Findings from a recent study published in Acta Ophthalmologica sought to determine the associations between systemic drugs and the incidence of diabetic macular edema (DME).
Give me some background first.
Currently, the pathogenesis of DME is complex and not very well understood; and environmental and genetic risk factors are likely key components of the disease.
To determine the connection to these environmental factors, the focus of this study was to identify any potential beneficial or deleterious links between systemic medications and DME.
Now, talk about the study.
In this retrospective cohort study performed in Finland, investigators utilized the administrative data from national Finnish health care registries of 150,353 patients with diabetes.
Patients who had purchased and received reimbursement for at least one insulin prescription and/or one oral antidiabetic (OAD) drug between January 1997 and December 2010 were included in the study.
Tell me more.
The primary endpoint was a diagnosis of DME, based on an International Classification of Diseases (ICD-10) code of H36.01.
A 16-year follow-up period took place from 1997 to 2010; a systemic medications review included 95 drugs.
Within this study was a nested case-control study that compared 2,630 DME cases to 13,144 age- and sex-matched controls without DME.
Findings?
Broadly, the incidence of DME was 1.80 per 1,000 person-years (95% confidence interval [CI] 1.73-1.87).
A lower incidence rate of DME was observed in females (incident rate ratio [IRR] 0.57, 95% CI 0.52-0.62) compared to males.
Go on…
The researchers observed that exposure to specific systemic drugs was associated with a lower risk of DME, including:
- Hormone replacement therapy estradiol (odds ratio [OR] 0.42, 95% CI 0.25-0.68)
- Temazepam (OR 0.23, 95% CI 0.08-0.62)
- Allopurinol (OR 0.61, 95% CI 0.43-0.86)
Anything else?
Exposure to other systemic medications was associated with an increased risk of DME, such as:
- Insulin or insulin analogs (OR 3.30, 95% CI 2.99-3.64)
- Sulfonylureas (OR 1.21, 95% CI 1.05-1.40)
- Diuretic furosemide (OR 1.90, 95% CI 1.61-2.24)
- Calcium channel blocker amlodipine (OR 1.53, 95% CI 1.34-1.75)
- Angiotensin-converting enzyme (ACE) inhibitor ramipril (OR 1.66, 95% CI 1.46-1.89)
- Enalapril (OR 1.38, 95% CI 1.16-1.64)
Talk about DME and hypertensive medication.
The study authors observed that certain anti-hypertensive therapies prescribed to prevent diabetic kidney disease were suspected to induce retinal hypoxia due to decreased perfusion pressure in the retinal capillaries—potentially contributing to the development of DME.
What about medication for hyperlipidemia?
A previous study by the same research group suggested that simvastatin may be involved in reducing pathological DME by decreasing permeability factors angiopoietin (Ang)-2 and vascular endothelial growth factor (VEGF).
According to the study authors, “Our findings provide additional evidence that control of blood lipid levels by using simvastatin represents a potential therapeutic strategy for delaying DME development.”
Any connection between insulin and DME?
Prior studies have shown that insulin or insulin analogs confer a heightened risk of DME due to an increased vascular leakage caused by the insulin treatment.
While the long-term use of oral metformin could potentially prevent the development of DME, only a moderate protective effect was observed in this study.
And hormonal treatments?
Estrogen has vasodilatory effects on retinal perfusion and decreased vascular resistance, which may have contributed to the overall incidence of DME to be 43% lower in females than males in this study.
Interestingly, exogenous estrogen has been shown to be protective against both DME and age-related macular degeneration (AMD).
Take home.
The results of this study suggest that collaborative efforts between eyecare practitioners and primary care physicians are key to managing DME patients by building awareness of systemic medications that may potentially contribute to DME development as an adverse side effect.
Further, as there has been a lack of large-scale studies evaluating the incidence of DME, these findings provide a foundation for further studies to elucidate the pathogenesis of complex DME.