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 Galanopoulos; Ashish Agar; Paul R. Healey; Alex W. Hewitt; John Landers; Robert J. Casson; Stuart L. Graham; Stuart MacGregor; Emmanuelle Souzeau; Owen M. Siggs; Jamie E. Craig

doi:10.1016/j.ogla.2020.12.002

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 Galanopoulos, 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 journal › Article › peer-review

12 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	411-420
Number of pages	10
Journal	Ophthalmology Glaucoma
Volume	4
Issue number	4
DOIs	https://doi.org/10.1016/j.ogla.2020.12.002
Publication status	Published - 1 Jul 2021

Keywords

Polygenic
Intraocular Pressure
Home Tonometry
IOP
glaucoma
Glaucoma
Polygenic risk score
Diurnal IOP
iCare HOME
Genetic risk prediction
Home tonometry
Intraocular pressure

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Qassim, A., Mullany, S., Awadalla, M. S., Hassall, M. M., Nguyen, T., Marshall, H., Kolovos, A., Schulz, A. M., Han, X., Gharahkhani, P., Galanopoulos, A., Agar, A., Healey, P. R., Hewitt, A. W., Landers, J., Casson, R. J., Graham, S. L., MacGregor, S., Souzeau, E., ... Craig, J. E. (2021). A Polygenic Risk Score Predicts Intraocular Pressure Readings Outside Office Hours and Early Morning Spikes as Measured by Home Tonometry. Ophthalmology Glaucoma, 4(4), 411-420. https://doi.org/10.1016/j.ogla.2020.12.002

@article{da08c70167704127b35a7482ba428bcf,

title = "A Polygenic Risk Score Predicts Intraocular Pressure Readings Outside Office Hours and Early Morning Spikes as Measured by Home Tonometry",

abstract = "PurposeIntraocular 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.DesignCross-sectional study.ParticipantsFour 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.MethodsParticipants 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 MeasuresHighest 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.ResultsReliable 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).ConclusionsA 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.",

keywords = "Polygenic, Intraocular Pressure, Home Tonometry, IOP, glaucoma, Glaucoma, Polygenic risk score, Diurnal IOP, iCare HOME, Genetic risk prediction, Home tonometry, Intraocular pressure",

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

year = "2021",

month = jul,

day = "1",

doi = "10.1016/j.ogla.2020.12.002",

language = "English",

volume = "4",

pages = "411--420",

journal = "Ophthalmology Glaucoma",

issn = "2589-4234",

publisher = "Elsevier B.V.",

number = "4",

}

Qassim, A, Mullany, S, Awadalla, MS, Hassall, MM, Nguyen, T, Marshall, H, Kolovos, A, Schulz, AM, Han, X, Gharahkhani, P, Galanopoulos, A, Agar, A, Healey, PR, Hewitt, AW, Landers, J, Casson, RJ, Graham, SL, MacGregor, S, Souzeau, E , Siggs, OM & Craig, JE 2021, 'A Polygenic Risk Score Predicts Intraocular Pressure Readings Outside Office Hours and Early Morning Spikes as Measured by Home Tonometry', Ophthalmology Glaucoma, vol. 4, no. 4, pp. 411-420. https://doi.org/10.1016/j.ogla.2020.12.002

TY - JOUR

T1 - A Polygenic Risk Score Predicts Intraocular Pressure Readings Outside Office Hours and Early Morning Spikes as Measured by Home Tonometry

AU - Qassim, Ayub

AU - Mullany, Sean

AU - Awadalla, Mona S.

AU - Hassall, Mark M.

AU - Nguyen, Thi

AU - Marshall, Henry

AU - Kolovos, Antonia

AU - Schulz, Angela M.

AU - Han, Xikun

AU - Gharahkhani, Puya

AU - Galanopoulos, Anna

AU - Agar, Ashish

AU - Healey, Paul R.

AU - Hewitt, Alex W.

AU - Landers, John

AU - Casson, Robert J.

AU - Graham, Stuart L.

AU - MacGregor, Stuart

AU - Souzeau, Emmanuelle

AU - Siggs, Owen M.

AU - Craig, Jamie E.

PY - 2021/7/1

Y1 - 2021/7/1

N2 - PurposeIntraocular 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.DesignCross-sectional study.ParticipantsFour 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.MethodsParticipants 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 MeasuresHighest 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.ResultsReliable 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).ConclusionsA 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.

AB - PurposeIntraocular 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.DesignCross-sectional study.ParticipantsFour 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.MethodsParticipants 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 MeasuresHighest 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.ResultsReliable 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).ConclusionsA 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.

KW - Polygenic

KW - Intraocular Pressure

KW - Home Tonometry

KW - IOP

KW - glaucoma

KW - Glaucoma

KW - Polygenic risk score

KW - Diurnal IOP

KW - iCare HOME

KW - Genetic risk prediction

KW - Home tonometry

KW - Intraocular pressure

UR - http://purl.org/au-research/grants/NHMRC/1150144

UR - http://purl.org/au-research/grants/NHMRC/1157571

UR - http://www.scopus.com/inward/record.url?scp=85106479114&partnerID=8YFLogxK

U2 - 10.1016/j.ogla.2020.12.002

DO - 10.1016/j.ogla.2020.12.002

M3 - Article

SN - 2589-4234

VL - 4

SP - 411

EP - 420

JO - Ophthalmology Glaucoma

JF - Ophthalmology Glaucoma

IS - 4

ER -

A Polygenic Risk Score Predicts Intraocular Pressure Readings Outside Office Hours and Early Morning Spikes as Measured by Home Tonometry

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