The APOE E4 allele is associated with faster rates of neuroretinal thinning in a prospective cohort study of suspect and early glaucoma

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dc.contributor.authorMullany, S.
dc.contributor.authorMarshall, H.
dc.contributor.authorDiaz-Torres, S.
dc.contributor.authorBerry, E.C.
dc.contributor.authorSchmidt, J.M.
dc.contributor.authorThomson, D.
dc.contributor.authorQassim, A.
dc.contributor.authorTo, M.-S.
dc.contributor.authorDimasi, D.
dc.contributor.authorKuot, A.
dc.contributor.authorKnight, L.S.W.
dc.contributor.authorHollitt, G.
dc.contributor.authorKolovos, A.
dc.contributor.authorSchulz, A.
dc.contributor.authorLake, S.
dc.contributor.authorMills, R.A.
dc.contributor.authorAgar, A.
dc.contributor.authorGalanopoulos, A.
dc.contributor.authorLanders, J.
dc.contributor.authorMitchell, P.
dc.contributor.authoret al.
dc.date.issued2022
dc.description.abstractPurpose: 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 celleinner 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 (b ¼ e0.13 mm/year; P ≤0.001). This finding was strongest in eyes affected by normal-tension glaucoma (NTG; b ¼ e0.20 mm/year; P ¼ 0.003). Apolipoprotein E E4 allele carriers were also more likely to be lost to followup (P ¼ 0.01) and to demonstrate a thinner average mGCIPL complex (70.9 mm vs. 71.9 mm; P ¼ 0.011) and pRNFL (77.6 mm vs. 79.2 mm; P ¼ 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.
dc.description.statementofresponsibilitySean Mullany, Henry Marshall, Santiago Diaz-Torres, Ella C. Berry, Joshua M. Schmidt, Daniel Thomson, Ayub Qassim, Minh-Son To, David Dimasi, Abraham Kuot, Lachlan S.W. Knight, Georgina Hollitt, Antonia Kolovos, Angela Schulz, Stewart Lake, Richard A. Mills, Ashish Agar, Anna Galanopoulos, John Landers, Paul Mitchell, Paul R. Healey, Stuart L. Graham, Alex W. Hewitt, Emmanuelle Souzeau, Mark M. Hassall, Sonja Klebe, Stuart MacGregor, Puya Gharahkhani, Robert J. Casson, Owen M. Siggs, Jamie E. Craig
dc.identifier.citationOphthalmology Science, 2022; 2(2):1-13
dc.identifier.doi10.1016/j.xops.2022.100159
dc.identifier.issn2666-9145
dc.identifier.issn2666-9145
dc.identifier.orcidSchmidt, J.M. [0000-0002-5862-7389]
dc.identifier.orcidHassall, M.M. [0000-0002-6180-7954]
dc.identifier.orcidCasson, R.J. [0000-0003-2822-4076]
dc.identifier.urihttps://hdl.handle.net/2440/137310
dc.language.isoen
dc.publisherElsevier BV
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1150144
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1157571
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1173390
dc.rightsª 2022 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
dc.source.urihttps://doi.org/10.1016/j.xops.2022.100159
dc.subjectAPOE
dc.subjectAPOE, apolipoprotein E
dc.subjectApolipoprotein E
dc.subjectBMES, Blue Mountains Eye Study
dc.subjectDementia
dc.subjectHTG, high-tension glaucoma
dc.subjectHVF, Humphrey visual field
dc.subjectIOP, intraocular pressure
dc.subjectNTG, normal-tension glaucoma
dc.subjectPOAG
dc.subjectPOAG, primary open-angle glaucoma
dc.subjectPROGRESSA, Progression Risk of Glaucoma: Relevant SNPs with Significant Association
dc.subjectRetinal Neurodegeneration
dc.subjectSD OCT, spectral-domain OCT
dc.subjectSE, standard error
dc.subjectSNP, single nucleotide polymorphism
dc.subjectmGCIPL, macular ganglion cell–inner plexiform layer
dc.subjectpRNFL, peripapillary retinal nerve fiber layer
dc.titleThe APOE E4 allele is associated with faster rates of neuroretinal thinning in a prospective cohort study of suspect and early glaucoma
dc.typeJournal article
pubs.publication-statusPublished

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