Genetic Risk of Cardiovascular Disease Is Associated with Macular Ganglion Cell–Inner Plexiform Layer Thinning in an Early Glaucoma Cohort

Henry Marshall, MBBS; Sean Mullany, MD; Xikun Han, PhD; Ella C. Berry, MChD; Mark M. Hassall, DPhil; Ayub Qassim, PhD; Thi Nguyen, BMSc(Optom); Georgina L. Hollitt, MBBS; Lachlan S.W. Knight, MOrth; Bronwyn Ridge, BA; Joshua Schmidt, PhD; Caroline Crowley, BDS; Angela Schulz, PhD; Richard A. Mills, PhD; Ashish Agar, PhD; Anna Galanopoulos, MBBS; John Landers, PhD; Paul R. Healey, PhD; Stuart L. Graham, PhD; Alex W. Hewitt, PhD; Robert J. Casson, DPhil; Stuart MacGregor, PhD; Owen M. Siggs, DPhil; Jamie E. Craig, DPhil

Ophthalmology Science (Mar 2022)

Genetic Risk of Cardiovascular Disease Is Associated with Macular Ganglion Cell–Inner Plexiform Layer Thinning in an Early Glaucoma Cohort

Henry Marshall, MBBS,
Sean Mullany, MD,
Xikun Han, PhD,
Ella C. Berry, MChD,
Mark M. Hassall, DPhil,
Ayub Qassim, PhD,
Thi Nguyen, BMSc(Optom),
Georgina L. Hollitt, MBBS,
Lachlan S.W. Knight, MOrth,
Bronwyn Ridge, BA,
Joshua Schmidt, PhD,
Caroline Crowley, BDS,
Angela Schulz, PhD,
Richard A. Mills, PhD,
Ashish Agar, PhD,
Anna Galanopoulos, MBBS,
John Landers, PhD,
Paul R. Healey, PhD,
Stuart L. Graham, PhD,
Alex W. Hewitt, PhD,
Robert J. Casson, DPhil,
Stuart MacGregor, PhD,
Owen M. Siggs, DPhil,
Jamie E. Craig, DPhil

Affiliations

Henry Marshall, MBBS: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia; Correspondence: Henry Marshall, MBBS, Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Sturt Road, Bedford Park, 5042, Adelaide, Australia.
Sean Mullany, MD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Xikun Han, PhD: Statistical Genetics Laboratory, QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia
Ella C. Berry, MChD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Mark M. Hassall, DPhil: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Ayub Qassim, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Thi Nguyen, BMSc(Optom): Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Georgina L. Hollitt, MBBS: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Lachlan S.W. Knight, MOrth: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Bronwyn Ridge, BA: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Joshua Schmidt, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Caroline Crowley, BDS: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Angela Schulz, PhD: Faculty of Health and Medical Sciences, Macquarie University, Sydney, Australia
Richard A. Mills, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Ashish Agar, PhD: Department of Ophthalmology, University of New South Wales, Sydney, Australia
Anna Galanopoulos, MBBS: Discipline of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, Australia
John Landers, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Paul R. Healey, PhD: Centre for Vision Research, University of Sydney, Sydney, Australia
Stuart L. Graham, PhD: Department of Ophthalmology, University of New South Wales, Sydney, Australia
Alex W. Hewitt, PhD: Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
Robert J. Casson, DPhil: Discipline of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, Australia
Stuart MacGregor, PhD: Statistical Genetics Laboratory, QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia
Owen M. Siggs, DPhil: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia; Garvan Institute of Medical Research, Sydney, Australia
Jamie E. Craig, DPhil: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia

Journal volume & issue: Vol. 2, no. 1
p. 100108

Abstract

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Purpose: To evaluate the association between genetic risk for cardiovascular disease and retinal thinning in early glaucoma. Design: Prospective, observational genetic association study Participants: Multicohort study combining a cohort of patients with suspect and early manifest primary open-angle glaucoma (POAG), a cohort of patients with perimetric POAG, and an external normative control cohort. Methods: A cardiovascular disease genetic risk score was calculated for 828 participants from the Progression Risk of Glaucoma: Relevant SNPs [single nucleotide polymorphisms] with Significant Association (PROGRESSA) study. Participants were characterized as showing either predominantly macular ganglion cell–inner plexiform layer (GCIPL), predominantly peripapillary retinal nerve fiber layer (pRNFL) or equivalent macular GCIPL and pRNFL spectral-domain OCT thinning. The cardiovascular disease genetic risk scores for these groups were compared to an internal reference group of stable suspected glaucoma and of an external normative population. Replication was undertaken by comparing the phenotypes of participants from the Australia New Zealand Registry of Advanced Glaucoma (ANZRAG) with the normative control group. Main Outcome Measures: Spectral-domain OCT and Humphrey Visual Field (HVF) change. Results: After accounting for age, sex, and intraocular pressure (IOP), participants with predominantly macular GCIPL thinning showed a higher cardiovascular disease genetic risk score than reference participants (odds ratio [OR], 1.76/standard deviation [SD]; 95% confidence interval [CI], 1.18–2.62; P = 0.005) and than normative participants (OR, 1.32/SD; 95% CI, 1.12–1.54; P = 0.002). This finding was replicated by comparing ANZRAG participants with predominantly macular GCIPL change with the normative population (OR, 1.39/SD; 95% CI, 1.05–1.83; P = 0.022). Review of HVF data identified that participants with paracentral visual field defects also demonstrated a higher cardiovascular disease genetic risk score than reference participants (OR, 1.85/SD; 95% CI, 1.16–2.97; P = 0.010). Participants with predominantly macular GCIPL thinning exhibited a higher vertical cup-to-disc ratio genetic risk score (OR, 1.48/SD; 95% CI, 1.24–1.76; P < 0.001), but an IOP genetic risk score (OR, 1.12/SD; 95% CI, 0.95–1.33; P = 0.179) comparable with that of the normative population. Conclusions: This study highlighted the relationship between cardiovascular disease and retinal thinning in suspect and manifest glaucoma cases.

Published in Ophthalmology Science

ISSN: 2666-9145 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Ophthalmology
Website: https://www.journals.elsevier.com/ophthalmology-science/

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