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. 2024 Feb 22;30(2):e13623. doi: 10.1111/srt.13623

Skin dark spot mapping and evaluation of brightening product efficacy using Line‐field Confocal Optical Coherence Tomography (LC‐OCT)

Randa Jdid 1,, Mélanie Pedrazzani 2, François Lejeune 1, Sébastien Fischman 2, Gabriel Cazorla 1, Sandra Forestier 1, Youcef Ben Khalifa 1
PMCID: PMC10883256  PMID: 38385854

Abstract

Background

Facial dark spots remain a significant challenge for the cosmetic industry, in terms of providing effective treatment. Using Line‐field Confocal Optical Coherence Tomography (LC‐OCT), we investigated the internal structural features of photo‐aging spot areas and evaluated the efficacy of a skin‐brightening cosmetic product.

Materials and Methods

Twenty‐six Asian female volunteers, aged between 29 and 65 years, applied a cosmetic product on their entire face twice a day for 2 months. LC‐OCT was used to evaluate the dermal‐epidermal junction (DEJ) undulation and the volume density of melanin in the epidermis at D0 and D56. Skin brightening and redness were also assessed by photography (SkinCam).

Results

Using LC‐OCT technology, various microscopic dark spot morphologies, spanning from minimally deformed DEJ to complex DEJ patterns, were identified. Dark spots characterized by slight deformities in the DEJ were predominantly observed in the youngest age group, while older volunteers displayed a wavier pattern. Furthermore, a total of 44 spots were monitored to evaluate the brightening product efficacy. A statistically significant reduction in melanin volumetric density of 7.3% in the spots and 12.3% in their surrounding area was observed after 56 days of product application. In line with these results, an analysis of color parameters using SkinCam reveals a significant increase in brightening and decrease in redness in both pigmented spots and the surrounding skin following application.

Conclusions

LC‐OCT proves to be a valuable tool for in‐depth dark spots characterization and assessment of skin brightening products, enabling various applications in the field of dermatological sciences.

Keywords: 3D imaging, aging spot, cartography, Line‐Field Confocal Optical Coherence Tomography (LC‐OCT), melanin density, pigmentation disorders, skin brightening product

1. INTRODUCTION

Melanin plays a crucial role in protecting the skin from UV damage and regulating alterations in skin color. However, overproduction and buildup of melanin can lead to various skin pigment irregularities, such as solar lentigines (SL), flat seborrheic keratosis (SK), melasma, freckles, and post‐inflammatory hyperpigmentation. 1 , 2 Typically, these pigmentation disorders manifest between the ages of 20 to 40, occurring more frequently in individuals with Fitzpatrick skin types III or IV. 3 Notably, among Asian women, pigmentary irregularities appear with increased severity and at an earlier life stage compared to French women. 4 These irregularities are more significant indicators of aging than wrinkles for women of Asian origin, and raise important concerns, particularly regarding their quality of life. 5 , 6

To better characterize these pigmentation disorders, numerous techniques have emerged. The conventional methods for quantifying skin melanin currently rely on invasive procedures such as histology. 7 , 8 These invasive approaches are impractical for repeated use, especially in cosmetic applications related to pigmentary skin disorders where monitoring treatment response is crucial. Lately, non‐invasive techniques for visualizing melanin based on its contrast have emerged, including dermatofluoroscopy, 9 reflectance confocal microscopy (RCM), 10 , 11 multiphoton microscopy, 12 , 13 and optical coherence tomography (OCT). 14 A recent technological advancement has introduced non‐invasive in vivo skin 3D imaging, with Line‐field Confocal Optical Coherence Tomography (LC‐OCT) emerging as a promising technique. LC‐OCT combines the advantages of reflectance confocal microscopy (RCM) and OCT to generate high‐resolution 3D images of skin architecture at a cellular level. 15 , 16 , 17 , 18 , 19 , 20 , 21

The non‐invasive LC‐OCT device (DAMAE Medical, Paris, France) produces images with vertical sections as in histological samples and horizontal sections similar to RCM images. This capability provides non‐invasive “virtual biopsies” with an isotropic spatial resolution of approximatively 1.3 μm. 15 , 16 Through integration with artificial intelligence (AI)‐based segmentation algorithms, LC‐OCT has been employed to quantify superficial dermis thickness, 22 , 23 epidermal thickness and dermal‐epidermal junction (DEJ) undulation in healthy skin, 18 , 24 as well as in pathological conditions such as inflammatory diseases. 25 Additionally, it has enabled to identify clear biomarkers of facial skin ageing. 24 At a cellular level, 3D LC‐OCT imaging has been used to characterize the keratinocyte network, assessing metrics such as density, volume, and shape of nuclei. 18 , 24 LC‐OCT has been employed to assess the efficacy of pigment‐reducing treatment in only a single recent case study. 26

By applying this innovative technique in the cosmetic field, the objective of this study was to investigate the ability of non‐invasive LC‐OCT 3D imaging to categorize pigmented spots based on DEJ undulation and melanin density, and to evaluate its reliability in assessing the brightening effect of a cosmetic serum.

