Can statins treat AMD effectively?

Key Points

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among older adults in developed countries, and with the aging population the problem is increasing.

Current therapy, which includes the vascular endothelial growth factor (VEGF) inhibitors, is limited to the late stage of the disease, when central vision is already under great threat, so even these new treatments make little impact on the rate of blindness. In my opinion, monthly intravitreal anti-VEGF injections, which are associated with some systemic exposure to anti-VEGF, will be replaced in the future by new drugs that are administered in a less invasive way.

At present, there is no effective treatment for early-stage AMD or for arresting its progression in the earliest phases. Epidemiologic, genetic, and pathological evidence, however, continues to accumulate, suggesting a possible link between cardiovascular disease risk factors and AMD, and this has led some researchers to suggest that the pathophysiology of these two diseases have similar causal pathways.¹

How do statins work?

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, generically termed statins, are the most commonly used lipid lowering drugs today; their efficacy has been proven in many studies. For instance, in the Heart Protection Study, which randomized more than 20,000 high-risk cardiovascular disease patients, the value of statins in reducing adverse cardiovascular events was proven beyond doubt.⁵

As a result, statins are now considered to be one of the most powerful classes of agents for the treatment of vascular disease,^6,7 and they are rapidly becoming frontline therapy for diabetes mellitus, hypertension, and other known vascular risk factors.

Recent experimental evidence suggests that statins appear to display additional cholesterol independent of pleiotropic effects, contributing to the prevention and inhibition of atherosclerosis. The statins' vascular pleiotropic effects include improvement of endothelial function, slowing the inflammation process, inhibition of thrombus formation, enhancement of plaque stability and decreasing oxidative stress.⁸

It has been suggested that statins could be beneficial in treating, and maybe even preventing AMD and this is based on a number of key points:

The association between the use of statins and AMD has been evaluated in many clinical studies; however the results have been contradictory. The objective of this review is to present some studies that have been conducted in this field, to evaluate the evidence that links statins with AMD and to discuss the rationale behind this type of therapy in the prevention and the treatment of AMD.

In conclusion...

In conclusion, there are potentially multiple biological bases for the protective effect of statins on the risk of AMD. With regards to the potential for a lipid lowering effect, cholesterol is a ubiquitous component of drusen in normal and AMD eyes.

Regarding the potential for pleiotropic effects, many of the same processes that occur in the atherosclerotic intima probably also occur in AMD; neovascularization is a major complication in both conditions, therefore, angiogenesis is a potential point of statin modulation. Taking into account that not all statins are equally effective, the challenge for future laboratory research will be to determine the best type and dosage of statins and also to determine which processes are modulated by statins in vivo and therefore are primarily responsible for the apparent beneficial effects observed in previous studies.

Clearly, further observational studies cannot adequately address many unanswered questions. I would therefore recommend that a randomized controlled trial be conducted to provide direct evidence of the effectiveness of specific types of statin in lowering the incidence and progression of AMD, so that this class of drug can either be promoted or eliminated for the treatment of this disease once and for all.