Mediation role of corneal biomechanical and topographic parameters in eye rubbing and keratoconus based on the Chinese keratoconus (CKC) cohort study

Kaili Yang¹Runqi Tu¹Liyan Xu¹Yuwei Gu¹Qi Fan¹Shanshan Yin¹Yi Yuan¹Anqi Chang¹Yifan Wang¹Chenchen Yin¹Yonghao Zang¹Chenjiu Pang¹Dr Daniela Oehring²Yibin Hao¹Shengwei Ren^1*

• ¹Henan Provincial People's Hospital, Zhengzhou, Henan Province, China
• ²University of Plymouth, Plymouth, England, United Kingdom

Several studies have shown that eye rubbing is associated with an increased risk of keratoconus (KC).However, the potential mediating roles between eye rubbing and KC remain largely unknown. Thus, this study aimed to explore the mediating roles of two specific factors, the inverse stiffness parameter at the first applanation (-SPA1) and maximal corneal keratometry (Kmax) values, in the relationship between eye rubbing and KC.A total of 395 KC patients and 396 controls from Chinese keratoconus (CKC) cohort study were included in this case-control analysis. Spearman correlation and generalized linear regression models were used to analyze the associations between the time of eye rubbing, -SPA1, Kmax and KC. Three mediation models (individual mediation, parallel multiple mediation and serial multiple mediation) were utilized to investigate the mediating roles of -SPA1 and Kmax in the relationship between eye rubbing and KC.After adjusting for confounding factors, the odds ratio (OR) and 95% confidence interval (CI) for the time of eye rubbing, -SPA1, and Kmax in relation to KC were 1.02(1.01, 1.04), 1.16(1.12, 1.19) and 3.86(2.52, 5.92), respectively. The individual mediation analysis indicated that the indirect effect of -SPA1 and Kmax were 0.084 and 0.056, respectively. The parallel multiple mediation analysis showed a total indirect effect of -SPA1 and Kmax of 0.081. Additionally, the serial multiple mediation analysis (the time of eye rubbing → -SPA1 → Kmax → KC) indicated that Kmax, following -SPA1, partially mediated the relationship between the time of eye rubbing and KC, with a total indirect effect of 0.024 (95% CI: 0.016-0.042), accounting for 14.5% of the total effect (the time of eye rubbing on KC)， while no significant indirect effect was found for Kmax alone.The individual, parallel, and serial mediation analyses consistently demonstrated the mediating roles of -SPA1 and Kmax in linking eye rubbing duration to KC progression. Notably, the serial mediation pathway (the time of eye rubbing → -SPA1 → Kmax → KC) exhibited a significant indirect effect.These findings confirm and complement the theoretical framework linking eye rubbing and KC, providing a reference for further exploring the pathogenesis of KC.