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

Ayub Qassim, Sean Mullany, Mona S. Awadalla, Mark M. Hassall, Thi Nguyen, Henry Marshall, Antonia Kolovos, Angela M. Schulz, Xikun Han, Puya Gharahkhani, Anna Galanopolous, Ashish Agar, Paul R. Healey, Alex W. Hewitt, John Landers, Robert J. Casson, Stuart L. Graham, Stuart MacGregor, Emmanuelle Souzeau, Owen M. SiggsJamie E. Craig

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)


    Purpose: 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: Four hundred seventy-three eyes from 239 participants with suspected or established primary open-angle glaucoma sampled from 4 outpatient clinics in Australia between August 2016 and December 2019.

    Methods: Participants underwent Icare HOME (Icare Oy, Vanda, Finland) tonometer measurements to record IOP 4 times daily for 5 days. Unreliable measurements were excluded. A minimum of 2 days with at least 3 reliable measurements were required. We used a validated IOP PRS derived from 146 IOP-associated variants in a linear regression model adjusted 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 spikes were defined by a higher early morning IOP than the maximum in-office hours IOP.

    Results: Reliable measurements were obtained from 334 eyes of 176 participants (mean age, 64 ± 9 years). Eyes in the highest IOP PRS quintile showed an early morning IOP increase of 4.3 mmHg (95% confidence interval [CI], 1.4–7.3; P = 0.005) and mean increase in IOP outside office hours of 2.7 mmHg (95% CI, 0.61–4.7; P = 0.013) than the lowest quintile, which were significant independently 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 show early morning IOP spikes than the lowest quintile (odds ratio 95% CI, 1.3–23.6; P = 0.023).

    Conclusions: A 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 during in-clinic hours, requiring more detailed clinical phenotyping using home tonometry, the results of which may guide additional interventions to improve IOP control.
    Original languageEnglish
    Pages (from-to)411-420
    Number of pages10
    JournalOphthalmology Glaucoma
    Issue number4
    Publication statusPublished - Jul 2021


    • Diurnal IOP
    • Genetic risk prediction
    • Glaucoma
    • Home tonometry
    • iCare HOME
    • Intraocular pressure
    • Polygenic risk score


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