Safety and efficacy of quercetin as an alternative to riboflavin in collagen cross-linking treatment

J Fr Ophtalmol. 2025 Nov;48(9):104667. doi: 10.1016/j.jfo.2025.104667. Epub 2025 Oct 24.

Abstract

Purpose: To evaluate the safety and efficacy of quercetin as an alternative to riboflavin in collagen cross-linking (CXL) treatment.

Methods: Australia-New Zealand rabbits (n=60) were divided into four groups: a control group (C group; no UVA exposure), a Tween 20 buffer group (T group; UVA irradiated), a riboflavin group (R group; UVA irradiated with riboflavin), and a quercetin group (Q group; UVA irradiated with quercetin). The corneal tissues were analyzed histologically and biomechanically on days 7 and 42 post-treatment.

Results: The biomechanical tests demonstrated a 50% increase in Young's modulus and a 21% increase in tensile strength in the R group compared to controls (P<0.05), confirming significant corneal stiffening. In contrast, the Q group showed an 18% increase in Young's modulus, but this was not statistically significant compared to controls (P>0.05). Histological analysis revealed no inflammation, corneal edema, or endothelial damage in any group. Keratocyte apoptosis was detected in the anterior stroma of the R and Q groups at day 7, with repopulation occurring by day 42.

Conclusion: While quercetin demonstrated some biomechanical effects; its impact on corneal stiffening was significantly lower than that of riboflavin, indicating its inefficacy as a photo-induced cross-linking agent.

Keywords: Cross-linking; Keratoconus; Kératocône; Module de Young; Quercetin; Quercétine; Riboflavin; Riboflavine; Réticulation; Young's modulus.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Biomechanical Phenomena / drug effects
  • Collagen* / chemistry
  • Cornea / drug effects
  • Cornea / pathology
  • Cross-Linking Reagents* / adverse effects
  • Cross-Linking Reagents* / pharmacology
  • Cross-Linking Reagents* / therapeutic use
  • Photochemotherapy / adverse effects
  • Photochemotherapy / methods
  • Photosensitizing Agents / adverse effects
  • Photosensitizing Agents / therapeutic use
  • Quercetin* / adverse effects
  • Quercetin* / pharmacology
  • Quercetin* / therapeutic use
  • Rabbits
  • Riboflavin* / adverse effects
  • Riboflavin* / pharmacology
  • Riboflavin* / therapeutic use
  • Treatment Outcome
  • Ultraviolet Rays

Substances

  • Quercetin
  • Riboflavin
  • Collagen
  • Cross-Linking Reagents
  • Photosensitizing Agents