Oxidative and antioxidative stress markers in keratoconus: a systematic review and meta-analysis

Valentin Navel*, Jean Malecaze, Bruno Pereira, Julien S. Baker, François Malecaze, Vincent Sapin, Frédéric Chiambaretta, Frédéric Dutheil

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

31 Citations (Scopus)


Purpose: To conduct a systematic review and meta-analysis on the levels of oxidative stress markers and antioxidants in keratoconus compared to healthy subject.

Method: The PubMed, Cochrane Library, Embase, Science Direct and Google Scholar databases were searched on 1st June 2020 for studies reporting oxidative and antioxidative stress markers in keratoconus and healthy controls. Main meta-analysis was stratified by type of biomarkers, type of samples (tears, cornea, aqueous humour and blood) and type of corneal samples (stromal cells, epithelium and endothelium).

Results: We included 36 articles, for a total of 1328 keratoconus patients and 1208 healthy controls. There is an overall increase in oxidative stress markers in keratoconus compared with healthy controls (standard mean deviation (SMD) = 0.94, 95% confidence interval (95% CI) 0.55–1.33), with a significant increase in reactive oxygen and nitrogen species (1.09, 0.41–1.78) and malondialdehyde (1.78, 0.83–2.73). There is an overall decrease in antioxidants in keratoconus compared with healthy controls (−0.63, −0.89 to −0.36), with a significant decrease in total antioxidant capacity/status (−1.65, −2.88 to −0.43), aldehyde/NADPH dehydrogenase (−0.77, −1.38 to −0.17), lactoferrin/transferrin/albumin (−1.92, −2.96 to −0.89) and selenium/zinc (−1.42, −2.23 to −0.61). Oxidative stress markers were higher in tears and in cornea of keratoconus than in aqueous humour, and antioxidants were decreased in tears, aqueous humour and blood without difference between sample type. Oxidative stress markers increased in stromal cells and antioxidants decreased in endothelium.

Conclusion: Oxidative stress markers and antioxidants were dysregulated in keratoconus, involving an imbalance of redox homeostasis in tears, cornea, aqueous humour and blood.

Original languageEnglish
Pages (from-to)e777-e794
Number of pages18
JournalActa Ophthalmologica
Issue number6
Early online date23 Dec 2020
Publication statusPublished - Sept 2021

Scopus Subject Areas

  • Ophthalmology

User-Defined Keywords

  • antioxidants
  • cornea
  • inflammation
  • keratoconus
  • oxidative damage
  • oxidative stress
  • reactive oxygen species
  • stroma
  • tears


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