Abstract
Mesotherapy has received public interest for rejuvenation; however, there is inconsistent and inadequate evidence of its efficacy. As aesthetic physicians, we believe the lack of efficacy for rejuvenation may be due to insufficient injection depth. The standards have not been updated for a long time, and thus doing so will provide patients with better results.
Keywords: rejuvenation, mesotherapy, skin thickness
Dr. Michel Pistor developed mesotherapy in 1952 to manage pain and vascular disorders. Mesotherapy is considered a drug delivery method and the skin acts as a natural time-release system. This method has several advantages―inexpensive equipment, lower required drug dosage in the target sites, faster efficacy, minimal invasiveness, and less attendant pain so that the treatment can be given on an outpatient basis. Mesotherapy is claimed to have a wide range of applications, especially in cosmetic dermatology, body-cellulite, fat dissolution, body contouring, skin-rejuvenation/glow, nonsurgical facelift, pigmentation disorders, hair telogen effluvium, and androgenetic alopecia1).
This method's effectiveness in different sites is not homogenous. It shows modest results in telogen effluvium, androgenetic alopecia, stretch marks, facial pigmentation, and body sculpting/contouring, whereas melasma results are doubtful2). Improvements in wrinkles, increased elasticity, and enhanced skin texture have been attributed to mesotherapy injection; however, it is rigorously proven3). This study focused on facial rejuvenation, with relatively good results.
These controversial results seem related to the treatment procedure. Researchers showed the method's potential effectiveness depends on several factors, including cocktail preparation procedures, materials, age, skin dryness, laxity, low elasticity, color, surface irregularity, the formation of pronounced skin markings, and wrinkles of different intensity4). Surprisingly, the influential factor of the injection depth is ignored, while the vital mechanism of effectiveness of mesotherapy is the exact injection in the target layer and depth of the skin.
In mesotherapy, injections are made into different layers of the skin, and the injection depth varies based on the desired goal. In brief, there are four different injection techniques corresponding to the four different injection depths. According to the historical method coined by Dr. Michel Pistor and later studies, a 2-4 mm depth is typical for facial rejuvenation5). Injections are given at an angle from the skin while applying light, constant positive pressure on the plunger. The practitioner rapidly flicks the wrist (mimics shaking a salt shaker or the action of a sewing machine), introducing a drop of solution at each site. This is a more discomforting procedure for the patient (Figure 1)6).
Figure 1.

The mesotherapy injection illustration.
Several pieces of research published in the last decade updated our knowledge of skin thickness, while the mesotherapy references have not changed. Therefore, it seems the injection was not performed based on updated skin thickness data. Based on the above depths that have been the standard of mesotherapy injections so far, one should not expect very effective results since the injection depths were inadequate. The average thickness of facial skin is presented in detail (Figure 2). According to a study conducted at Texas University, the Relative Thickness Index showed a 0.5-1.12 mm average skin thickness range for facial skin (Table 1).
Figure 2.

Dermal (epidermal) relative thickness values 6).
Table 1.
Relative Thickness Index and Average Skin Thickness 7).
| Site | Average Skin Thickness | Relative skin thickness index (±SD) |
|---|---|---|
| Upper lip | 0.83 ± 0.17 | 2.26 ± 0.53 |
| Chin | 1.15 ± 0.11 | 3.14 ± 0.46 |
| Upper eyelid | 0.38 ± 0.09 | 1 ± 0.00 |
| Lower eyelid | 0.82 ± 0.21 | 2.18 ± 0.417 |
| Forehead | 1.07 ± 0.09 | 2.85 ± 0.59 |
| Right cheek | 1.17 ± 0.08 | 2.97 ± 0.66 |
| Left cheek | 1.05 ± 0.45 | 3.22 ± 0.62 |
| Right neck | 0.52 ± 0.23 | 1.49 ± 0.82 |
| Left neck | 0.54 ± 0.02 | 1.53 ± 0.7 |
According to another recent study, the thickness of the face dermis and epidermis are reportedly (1.96-0.7 mm) and (0.06-0.029 mm)8). In a Korean study, the average range of facial skin thickness was reportedly 0.5-1.1 mm9). In a more recent study, Kim et al. reported the skin was thinnest at the radix and dorsum (1.51 ± 0.55 mm) and thickest in the infraorbital region (1.97 ± 0.84 mm)10).
Previous studies7-11) reveal that the injection depth range of 2-4 mm may reach the hypodermis in most facial regions. Another point is the considerable difference in skin thickness in different facial areas. Study results indicated that dermis thickness could vary 4-8 times between different facial areas. Using the average upper eyelid skin thickness as a measure, the nasal tip skin thickness was 3.30-folds thicker, and the brow/forehead was 2.8-fold thicker6). Therefore, optimal full-face treatment may not be provided with a single fixed injection depth. The strict and old instructions could collapse the results of mesotherapy in many cases. In a few cases, a structured 2-4 mm injection depth may accidentally match case characters.
According to our 12-25 years of experience as clinicians and instructors, we do not recommend an exact specific depth in the full facial mesotherapy. The trained practitioner should earn enough knowledge and stay up to date based on new findings to understand the particular depth required for injection case by case in different face areas. The injector should always know where the needle tip is; the most common error of new injectors is injecting too deep.
Additionally, as mesotherapy practitioners for the last 10 years, our experience indicated that shallow injections are more effective than deeper injections in the facial area aiming for rejuvenation. The epidermis thickness for reaching the minimal depths considered acceptable by dermatology and histology references is between 0.5 and 1.5 mm. These depths must be passed through to reach the dermis, and it is best to use trigonometric relations to determine the depth of needle entry for injecting any substance to a depth of around 1 mm. We should consider trigonometric rules. In our experience, the best measure to ensure that the intraepidermal injection reaches the epidermis is to inject the needle with an approximate 15° angle as deep as a maximum of 1 mm. The functional depth will decrease since the needle would be entering obliquely at an angle. In other words, the depth of injection changes by the angle of injection. At a 90° angle, the injection depth is determined by the degree of needle penetration. At mesotherapy injection, the injection is not done at 90°, thus we should consider the depth change by angle change. In Figure 1, the method of injection is clearly indicated. A depth of 1 mm must be entered to reach the dermis area, and a quarter of the vertical depth will be reduced by entering the needle at a 15° angle. Therefore, if the needle enters the skin by a maximum of 1 mm, it will have reached the depth of 0.75 as the sin α of 15° is around 0.25 (Figure 3). In this case, we assure that the injected material reached exactly in the dermis area as the 0.75 mm is almost the mean of dermis thickness in different cases.
Figure 3.

Depth change according to the angle of injection.
Finally, proper treatment includes following the established updated research results for spacing, dose per injection, total dose, the depth of injection, using the proper formulation with the proper concentration, and avoiding high pressure during injections. Untrained or self-taught injectors should strictly avoid this technique.
Author Contributions: SN developed the idea and checked the draft. AM drafted the manuscript.
Conflicts of Interest: There are no conflicts of interest.
Ethical Approval: Ethical approval was not required for this study as there were no participants, and this article presents technical notes based on the authors' experiences.
Consent to Participate: Informed consent for participation was waived for this study as there were no participants, and this article presents technical notes based on the authors' experiences.
Consent for Publication: Informed consent for publication was waived for this study as there were no participants and this article presents technical notes based on the authors' experiences.
Ethical Considerations: Informed consent and ethical approval were not required for this study as there were no participants, and this article presents technical notes based on the authors' experiences.
Supplementary Material
References
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