Tretinoin for Photodamaged Facial Skin: Systematic Review and Meta-Analysis of Randomized Controlled Trials

Tretinoin for Photodamaged Facial Skin: Systematic Review and Meta-Analysis of Randomized Controlled Trials

Authors

Keywords:

Tretinoin, Photodamaged skin, Facial skin, Systematic review, Meta-analysis

Abstract

Introduction: Randomized controlled trials have suggested that tretinoin, a topical retinoid, can improve wrinkling in photodamaged skin; however, its overall effectiveness remains subject of debate.

Objectives: This study evaluated the efficacy and safety of tretinoin in treating facial wrinkles induced by photodamage.

Method: We systematically searched the PubMed, EMBASE, and Cochrane CENTRAL databases from their inception to 16 January 2024 to identify randomized controlled trials comparing topical tretinoin with vehicle treatments. Data were synthesized using a random effects model, and sensitivity analyses were performed to evaluate the robustness of the results in the presence of potential bias.

Results: This study identified eight trials (1,361 patients; median age range 29–76 years; average follow-up duration, 16 weeks to 2 years) that met the inclusion criteria. Compared with the vehicle, topical tretinoin significantly improved clinical signs of facial photodamage. Improvements were observed in both fine wrinkles (mean difference [MD]: 0.412; 95% confidence interval [CI]: 0.233–0.590; P<0.001) and coarse wrinkles (MD: 0.245; 95% CI: 0.119–0.370; P<0.001). Sensitivity analyses confirmed the robustness of these findings.

Conclusion: Topical tretinoin is a safe and effective treatment for fine and coarse facial wrinkles resulting from photodamage.

References

Weiss JS, Ellis CN, Headington JT, Tincoff T, Hamilton TA, Voorhees JJ. Topical tretinoin improves photoaged skin. A double-blind vehicle-controlled study. JAMA. 1988;259(4):527-532. PMID: 3336176.

Nyirady J, Bergfeld W, Ellis C, et al. Tretinoin cream 0.02% for the treatment of photodamaged facial skin: a review of 2 double-blind clinical studies. Cutis. 2001;68(2):135-142. PMID: 11534915.

Motamedi M, Chehade A, Sanghera R, Grewal P. A Clinician's Guide to Topical Retinoids. J Cutan Med Surg. 2022;26(1):71-78. DOI:10.1177/12034754211035091. PMID: 34292058

Kang S, Bergfeld W, Gottlieb AB, et al. Long-term efficacy and safety of tretinoin emollient cream 0.05% in the treatment of photodamaged facial skin: a two-year, randomized, placebo-controlled trial. Am J Clin Dermatol. 2005;6(4):245-253. DOI:10.2165/00128071-200506040-00005. PMID: 16060712.

Olsen EA, Katz HI, Levine N, et al. Tretinoin emollient cream: a new therapy for photodamaged skin. J Am Acad Dermatol. 1992;26(2 Pt 1):215-224. DOI:10.1016/0190-9622(92)70030-j. PMID: 1552056.

Andreano JM, Bergfeld WF, Medendorp SV. Tretinoin emollient cream 0.01% for the treatment of photoaged skin. Cleve Clin J Med. 1993;60(1):49-55. DOI:10.3949/ccjm.60.1.49. PMID: 8443935.

Lowe PM, Woods J, Lewis A, Davies A, Cooper AJ. Topical tretinoin improves the appearance of photo damaged skin. Australas J Dermatol. 1994;35(1):1-9. DOI:10.1111/j.1440-0960.1994.tb01790.x. PMID: 7998893.

Weiss JS, Shavin JS, Nighland M, Grossman R. Tretinoin microsphere gel 0.1% for photodamaged facial skin: a placebo-controlled trial. Cutis. 2006;78(6):426-432. PMID: 17243432.

Lau M, Mineroff Gollogly J, Wang JY, Jagdeo J. Cosmeceuticals for antiaging: a systematic review of safety and efficacy. Arch Dermatol Res. 2024;316(5):173. Published 2024 May 17. DOI:10.1007/s00403-024-02908-2. PMID: 38758222.

Chan LKW, Lee KWA, Lee CH, et al. Cosmeceuticals in photoaging: A review. Skin Res Technol. 2024;30(9):e13730. DOI:10.1111/srt.13730. PMID: 39233460.

