The Role of Anti-VEGF Therapy in Diabetic Macular Edema

Peter Salgo, MD: We have treatment options. You mentioned laser photocoagulation. That was always out there and I, as an internist, know that from way back.

There’s surgery, intraocular corticosteroids, and then there’s the anti-vascular endothelial growth factor therapies which are, in my experience, relatively new on the market but very promising. How do you prioritize these? How do you put them in some sort of sequence?

Rishi P. Singh, MD: In this day and age, anti-VEGF therapy, or anti-vascular endothelial growth factor therapy, is considered first-line treatment.

And this therapy has been pioneered over many, many years. But the past seven or eight years has really been the genesis and the usage of this in clinical practice. It was actually derived from the fact that they did samples of peoples’ eyes and determined this was a factor that was causing a lot of patients to develop diabetic retinopathy.

Therefore, inhibiting this factor led to a lot of people developing improved diabetic macular edema and improved retinopathy scores as a result of this. In fact, by giving these treatments, you can not only improve diabetic macular edema but you can improve diabetic retinopathy scores in those patients within those clinical trials.

Corticosteroids are another alternative agent. Steroids—we’re all used to. The biggest problem with steroids is their side effect profile. Cataract and glaucoma are the two big ones.

Peter Salgo, MD: If I may, the problem with steroids is that they’re steroids.

Rishi P. Singh, MD: That’s correct. And the glucocorticoid effect doesn’t get obviated, even with giving these steroids. That’s where this is coming from with both the cataract and the glaucoma perspective.

Laser photocoagulation is still used on occasion, and in combination with the two other therapies I mentioned before. And surgery is a last ditch option for a lot of patients, unless there’s other major tractional, or changes in the retina, that are necessitating that.

It’s actually not that same way in other countries. Surgery is actually the primary option. But in this country, typically anti-vascular endothelial growth factor and corticosteroids is the primary option for treatment.

Peter Salgo, MD: How much of a problem with steroids is that they are hyperglycemic agents, or hyperglycemia-inducing agents, which make the problem potentially worse as opposed to just the anti-inflammatory agents?

John W. Kitchens, MD: When given in the eye, we don’t see an increase in systemic blood sugars. So we’re actually injecting these medications into the vitreous cavity, through the white part of the eye, the sclera. So we really don’t see a bump up in patients’ blood sugars.

Peter Salgo, MD: So this is a primary problem with the direct effect of steroids, not a secondary effect from hyperglycemia?

John W. Kitchens, MD: Correct.

Steven Peskin, MD, MBA, FACP: The cataract or glaucoma.

John W. Kitchens, MD: That’s right.

Peter Salgo, MD: So, now, if you’re going to put these in some sort of hierarchical order. Somebody comes to you with diabetic macular edema—this shopping list of potentials, the order has shifted. It’s reorganized itself. Where do you start?

John W. Kitchens, MD: We had that same question several years ago and we actually have a great organization called the DRCR Network. It stands for Diabetic Research Clinical Network, and basically it’s a group of about 100 practices in the United States that ask these questions and answer them independently.

And, basically, they wanted to know which is better? Laser, laser and steroids, or anti-vascular endothelial growth factor therapy with either early laser or alone.

It’s called the Diabetic Retinopathy Clinical Research Protocol Eye Study, and it showed, without a doubt, that the anti-vascular endothelial growth factor therapy was the gold standard. And that really was a sea change for what we do. We no longer now say, “Well, maybe laser is better, maybe this patient needs steroids first.”

Almost everyone now starts with anti-vascular endothelial growth factor therapy. There are certain instances where you can add laser and maybe reduce the burden of treatment. The five year extension on that study actually showed something pretty amazing, which was we were modifying the disease.

So, patients in that study the first year received nine injections in the eye of anti-vascular endothelial growth factor therapy, but the second year they only received three, and in the third year, two, and the fourth year, one, and the fifth year, no injections. You saw a decreasing number of injections needed over time to control their diabetic macular edema.

Peter Salgo, MD: Are you actually telling me that you’re turning the disease process off with anti-vascular endothelial growth factor therapy?

John W. Kitchens, MD: Not just the macular edema, but also the diabetic retinopathy. As Rishi said, we see improvements in diabetic retinopathy scores, two step improvements in patients 30%-40% of the time. And in the worst patients, those with very severe nonproliferative retinopathy or worse, that can be 60%-70% of the time that we see a 2-step improvement. So you’re taking the worst of the worst and you’re pulling them out of the fire.