2. MATERIALS AND METHODS

2.1. Panel recruitment

A panel comprising 28 Asian female volunteers exhibiting facial pigment irregularities and aged between 29 and 65 years old was enrolled in this study. The participants were divided into two age groups, < 50 years old (G1) and > 50 years old (G2). The investigation was performed in Paris, France, from November 15, 2020, to January 15, 2021, to minimize the influence of residual summer tanning. The study was conducted in accordance with the principles of the Declaration of Helsinki, and written informed consent was obtained from all participants. Exclusion criteria encompassed pregnancy and breastfeeding, non‐compliance with cosmetic guidelines, the use of anti‐aging or lightening products, exfoliants and scrubs, tattoos or permanent make‐up, scars on the study areas, dermatological lesions, a history of aesthetic procedures and general or skin diseases. Additionally, women using topically or systemically administered treatments (such as anti‐inflammatory drugs, corticosteroids, vitamin‐based treatments, or antihistamines) were ineligible for inclusion. Women had to respect all these criteria during the study.

2.2. Skin dark spot cartography using LC‐OCT device

LC‐OCT (DAMAE Medical, France, Paris) 15 , 16 , 17 , 18 , 19 , 20 , 21 is a non‐invasive imaging technique based on interferometry and low‐coherence light principles. This technology involves splitting a near‐infrared light beam into two arms, with one directed at the target tissue and the other sent to a reference mirror. The reflected light from both arms is then combined, and interference patterns are analyzed. LC‐OCT can thus generate high‐resolution cross‐sectional images of biological tissues, aligning with conventional OCT orientation. Additionally, LC‐OCT provides other imaging modalities, including horizontal images (“en face”) and 3D stacks. The device produces vertical and horizontal sectional images at a rate of eight frames per second, with a depth penetration of approximately 500 μm. LC‐OCT has an axial resolution of 1.1 μm, a lateral resolution of 1.3 μm, and a field of view of 1.2 mm × 0.5 mm (vertical) and 1.2 mm × 0.5 mm (horizontal). In conjunction with microscopic imaging, the device offers a color macroscopic imaging modality along with real‐time localization of the imaged region, facilitating precise targeting of the area of interest. This macroscopic surface image encompasses a 2.5 mm diameter field of view with a resolution of approximately 5 μm. 27

The LC‐OCT device was used for in vivo imaging of pigmented spots pre‐selected by the dermatologist. The procedure for in vivo human skin imaging consists in applying a drop of paraffin oil between the skin and the glass window of the handheld probe. The resulted 3D stacks were visually examined and categorized based on dermal‐epidermal junction [DEJ] undulation and melanin volumetric density, enabling the creation of a 3D atlas of pigmented lesions.

2.2.1. Dermal‐epidermal junction (DEJ) segmentation

A skin layer segmentation algorithm, previously developed and described, 24 , 28 , 29 was used to obtain 3D segmentations of distinct skin interfaces: skin surface, end of stratum corneum and dermal‐epidermal junction. To ensure the precision and reliability of the segmentation outcomes, a trained expert conducted a validation process, wherein visual inspection of processed images was employed.

The percentage of DEJ undulation was calculated from the segmentations as follows:

%UDEJ=(SDEJ/SROI1)×100,

where SDEJ represents the area of the dermo‐epidermal interface and SROI the total horizontal area of the LC‐OCT image excluding regions corresponding to hair follicles. 18

2.2.2. Melanin quantification

Melanin segmentation in 3D LC‐OCT stacks was achieved through the integration of an artificial intelligence algorithm, developed by DAMAE Medical. Subsequently, the volumetric density of melanin within the epidermis was computed. To ensure precise melanin quantification, an algorithm specifically designed for the segmentation of melanin in 3D LC‐OCT volumes was developed and validated. The architecture employed in this algorithm is based on a fundamental 3D U‐net model. To generate training data, a semi‐automatic algorithm was used to segment melanin in 108 patches of 3D image stacks containing pigmented regions. These segmented patches were subsequently employed for the training of the model. The performance of the algorithm was validated through experiments involving a panel of 29 women with Fitzpatrick's phototypes ranging from I to VI. Melanin volumetric density was determined by calculating the ratio of the number of pixels corresponding to melanin within the acquired 3D LC‐OCT images to the total number of pixels in the epidermis. The results from the validation experiments are available in Figure 1 of the supporting information.

FIGURE 1.

FIGURE 1

Diverse spot types characterized by dermal‐epidermal Junction (DEJ) morphology. (A) Description of spot categories using different LC‐OCT imaging modalities: vertical LC‐OCT images with 3D segmentation of the DEJ (green, left panel) and horizontal LC‐OCT images at the depth of the DEJ (right panel). Three primary classes emerge: little deformed DEJ (category 1), DEJ with regular papillae (category 2), and DEJ with complex deformation (category 3). (B) Boxplot illustrating the progressive changes in DEJ undulation and in volumetric melanin density across the three DEJ categories.

