Pathophysiology of Diabetic Macular Edema

Nancy Holekamp, MD: Dr Rahimy, Dr Coney said that DME [diabetic macular edema] can occur at any stage of diabetic retinopathy, but could you walk us through the progression of diabetic retinopathy and how DME occurs?

Ehsan Rahimy, MD: We know that the risk of developing DME increases with one’s own severity of underlying diabetic retinopathy. In general, we’re dealing with patients who—whether they come to us, or optometrists or other ophthalmologists for their diabetic screening—either do or don’t have signs of diabetic retinopathy. For those who do have retinopathy, we grade it in terms of a severity score as either mild, moderate, severe, or in the most advanced stages, they’ve progressed to proliferative disease. There have been some nice studies done, now that we have access to big data, not just in our field but all of medicine. We’ve seen some of these studies that show the risk of developing DME, as we would anticipate, increases with the severity score of diabetic retinopathy. One of our colleagues…has presented this at meetings; it was a large US claims database study. It looked at 5 years into diagnosis, your risk of developing DME was over 60% if you had severe nonproliferative diabetic retinopathy [NPDR]. It could be as low as 15% risk for people at the mild stage; moderate was somewhere in between. The risk of having DME if you were fully into proliferative disease was lower, about 28%, which is an interesting finding. We’ve seen it mirrored in some of our own clinical trials. When we look at PANORAMA, Protocol W—some of these studies that look at the progression rates of diabetic retinopathy—patients either trend toward developing proliferative disease or DME, and there tends to not be much of an overlap. Prior to that, we know that the risk of developing DME increases with your stage of NPDR.

Nancy Holekamp, MD: Let’s delve into the pathophysiology of not only diabetic retinopathy, but diabetic macular edema. In my clinics, patients just think they have high blood sugar, and they’re wondering how it’s affecting their retina. Dr Coney, can you describe the pathophysiology of diabetic retinopathy and diabetic macular edema?

Joseph M. Coney, MD: It’s the hyperglycemia that begins this process, and there’s a cascade of issues that occur when someone is developing both diabetic edema and diabetic retinopathy. It begins with the oxidative stress and inflammation, which leads to a breakdown in the vascular endothelial system— what we call a dysfunction—and this can lead to ischemic changes. These changes can lead to the upregulation of certain proteins in the eye, which leads to the breakdown of blood-retinal barriers and leakage. This is called a vascular endothelial growth factor, which can lead to abnormal vessels. We can see these vessels in the front of the eye, in the back of the eye. It leads to increased vascular permeability, which we see as diabetic edema. In the latest stages, when those vessels grow, they bleed and become a vitreous hemorrhage. Sometimes it develops a tractional retinal detachment. That’s the entire spectrum, but the majority of things lead from a lack of circulation, which stimulates this cascade.

Nancy Holekamp, MD: Many of our patients with diabetic retinopathy also have nephropathy or neuropathy. How do you tie, say, the retina and the kidney together?

Joseph M. Coney, MD: Most of my patients already have nephropathy because they’re coming in at an advanced state. Eye disease is another advanced state of diabetes. Unfortunately, nephropathy, or kidney disease, or diabetic kidney disease, happens in a third of the patients who have a diabetic eye disease. There’s a direct correlation that as the severity of retinopathy progresses, so does your kidney function. It’s also a direct correlation to having a high urine albumin-to-creatinine ratio as well as low GFR [glomerular filtration rate]. Those individuals are more likely to have abnormal kidney function when they have diabetes. There’s also a direct correlation with blood pressure. When kidneys are not well regulated, your blood pressure or hypertension can also be high, and even if people have adequate glycemic control, blood pressure can still worsen diabetic retinopathy.

Nancy Holekamp, MD: I appreciate that DME is like a biomarker for some of our sickest patients with diabetes. I am aware of a study…that showed that patients with diabetic macular edema on average saw doctors 25 times a year. This means they were going to the doctor at least twice a month, which usually doesn’t include their eye doctor. It’s a large burden to have not only diabetes, but diabetic retinopathy and diabetic macular edema.

Thanks to all of you for this rich and informative discussion, and thank you for watching this HCPLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

Transcript edited for clarity.