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 ([3 = -0.13 & mu;m/year; P <0.001). This finding was strongest in eyes affected by normal-tension glaucoma (NTG; [3 = -0.20 & mu;m/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 & mu;m vs. 71.9 & mu;m; P = 0.011) and pRNFL (77.6 & mu;m vs. 79.2 & mu;m; 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. Ophthalmology Science 2022;2:100159 & COPY; 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/).

Automated summary

This study investigated the association between the APOE E4 dementia-risk allele and prospective longitudinal retinal thinning in suspect and early manifest glaucoma. The results showed that individuals carrying the APOE E4 allele had faster rates of retinal thinning, particularly in eyes affected by normal-tension glaucoma.