When was topical tretinoin (all-trans retinoic acid) first used in humans for corneal epithelial wound healing?

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Historical Use of Topical Tretinoin for Corneal Epithelial Wound Healing

Topical tretinoin (all-trans retinoic acid) has not been documented in any major ophthalmology guidelines as a standard treatment for corneal epithelial wound healing, and there is no evidence in the provided literature indicating when it was first used specifically for this purpose in humans.

Current Approaches to Corneal Epithelial Wound Healing

The American Academy of Ophthalmology's guidelines on corneal edema and opacification do not mention tretinoin as a treatment for corneal epithelial wound healing 1. Instead, they recommend several other approaches:

Established Treatments for Corneal Epithelial Defects

  • Topical antibiotics to prevent secondary bacterial infection 1, 2
  • Bandage contact lenses to promote healing in cases of delayed epithelialization 1
  • Amniotic membranes (as onlay protective flaps or inlay tissue substitutes) to promote healing through anti-inflammatory, anti-angiogenic, and prohealing mediators 1
  • Autologous serum, cord blood tears, and platelet-rich plasma for persistent epithelial defects 1
  • Nerve growth factor for neurotrophic keratopathy 1

Other Agents Mentioned in Guidelines

  • Oral doxycycline, topical N-acetylcysteine, and medroxyprogesterone to inhibit matrix metalloproteinases 1
  • Substance P and insulin-like growth factor-1, fibronectin, and thymosin beta 4 (investigational) 1

Tretinoin in Dermatology vs. Ophthalmology

While topical tretinoin has been extensively studied and used in dermatology for over 40 years 3, primarily for acne vulgaris and photodamage 1, 3, the provided evidence does not indicate its use for corneal epithelial wound healing.

Dermatological Wound Healing Research

  • Studies have shown mixed results regarding tretinoin's effect on epithelial wound healing in skin:
    • Pretreatment with tretinoin before skin wounding accelerated epithelial healing in a porcine model 4
    • However, continued tretinoin treatment directly on wounds retarded reepithelialization and caused persistent inflammation 4
    • Short-contact tretinoin therapy has been studied for chronic leg ulcerations to stimulate granulation tissue 5

Potential Concerns for Ophthalmic Use

  • The irritant properties of tretinoin noted in dermatological applications 6, 4 would be particularly problematic for the sensitive corneal epithelium
  • The persistent inflammation and fibroplasia observed with tretinoin treatment on skin wounds 4 could potentially compromise corneal transparency

Current Research on Corneal Epithelial Healing

Recent research has focused on other agents for corneal epithelial healing:

  • Coenzyme Q10 with Vitamin E has shown promising results in experimental models for corneal epithelial organization 7
  • Sodium hyaluronate and xanthan gum preparations are being studied 7

Conclusion

Based on the provided evidence, there is no documentation of when topical tretinoin was first used in humans specifically for corneal epithelial wound healing. The current ophthalmology guidelines and literature do not recommend tretinoin for this purpose, instead focusing on other therapeutic approaches that have demonstrated efficacy and safety for corneal epithelial defects.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Corneal Abrasion Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

40 years of topical tretinoin use in review.

Journal of drugs in dermatology : JDD, 2013

Research

Topical tretinoin and epithelial wound healing.

Archives of dermatology, 1989

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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