Investigative ophthalmology & visual science · 2026
Apolipoprotein E2/2 (APOE2/2) Genotype Is Associated With Reduced Choroidal Thickness.
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Borchert Grace A, Ferreira Lino A F, Raji Shabnam, Yu Jing, Segovia Matias, MacLaren Robert E, Downes Susan M, Cehajic-Kapetanovic Jasmina, Xue Kanmin, De Silva Samantha R
Аннотация
PURPOSE: Age-related macular degeneration (AMD) is a leading cause of visual impairment in individuals >50 years. The APOE2 allele has been associated with increased AMD risk compared to the common APOE3 allele. However, the retinal phenotype of APOE2/2 individuals has not been characterized. This study aimed to compare the macular structure and function of APOE2/2 versus APOE3/3 homozygous individuals.
METHODS: Age- and sex-matched participants with APOE2/2 and APOE3/3 genotypes were prospectively recruited from the Oxford Biobank. Phenotyping included best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), microperimetry, refractive error, multimodal retinal imaging, fasting lipid profile, and EPIC-Norfolk food frequency questionnaires. A linear mixed model of paired eye measurements with a subject-specific random intercept was applied, including age, sex, smoking status and refractive error as covariates. Findings were compared to similar UK Biobank cohorts.
RESULTS: 24 participants were recruited: 12 APOE2/2 and 12 APOE3/3 (mean age 60.5 ± 5.7 (standard deviation) years, female/male 1:1; 87.5% non-smokers). Serum triglycerides were significantly higher in APOE2/2 participants (1.8 vs. 1.03 mM, P = 0.010). A novel finding of reduced choroidal thickness was found in APOE2/2 compared to APOE3/3 participants after multivariate analysis controlling for age, sex, smoking status and refractive error (estimated difference 57.8 µm, P = 0.02). Optical coherence tomography segmentation showed a trend toward reduced retinal thickness in APOE2/2 compared to APOE3/3 participants, but did not reach statistical significance. No differences in BCVA, LLVA, or retinal sensitivity were detected. Diet and background AMD genetic risk were comparable.
CONCLUSIONS: We report a novel genotype-phenotype association of reduced choroidal thickness in individuals homozygous for APOE2/2 compared with normative APOE3/3 controls.
METHODS: Age- and sex-matched participants with APOE2/2 and APOE3/3 genotypes were prospectively recruited from the Oxford Biobank. Phenotyping included best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), microperimetry, refractive error, multimodal retinal imaging, fasting lipid profile, and EPIC-Norfolk food frequency questionnaires. A linear mixed model of paired eye measurements with a subject-specific random intercept was applied, including age, sex, smoking status and refractive error as covariates. Findings were compared to similar UK Biobank cohorts.
RESULTS: 24 participants were recruited: 12 APOE2/2 and 12 APOE3/3 (mean age 60.5 ± 5.7 (standard deviation) years, female/male 1:1; 87.5% non-smokers). Serum triglycerides were significantly higher in APOE2/2 participants (1.8 vs. 1.03 mM, P = 0.010). A novel finding of reduced choroidal thickness was found in APOE2/2 compared to APOE3/3 participants after multivariate analysis controlling for age, sex, smoking status and refractive error (estimated difference 57.8 µm, P = 0.02). Optical coherence tomography segmentation showed a trend toward reduced retinal thickness in APOE2/2 compared to APOE3/3 participants, but did not reach statistical significance. No differences in BCVA, LLVA, or retinal sensitivity were detected. Diet and background AMD genetic risk were comparable.
CONCLUSIONS: We report a novel genotype-phenotype association of reduced choroidal thickness in individuals homozygous for APOE2/2 compared with normative APOE3/3 controls.