A large observational study published in the British Journal of Ophthalmology suggests that high levels of high-density lipoprotein (HDL) cholesterol, commonly known as ‘good’ cholesterol, may be linked to an increased risk of glaucoma in individuals over 55 years of age. In contradiction, low-density lipoprotein (LDL) cholesterol, typically considered ‘bad’ for health, appears to be associated with a lower risk of eye disease.
Glaucoma can lead to irreversible vision loss or total blindness and is projected to affect approximately 112 million people worldwide by 2040. Risk factors for glaucoma include age, ethnicity, intraocular pressure (IOP), and family history. Recent research has also suggested a link between abnormal lipid levels and eye diseases such as macular degeneration and diabetic retinopathy. However, studies examining the connection between cholesterol and glaucoma have yielded inconsistent results.
To clarify this relationship, Ma et al. analyzed data from 400,229 participants aged 40 to 69 in the UK Biobank Study. These individuals completed health questionnaires, underwent interviews, and provided blood samples for lipid profile analysis. Over an average follow-up period of 14 years, 6,868 participants (nearly 2%) developed glaucoma.
Compared to those who did not develop glaucoma, affected participants were generally older, more likely to be of non-white ethnicity, and had higher levels of HDL cholesterol but lower levels of LDL cholesterol. They also exhibited a higher waist-to-hip ratio, a common indicator of central obesity. Additionally, they were more likely to be ex-smokers, and statin users, and have underlying conditions such as diabetes, high blood pressure, and cardiovascular disease.
Detailed analysis of blood test results revealed a surprising pattern: higher levels of HDL cholesterol were associated with an increased risk of glaucoma, while higher levels of LDL cholesterol, total cholesterol, and triglycerides correlated with a lower risk. Participants with the highest HDL cholesterol levels were 10% more likely to develop glaucoma than those with the lowest levels. Each standard deviation (SD) increase in HDL cholesterol was linked to a 5% increase in glaucoma risk.
Conversely, participants with the highest levels of LDL cholesterol and triglycerides were 8% and 14% less likely, respectively, to develop glaucoma. Additionally, each SD increase in LDL cholesterol, total cholesterol, and triglycerides lowered glaucoma risk by 4%, 3%, and 4%, respectively. However, these associations were only observed in individuals over 55, with no significant correlation found in those aged 40 to 55. The effects also varied based on sex and type of glaucoma. Posch Pertl et al. conducted a systematic review that found an association between glaucoma and high total cholesterol levels, as well as low HDL levels.
The researchers constructed a polygenic risk score numerical measure of genetic susceptibility to disease using genetic data from the participants. This analysis showed that each additional genetic risk factor increased glaucoma odds by 5%. However, there were no significant individual associations between LDL cholesterol, total cholesterol, or triglycerides and glaucoma risk.
As an observational study, the findings cannot establish a direct cause-and-effect relationship. The researchers acknowledged several limitations, including the fact that blood samples were not taken after fasting and were collected only at a single time point. Additionally, since UK Biobank participants are predominantly of European ancestry, the results may not be generalizable to other ethnic groups.
The study challenges traditional views on cholesterol’s role in eye health, suggesting a need to reassess lipid management for glaucoma risk. Researchers and healthcare professionals may need to revisit cholesterol guidelines, especially for older adults. Further studies are essential to determine whether cholesterol-lowering medications, like statins, influence glaucoma risk and if targeted interventions can mitigate potential eye health effects.
References
- Ma Y, Wu Y, Hu L, Chen W, Zhang X, Zheng D, et al. Associations between serum lipids and glaucoma: a cohort study of 400 229 UK Biobank participants. British Journal of Ophthalmology [Internet]. 2025 Jan 15 [cited 2025 Feb 7]; Available from: https://bjo.bmj.com/content/early/2025/01/14/bjo-2024-326062
- Jenkins AJ, Grant MB, Busik JV. Lipids, hyperreflective crystalline deposits and diabetic retinopathy: potential systemic and retinal-specific effect of lipid-lowering therapies. Diabetologia. 2022 Apr;65(4):587–603.
- Posch‐Pertl L, Michelitsch M, Wagner G, Wildner B, Silbernagel G, Pregartner G, et al. Cholesterol and glaucoma: a systematic review and meta‐analysis. Acta Ophthalmol. 2022 Mar;100(2):148–58.