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The APOE E4 Allele Is associated with faster rates of neuroretinal thinning in a prospective cohort study of suspect and early Glaucoma


Mullany, S and Marshall, H and Diaz-Torres, S and Berry, EC and Schmidt, JM and Thomson, D and Qassim, A and To, MS and Dimasi, D and Kuot, A and Knight, LSW and Hollitt, G and Kolovos, A and Schulz, A and Lake, S and Mills, RA and Agar, A and Galanopoulos, A and Landers, J and Mitchell, P and Healey, PR and Graham, SL and Hewitt, AW and Souzeau, E and Hassall, MM and Klebe, S and MacGregor, S and Gharahkhani, P and Casson, R and Siggs, OM and Craig, JE, The APOE E4 Allele Is associated with faster rates of neuroretinal thinning in a prospective cohort study of suspect and early Glaucoma, Ophthalmology science, 19, (2) Article 100159. ISSN 2666-9145 (2022) [Refereed Article]

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DOI: doi:10.1016/j.xops.2022.100159


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.

Item Details

Item Type:Refereed Article
Keywords:APOE; APOE, apolipoprotein E; Apolipoprotein E; BMES, Blue Mountains Eye Study; Dementia; HTG, high-tension glaucoma; HVF, Humphrey visual field; IOP, intraocular pressure; NTG, normal-tension glaucoma; POAG; POAG, primary open-angle glaucoma; PROGRE
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Treatment of human diseases and conditions
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:155609
Year Published:2022
Deposited By:Menzies Institute for Medical Research
Deposited On:2023-03-02
Last Modified:2023-03-02

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