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

<p><strong>Purpose:</strong> 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.</p> <p><strong>Design:</strong> Retrospective analysis of prospective cohort data.</p> <p><strong>Participants:</strong>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.</p> <p><strong>Methods</strong>: 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.</p> <p><strong>Main outcome measures:</strong> Longitudinal rates of thinning in the macular ganglion cell-inner plexiform layer (mGCIPL) complex and the peripapillary retinal nerve fiber layer (pRNFL).</p> <p><strong>Results:</strong>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.</p> <p><strong>Conclusions:</strong> 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.</p>