Ophthalmology · 13 authors, 10 centres
This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.
Higher total cholesterol, HDL-C, and LDL-C were associated with higher intraocular pressure (IOP) in two large UK cohorts, while triglycerides showed an inverse association in one cohort. The effect sizes were modest but could have clinical significance for glaucoma risk. These findings suggest serum lipids may be modifiable risk factors for elevated IOP.
**Background:** Elevated intraocular pressure (IOP) is a major risk factor for glaucoma, and identifying modifiable systemic associations may provide insight into pathophysiology. Serum lipids are routinely measured, modifiable cardiovascular risk factors, but previous studies on their association with IOP have been inconsistent, often limited by small sample sizes, Asian populations, and inadequate adjustment for confounders like BMI, diabetes, and medication use. This study aimed to examine the association of total cholesterol (TC), HDL-C, LDL-C, and triglycerides with corneal-compensated IOP (IOPcc) in two large UK cohorts.
**Methods:** This cross-sectional analysis included 94,323 participants from UK Biobank (mean age 56.8 years, 53.1% women) and 6,230 from EPIC-Norfolk (mean age 68.6 years, 56.0% women). Serum lipids were measured from nonfasting blood samples using standard biochemical assays (Beckman Coulter AU5800 in UK Biobank; RA1000 analyzer in EPIC-Norfolk). IOPcc was measured using the Ocular Response Analyzer (ORA) noncontact tonometer. Multivariate linear regression was used to examine associations, adjusting for age, sex, ethnicity, Townsend deprivation index, BMI, height, systolic blood pressure, smoking, alcohol use, diabetes status, statin use, oral β-blocker use, and spherical equivalent. Standardized β coefficients were reported per 1-standard deviation (SD) increase in lipid levels. Sensitivity analyses included sex stratification, exclusion of statin users, adjustment for multiple lipids simultaneously, and restriction to White ethnicity.
**Key Results:** In UK Biobank, each 1-SD increase in TC was associated with 0.09 mmHg higher IOPcc (95% CI 0.06–0.11, p<0.001); for HDL-C, 0.11 mmHg (95% CI 0.08–0.13, p<0.001); for LDL-C, 0.07 mmHg (95% CI 0.05–0.09, p<0.001). Triglycerides showed an inverse association: –0.05 mmHg per 1-SD (95% CI –0.08 to –0.03, p<0.001). In EPIC-Norfolk, associations were stronger: TC 0.19 mmHg (95% CI 0.07–0.31, p=0.001), HDL-C 0.14 mmHg (95% CI 0.03–0.25, p=0.016), LDL-C 0.17 mmHg (95% CI 0.06–0.29, p=0.003). Triglyceride association was not significant in EPIC-Norfolk (β=–0.05, p=0.30). Quartile analyses showed linear trends: highest vs. lowest quartile of TC in UK Biobank: β=0.23 mmHg (p<0.001); in EPIC-Norfolk: β=0.43 mmHg (p=0.008). For HDL-C highest quartile in UK Biobank: β=0.30 mmHg (p<0.001); for LDL-C: β=0.18 mmHg (p<0.001) in UK Biobank and β=0.48 mmHg (p=0.004) in EPIC-Norfolk. Apolipoprotein A and B were also positively associated with IOPcc in UK Biobank (A: 0.11 mmHg, p<0.001; B: 0.08 mmHg, p<0.001). Sensitivity analyses adjusting for multiple lipids simultaneously showed minimal attenuation. Sex-stratified analyses revealed stronger associations in men, particularly for HDL-C (interaction p<0.001). Results were robust to exclusion of statin users and adjustment for BMI.
**Clinical Implications:** Although the effect sizes are modest (e.g., 0.43 mmHg difference between highest and lowest TC quartile in EPIC-Norfolk), they are comparable to known genetic risk variants for glaucoma (e.g., TMC01). The collective effect of multiple lipid abnormalities could exceed 1 mmHg, which may be clinically relevant for glaucoma conversion or progression. Serum lipids are modifiable through diet, lifestyle, and medication, suggesting potential for targeted interventions to influence IOP. However, the cross-sectional design precludes causal inference, and future research (e.g., Mendelian randomization) is needed to establish causality. The study's strengths include large sample size, replication in two independent cohorts, comprehensive covariate adjustment, and use of IOPcc to minimize corneal biomechanical confounding. Limitations include cross-sectional design, potential recall bias, nonfasting samples, and missing data. Overall, these findings support a positive association between TC, HDL-C, LDL-C, and IOP, and an inverse association with triglycerides, warranting further investigation into causal mechanisms and clinical utility.