The APOE E4 Allele Is Associated with Faster Rates of Neuroretinal Thinning in a Prospective Cohort Study of Suspect and Early Glaucoma

Sean Mullany, MD; Henry Marshall, MD; Santiago Diaz-Torres; Ella C. Berry, MChD; Joshua M. Schmidt, PhD; Daniel Thomson, PhD; Ayub Qassim, MBBS, PhD; Minh-Son To, MD, PhD; David Dimasi, PhD; Abraham Kuot, PhD; Lachlan S.W. Knight; Georgina Hollitt, MBBS; Antonia Kolovos, MD; Angela Schulz, PhD; Stewart Lake, MBChB; Richard A. Mills, MBBS, PhD; Ashish Agar, MBBS, PhD; Anna Galanopoulos, MBBS; John Landers, MBBS, PhD; Paul Mitchell, MBBS, PhD; Paul R. Healey, MBBS, PhD; Stuart L. Graham, MBBS, PhD; Alex W. Hewitt, MBBS, PhD; Emmanuelle Souzeau, PhD; Mark M. Hassall, MBBS, DPhil; Sonja Klebe, MBBS, PhD; Stuart MacGregor, PhD; Puya Gharahkhani, PhD; Robert J. Casson, MBBS, DPhil; Owen M. Siggs, MD, DPhil; Jamie E. Craig, MBBS, DPhil

Ophthalmology Science (Jun 2022)

The APOE E4 Allele Is Associated with Faster Rates of Neuroretinal Thinning in a Prospective Cohort Study of Suspect and Early Glaucoma

Sean Mullany, MD,
Henry Marshall, MD,
Santiago Diaz-Torres,
Ella C. Berry, MChD,
Joshua M. Schmidt, PhD,
Daniel Thomson, PhD,
Ayub Qassim, MBBS, PhD,
Minh-Son To, MD, PhD,
David Dimasi, PhD,
Abraham Kuot, PhD,
Lachlan S.W. Knight,
Georgina Hollitt, MBBS,
Antonia Kolovos, MD,
Angela Schulz, PhD,
Stewart Lake, MBChB,
Richard A. Mills, MBBS, PhD,
Ashish Agar, MBBS, PhD,
Anna Galanopoulos, MBBS,
John Landers, MBBS, PhD,
Paul Mitchell, MBBS, PhD,
Paul R. Healey, MBBS, PhD,
Stuart L. Graham, MBBS, PhD,
Alex W. Hewitt, MBBS, PhD,
Emmanuelle Souzeau, PhD,
Mark M. Hassall, MBBS, DPhil,
Sonja Klebe, MBBS, PhD,
Stuart MacGregor, PhD,
Puya Gharahkhani, PhD,
Robert J. Casson, MBBS, DPhil,
Owen M. Siggs, MD, DPhil,
Jamie E. Craig, MBBS, DPhil

Affiliations

Sean Mullany, MD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia; Correspondence: Sean Mullany, MD, Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Flinders Drive, Bedford Park, Adelaide, South Australia 5042, Australia.
Henry Marshall, MD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Santiago Diaz-Torres: QIMR Berghofer Medical Research Institute, Brisbane, Australia
Ella C. Berry, MChD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Joshua M. Schmidt, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Daniel Thomson, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Ayub Qassim, MBBS, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Minh-Son To, MD, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
David Dimasi, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Abraham Kuot, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Lachlan S.W. Knight: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Georgina Hollitt, MBBS: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Antonia Kolovos, MD: 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
Stewart Lake, MBChB: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Richard A. Mills, MBBS, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Ashish Agar, MBBS, 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, MBBS, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Paul Mitchell, MBBS, PhD: Centre for Vision Research, University of Sydney, Sydney, Australia
Paul R. Healey, MBBS, PhD: Centre for Vision Research, University of Sydney, Sydney, Australia
Stuart L. Graham, MBBS, PhD: Faculty of Health and Medical Sciences, Macquarie University, Sydney, Australia
Alex W. Hewitt, MBBS, PhD: Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
Emmanuelle Souzeau, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Mark M. Hassall, MBBS, DPhil: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Sonja Klebe, MBBS, PhD: Department of Pathology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia
Stuart MacGregor, PhD: QIMR Berghofer Medical Research Institute, Brisbane, Australia
Puya Gharahkhani, PhD: QIMR Berghofer Medical Research Institute, Brisbane, Australia
Robert J. Casson, MBBS, DPhil: Discipline of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, Australia
Owen M. Siggs, MD, DPhil: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia; Garvan Institute of Medical Research, Darlinghurst, Australia
Jamie E. Craig, MBBS, DPhil: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, Australia

Journal volume & issue: Vol. 2, no. 2
p. 100159

Abstract

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Purpose: To investigate the association between the apolipoprotein E (APOE) E4 dementia-risk allele and prospective longitudinal retinal thinning in a cohort study of suspect and early manifest glaucoma. Design: Retrospective analysis of prospective cohort data. Participants: This study included all available eyes from participants recruited to the Progression Risk of Glaucoma: Relevant SNPs [single nucleotide polymorphisms] with Significant Association (PROGRESSA) study with genotyping data from which APOE genotypes could be determined. Methods: Apolipoprotein E alleles and genotypes were determined in PROGRESSA, and their distributions were compared with an age-matched and ancestrally matched normative cohort, the Blue Mountains Eye Study. Structural parameters of neuroretinal atrophy measured using spectral-domain OCT were compared within the PROGRESSA cohort on the basis of APOE E4 allele status. Main Outcome Measures: Longitudinal rates of thinning in the macular ganglion cell–inner plexiform layer (mGCIPL) complex and the peripapillary retinal nerve fiber layer (pRNFL). Results: Rates of mGCIPL complex thinning were faster in participants harboring ≥1 copies of the APOE E4 allele (β = –0.13 μm/year; P ≤0.001). This finding was strongest in eyes affected by normal-tension glaucoma (NTG; β = –0.20 μm/year; P = 0.003). Apolipoprotein E E4 allele carriers were also more likely to be lost to follow-up (P = 0.01) and to demonstrate a thinner average mGCIPL complex (70.9 μm vs. 71.9 μm; P = 0.011) and pRNFL (77.6 μm vs. 79.2 μm; P = 0.045) after a minimum of 3 years of monitoring. Conclusions: The APOE E4 allele was associated with faster rates of mCGIPL complex thinning, particularly in eyes with NTG. These results suggest that the APOE E4 allele may be a risk factor for retinal ganglion cell degeneration in glaucoma.

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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