Obesity and Keratoconus: A Mediation Study Based on the Chinese Keratoconus Cohort

Purpose: Growing evidence indicates a strong association between obesity and keratoconus (KC), although the potential mediating factors remain largely unknown. This study aimed to explore the potential pathways through which corneal biomechanical and topographic parameters might link obesity and KC using structural equation modeling (SEM). Methods: This case-control study included 759 participants (363 patients with KC and 396 controls) from the Chinese Keratoconus (CKC) Cohort Study. Associations among body mass index (BMI), corneal biomechanical parameters, topographic parameters, and KC were analyzed using generalized linear regression models. SEM was used to construct latent variables for corneal biomechanical and topographic parameters. Three mediation models (single, parallel multiple, and serial multiple mediation) were used to examine the mediating roles of these parameters in the association between BMI and KC. Results: After adjusting for confounders, the odds ratio (OR) for BMI and KC was 1.14 (95% confidence interval [CI] = 1.07-1.22). All corneal biomechanical and topographic parameters showed significant associations with KC (P < 0.05). In the single mediation model, the indirect effect of corneal biomechanical parameters was 0.023 (95% CI = 0.002-0.045), whereas that of topographic parameters was 0.049 (95% CI = 0.023-0.073). The parallel multiple mediation model yielded a total indirect effect of 0.033 (95% CI = 0.013-0.053), with significant pathways through corneal biomechanical parameters (effect = 0.011, 95% CI = 0.000-0.022, 17.2% of total effect) and topographic parameters (effect = 0.022, 95% CI = 0.010-0.038, 35.4% of total effect). A serial mediation pathway was also identified, in which BMI correlated with corneal biomechanical parameters, which subsequently linked to topographic parameters and then KC (effect = 0.021, 95% CI = 0.002-0.039, 32.3% of total effect). Conclusions: Higher BMI was associated with KC. The association between BMI and KC may be partially explained by alterations in corneal biomechanical and topographic parameters, providing a statistical model for understanding potential underlying links in the disease. Translational Relevance: For patients with obesity, KC-related screening should be emphasized, and health management for patients with KC and obesity should be strengthened in clinical practice.