A polygenic risk score predicts intraocular pressure readings outside office hours and early morning spikes as measured by home tonometry

Abstract

OBJECTIVE: Intraocular pressure (IOP) elevations may occur in early morning or outside office hours and can be missed during routine in-clinic IOP measurements. Such fluctuations or peaks likely contribute to glaucoma progression. We sought to investigate the relationship between an IOP polygenic risk score (PRS) and short-term IOP profile. DESIGN: Cross-sectional study. PARTICIPANTS: 473 eyes from 239 participants with suspected or established primary open angle glaucoma sampled from the PROGRESSA study from four outpatient ophthalmology clinics in Australia between August 2016 and December 2019. METHODS: Participants underwent Icare HOME tonometer measurements to record IOP four times a day for five days. Unreliable measurements were excluded. A minimum of two days with at least three reliable measurements were required. We used a previously-validated IOP PRS derived from 146 common IOP-associated variants in a linear regression model with adjustment for central corneal thickness and age. MAIN OUTCOME MEASURES: Highest recorded early-morning IOP, and mean IOP within and outside office hours. Early-morning IOP spikers were defined as eyes with a higher early-morning IOP than the highest recorded IOP during office hours. RESULTS: 334 eyes from 176 participants (mean age 64 years, SD 9) generated reliable measurements for inclusion. Eyes in the highest IOP PRS quintile had an early-morning IOP increase by 4.3 mmHg (95% confidence interval [CI] 1.4-7.3; P = 0.005) and mean IOP outside office hours increase of 2.7 mmHg (95% CI 0.61-4.7; P = 0.013) than the lowest quintile, which were independently significant after accounting for a recent in-clinic IOP measured by Goldmann applanation tonometry. Eyes in the highest PRS quintile were 5.4-fold more likely to be early-morning IOP spikers than the lowest quintile (odds ratio 95% CI 1.3-23.6; P = 0.023) CONCLUSION: A previously validated IOP PRS was associated with higher early-morning IOP, and mean IOP outside office hours. These findings support a role for genetic risk prediction of susceptibility to elevated IOP that may not be apparent in-clinic hours, requiring more detailed clinical phenotyping using home tonometry, the results of which may guide additional interventions to improve IOP control.