Take-home message: While it is still unclear why some patients respond well to anti-VEGF therapy and others do not, a new post hoc analysis of the DRCR.net Protocol I data may help physician make more efficient use of therapy by more quickly identifying which category each patient is in.
By Laird Harrison; Reviewed by Pravin Dugel, MD
Los Angeles—Clinicians can predict a patient’s long-term response to anti-vascular endothelial growth factor (VEGF) treatment of diabetic macular edema (DME) after three injections, researchers said.
“I do think this has potential to change our practice,” said Pravin Dugel, MD, managing partner at Retinal Consultants of Arizona, Phoenix, Arizona and a clinical professor at the University of Southern California Eye Institute, Keck School of Medicine in Los Angeles. He presented the finding at the American Academy of Ophthalmology 2015 meeting.
The researchers based their conclusions on a post hoc analysis of the Protocol I 3-year phase III trial of 854 eyes in 691 patients with DME conducted by the Diabetic Retinopathy Clinical Research Network.
That study compared prompt versus delayed laser treatment in eyes treated with ranibizumab for diabetic macular edema.
In their analysis, Dr. Dugel and his colleagues assessed outcomes in three cohorts based on best-corrected visual acuity observed.
After giving the patients three injections in 12 weeks, they divided them into three cohorts: those who gained less than five ETDRS letters of best-corrected visual acuity, those who gained five to nine letters, and those who gained 10 or more letters.
They found a close correlation between the letters gained at 12 weeks and the letters gained at three years. The differences among the cohorts were statistically significant (p
Change in Mean BCVA
Mean Letters Gained at 12 weeks
Mean Letters Gained at 3 years
≥ 10 Letters
(2015. An Analysis of Diabetic Retinotherapy Clinical Research Network PROTOCOL I Data Study)
The finding is not a surprise, because it corresponds to anecdotal reports, Dr. Dugel said. But it provides useful confirmation of what many had suspected. “I think it’s very, very useful for us clinically to be able to say this patient is likely to respond or this patient is not, and which one should be treated with other therapies,” he said.
If the patients do not respond after three injections of an anti-VEGF medication, clinicians can then try dexamethasone intravitreal implants. This drug may last for 3-5 months, Dr. Dugel said. If the fluid repeatedly returns, a clinician could next offer a fluocinolone acetonide intravitreal implant, which is a non-biodegradable device and may last for three years, he said.
If patients who aren’t responding to anti-VEGF therapy don’t switch to one of these alternatives quickly enough, they could lose visual acuity that might have been preserved. “We may be leaving vision on the table,” Dr. Dugel said. “We don’t have definitive data to show that as yet, but it’s a reasonable assumption based on earlier studies.”
It is not yet clear why some patients with DME respond well to anti-VEGF therapy and some do not, he said. There may be a natural progression of the disease from a primarily permeability driven phase to a primarily inflammation driven phase. Environmental and genetic factors may both play a role and research may lead to other tests.
“At some point we may have a genetic marker or a biomarker, but until then, this gives us an ability to distinguish patients with a high degree of accuracy,” he said.
Pravin Dugel, MD
E: [email protected]
This article was adapted from Dr. Dugel’s presentation at the 2015 meeting of the American Academy of Ophthalmology. Dr. Dugel reports financial relationships with Abbott Medical Optics, Acucela, Alcon Laboratories, Alimera Sciences, Allergan, Digisight, Genentech, Novartis Pharmaceuticals Corp., Ophthotech, Ora, Regeneron and ThromboGenics.