High Polygenic Risk Is Associated with Earlier Initiation and Escalation of Treatment in Early Primary Open-Angle Glaucoma.
Marshall Henry N, Mullany Sean, Han Xikun, Qassim Ayub, He Weixiong, Hassall Mark M, Schmidt Joshua, Thomson Daniel, Nguyen Thi Thi, Berry Ella C
AI Summary
High polygenic risk for glaucoma predicts earlier initiation and escalation of IOP-lowering treatment, suggesting genetic testing could guide personalized management strategies.
Abstract
Purpose
To assess the association between a glaucoma polygenic risk score (PRS) and treatment outcomes in primary open-angle glaucoma.
Design
Prospective, observational cohort study.
Participants
Participants from the Progression Risk of Glaucoma: Relevant SNPs with Significant Association Study were divided into a cohort with suspect glaucoma who were treatment naive at enrollment and one with early manifest and suspect glaucoma receiving treatment at enrollment.
Methods
A per-allele weighted glaucoma PRS was calculated for 1107 participants. Multivariable mixed-effects Cox proportional regression analysis assessed the association between PRS and time to commencement of intraocular pressure (IOP)-lowering therapy in 416 patients with suspect glaucoma who were treatment naive at study enrollment. Secondary analysis evaluated the association between PRS and escalation of IOP-lowering therapy among 691 patients with suspect and early manifest glaucoma who were receiving IOP-lowering therapy at enrollment.
Main outcome measures
Commencement or escalation of IOP-lowering therapy.
Results
A higher PRS was associated with a greater risk of commencing IOP-lowering therapy within 5 years (hazard ratio [HR], 1.45 per 1 standard deviation [/SD]; 95% confidence interval [CI], 1.27-1.62; P < 0.001). Participants in the upper population-based quintile showed a 3.3 times greater risk of commencing therapy by 5 years than those in the lowest quintile (HR, 3.30; 95% CI, 1.63-6,70; P < 0.001) and a 5.4 times greater risk of commencing IOP-lowering therapy by 2 years than the those in the lowest quintile (HR, 5.45; 95% CI, 2.08-14.25; P < 0.001). A higher PRS was associated with a greater risk of treatment escalation among patients receiving treatment at enrollment (HR, 1.19/SD; 95% CI, 1.09-1.31; P < 0.001). In combined analysis of all participants, participants in the top population-based quintile were at 2.3 times greater risk of requiring initiation or escalation of IOP-lowering therapy than those in the lowest quintile (HR, 2.33; 95% CI, 1.75-3.01; P < 0.001).
Conclusions
This study demonstrated novel associations between glaucoma polygenic risk and risk of commencement or escalation of IOP-lowering therapy, building on previous work highlighting the potential clinical usefulness of genetic risk stratification in glaucoma.
Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.
MeSH Terms
Shields Classification
Key Concepts4
A higher glaucoma polygenic risk score (PRS) was associated with a greater risk of commencing intraocular pressure (IOP)-lowering therapy within 5 years (hazard ratio [HR], 1.45 per 1 standard deviation [/SD]; 95% confidence interval [CI], 1.27-1.62; P < 0.001) in 416 patients with suspect glaucoma who were treatment naive at study enrollment.
Participants in the upper population-based quintile of glaucoma polygenic risk score (PRS) showed a 3.3 times greater risk of commencing intraocular pressure (IOP)-lowering therapy by 5 years than those in the lowest quintile (HR, 3.30; 95% CI, 1.63-6.70; P < 0.001) in 416 patients with suspect glaucoma who were treatment naive at study enrollment.
A higher glaucoma polygenic risk score (PRS) was associated with a greater risk of treatment escalation among 691 patients with suspect and early manifest glaucoma who were receiving intraocular pressure (IOP)-lowering therapy at enrollment (HR, 1.19/SD; 95% CI, 1.09-1.31; P < 0.001).
In a combined analysis of 1107 participants with suspect and early manifest glaucoma, participants in the top population-based quintile of glaucoma polygenic risk score (PRS) were at 2.3 times greater risk of requiring initiation or escalation of intraocular pressure (IOP)-lowering therapy than those in the lowest quintile (HR, 2.33; 95% CI, 1.75-3.01; P < 0.001).
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