High polygenic risk linked to earlier treatment initiation, escalation in glaucoma

High glaucoma polygenic risk score (PRS) shows a significant association with earlier initiation or escalation of intraocular pressure (IOP)-lowering therapy, according to a study, noting the potential usefulness of genetic risk stratification in glaucoma.

A team of investigators calculated a per-allele weighted glaucoma PRS for 1,107 participants. They performed multivariable mixed-effects Cox proportional regression analysis to assess the relationship between PRS and time to commencement of IOP-lowering therapy in 416 patients with suspect glaucoma who were treatment-naïve at enrolment.

In secondary analysis, the investigators assessed the association between PRS and escalation of IOP-lowering therapy in 691 patients with suspect and early manifest glaucoma who received IOP-lowering therapy at enrolment.

A higher PRS correlated with a higher risk of initiating IOP-lowering therapy within 5 years (hazard ratio [HR], 1.45, 95 percent confidence interval [CI], 1.27‒1.62; p<0.001).

Participants in the upper vs lowest population-based quintile had 3.3-times greater risk of starting therapy by 5 years (HR, 3.30, 95 percent CI, 1.63‒6.70; p<0.001) and 5.4-times higher risk by 2 years (HR, 5.45, 95 percent CI, 2.08‒14.25; p<0.001).

In addition, a high PRS correlated with an increased risk of treatment escalation among patients receiving treatment at enrolment (HR, 1.19, 95 percent CI, 1.09‒1.31; p<0.001).

Combined analysis revealed that participants in the top population-based quintile had 2.3 times higher risk of requiring initiation or escalation of IOP-lowering therapy than those in the lowest quintile (HR, 2.33, 95 percent CI, 1.75‒3.01; p<0.001).