Zhou Xiaoyu, Xu Jiahao, Duan Xuanchu
Hunan Engineering Research Center for Glaucoma with Artificial Intelligence in Diagnosis and Application of New Materials, Changsha Glaucoma Diagnosis and Treatment Technology Innovation Center, Aier Glaucoma Institute, Changsha Aier Eye Hospital, Changsha, Hunan Province, China.
Aier Academy of Opthamology, Central South University, Changsha, China.
Ophthalmol Sci. 2025 Feb 18;5(4):100742. doi: 10.1016/j.xops.2025.100742. eCollection 2025 Jul-Aug.
To investigate the bidirectional causal relationships between corneal biomechanics (corneal hysteresis [CH] and corneal resistance factor [CRF]) and glaucoma subtypes or intraocular pressure (IOP), and to evaluate the mediating role of IOP in these associations.
Bidirectional univariable 2-sample Mendelian randomization (MR), multivariable MR, and mediation MR study using genome-wide association study (GWAS) summary statistics.
Genetic data from large-scale GWAS cohorts of European ancestry, including individuals with measurements of CH/CRF, glaucoma subtypes (primary open-angle glaucoma [POAG], primary angle-closure glaucoma [PACG], normal-tension glaucoma [NTG], exfoliation glaucoma [XFG], juvenile open-angle glaucoma [JOAG], glaucoma suspect, neovascular glaucoma, secondary glaucoma, and other unspecified glaucoma), and glaucoma endophenotypes (IOP, retinal nerve fiber layer thickness, vertical cup-to-disc ratio).
Bidirectional univariable 2-sample MR analyses were performed to assess the causal effects between CH/CRF and glaucoma subtypes. Multivariable MR and mediation analysis were used to evaluate the role of IOP. Inverse-variance weighted, weighted median, MR-Egger regression, and MR-Pleiotropy RESidual Sum and Outlier were used to evaluate the causal effects, pleiotropy, and heterogeneity.
The primary outcomes included causal estimates (odds ratios or β-coefficients) for the associations between CH/CRF and glaucoma subtypes (POAG, PACG, NTG, XFG, JOAG, neovascular glaucoma, etc.) and the mediation effects of IOP. Secondary outcomes included relationships between glaucoma medication or surgery and CH/CRF.
Corneal hysteresis and CRF were causally associated with increased risks of total glaucoma and most subtypes, except for the protective effect of CH against neovascular glaucoma. Both CH and CRF elevated IOP. Adjusting for IOP attenuated CH/CRF-glaucoma associations. Glaucoma inversely affected CH but positively influenced CRF. Glaucoma surgery reduced CH and CRF.
This study suggests that CH and CRF are risk factors for glaucoma and its subtypes, with IOP playing a mediating role in this relationship. These findings highlight the role of corneal biomechanics in glaucoma pathophysiology and clinical management.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
研究角膜生物力学（角膜滞后 [CH] 和角膜阻力因子 [CRF]）与青光眼亚型或眼压（IOP）之间的双向因果关系，并评估眼压在这些关联中的中介作用。
使用全基因组关联研究（GWAS）汇总统计数据进行双向单变量双样本孟德尔随机化（MR）、多变量MR和中介MR研究。
来自欧洲血统大规模GWAS队列的遗传数据，包括测量了CH/CRF、青光眼亚型（原发性开角型青光眼 [POAG]、原发性闭角型青光眼 [PACG]、正常眼压性青光眼 [NTG]、剥脱性青光眼 [XFG]、青少年开角型青光眼 [JOAG]、青光眼可疑、新生血管性青光眼、继发性青光眼和其他未指定的青光眼）以及青光眼内表型（眼压、视网膜神经纤维层厚度、垂直杯盘比）的个体。
进行双向单变量双样本MR分析，以评估CH/CRF与青光眼亚型之间的因果效应。使用多变量MR和中介分析来评估眼压的作用。采用逆方差加权、加权中位数、MR-Egger回归以及MR-多效性残差和离群值方法来评估因果效应、多效性和异质性。
主要结局包括CH/CRF与青光眼亚型（POAG、PACG、NTG、XFG、JOAG、新生血管性青光眼等）之间关联的因果估计值（比值比或β系数）以及眼压的中介效应。次要结局包括青光眼药物治疗或手术与CH/CRF之间的关系。
角膜滞后和CRF与全青光眼及大多数亚型的风险增加存在因果关联，但CH对新生血管性青光眼具有保护作用除外。CH和CRF均会升高眼压。校正眼压后，CH/CRF与青光眼的关联减弱。青光眼对CH有反向影响，但对CRF有正向影响。青光眼手术会降低CH和CRF。
本研究表明，CH和CRF是青光眼及其亚型的危险因素，眼压在这种关系中起中介作用。这些发现突出了角膜生物力学在青光眼病理生理学和临床管理中的作用。
在本文末尾处的脚注和披露中可能会找到专有或商业披露信息。
