Early Steroid Switch May Improve Visual Acuity for Some DME Patients

SAN ANTONIO — Visual acuity in patients with diabetic macular edema (DME) improved significantly after an early switch to a dexamethasone implant following inadequate response to anti-VEGF therapy, a multicenter retrospective analysis showed.

Best corrected visual acuity (BCVA) improved by 10 letters from baseline and retinal thickening decreased by almost 40% in 58 patients who switched to the dexamethasone implant after as many as three intravitreal injections of bevacizumab or aflibercept (Eylea). Both outcomes also were significantly improved from the time of the switch, reported Shawn Kavoussi, MD, of the Texas Retina Center in Houston, at the American Society of Retina Specialists meeting.

“There is no doubt that anti-VEGF treatment has completely transformed the outlook for millions of patients with retinal vascular disease since the mid-2000s and remains the gold standard and the first-line therapy,” said Kavoussi. “But there are certain patients who just don’t respond, and if steroids are introduced early enough, steroids may be another option.”

Clinical trials of anti-VEGF therapy showed that a proportion of patients with DME derive little benefit from treatment. In the Protocol I EARLY analysis of ranibizumab (Lucentis), about 40% of patients had a less than five-letter improvement in visual acuity at 12 weeks. In the Protocol T EARLY analysis, 25-35% of patients treated with ranibizumab or aflibercept had fewer than five letters of improvement at 12 weeks. In Protocol I and Protocol T, early suboptimal response predicted long-term suboptimal response, said Kavoussi.

“Maybe certain patients need a different mechanism of action,” he suggested.

In Protocol U with ranibizumab, dexamethasone was associated with anatomic improvement but not better visual acuity. However, patients received three intravitreal injections prior to enrollment and another three after enrollment, which meant that all the patients had DME for 6 months or more before exposure to a steroid.

“That begs the question: How about giving steroids earlier?” said Kavoussi.

The question led to a retrospective analysis of 58 patients who had received no more than three anti-VEGF injections, which resulted in a less than five-letter improvement and a less than 200-μm reduction in central retinal thickening (CRT). They were switched to a 0.7-mg dexamethasone implant and followed for at least 6 weeks.

The patients were treated at six different centers, and all of them received either bevacizumab or aflibercept. Baseline BCVA was 55 letters and CRT was 453 μm. After anti-VEGF therapy, mean BCVA improved by only two letters and mean CRT was 412 μm. Neither difference from baseline achieved statistical significance.

Following the switch to dexamethasone, mean BCVA improved to 65 letters (P=0.0001 vs baseline, P=0.003 vs after anti-VEGF treatment) and CRT decreased to 280 μm (P<0.0001 vs baseline and after anti-VEGF treatment).

Kavoussi acknowledged the limitations of a retrospective analysis, but noted that the findings reflect real-world clinical experience with anti-VEGF treatment and dexamethasone. Collectively, the data suggest a larger prospective study might be warranted.

During the discussion that followed the presentation, one of the moderators posed the question of patient selection for early switch to steroids.

“When you think about an early switch, would you base it on the number of injections or the amount of fluid remaining after so many injections? What is your thought process?” asked Sophie J. Bakri, MD, of the Mayo Clinic in Rochester, Minnesota.

“It’s a combination of all of the above,” Kavoussi responded. “There are a lot of options to offer to the patients from anti-VEGF injections to steroid injection to focal laser to PRP [pan-retinal photocoagulation] laser. You have to look at the whole picture. Access to care: How often can patients come in? What is their reticence to receiving monthly injections? Do they want something that is longer acting?”

“We had a great talk earlier about patient loss to follow-up during treatment, but another issue is lost to coming in for the first time,” Kavoussi continued. “We don’t know how long these patients are symptomatic or maybe don’t even realize they have vision loss in one eye before they come through our door for the first time. They may have had 6 months of DME before they reach our chairs, so we have to dry them up as quickly as possible.”