Do commonly used systemic medications influence the risk of diabetic eye diseases independent of underlying conditions? A Mendelian randomization study published in Journal of Diabetes Research evaluated genetic evidence linking medication classes with ocular complications in diabetes.

The analysis used genome-wide association study (GWAS) summary statistics for 23 medication classes and five diabetic eye diseases. Univariable Mendelian randomization (UVMR) was first performed to identify associations. Multivariable Mendelian randomization (MVMR) was then used to adjust for key comorbidities, including hypertension and type 2 diabetes mellitus (T2DM). Additional analyses explored biological pathways.

In UVMR analyses, drugs used in diabetes and agents targeting the renin–angiotensin system showed associations with increased risk of diabetic eye diseases. In MVMR models, diabetes drugs remained associated with diabetic maculopathy (DMac) (odds ratio [OR] 1.44; p = 1.31 × 10⁻¹¹), diabetic retinopathy (DR) (OR 1.23; p = 1.26 × 10⁻⁸), neovascular glaucoma (OR 1.19; p = 0.003), and senile cataract (OR 1.10; p = 9.25 × 10⁻¹²), independent of T2DM liability. Thyroid preparations also showed associations with DMac (OR 1.26; p = 4.35 × 10⁻¹⁰), DR (OR 1.17; p = 9.53 × 10⁻¹⁰), and cataract (OR 1.04; p = 0.004) after adjusting for hypothyroidism. Adrenergic inhalants were associated with cataract (OR 1.07; p = 0.008) after adjusting for asthma.

Pathway analyses identified hormone transport and mitogen-activated protein kinase (MAPK) signaling as potential biological pathways. These findings provide genetic evidence supporting associations between specific medication classes and diabetic eye diseases independent of comorbidities.