Clearly, anti-VEGF treatment is not a general solution for treatment of diabetic eye disease–as up to 30% of patients with diabetic retinopathy have an incomplete response to treatment and in about 40% of patients, proliferative diabetic retinopathy (PDR) is not sufficiently controlled.
The explanation for the limited success achieved with anti-VEGF treatment may be related to uncontrolled inflammation, considering evidence that vitreous levels of inflammatory mediators in eyes of patients with PDR are significantly higher than in controls without diabetes and increase as diabetic retinopathy progresses.
“Control of inflammation may be an insufficiently addressed therapeutic target for diabetic eye disease,” Dr. Garweg said.
He noted that adipocytes may be one source of these cytokines at the systemic level. In that regard, it is noteworthy that gastric bypass or banding, though they do not reduce the number of adipocytes, lead to improvements in blood glucose control and inflammatory markers.
Furthermore, systemic treatment of patients with PDR using the interleukin-1 receptor antagonist anakinra (Kineret, Amgen Inc.) has been shown to improve hyperglycemia and rheumatological activity and to stabilize visual function, albeit without an effect on markers of systemic inflammation.
Similarly, treatment with systemic interleukin-1beta inhibition using canakinumb (Ilaris, Novartis) in patients with PDR was shown to stop progression of retinal neovascularization, stabilize visual acuity and induce a mild reduction in retinal edema together with an improvement in glycemic control measured by HbA1c, again without a change in systemic inflammatory markers.