Causal Association Between Commonly Used Medicines and Diabetes-Related Eye Diseases: Univariable and Multivariable...

Area of Science:

• Ophthalmology
• Pharmacogenomics
• Genetic Epidemiology

Background:

• Diabetic patients often require multiple medications (polypharmacy).
• The causal impact of these medications on ocular complications like diabetic retinopathy (DR), diabetic maculopathy (DMac), and glaucoma is not well understood due to confounding factors in observational studies.

Purpose of the Study:

• To investigate the causal effects of common medication classes on the risk of developing diabetic eye diseases.
• To differentiate medication effects from comorbidities like type 2 diabetes and hypothyroidism.

Main Methods:

• A Mendelian randomization (MR) study was conducted using genome-wide association study (GWAS) summary statistics for 23 medication classes and five diabetic eye diseases.
• Multivariable MR (MVMR) was used to adjust for key comorbidities, and enrichment analyses explored underlying biological pathways.

Main Results:

• Univariable MR indicated associations between several medication classes (including diabetes drugs and renin-angiotensin system agents) and increased risk of diabetic eye diseases.
• MVMR confirmed robust causal links for diabetes drugs with DMac, DR, neovascular glaucoma, and senile cataract, independent of type 2 diabetes.
• Thyroid preparations showed significant associations with DMac, DR, and senile cataract, independent of hypothyroidism. Adrenergic inhalants were linked to senile cataract, independent of asthma.

Conclusions:

• Genetic evidence supports comorbidity-independent causal relationships between specific systemic medications (notably diabetes and thyroid drugs) and ocular complications.
• These findings underscore the importance of ophthalmological monitoring for diabetic patients using these medications.