Mullany, S.Marshall, H.Diaz-Torres, S.Berry, E.C.Schmidt, J.M.Thomson, D.Qassim, A.To, M.-S.Dimasi, D.Kuot, A.Knight, L.S.W.Hollitt, G.Kolovos, A.Schulz, A.Lake, S.Mills, R.A.Agar, A.Galanopoulos, A.Landers, J.Mitchell, P.et al.2023-01-252023-01-252022Ophthalmology Science, 2022; 2(2):1-132666-91452666-9145https://hdl.handle.net/2440/137310Purpose: 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.enª 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/).APOEAPOE, apolipoprotein EApolipoprotein EBMES, Blue Mountains Eye StudyDementiaHTG, high-tension glaucomaHVF, Humphrey visual fieldIOP, intraocular pressureNTG, normal-tension glaucomaPOAGPOAG, primary open-angle glaucomaPROGRESSA, Progression Risk of Glaucoma: Relevant SNPs with Significant AssociationRetinal NeurodegenerationSD OCT, spectral-domain OCTSE, standard errorSNP, single nucleotide polymorphismmGCIPL, macular ganglion cell–inner plexiform layerpRNFL, peripapillary retinal nerve fiber layerJournal article10.1016/j.xops.2022.1001592023-01-25611061Schmidt, J.M. [0000-0002-5862-7389]Hassall, M.M. [0000-0002-6180-7954]Casson, R.J. [0000-0003-2822-4076]