Lipid levels a glaucoma risk?

Glaucoma appears to be associated with high total cholesterol and low high-density lipoprotein (HDL) levels, according to a systematic review and meta-analysis of observational studies.

In this meta-analysis, individuals with glaucoma had significantly higher total cholesterol levels than those without (mean difference [MD], 7.9 mg/dL; p=0.001). The results remained significant even after excluding studies that may have contributed to overall heterogeneity, the researchers noted.

Mean HDL levels were significantly lower among individuals with vs without glaucoma (MD, –2.0 mg/dL; p=0.001), which also remained significant after excluding studies that could have influenced heterogeneity. [Acta Ophthalmol 2022:100:148-158]

Individuals with glaucoma had higher mean low-density lipoprotein (LDL) levels than those without glaucoma, but the finding lacked statistical significance (MD, 6.1 mg/dL; p=0.251).

The statin factor

“[I]t might be interesting to see whether statins, which additionally increase HDL levels … may be even better in reducing glaucoma development than statins pre-eminently reducing LDL,” said the researchers. Indeed, evidence suggest that statins may protect against the development and progression of glaucoma. [Invest Ophthalmol Vis Sci 2016;57:2729-2748; Arch Ophthalmol 2004;122:822-826; JAMA Ophthalmol 2017;135:263-267]

On subgroup analysis excluding patients on lipid-lowering drugs, there were smaller mean differences in total cholesterol (MD, 3.7 vs 8.8 mg/dL), HDL (MD, –0.7 vs –2.5), and LDL levels (MD, 4.3 vs 6.1) between glaucoma and control patients.

Nonetheless, statin use is considered a potential confounder in the review, noted the researchers. “[C]onfounding by indication is a possibility … and our findings may be exaggerated.” Meta-regression also could not be performed owing to the small number of trials reporting on patients taking lipid-lowering drugs.

“Otherwise, it could be that patients taking lipid-lowering drugs have high cholesterol … [Therefore,] studies excluding these patients had smaller mean differences. This would support our notion that cholesterol plays a role in the development of glaucoma,” they said.

IOP lowering not sufficient

“Lowering of intraocular pressure (IOP) … remains the most important treatment strategy in glaucoma … However, in some patients, IOP lowering does not seem sufficient to stop the progression of visual field loss,” said the researchers.

“[A]dditional risk factors may also matter,” they continued, one of which being lipid levels, as polymorphisms in genes encoding proteins essential for lipid metabolism have been linked to glaucoma. [Hum Mol Genet 2017;26:R21-R27]

The review and meta-analysis included 29 observational studies, 26 of which reporting relative information for quantitative analysis of cholesterol parameters between adults with (n=7,196) and without (n=350,441) glaucoma.

“[Our findings] may support the conjecture that lipid levels pose an additional risk for glaucoma development,” said the researchers. “[However,] heterogeneity was substantial, and causality cannot be presumed from identified observational studies.”

The large heterogeneity may have been driven by the inclusion of different types of glaucoma (including incident, open-angle, primary open-angle, normal-tension, pseudo-exfoliation glaucoma). Other contributing factors were the differences in inclusion and exclusion criteria across studies evaluated.