# Decoding the Cornea-Glaucoma Association: Evidence From Mendelian Randomization

## TL;DR

This study investigates the genetic relationship between corneal thickness, corneal dystrophy, and glaucoma using Mendelian randomization to determine if these factors causally influence each other.

## Contribution

The study provides new evidence using Mendelian randomization to assess causal links between corneal traits and glaucoma, offering insights into their potential clinical relevance.

## Key findings

- No significant causal link was found between central corneal thickness (CCT) and open-angle glaucoma (OAG) in one-sample MR.
- Two-sample MR suggested a positive association between CCT and OAG.
- No association was found between Fuchs endothelial corneal dystrophy (FECD) and OAG.

## Abstract

We combined classical association analyses with one-sample and two-sample Mendelian randomization (MR), to comprehensively assess the causal relation among central corneal thickness (CCT), corneal hysteresis, Fuchs endothelial corneal dystrophy (FECD), and open-angle glaucoma (OAG).

We analyzed data from a large population-based cohort study (the Rotterdam Study), an FECD case-control study, and genome wide association study summary statistics. We defined OAG as reproducible visual field loss, independent of IOP. Multivariable regression was performed. One-sample MR was performed using the same regression models, with the corresponding genetic risk score (GRS) as independent variable. Two-sample MR was performed using inverse variance weighted, MR Egger, weighted median, simple mode, and weighted mode methods.

In total, 303 participants with OAG and 10,598 controls from the Rotterdam Study were included, with 753 FECD cases from the FECD cohort. The odds ratio (OR) 95% confidence interval (CI) of OAG was 0.67 (95% CI = 0.56–0.81) per standard deviation (SD) increase in CCT (P < 0.001). However, one-sample MR showed no significant association between a CCT-GRS and OAG (P = 0.688). Two-sample MR found an OR (95% CI) of 1.23 (95% CI = 1.06–1.42) for each SD increase in the CCT instrumental variable. We observed no association between an FECD-GRS and OAG (P = 0.946).

We found no evidence for a causal link between CCT and OAG. Nevertheless, CCT measurements are still valuable for population-based risk stratification. We found no clear relationship between FECD and OAG.