Background: A series of clinical trials lasting up to 4 years had demonstrated that topical tretinoin improves facial appearance by reducing the visible signs of photodamage.
Objective: This paper reviews the studies designed to explore the relationship between clinical improvement and histologic changes.
Methods: Histologic changes in biopsies taken at various time points from clinical trial participants were examined by pathologists blinded to treatment regimens.
Results: Histologic evaluations of photodamaged skin during the course of treatment with tretinoin have revealed an array of time-dependent morphologic changes which can be classified as early, intermediate, and late. Initial changes in fine wrinkling and texture appear to correlate with epidermal mucin and compaction of the stratum corneum, but the latter is transient and ultimately returns to pre-treatment levels. Alterations in dermal matrix components have been noted with prolonged treatment. Partial restoration of the dermal collagen by new synthesis may contribute to the sustained improvement in fine wrinkling noted even when the treatment frequency is reduced from daily to three times weekly. As treatment is continued beyond 24 months, the collagen organization continues to improve and elastosis continues to decrease. Increases in epidermal and dermal mucin and decreases in epidermal melanin are consistent throughout the treatment period. The reduction in the hyperpigmentation of photodamage is comparable with the histologic and clinical improvements seen when tretinoin is used to treat conditions such as melasma. No adverse effects on the histopathology of the skin are noted with long-term exposure to tretinoin. Neither keratinocyte nor melanocyte atypia is detected.
Conclusions: Although there does not seem to be a direct correlation between histologic changes and clinical improvement, the major structural changes appear to be directed at restoring the skin to the pre-sun-damaged state.