2.3. Study protocol for brightening product application

Participants were instructed to apply a brightening product twice daily, in the morning and evening, to their entire face, excluding the eyes area. The application involved using circular motions radiating from the center of the face outward. This regimen was to be followed consistently for a duration of 2 months. Five 30 mL vials were given to each participant; the vials were weighed at the beginning and end of the study. Throughout the study period, participants were strictly instructed to avoid sun exposure, and the use of only a designated moisturizing cream was permitted. Participants were asked to visit the research center at D0 (baseline prior to product application), at 1 month (D28, after 28 days of repeated product applications) and at 2 months (D56, after 56 days of repeated product applications). At D0, a dermatologist evaluated each participant to characterize pigmented spots, with a maximum of three spots selected for follow‐up. A spot‐free control area, located as close as possible to the chosen spot area, was designated for each selected spot. LC‐OCT 3D imaging and SkinCam system were used to assess the product's efficacy. Any potential cutaneous irritation was assessed at each visit, and women had the option to contact the dermatologist in case of any concerns or complaints.

2.4. Assessment of brightening effect of the cosmetic product

2.4.1. LC‐OCT 3D imaging

LC‐OCT was employed to assess the impact of the cosmetic product through 3D imaging, examining the volumetric density of melanin in the epidermis and DEJ undulation, as previously detailed, both at the baseline (D0) and the conclusion of the study (D56).

2.4.2. SkinCam system

To investigate the macroscopic brightening effect of the product on pigmented spots after application in a full‐face design, the SkinCam probe (Newtone Technologies) was employed to capture images of the spots and measure their colorimetric parameters. 30 , 31 Measurements with the SkinCam probe were conducted at each visit (D0, D28, and D56). The selected spots were automatically identified and segmented within pigmented spots and their surrounding skin. The colorimetric parameters were assessed based on the L*a*b color space defined by the International Commission on Illumination, which comprises three dimensions: L* for lightness, and a* and b* for the color channels green‐red and blue‐yellow, respectively. Skin color parameters (L*, a*, b*) were calculated for all selected spots and their surrounding areas. In skin color analysis, an increase in L* results in an increase of skin lightness; a decrease in a* corresponds to a decrease of skin redness; and a decrease of b* results in a decrease of skin yellowness. 30

2.5. Statistical analysis

Statistical analysis was conducted using R software version 4.2.2. A one‐way analysis of variance evaluated the potential differences in volumetric density of melanin, as measured by LC‐OCT, among the six phototypes. To assess the impact of the skincare product between D0 and D56 post‐treatment, paired Student's t‐tests or Wilcoxon signed‐rank tests were performed separately for both the dark spot and its surrounding area. For metrics with non‐normally distributed data, the appropriate test was selected. A p‐value threshold of 0.05 was used to define statistical significance.

3. RESULTS

3.1. Study population

The demographic characteristics of the study population are presented in Table 1. A total of 26 participants of Asian women successfully completed the study, while two individuals withdrew from participation due to unavailability. The mean age of the cohort was 49.2 years (± 11.2), with the majority manifesting phototypes III (42.3%) and IV (46.2%). The average age of Group 1 (G1) is 37 years old, whereas it is 59.6 years old for Group 2 (G2).

TABLE 1.

Population characteristics.

All patients (= 26)

G1

(N = 12)

G2

(N = 14)

Age. years [mean ± (SD)] 49.2 (± 11.2) 37.1 ± (3.9) 59.6 ± (3.5)
Minimum Age 29 29 52
Maximum Age 65 43 65
Phototype: n (%)
II 3 (11.5%) 2 (16.7%) 1 (7.2%)
III 11 (42.3%) 6 (50.0%) 5 (35.7%)
IV 12 (46.2%) 4 (33.3%) 8 (57.1%)

Abbreviations: G1, group 1; G2, group 2; SD, standard deviation.

3.2. Cartography of dark spot internal structures

Figure 1 illustrates a diverse array of morphologies observed in the 44 examined dark spots, ranging from minimally deformed DEJ configurations to intricate DEJ patterns characterized by distorted rete ridges (Figure 1A). The spots were categorized into three groups: category 1 (minimal DEJ deformation), category 2 (circular papillae DEJ), and category 3 (complex DEJ deformation). Tukey post‐hoc analyses revealed a significant difference in terms of DEJ undulation between DEJ categories 1 and 2 (= 0.02) and between DEJ categories 1 and 3 (= 0.02), but no significant difference was observed in terms of volumetric melanin density (Figure 1B).

Additionally, a correlation between the DEJ aspect and the participants’ age was observed (Figure 2). Dark spots with minimal DEJ deformation were predominantly observed in the youngest age group (62% in G1 vs. 38% in G2), while older volunteers displayed complex and distorted rete ridges (83% in G2 vs. 17% in G1). Dark spots with moderate DEJ waviness were equally distributed between the younger and older age groups.

FIGURE 2.

FIGURE 2

Percentage of spots within the three DEJ categories stratified by age groups (G1: < 50 years old, N = 12; and G2: > 50 years old, N = 14).

3.3. Effect of the brightening skincare serum application

Using the LC‐OCT device, we evaluated the melanin volumetric density within the 44 pigmented spots and their adjacent regions at baseline (D0) and after a 56‐day application of the product (Figure 3). A statistically significant reduction in melanin volumetric density of 7.3% within the spots (p = 0.01) and 12.3% in their adjacent areas (p < 0.001) was observed after 56 days of treatment (Table 2, Figure 3A). However, there were no substantial changes in DEJ undulation following the treatment, neither within the pigmented lesions nor their adjacent skin regions (Table 2, Figure 3B).

