A New Tool for Preventing Progression of Diabetic Retinopathy
By A.Paul Chous, MA, OD, FAAO
Diabetic retinopathy remains one of the leading causes of vision loss and blindness in Americans, despite advances in treating both diabetes and severe diabetic retinopathy. Although the majority of people with diabetes will develop some degree of retinopathy, most do not develop sight-threatening retinopathy (STR — defined as proliferative diabetic retinopathy and/or diabetic macular edema). Still, about 1.3 million Americans with diabetes have progressed to STR and more will likely do so as rates of diabetes continue to grow (see my last column, "Rising Rates of Diabetic Retinopathy Not Entirely Bad News").
The major risk factors for developing STR include duration of diabetes (in general, the longer you have diabetes, the higher the risk), the quality of metabolic control (higher A1C — especially within the first five years of diagnosis — and higher blood pressure over time increase the risk of STR), and having already developed milder retinopathy (patients with mild retinopathy are more likely to develop STR over time than are patients with no retinopathy, all things being equal).
Preventing type 2 diabetes in the first place, by becoming more physically active and losing excess weight, is a great way to lower the incidence of STR. Tight metabolic control is also a great way to lower the incidence of STR in people who already have diabetes but have not yet developed retinopathy. But what about patients who already have mild diabetic retinopathy — something the vast majority of those of us with diabetes will eventually develop? How do we prevent the progression to more severe stages of retinopathy and, ultimately, to STR that threatens vision in these folks?
The cornerstone for preventing retinopathy progression is achieving tighter metabolic control, as every 10% drop in A1C (e.g., from an 8% to a 7.2%) lowers the risk of retinopathy progression about 40%, based on analysis of type 2 patients in the United Kingdom Prospective Diabetes Study (UKPDS) and type 1 patients in the Diabetes Control and Complication Trial (DCCT). Patients with blood pressure levels less than 140/90 are also less likely to have retinopathy progress. In the last several years, new evidence has become available showing that type 2 patients with early retinopathy are significantly less likely to progress to more severe stages if they are treated with a medication called fenofibrate (trade names include TriCor, Trilipix, Triglide, Lipofen, Antara, and Fenoglide).
Fenofibrate typically is used to lower blood triglyceride levels, which are linked to cardiovascular disease and are often elevated in type 2 diabetes. In addition, it appears to modestly lower LDL (bad) cholesterol and raise HDL (good) cholesterol. The FIELD study (Fenofibrate Intervention and Event Lowering in Diabetes) showed that patients with type 2 diabetes and mild retinopathy who were treated with fenofibrate were 78% less likely to have significant progression of retinopathy requiring laser therapy over 4 years. The effect was much smaller for patients without pre-existing retinopathy. In addition, a sub-study of the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes) called ACCORD-Eye also showed that type 2 patients with mild retinopathy were 40% less likely to have significant progression of their retinopathy that required laser treatment to prevent vision loss over five years. Again, these positive effects were present but much weaker in patients without pre-existing retinopathy. These two studies looked at more than 11,000 type 2 patients over 4-5 years. Exactly how fenofibrate prevents retinopathy progression is still being investigated, but basic research shows the drug has antioxidant, anti-inflammatory, and neuro-protective effects in cultured retinal cells and animal models of retinopathy.
Like all medications, fenofibrate can have side effects, including nausea, diarrhea, and muscle pain (especially in patients who are also being treated with a statin medication). Increased blood homocysteine levels can also occur.
In an editorial perspective recently published in the American Journal of Ophthalmology, the authors write that, "There are now robust and consistent clinical data to recommend fenofibrate as an adjunctive treatment for early diabetic retinopathy in patients with type 2 diabetes mellitus, taking into account the risks vs. benefits of therapy. Further elucidating its mode of action will help to refine how best to use fenofibrate in the management of diabetic retinopathy." I want every patient with diabetes and especially those of us with early retinopathy to be aware of these findings, and to talk with your doctor about the possible benefits of adding fenofibrate to your defenses against vision loss from diabetes.
For more information on diabetic eye disease, consult Dr. Chous’ book Diabetic Eye Disease: Lessons From a Diabetic Eye Doctor, Fairwood Press, Seattle, 2003.
NOTE: The information is not intended to be a replacement or substitute for consultation with a qualified medical professional or for professional medical advice related to diabetes or another medical condition. Please contact your physician or medical professional with any questions and concerns about your medical condition.
Wong, TY, R. Simo, P. Mitchell. 2012. Fenofibrate — a potential systemic treatment for diabetic retinopathy? American Journal of Ophthalmology 154(1): 6-12.
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