O'Connor AA, Lowe PM, Shumack S, Lim AC. Chemical peels: A review of current practice. Australas J Dermatol. 2018;59(3):171-181. DOI:10.1111/ajd.12715. PMID:29064096.

Fitzpatrick RE, Goldman MP, Satur NM, Tope WD. Pulsed carbon dioxide laser resurfacing of photo-aged facial skin. Arch Dermatol. 1996;132(4):395-402. PMID: 8629842.

Guida S, Ciardo S, Galadari H, et al. Correlating Optical Coherence Tomography and Other Noninvasive Imaging Features With Atrophic and Hypertrophic Skin Photoaging. Int J Dermatol. 2025;64(8):1441-1445. DOI:10.1111/ijd.17799. PMID: 40248983.

Hanna E, Xing L, Taylor JH, Bertucci V. Role of botulinum toxin A in improving facial erythema and skin quality. Arch Dermatol Res. 2022;314(8):729-738. DOI:10.1007/s00403-021-02277-0. PMID: 34519860.

Sachs DL, Varani J, Chubb H, et al. Atrophic and hypertrophic photoaging: Clinical, histologic, and molecular features of 2 distinct phenotypes of photoaged skin. J Am Acad Dermatol. 2019;81(2):480-488. DOI:10.1016/j.jaad.2019.03.081. PMID: 30954583.

Rovatti PP, Pellacani G, Guida S. Hyperdiluted Calcium Hydroxylapatite 1: 2 for Mid and Lower Facial Skin Rejuvenation: Efficacy and Safety. Dermatol Surg. 2020;46(12):e112-e117. DOI:10.1097/DSS.0000000000002375. PMID: 32205749.

Somenek M. Hyperdilute Calcium Hydroxylapatite for the Treatment of Perioral Rhytids: A Pilot Study. Aesthet Surg J Open Forum. 2024;6:ojae021. Published 2024 Apr 5. DOI:10.1093/asjof/ojae021. PMID: 38660236.

TJ Higgins JPT, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, Cochrane Handbook for Systematic Reviews of Interventions version 6.5, Cochrane, 2024.

Weinstein GD, Nigra TP, Pochi PE, et al. Topical tretinoin for treatment of photodamaged skin. A multicenter study. Arch Dermatol. 1991;127(5):659-665. PMID: 2024983.

Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. Published 2019 Aug 28. DOI:10.1136/bmj.l4898. PMID: 31462531.

Fisher GJ, Voorhees JJ. Molecular mechanisms of retinoid actions in skin. FASEB J. 1996;10(9):1002-1013. DOI:10.1096/fasebj.10.9.8801161. PMID: 8801161.

Chapellier B, Mark M, Messaddeq N, et al. Physiological and retinoid-induced proliferations of epidermis basal keratinocytes are differently controlled. EMBO J. 2002;21(13):3402-3413. DOI:10.1093/emboj/cdf331. PMID: 12093741.

Varani J, Zeigler M, Dame MK, et al. Heparin-binding epidermal-growth-factor-like growth factor activation of keratinocyte ErbB receptors Mediates epidermal hyperplasia, a prominent side-effect of retinoid therapy. J Invest Dermatol. 2001;117(6):1335-1341. DOI:10.1046/j.0022-202x.2001.01564.x. PMID: 11886492.

Rittié L, Varani J, Kang S, Voorhees JJ, Fisher GJ. Retinoid-induced epidermal hyperplasia is mediated by epidermal growth factor receptor activation via specific induction of its ligands heparin-binding EGF and amphiregulin in human skin in vivo. J Invest Dermatol. 2006;126(4):732-739. DOI:10.1038/sj.jid.5700202. PMID: 16470170.

Pintea A, Manea A, Pintea C, et al. Peptides: Emerging Candidates for the Prevention and Treatment of Skin Senescence: A Review. Biomolecules. 2025;15(1):88. Published 2025 Jan 9. DOI:10.3390/biom15010088. PMID: 39858482.

Aldag C, Nogueira Teixeira D, Leventhal PS. Skin rejuvenation using cosmetic products containing growth factors, cytokines, and matrikines: a review of the literature. Clin Cosmet Investig Dermatol. 2016;9:411-419. Published 2016 Nov 9. DOI:10.2147/CCID.S116158. PMID: 27877059.

Published

2025-10-31

How to Cite

1.
Huang HY, Lee LTJ. Tretinoin for Photodamaged Facial Skin: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Dermatol Pract Concept. 2025;15(4). doi:10.5826/dpc.1504a5172

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