Association between pre-mortem chemotherapy exposure and reduced endothelial cell density in donor corneas

To evaluate whether pre-mortem exposure to systemic chemotherapy is associated with reduced endothelial cell density (ECD) in post-mortem donor corneas.

This retrospective cohort study included 912 donor corneas evaluated at a tertiary cornea bank between 2013 and 2024. Donors with a documented history of malignancy who received systemic chemotherapy, with or without head and neck radiation, within 10 years before death were compared with age-matched donors without malignancy. Endothelial parameters, including ECD, coefficient of variation and hexagonality, were assessed using ex vivo specular microscopy. Univariate analyses and multivariable linear regression models were used to identify independent predictors of ECD.

Mean ECD was significantly lower in donors with chemotherapy exposure compared with controls (2272±547 vs 2432±475 cells/mm²; p<0.001). Endothelial morphologic parameters did not differ between groups. Age-stratified analyses demonstrated that decreased ECD was most pronounced in donors aged 51 years and older, whereas differences in younger donors did not reach statistical significance. Head and neck radiation exposure was not associated with additional ECD reduction. In multivariable analysis, chemotherapy exposure remained an independent predictor of lower ECD (β = -108.05 cells/mm²; p<0.001) after adjusting for age, sex, systemic comorbidities and lens status.

Pre-mortem exposure to systemic chemotherapy was independently associated with reduced ECD in donor corneas. These findings identify systemic cancer treatment as an under-recognised determinant of donor endothelial health and may have implications for donor screening and graft allocation strategies.