FIGURE 3.

FIGURE 3

Volumetric melanin density analysis in response to treatment over time. Boxplot depicting the dynamic changes in volumetric melanin density (A) and DEJ deformation (B) within skin spots (“SPOT”) and their surrounding regions (“FACE”) at both baseline (D0) and after 56 days of treatment (D56). ns: not significant, **: p‐value < 0.01 and ***: p‐value < 0.001.

TABLE 2.

Changes of LC‐OCT metrics in spots and their surrounding areas in different experimental periods (Mean ± SD, n = 44).

Volumetric melanin density DEJ undulation (%)
D0 D56 p‐value D0 D56 p‐value
Spots 0.049 ± 0.018 0.045 ± 0.018 0.011 (Paired t‐test) 11.1 ± 7.8 9.9 ± 9.5 0.19 (Wilcoxon signed‐rank test)
Surrounding areas 0.032 ± 0.012 0.027 ± 0.011 0.00051 (Paired t‐test) 8.1 ± 7.4 7.8 ± 6.8 0.96 (Wilcoxon signed‐rank test)

LC‐OCT images of the spots illustrate the change in melanin contrast across the epidermis at D56 compared to the baseline at D0 (Figure 4). Cosmetic product application seems to reduce the presence of melanin in the epidermis.

FIGURE 4.

FIGURE 4

Representative LC‐OCT images illustrating the impact of treatment on a spot featuring regular papillae at the dermal‐epidermal junction (DEJ). The first column exhibits horizontal LC‐OCT images covering the entire field of view, measuring 1200 × 500 microns at DEJ depth. Subsequent columns display magnified views (both vertical and horizontal) at D0 and D56 of 3 papillae demarcated by the white rectangle, with melanin and DEJ segmentation highlighted in yellow and green, respectively.

The results were further substantiated by macroscopic color analysis using SkinCam photos capturing the pigmented spots and their surrounding areas. Visual inspection reveals the brightening effect of the product on both the pigmented spots and surrounding areas at D28 and D56 compared to the baseline at D0 (Figure 5A). At D56, a statistically significant increase in the L* parameter was observed in pigmented spots (+2.1%, = 0.04), indicating a brightening effect (Table 3, Figure 5B). Subsequent to treatment initiation, both D28 and D56 revealed statistically significant decreases in the a* parameter (−3.3%, = 0.0002 and −4.3%, < 0.001, respectively), suggesting a reduction in the redness within the analyzed area (Table 3, Figure 5C). Conversely, no significant variations were observed in the b* parameter (Table 3, Figure 5D). These trends were also consistently observed in the surrounding skin regions as the brightening product was applied to the entire face and not only on the pigmented spots.

FIGURE 5.

FIGURE 5

Color parameter analysis using SkinCam system over time. (A) SkinCam images illustrating the change in visible color of the pigmented spot and the adjacent surrounding skin after brightening product application (D0 vs D28 and D56). (B) Box plot representing the temporal variations in the L* parameter, (C) a* parameter and (D) b* color parameter. ns: not significant, *: p‐value < 0.05, **: p‐value < 0.01 and ***: p‐value < 0.001.

TABLE 3.

Changes of Skincam parameters in spots and their surrounding areas in different experimental periods (Mean ± SD, n = 44 spots).

L* a* b*
D0 D28 D56 p‐value D0 D28 D56 p‐value D0 D28 D56 p‐value
Spots 57. 4 ± 4.7 57.7 ± 5.0 58.3 ± 5.1 0.04 26.0 ± 4.0 25.4 ± 4.2 25.2 ± 4.0 <0.001 32.1 ± 3.7 32.6 ± 3.8 31.9 ± 4.3 0.47
D28‐D0 +1.0% 0.69 ‐3.3% 0.0002 0.2% 0.92
D56‐D0 +2.1% 0.04 ‐4.3% <0.001 ‐0.5 % 0.67
Surrounding areas 62.6 ± 4.2 63.1 ± 4.2 63.6 ± 4.5 0.007 21.8 ± 3.7 21.0 ± 3.7 20.9 ± 3.8 <0.001 26.4 ± 4.4 26.8 ± 4.3 26.3 ± 4.5 0.66
D28‐D0 +1.0% 0.40 ‐4.0% 0.0008 0.4% 0.92
D56‐D0 +2.0% 0.006 ‐5.5% <0.001 ‐0.5% 0.85

3.4. Tolerance

No subjects exhibited adverse events, signs of intolerability, or reported sensations of discomfort throughout the duration of the study.

4. DISCUSSION

Real‐time non‐invasive monitoring of pigmented spots poses a significant challenge for the global cosmetic industry. In this study, we established a cartography of the dark spots according to the DEJ pattern using non‐invasive LC‐OCT 3D imaging. Furthermore, we demonstrated, using both macroscopic and microscopic assessments, the brightening effect of a cosmetic product after a 2‐month application period by a panel of Asian female volunteers.

