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Peer-reviewedCC BY-NC 4.0Dermatology and Therapy

AI-Assisted Quantitative Reflectance Confocal Microscopy Reveals Modulation of Senescence-Associated Epidermal Morphometric Features by a Topical TGF-β Mimetic, XEP™-716 Miniprotein™

  • Hanane Chajra1
  • Nicolas Rayroux2
  • Corinne Granger3
  • Lionel Breton4
  • Pedro Contreiras PInto5
  • Thibaut Saguet6
  • Jean-Marc Le Doussal1
6 affiliations
  1. 1Activen, Epalinges, Switzerland
  2. 2Remora Biotech, Epalinges, Switzerland
  3. 3Stella Polaris Europe, Paris, France
  4. 4CILIA Consulting, Paris, France
  5. 5PhD Trials®, Lisbon, Portugal
  6. 6TS-Consulting, Olivet, France
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Abstract

Introduction: Epidermal aging is characterized by progressive structural alterations, including reduced keratinocyte density, altered cellular morphology, and widened intercellular spacing (ICS). Reflectance confocal microscopy (RCM) combined with artificial intelligence (AI)-assisted image analysis enables non-invasive quantification of these changes in vivo. This secondary analysis of RCM images reported in a previously published randomized split-face clinical trial aimed to identify quantitative morphometric features associated with chronological aging and to evaluate their modulation following topical application of the transforming growth factor-beta (TGF-β) mimetic XEP™-716 Miniprotein™ (Activen SA, Lausanne. Switzerland).

Methods: Previously acquired baseline RCM images from 49 women (age 40–60 years) were analyzed for associations with chronological age. Treatment effects were assessed in 25 women from the 2.5% arm of a 56-day randomized, double-blind, split-face study comparing XEP™-716 Miniprotein™ 2.5% with vehicle. AI-assisted image analysis quantified keratinocyte density, cellular circularity, and ICS in the stratum granulosum (SG) and the stratum spinosum (SS). Cells with circularity ≤ 0.439 were classified as low-circularity cells and those ≥ 0.440 circularity as morphologically normal. Treatment effects were assessed using linear mixed-effects models.

Results: Stratum granulosum total and normal keratinocyte densities were nominally significantly associated with age (p = 0.015 and p = 0.023, respectively). Compared with vehicle, XEP™-716 Miniprotein™ used at 2.5% was associated with nominally significant increases in normal keratinocyte density (p = 0.028) and the circularity of low-circularity cells (p = 0.018), and with decreases in ICS thickness (p = 0.030) and low-circularity cell density (p = 0.044) in the SG. In the SS, there was a non-significant trend towards reduced low-circularity cell density (p = 0.075).

Conclusion: Artificial intelligence-assisted quantitative RCM can identify age-associated epidermal morphometric features, predominantly in the SG, and detect their modulation following topical treatment. XEP™-716 Miniprotein™ at 2.5% showed consistent treatment-associated changes across several morphometric parameters with nominal statistical significance. These exploratory findings warrant prospective validation against molecular senescence markers and functional barrier measurements.

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Cite

BibTeXRIS
BibTeX
@article{chajra2026aiassisted,
  title = {{AI-Assisted Quantitative Reflectance Confocal Microscopy Reveals Modulation of Senescence-Associated Epidermal Morphometric Features by a Topical TGF-β Mimetic, XEP™-716 Miniprotein™}},
  author = {Hanane Chajra and Nicolas Rayroux and Corinne Granger and Lionel Breton and Pedro Contreiras PInto and Thibaut Saguet and Jean-Marc Le Doussal},
  journal = {Dermatology and Therapy},
  year = {2026},
  month = oct,
  doi = {10.1007/s13555-026-01945-1},
  url = {https://doi.org/10.1007/s13555-026-01945-1},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - AI-Assisted Quantitative Reflectance Confocal Microscopy Reveals Modulation of Senescence-Associated Epidermal Morphometric Features by a Topical TGF-β Mimetic, XEP™-716 Miniprotein™
AU  - Hanane Chajra
AU  - Nicolas Rayroux
AU  - Corinne Granger
AU  - Lionel Breton
AU  - Pedro Contreiras PInto
AU  - Thibaut Saguet
AU  - Jean-Marc Le Doussal
PY  - 2026
DA  - 2026/10/01
JO  - Dermatology and Therapy
DO  - 10.1007/s13555-026-01945-1
UR  - https://doi.org/10.1007/s13555-026-01945-1
AB  - Introduction: Epidermal aging is characterized by progressive structural alterations, including reduced keratinocyte density, altered cellular morphology, and widened intercellular spacing (ICS). Reflectance confocal microscopy (RCM) combined with artificial intelligence (AI)-assisted image analysis enables non-invasive quantification of these changes in vivo. This secondary analysis of RCM images reported in a previously published randomized split-face clinical trial aimed to identify quantitative morphometric features associated with chronological aging and to evaluate their modulation following topical application of the transforming growth factor-beta (TGF-β) mimetic XEP™-716 Miniprotein™ (Activen SA, Lausanne. Switzerland).  Methods: Previously acquired baseline RCM images from 49 women (age 40–60 years) were analyzed for associations with chronological age. Treatment effects were assessed in 25 women from the 2.5% arm of a 56-day randomized, double-blind, split-face study comparing XEP™-716 Miniprotein™ 2.5% with vehicle. AI-assisted image analysis quantified keratinocyte density, cellular circularity, and ICS in the stratum granulosum (SG) and the stratum spinosum (SS). Cells with circularity ≤ 0.439 were classified as low-circularity cells and those ≥ 0.440 circularity as morphologically normal. Treatment effects were assessed using linear mixed-effects models.  Results: Stratum granulosum total and normal keratinocyte densities were nominally significantly associated with age (p = 0.015 and p = 0.023, respectively). Compared with vehicle, XEP™-716 Miniprotein™ used at 2.5% was associated with nominally significant increases in normal keratinocyte density (p = 0.028) and the circularity of low-circularity cells (p = 0.018), and with decreases in ICS thickness (p = 0.030) and low-circularity cell density (p = 0.044) in the SG. In the SS, there was a non-significant trend towards reduced low-circularity cell density (p = 0.075).  Conclusion: Artificial intelligence-assisted quantitative RCM can identify age-associated epidermal morphometric features, predominantly in the SG, and detect their modulation following topical treatment. XEP™-716 Miniprotein™ at 2.5% showed consistent treatment-associated changes across several morphometric parameters with nominal statistical significance. These exploratory findings warrant prospective validation against molecular senescence markers and functional barrier measurements.
SN  - 2193-8210
SN  - 2190-9172
ER  -