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

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 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- and ancestrally-matched normative cohort, the Blue Mountains Eye Study (BMES). Structural parameters of neuroretinal atrophy measured using spectral-domain optical coherence tomography (SD-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 complex (mGCIPL) and the peripapillary retinal nerve fibre layer (pRNFL). Results Rates of mGCIPL thinning were faster in participants harbouring ≥1 copy of the APOE E4 allele (β=-0.13μm/year; p=<0.001). This finding was strongest in eyes affected by normal-tension glaucoma (β=-0.20μm/year; p=0.003). Apolipoprotein E E4 allele carriers were also more likely to be lost to follow-up (p=0.01) and demonstrated a thinner average mGCIPL (70.9μm vs. 71.9μm; p=0.011) and pRNFL (77.6μm vs. 79.2μm; p=0.045) after a minimum of three years of monitoring. Conclusions The APOE E4 allele was associated with faster rates of mCGIPL thinning, particularly in NTG eyes. These results suggest the APOE E4 allele may be a risk factor for retinal ganglion cell degeneration in glaucoma.