Name

Marqueurs du stress oxydatifs et antioxydants dans le kératocône: une revue systématisée de la littérature et méta-analyses

Keratoconus (KC) is classically defined as a noninflammatory corneal disease. However, the pathogenic processes of the disease are still unknown, and many questions persist on the triggering and progression of ectasia. We aimed to conduct a systematic review and meta-analysis on the levels of oxidative stress markers and antioxidants in KC compared to healthy subject.

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 KC and healthy controls. Main meta-analysis was stratified by type of biomarkers, type of samples (tears, cornea, aqueous humor, and blood), and type of corneal samples (stromal cells, epithelium, and endothelium).

We included 36 articles, for a total of 1328 KC patients and 1208 healthy controls. There is an overall increase in oxidative stress markers in KC compared with healthy controls (Standard Mean Deviation (SMD) = 0.94, 95% confidence interval (95CI) 0.55 to 1.33), with a significant increase in reactive oxygen and nitrogen species (1.09, 0.41 to 1.78) and malondialdehyde (1.78, 0.83 to 2.73). There is an overall decrease in antioxidants in KC 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), selenium/zinc (-1.42, -2.23 to -0.61). Oxidative stress markers were higher in tears and in cornea of KC than in aqueous humor, and antioxidants were decreased in tears, aqueous humor and blood without difference between sample type. Oxidative stress markers increased in stromal cells and antioxidants decreased in endothelium.

Oxidative stress is a complex homeostasis pathway implicated in several diseases, that could be dysregulated in KC. However, the complex antioxidant pathways could counterbalance the daily ROS generations produced by cells metabolism and environmental aggressions in tears, corneal tissues and endo-ocular fluids. In this systematic review and meta-analysis, we underlined that imbalance between oxidative stress and antioxidants seems to be a central process in the pathophysiology of KC. We highlighted that oxidative stress markers were increased and antioxidants decreased in several samples of KC compared to healthy subjects. Thus, we could propose that KC is a corneal disease involving corneal ectasia, promoting by an imbalance of redox homeostasis in tears, corneal tissues, aqueous humor, and blood. Considering that oxidative stress markers and antioxidants were significantly increased and decreased in blood of KC, this corneal disease seems to be also associated with systemic redox imbalance. Interestingly, we identified a geographical tropism of the imbalance of redox homeostasis in KC. Even if we included a majority of case control studies, overall methodological quality was reasonably good without major comparability and selection bias between KC and control groups, with a large volume of data available (1328 KC vs 1208 healthy controls). Considering these results, we could better understand the complexity of pathological process in KC, and may consider innovative therapies related with inflammatory hypothesis of KC.

Oxidative stress markers and antioxidants were dysregulated in KC, involving an imbalance of redox homeostasis in tears, cornea, aqueous humor and blood.