The LC‐OCT 3D images offer a non‐invasive way of conducting “virtual biopsies” allowing for the morphological characterization of DEJ in dark spots. In this study, we successfully classified these spots into three categories based on rete ridges deformation: those with a minimally deformed DEJ, those exhibiting regular circular papillae, and those with a complex structure. Notably, dark spots with a minimally deformed DEJ were predominantly observed in the youngest age group, whereas the older volunteers exhibited a more complex DEJ pattern with wavier rete ridges. We did not observe a significant difference in terms of epidermal volumetric melanin density between the three categories. These findings may be associated with the progressive accumulation of melanin in the basal layer of the epidermis with aging. Consistent with these observations, a 5‐year follow‐up study on the morphology of solar lentigines, using RCM images, revealed compressive forces acting on the dermal–epidermal junction and a localized state of hyperproliferation due to melanin accumulation. The study noted a progression and worsening of these morphological parameters in vivo over a 5‐year period. 32 Histological findings further support these observations, indicating that the accumulation of melanin in the basal layers of the epidermis leads to the elongation of rete ridges. This effect becomes more pronounced with the presumed age of the lesion. 8 , 33 Thus, the excessive production and accumulation of melanin in the epidermis can disturb cellular communication at the DEJ, causing imbalances in cell proliferation and maturation. This cellular disruption forms a compressive deformation of the dermal papillae and becomes more pronounced with age due to the extended process of skin renewal. 32 , 34

Following an exploration of spot morphologies using LC‐OCT imaging, we applied this technique to monitor the effectiveness of a brightening serum cosmetic product on Asian volunteers with an objective assessment of melanin levels in the spots. Results showed that melanin density levels were reduced by 7% within the dark spots and 12% within their surrounding area after 2 months of full‐face application by Asian women. The observed skin‐brightening effect, validated by the SkinCam tool, became apparent within the first month of treatment and persisted throughout the study, suggesting a relatively rapid efficacy compared to other products in clinical trials. 35 , 36 , 37

Clinical studies often rely on clinical scoring as a single endpoint to assess the brightening effect of active ingredients on solar lentigines. 35 , 36 , 38 For instance, a reduction in hyperpigmentation or a notable decrease in melanin score was observed after 3 months of using a hydroquinone cream. 35 In other studies, the decrease in melanin load (Melanin Index, MI) was evaluated using Mexameter measurement 39 , 40 to assess the brightening effect of 2% hydroquinone‐cyclodextrin 39 or 4 n‐butylresorcinol 40 after 2 months of application by Asian volunteers. However, the Mexameter, a spectrometric device, 41 lacks the capability to provide data on epidermal structure, a feature offered by imaging tools such as LC‐OCT. 26 RCM was also used to assess the effectiveness of dermocosmetic brightening products. 37 The researchers noted a notable reduction in the brightness and contrast of papillae through a semi‐quantitative assessment/scoring based on 2D horizontal images. 37 The disparity in the assessment tools' performance and metrics complicates direct comparisons between our brightening product effectiveness and that of other products. Standardization in experimental designs for evaluating diverse brightening products is essential to establish an objective measure of their efficacy.

To understand in depth, the impact of the brightening product on melanin, LC‐OCT 3D images were captured before and after treatment. Following 2 months of cosmetic product application, melanin appeared less concentrated in the epidermis. This reduction in content appears to be accompanied by a change in the distribution of melanin within the epidermis. Thus, at D0 melanin was predominantly concentrated in the deeper papillary region and at D56, melanin appears to be more evenly distributed across the epidermis. This finding aligns with that of Razi et al.’s case study, illustrating a reduction in pigmentation in LC‐OCT 3D images following chemical peel spot treatment, attributed to the upward migration of melanin through epidermis. 26 Similar results were also noted in a study examining the effects of retinoids on photoaged skin using in vivo multiphoton 3D imaging, where the primary impact of retinoids on pigmentation was attributed to skin renewal rather than having a direct influence on melanogenesis. 42 We should note herein that multiphoton 3D imaging tool has limitations in terms of field of view, typically around 130 × 130 μm2, and it requires a longer acquisition time of 7–10 min to assemble a complete 3D z‐stack. 13 , 42 The authors emphasize that a larger skin area would provide a more precise measurement for melanin assessment and evaluating melanin heterogeneity in skin disorders. 13 This is where LC‐OCT 3D imaging, used in our study, excels providing a larger imaging area (1.2 × 0.5 × 0.5 mm3) in just 30 s.

Morphological parameters were also assessed during the use of the brightening product. Notable changes in DEJ undulation were not observed following 2 months of treatment in both pigmented spots and their adjacent skin regions. However, Arginelli et al. demonstrated a quantitative restriction of natural DEJ destructuring on solar lentigines with the use of a dermocosmetic brightening product over a 12‐month follow‐up period. 37 Taken together, these findings suggest that the modulation in DEJ pattern seems to be not detectable in a short time frame, as in the present study. Future investigations with an extended treatment duration are needed to validate the long‐term efficacy of our brightening product in correcting DEJ. Considering the widely acknowledged strategy of treatment combination in the cosmetics industry, 43 , 44 it could be advisable to explore the potential of combining various agents with distinct modes of action to enhance the effectiveness of our brightening cosmetic product. Additionally, complementing the treatment with a dietary regimen or supplements rich in vitamins that promote skin renewal, 45 could contribute to the gradual repair of the DEJ.

