UPFRONT

Protocol T and Beyond

Peter K. Kaiser, MD

The Diabetic Retinopathy Clinical Research Network (DRCRnet) Protocol T, comparing aflibercept, bevacizumab, and ranibizumab for the treatment of center-involving diabetic macular edema, was a landmark study that will hopefully be the model for future comparative studies. Without these data, we would have little to guide us in determining the best therapy for our diabetic patients. At one year, there was a clear benefit of aflibercept over the other drugs. So we anxiously awaited the second-year results. Would the benefit change?

At the Macula Society Meeting in Miami, FL, the two-year results of the DRCRnet’s Protocol T were reported. The improvements in visual acuities were maintained for all drugs, and the numbers of injections and visits were reduced in the second year.

Interestingly, there was no significant difference in the number of injections among the drugs. While the significant VA improvement seen in year 1 was maintained for aflibercept over bevacizumab, the delta with ranibizumab was no longer significant. Moreover, in patients with good baseline vision, the differences were again not relevant.

There are many questions we all have after seeing the data for the first time that I am sure the DRCRnet will address. For example, was there a difference in the area under the curve among the drugs? Why didn’t the VA results mirror the anatomic results? Did the increased use of laser in some groups help or hinder visual improvement? How can we incorporate the convoluted treatment protocol into our clinical practice to achieve similar visual results? Did the mandatory additional injections mandated by the protocol improve outcomes over a more common PRN approach?

For now, however, the study results and vast differences in cost certainly suggests that bevacizumab is the most appropriate drug for eyes with good baseline vision, and a labeled drug appears better for those who don’t. Whether we are leaving vision on the table in patients with poor baseline vision who we start on bevacizumab and later switch to another drug remains to be proved. But what do we do with patients who respond poorly to anti-VEGF agents? Is there a role for other drugs or treatment combinations? Many of these dilemmas are discussed in this issue, where we look beyond the DRCRnet at recalcitrant DME cases. Finally, can we extrapolate the results of the DRCRnet’s Protocol T to other retinal vascular diseases?

In this issue, we look at another comparative effectiveness study for retinal vein occlusion — SCORE2 — as well as data from studies that can help to guide our treatment in these eyes until we have the results of the study.

Like the landmark diabetes laser studies in the past, retina continues to lead our field in providing guidance for the best treatments for these common blinding conditions.