This transcript has been edited for clarity.
Michael A. Singer, MD: For this month’s Retina Minute, I have the honor of interviewing my dear friend, Christopher Riemann, MD, who recently presented data on the NEW DAY trial evaluating fluocinolone acetonide for diabetic macular edema (DME). Chris, can you explain the NEW DAY trial and what you found?
Christopher D. Riemann, MD: Absolutely, Mike. Thanks for the opportunity to discuss this.
One of the key unmet needs with the fluocinolone acetonide (FAc) implant (Iluvien; ANI Pharmaceuticals) has been prospective, head-to-head data compared with anti-VEGF therapy. The NEW DAY trial addressed that by randomizing approximately 300 patients with DME into 2 groups. One group received the fluocinolone acetonide (FAc) implant on day 0, and the other received 5 monthly loading doses of aflibercept 2 mg (Eylea; Regeneron). Patients were then followed for a total of 18 months in the FAc group and 14 months after loading in the aflibercept group, with evaluation of the need for supplemental (rescue) injections.
The primary endpoint was the mean number of supplemental aflibercept injections required from baseline through month 18. Secondary endpoints included total injection burden, proportion of patients not requiring rescue therapy, time to first supplemental treatment, and change in visual acuity.
Baseline characteristics were well balanced between groups. Top-line results showed that the FAc group required a mean of 2.4 rescue injections over 18 months, compared with 2.5 rescue injections over 14 months in the aflibercept group. Despite similar rescue rates, this reflects fewer treatment opportunities in the aflibercept arm due to the shorter follow-up window.
When adjusting for time, there was a 28% reduction in the likelihood of requiring rescue therapy at any given visit in the FAc group. Total injection burden was notably lower: 3.4 injections in the FAc group (including the initial implant) vs 7.2 injections in the aflibercept group due to loading. Time to first supplemental treatment was also longer with FAc—185 days vs 133 days after the final aflibercept loading dose—and this difference was statistically significant.
In terms of visual acuity and OCT outcomes, both groups achieved similar functional and anatomic results. The aflibercept group showed rapid early improvement followed by a “sawtooth” pattern over time, whereas the FAc group demonstrated a slower onset but more stable, sustained anatomic control without fluctuation.
Safety profiles were generally comparable. There was 1 case of endophthalmitis in the aflibercept group and none in the FAc group. As expected, cataract rates were higher with FAc (44% vs 18%), and cataract surgery was performed in 28% of FAc patients vs 7% in the aflibercept group.
Regarding intraocular pressure (IOP), all patients were required to be prior steroid nonresponders before enrollment. Even so, IOP elevations occurred in 15.6% of FAc patients vs 3.3% in the aflibercept group. These were generally manageable with topical therapy; a small number required laser, and a few required incisional surgery.
Dr. Singer: How did cataract development affect visual outcomes?
Dr. Riemann: That’s an important point. Cataract progression can reduce visual acuity, so when we stratified patients, those who remained phakic and developed cataracts experienced declines in vision. However, patients who were pseudophakic throughout—or who underwent cataract surgery during the study—had the best visual outcomes gaining 10 letters, more than any other treatment group.
The key takeaway is that although steroids increase cataract risk, visual outcomes after cataract surgery are excellent. That’s one of the most important findings of the study.
Dr. Singer: What percentage of patients did not require rescue therapy?
Dr. Riemann: Approximately 30% in both groups.
Dr. Singer: Given that the study did not meet its primary endpoint but showed several positive signals, how do you see these data influencing clinical practice?
Dr. Riemann: That’s the key question. I’ve long believed steroids are underutilized in DME, and this study provides prospective level 1 evidence to support their use.
The low-dose fluocinolone acetonide implant delivers continuous corticosteroid for up to 3 years. With similar visual and anatomic outcomes and roughly half the number of injections, I think this supports earlier use—especially in pseudophakic patients.
After discussing cataract risk and the likelihood of good outcomes following surgery, I think it’s reasonable to consider fluocinolone acetonide even as primary therapy in selected patients. Of course, reimbursement remains a practical barrier.
Still, the idea that a substantial proportion of patients can do well without rescue therapy after a single treatment over 18 months is compelling.
Dr. Singer: What about steroid challenge testing? Did this study change your approach?
Dr. Riemann: In the study, patients underwent a steroid challenge with difluprednate 4 times daily for 2 weeks. In my practice, I typically use prednisolone acetate 1% for about 4 weeks.
What’s important here is that this is among the first prospective data sets showing IOP outcomes following a topical steroid challenge before long-acting steroid implantation. The safety profile observed suggests that a topical steroid challenge may be sufficient, potentially avoiding the need for invasive testing with intravitreal steroids.
Dr. Singer: Any final thoughts?
Dr. Riemann: We’re seeing comparable vision and anatomy with significantly reduced treatment burden. In the real world, adherence is a major challenge. If we can achieve similar outcomes with fewer injections, that’s meaningful for patients.
We’ve had a true sustained-release therapy for years. Now we have prospective, head-to-head data supporting its earlier use in appropriately selected patients.
Dr. Singer: Chris, thank you. This is an important discussion and gives us a lot to think about in managing DME. RP
