with a view to improving their design.     

Treatment of Acne Scars and Wrinkles in Asian Patients Using Carbon-Dioxide Fractional Laser Resurfacing: Its Effects on Skin Biophysical Profiles

Background

Although ablative fractional resurfacing is known to be effective against photoaging and acne scars, studies on its efficacy, safety and changes in the skin characteristics of Asians are limited.

Objective

The aim of this study is to assess the efficacy and safety of carbon dioxide fractional laser (CO₂FL) in Koreans treated for wrinkles and acne scars, and to define the changes in skin characteristics during recovery period.

Methods

We administered one session of CO₂FL on 10 acne scar patients and 14 wrinkles patients with skin types IV and V. The surveillance of efficacy and side effects along with the measurement of biophysical properties was carried out before 1 day, 1 week, 1 month and 3 months after treatment.

Results

Using a non-invasive method, skin barrier damage, erythema and bronzing of skin during the recovery period were assessed, and all of the items eventually returned to the pre-treatment level. Skin elasticity was measured in the wrinkle group, and the statistically significant effect was sustained throughout the next three months. The outcome of treatment was found to be better than ''moderate improvement'' in both the acne scar and wrinkle groups. Further, there were no serious side effects three months post-procedure.

Conclusion

CO₂ FL is thought to be an effective and safe method for treating moderate to severe acne scars and wrinkles in Asians.     

Evaluation of effectiveness of tranexamic acid as mesotherapy in improvement of periorbital wrinkling in a trial study

Background

Tranexamic acid is used to treat pigmented disorder in dermatology for a long time however there are limited data for effectiveness of tranexamic acid for rejuvenation and improvement of wrinkle. Here we want to find the effectiveness of tranexamic acid as mesotherapy in improvement of periorbital wrinkle in a clinical trial study.

Methods

Patients with melasma who were treated with 4 session of tranexamic acid mesotherapy at intervals on 1 week were evaluated with Visioface device before starting and 1 month after last course of treatment. The outcomes including volume, area, area percent, and depth were measured by Visioface device.

Results

Mean of periorbital wrinkles volume before and after procedure were 89 271 and 74 639 pixel³ (px³), respectively. Very significant difference with p-value of <0.001 was detected at volume of patient wrinkles before and after treatment. Moreover, the mean of area (and area percent) of their periorbital wrinkles before and after therapeutic method were 8481 Px³ (1.131%) and 7184 Px³ (0.646%), respectively, with significant differences (both have p-value of <0.001).Mean of periorbital wrinkles depth at before and after treatment were 9.8 and 9.6, respectively, without remarkable difference (p-value was 0.257).

Conclusion

Tranexamic acid mesotherapy significantly leads to reduced volume and area of wrinkles. Injection of tranexamic acid as mesotherapy seems to be effective in improvement of periorbital wrinkling.