5. CONCLUSIONS

This pioneering study has brought to light the utility of non‐invasive LC‐OCT 3D imaging technology as a valuable instrument for characterizing the dermal‐epidermal junction (DEJ) morphology and the melanin volumetric density in photo‐aging spots. Furthermore, LC‐OCT facilitates real‐time evaluation of the efficacy of skin‐brightening products, providing compelling evidence that our serum cosmetic product not only effectively addresses pigmented spots but also enhances the overall skin brightness in treated areas. These noteworthy advancements signify a breakthrough, paving the way for future opportunities in delivering a more precise and personalized approach to skincare, aligning with consumer demands for enhanced skin pigmentation and overall skin quality. The incorporation of LC‐OCT as an adjunct tool in the domains of dermatology and cosmetics holds considerable promise for advancing the field of dermatological sciences.

CONFLICT OF INTEREST STATEMENT

The authors have no conflicts of interest to declare.

ETHICS STATEMENT

All participants provided written informed consent and a photo consent statement before starting the study.

Supporting information

Supporting Information

ACKNOWLEDGMENTS

The authors of this paper would like to thank Newtone Technologies for their support in using the SkinCam and analyzing the data generated by this device.

Jdid R, Pedrazzani M, Lejeune F, et al. Skin dark spot mapping and evaluation of brightening product efficacy using Line‐field Confocal Optical Coherence Tomography (LC‐OCT). Skin Res Technol. 2024;30:e13623. 10.1111/srt.13623

Randa Jdid and Mélanie Pedrazzani contribute equally to this work.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.

