Potency Matters: The Role of Statin Intensity in Modulating Risk for Age-Related Macular Degeneration

Abstract

Purpose

Age-related macular degeneration (AMD) is a leading cause of vision loss. Statins, primarily used for cardiovascular disease prevention, may have pleiotropic effects on AMD, but existing evidence is inconclusive.

This study investigated the association between statin intensity (high, moderate, low) and the risk of AMD in patients with type 2 diabetes and dyslipidemia.

Design

A retrospective clinical cohort study using de-identified electronic health records from the US Collaborative Network.

Methods

Adults aged 40 years or older with type 2 diabetes, dyslipidemia, and at least 1 ophthalmologic visit were included from 2014 to 2024 Patients with confounding conditions (liver disease, HIV, etc.) and prior AMD diagnoses were excluded. Propensity score matching was used to balance covariates between statin intensity cohorts and a treatment-naïve control group.

Intensity groups included: high-intensity statin therapy (rosuvastatin 20-40 mg or atorvastatin 40-80 mg), high-intensity-naïve, medium-intensity statin therapy (rosuvastatin [5 mg, 10 mg], simvastatin [20 mg, 40 mg], fluvastatin [80 mg], pravastatin [40 mg, 80 mg], lovastatin [40 mg], atorvastatin [10 mg, 20 mg], or pitavastatin [1 mg, 2 mg, 4 mg]), and low-intensity statin therapy (simvastatin 5-10 mg, pravastatin 10-20 mg, lovastatin 10-20 mg, or fluvastatin 20-40 mg).

Main Outcome Measures

Incidence of combined AMD (nonexudative and exudative), nonexudative AMD, exudative AMD, and all-cause mortality at 6 months, 1 year, 3 years, and 5 years after the index event. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazard regression models.

Results

After matching, a total of 20 282 patients were included. High-intensity statin use was associated with a reduced risk of combined AMD at 3 and 5 years (HR: 0.74 (95% CI: 0.57-094) and 0.79 (95% CI: 0.62-0.98), respectively). Medium-intensity statin therapy was associated with a significantly lower risk of combined AMD (HR range: 0.49 [95% CI 0.55-0.91] to 0.77 [95% CI: 0.60-0.98]) and exudative AMD (HR range: 0.19 [0.06-0.054] to 0.62 [95% CI: 0.40-0.96]) at all follow-up points. All statin intensities were associated with reduced all-cause mortality.

Conclusions

In this study of patients with type 2 diabetes and dyslipidemia, medium- and high-intensity, but not low-intensity, statin therapies were associated with a reduced risk of AMD. Further research is needed to confirm these findings and elucidate the underlying mechanisms.