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 [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.
(© 2022 by the American Academy of Ophthalmology.)