REFERENCES

  • 1. Ferreira AM, De Souza AA, Koga RDCR, et al. Anti‐melanogenic potential of natural and synthetic substances: application in zebrafish model. Molecules. 2023;28:1053. doi: 10.3390/molecules28031053 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Ortonne J‐P, Bissett DL. Latest insights into skin hyperpigmentation. J Investig Dermatol Symp Proc. 2008;13:10–14. doi: 10.1038/jidsymp.2008.7 [DOI] [PubMed] [Google Scholar]
  • 3. Syder NC, Quarshie C, Elbuluk N. Disorders of facial hyperpigmentation. Dermatol Clin. 2023;41:393–405. doi: 10.1016/j.det.2023.02.005 [DOI] [PubMed] [Google Scholar]
  • 4. Tschachler E, Morizot F. Ethnic differences in skin aging. In: Gilchrest BA, Krutmann J, editors. Skin Aging, Springer‐Verlag; 2006:23–31. doi: 10.1007/3-540-32953-6_3 [DOI] [Google Scholar]
  • 5. Goh SH. The treatment of visible signs of senescence: the Asian experience. Br J Dermatol. 1990;122:105–109. doi: 10.1111/j.1365-2133.1990.tb16134.x [DOI] [PubMed] [Google Scholar]
  • 6. Kang HY. Melasma and aspects of pigmentary disorders in Asians. Ann Dermatol Venereol. 2012;139:S144–S147. doi: 10.1016/S0151-9638(12)70126-6 [DOI] [PubMed] [Google Scholar]
  • 7. Tadokoro T, Yamaguchi Y, Batzer J, et al. Mechanisms of skin tanning in different racial/ethnic groups in response to ultraviolet radiation. J Invest Dermatol. 2005;124:1326–1332. doi: 10.1111/j.0022-202X.2005.23760.x [DOI] [PubMed] [Google Scholar]
  • 8. Cario‐Andre M, Lepreux S, Pain C, Nizard C, Noblesse E, Taïeb A. Perilesional vs. lesional skin changes in senile lentigo: pathology of senile lentigo. J Cutan Pathol. 2004;31:441–447. doi: 10.1111/j.0303-6987.2004.00210.x [DOI] [PubMed] [Google Scholar]
  • 9. Szyc Ł, Scharlach C, Haenssle H, Fink C. In vivo two‐photon‐excited cellular fluorescence of melanin, NAD(P)H, and keratin enables an accurate differential diagnosis of seborrheic keratosis and pigmented cutaneous melanoma. J Biomed Opt. 2021;26:075002. doi: 10.1117/1.JBO.26.7.075002 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Rajadhyaksha M, González S, Zavislan JM, Rox Anderson R, Webb RH. In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology11the authors have declared conflict of interest. J Invest Dermatol. 1999;113:293–303. doi: 10.1046/j.1523-1747.1999.00690.x [DOI] [PubMed] [Google Scholar]
  • 11. Gougeon S, Hernandez E, Chevrot N, et al. Evaluation of a new connected portable camera for the analysis of skin microrelief and the assessment of the effect of skin moisturisers. Skin Res Technol. 2023;29:e13190. doi: 10.1111/srt.13190 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Lentsch G, Balu M, Williams J, et al. In vivo multiphoton microscopy of melasma. Pigment Cell Melanoma Res. 2019;32:403–411. doi: 10.1111/pcmr.12756 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Pena A‐M, Baldeweck T, Decencière E, et al. In vivo multiphoton multiparametric 3D quantification of human skin aging on forearm and face. Sci Rep. 2022;12:14863. doi: 10.1038/s41598-022-18657-z [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. Chen I‐L, Wang Y‐J, Chang C‐C, et al. Computer‐aided detection (CADe) system with optical coherent tomography for melanin morphology quantification in melasma patients. Diagnostics. 2021;11:1498. doi: 10.3390/diagnostics11081498 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Ogien J, Levecq O, Azimani H, Dubois A. Dual‐mode line‐field confocal optical coherence tomography for ultrahigh‐resolution vertical and horizontal section imaging of human skin in vivo. Biomed Opt Express. 2020;11:1327. doi: 10.1364/BOE.385303 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Ogien J, Daures A, Cazalas M, Perrot J‐L, Dubois A. Line‐field confocal optical coherence tomography for three‐dimensional skin imaging. Front Optoelectron. 2020;13:381–392. doi: 10.1007/s12200-020-1096-x [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Monnier J, Tognetti L, Miyamoto M, et al. In vivo characterization of healthy human skin with a novel, non‐invasive imaging technique: line‐field confocal optical coherence tomography. J Eur Acad Dermatol Venereol. 2020;34:2914–2921. doi: 10.1111/jdv.16857 [DOI] [PubMed] [Google Scholar]
  • 18. Chauvel‐Picard J, Bérot V, Tognetti L, et al. Line‐field confocal optical coherence tomography as a tool for three‐dimensional in vivo quantification of healthy epidermis: a pilot study. J Biophotonics. 2022;15:e202100236. doi: 10.1002/jbio.202100236 [DOI] [PubMed] [Google Scholar]
  • 19. Dubois A, Levecq O, Azimani H, et al. Line‐field confocal optical coherence tomography for high‐resolution noninvasive imaging of skin tumors. J Biomed Opt. 2018;23(10):106007. doi: 10.1117/1.JBO.23.10.106007 [DOI] [PubMed] [Google Scholar]
  • 20. Dubois A, Levecq O, Azimani H, et al. Line‐field confocal time‐domain optical coherence tomography with dynamic focusing. Opt Express. 2018;26:33534. doi: 10.1364/OE.26.033534 [DOI] [PubMed] [Google Scholar]
  • 21. Schuh S, Ruini C, Perwein MKE, et al. Line‐field confocal optical coherence tomography: a new tool for the differentiation between nevi and melanomas? Cancers. 2022;14:1140. doi: 10.3390/cancers14051140 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Pedrazzani M, Breugnot J, Rouaud‐Tinguely P, et al. Comparison of line‐field confocal optical coherence tomography images with histological sections: validation of a new method for in vivo and non‐invasive quantification of superficial dermis thickness. Skin Res Technol. 2020;26:398–404. doi: 10.1111/srt.12815 [DOI] [PubMed] [Google Scholar]
  • 23. Ayadh M, Abellan M‐A, Figueiredo S, et al. LC‐OCT imaging for studying the variation of morphological properties of human skin in vivo according to age and body area: the forearm and the thigh. Dermis 212 n.d.
