Potential for Collider Bias in Studies Examining the Association of Central Corneal Thickness with Glaucoma

PURPOSE. Central corneal thickness (CCT) may be biologically related to glaucoma or observed as associated with glaucoma simply due to its effect on intraocular pressure (IOP) measurement. We aimed to determine if the previously reported CCT-glaucoma associations, in which the analyses were adjusted for IOP or participants were selected on IOP, could be explained by collider bias. METHODS. We simulated datasets mimicking a longitudinal population-based study (Los Angeles Latino Eye Study) and a trial (Ocular Hypertension Treatment Study) such that: (i) CCT was not truly associated with glaucoma, (ii) CCT and true IOP both contribute to measured IOP, and (iii) true IOP contributes to glaucoma risk.We then tested whether an association between CCT and glaucoma could be spuriously induced simply by adjusting for or selecting on measured IOP. RESULTS. A thinner CCT was significantly associated with higher glaucoma incidence in the simulated longitudinal population-based study when adjusted for measured IOP, but not crudely (unadjusted). A thinner CCT was crudely associated with glaucoma incidence in the simulated trial in which the participants were selected for high measured IOP. Effect sizes in the simulations were similar to those observed in the original studies. CONCLUSIONS. Our findings question whether CCT is biologically associated with glaucoma and suggest that current evidence may be due to collider bias. This indicates that CCT alone cannot be used as a factor to identify people at high risk of glaucoma in the general population. Using CCT in combination with IOP may be superior to using IOP alone.