Plasma caffeine level as a protective factor against age-related eye diseases: a two-sample Mendelian randomisation...

Area of Science:

• Ophthalmology
• Genetics
• Pharmacology

Background:

• Inconsistent findings exist regarding caffeine intake and age-related eye diseases (ARED).
• Variations in caffeine assessment methods may explain previous study discrepancies.
• Genetic approaches offer a robust method to investigate causal relationships.

Purpose of the Study:

• To investigate the association between genetically predicted plasma caffeine levels and four major ARED: senile cataract, diabetic retinopathy (DR), glaucoma, and age-related macular degeneration (AMD).
• To explore potential causal effects on specific glaucoma subtypes (POAG, PACG) and the role of intraocular pressure (IOP) as a mediator.

Main Methods:

• A two-sample Mendelian randomisation study design was employed.
• Genome-wide association study data for genetically predicted plasma caffeine (n=9876) and clinical records for ARED from the FinnGen Consortium were utilized.
• Mediation analysis was performed to assess the role of IOP in the caffeine-glaucoma association.

Main Results:

• Elevated genetically predicted plasma caffeine was associated with a reduced risk of senile cataract (OR 0.84), DR (OR 0.81), and overall glaucoma (OR 0.83).
• A significant association was found with reduced risk for primary angle closure glaucoma (PACG) (OR 0.74), but not primary open-angle glaucoma (POAG) or AMD.
• Intraocular pressure (IOP) partially mediated the effect of caffeine on glaucoma, accounting for 41% of the association.

Conclusions:

• Higher plasma caffeine levels appear to have a protective effect against senile cataract, diabetic retinopathy, and certain types of glaucoma.
• The findings provide strong genetic evidence supporting caffeine's potential role in mitigating ARED risk.
• These results suggest potential therapeutic implications for caffeine in the prevention or management of specific age-related eye conditions.