  • 24. Bonnier F, Pedrazzani M, Fischman S, et al. Line‐field confocal optical coherence tomography coupled with artificial intelligence algorithms to identify quantitative biomarkers of facial skin ageing. Sci Rep. 2023;13:13881. doi: 10.1038/s41598-023-40340-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. Orsini C, Trovato E, Cortonesi G, et al. Line‐field confocal optical coherence tomography: new insights for psoriasis treatment monitoring. J Eur Acad Dermatol Venereol. 2023:325. doi: 10.1111/jdv.19568 [DOI] [PubMed] [Google Scholar]
  • 26. Razi S, Raquepo TM, Truong TM, Rao B. Analyzing the effects of a chemical peel on post‐inflammatory hyperpigmentation using line‐field confocal optical coherence tomography. Skin Res Technol. 2023;29:e13496. doi: 10.1111/srt.13496 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. Latriglia F, Ogien J, Fischman S, Pedrazzani M, Dubois A. Advances of LC‐OCT technology for diagnostic support in dermatology. In: Lilge LD, Huang Z, editors. Transl. Biophotonics Diagn. Ther. III, SPIE; 2023:55. doi: 10.1117/12.2670911 [DOI] [Google Scholar]
  • 28. Ronneberger O, Fischer P, Brox T. U‐Net: Convolutional Networks for Biomedical Image Segmentation 2015. doi: 10.48550/ARXIV.1505.04597 [DOI]
  • 29. Thamm JR, Daxenberger F, Viel T, et al. Artificial intelligence‐based PRO score assessment in actinic keratoses from LC‐OCT imaging using Convolutional Neural Networks. J Dtsch Dermatol Ges.1359‐1366, 2023:ddg.15194. doi: 10.1111/ddg.15194 [DOI] [PubMed] [Google Scholar]
  • 30. Maudet A, Le Bec J, Flament F, et al. Analysis of images supplied by Skincam® can record the changes of some scar features that occur over time. Comparisons with the assessments of dermatologist and patients’ perception. J Cosmet Dermatol. 2023;22:1334–1343. doi: 10.1111/jocd.15575 [DOI] [PubMed] [Google Scholar]
  • 31. Nkengne A, Robic J, Seroul P, Gueheunneux S, Jomier M, Vie K. SpectraCam ® : a new polarized hyperspectral imaging system for repeatable and reproducible in vivo skin quantification of melanin, total hemoglobin, and oxygen saturation. Skin Res Technol. 2018;24:99–107. doi: 10.1111/srt.12396 [DOI] [PubMed] [Google Scholar]
  • 32. Pollefliet C, Corstjens H, González S, Hellemans L, Declercq L, Yarosh D. Morphological characterization of solar lentigines by in vivo reflectance confocal microscopy: a longitudinal approach. Int J Cosmet Sci. 2013;35:149–155. doi: 10.1111/ics.12016 [DOI] [PubMed] [Google Scholar]
  • 33. Nizard C, Cario‐André M, Lepreux S, et al. Epidermal dermal junction and spots in human skin: abstracts. Int J Cosmet Sci. 2008;27:62–66. doi: 10.1111/j.1467-2494.2004.00254_13.x [DOI] [Google Scholar]
  • 34. Bonté F, Girard D, Archambault J‐C, Desmoulière A. Skin changes during ageing. In: Harris JR, Korolchuk VI, editors. Biochem. Cell Biol. Ageing Part II Clin. Sci., vol. 91, Springer Singapore; 2019:249–280. doi: 10.1007/978-981-13-3681-2_10 [DOI] [PubMed] [Google Scholar]
  • 35. Dreher F, Draelos ZD, Gold MH, Goldman MP, Fabi SG, Puissegur Lupo ML. Efficacy of hydroquinone‐free skin‐lightening cream for photoaging. J Cosmet Dermatol. 2013;12:12‐17. doi: 10.1111/jocd.12025 [DOI] [PubMed] [Google Scholar]
  • 36. Cameli N, Abril E, Agozzino M, Mariano M. Clinical and instrumental evaluation of the efficacy of a new depigmenting agent containing a combination of a retinoid, a phenolic agent and an antioxidant for the treatment of solar lentigines. Dermatology. 2015;230:360–366. doi: 10.1159/000379746 [DOI] [PubMed] [Google Scholar]
  • 37. Arginelli F, Greco M, Ciardo S, et al. Efficacy of D‐pigment dermocosmetic lightening product for solar lentigo lesions of the hand: a randomized controlled trial. PLOS ONE. 2019;14:e0214714. doi: 10.1371/journal.pone.0214714 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Campanati A, Giannoni M, Scalise A, et al. Efficacy and safety of topical pidobenzone 4% as adjuvant treatment for solar lentigines: result of a randomized, controlled, clinical trial. Dermatology. 2016;232:478–483. doi: 10.1159/000447356 [DOI] [PubMed] [Google Scholar]
  • 39. Petit L, Pierard G. Analytic quantification of solar lentigines lightening by a 2% hydroquinone‐cyclodextrin formulation. J Eur Acad Dermatol Venereol. 2003;17:546–549. doi: 10.1046/j.1468-3083.2003.00808.x [DOI] [PubMed] [Google Scholar]
  • 40. Huh SY, Shin J‐W, Na J‐I, Huh C‐H, Youn S‐W, Park K‐C. Efficacy and safety of liposome‐encapsulated 4‐ n ‐butylresorcinol 0.1% cream for the treatment of melasma: A randomized controlled split‐face trial. J Dermatol. 2010;37:311–315. doi: 10.1111/j.1346-8138.2010.00787.x [DOI] [PubMed] [Google Scholar]
  • 41. Park ES, Na JI, Kim SO, Huh CH, Youn SW, Park KC. Application of a pigment measuring device – Mexameter®– for the differential diagnosis of vitiligo and nevus depigmentosus. Skin Res Technol. 2006;12:298–302. doi: 10.1111/j.0909-752X.2006.00187.x [DOI] [PubMed] [Google Scholar]
  • 42. Tancrède‐Bohin E, Baldeweck T, Brizion S, et al. In vivo multiphoton imaging for non‐invasive time course assessment of retinoids effects on human skin. Skin Res Technol. 2020;26:794–803. doi: 10.1111/srt.12877 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43. Kim H, Choi H‐R, Kim D‐S, Park K‐C. Topical hypopigmenting agents for pigmentary disorders and their mechanisms of action. Ann Dermatol. 2012;24(1):1–6. doi: 10.5021/ad.2012.24.1.1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44. González‐Molina V, Martí‐Pineda A, González N. Topical treatments for melasma and their mechanism of action. J Clin Aesthetic Dermatol. 2022;15:19–28. [PMC free article] [PubMed] [Google Scholar]
  • 45. Lucock MD. The evolution of human skin pigmentation: a changing medley of vitamins, genetic variability, and uv radiation during human expansion. Am J Biol Anthropol. 2023;180:252–271. doi: 10.1002/ajpa.24564 [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supporting Information

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.


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