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 Riemann, MD: Absolutely, Mike. Thanks for the opportunity to discuss this super important trial and the really impactful insights it reveals.
One of the key unmet needs with the fluocinolone acetonide (FAc) implant (Iluvien; ANI Pharmaceuticals) for the treatment of DME has been prospective, head-to-head data compared with anti-VEGF therapy. NEW DAY addressed that by randomizing approximately 300 DME patients into 2 groups. One group received the fluocinolone acetonide implant on day 0 and was followed for 18 months, and the other received 5 monthly loading doses of aflibercept 2 mg (Eylea; Regeneron) and was followed for 14 months afterward. The total duration of the trial was 18 months for both arms.
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, change in OCT anatomy, 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 injection count, 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 including the 5 loading doses.
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 later in follow-up, 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% of aflibercept patients.
Regarding intraocular pressure (IOP), all patients were required to be prior steroid nonresponders before enrollment—so “on label” treatment. The protocol prescribed steroid challenge was difluprednate topical eyedrops for 2 weeks. 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 – ending the study pseudophakic – had the best visual outcomes, regardless of treatment group.
The key takeaway is that although steroids increase cataract risk, visual outcomes after cataract surgery in patients who received FAc were superb and best in class. That’s super useful information.
Dr. Singer: What percentage of patients did not require rescue therapy?
Dr. Riemann: Approximately 60% 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 a key question. NEW DAY did not strictly meet the planned superiority endpoint but it clearly met an ad hoc noninferiority endpoint and it did so with a striking reduction in treatment burden. I’ve long believed steroids are underutilized in DME, and NEW DAY provides prospective level 1 evidence to support their implementation and supporting an earlier switch to FAc.
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. In pseudophakic patients, the data is stunning but even in phakic patients, a switch to FAc is rational, reasonable and may be a good idea.
After discussing cataract risk and the likelihood of good outcomes following surgery, I think it’s reasonable to even consider fluocinolone acetonide as primary therapy in selected patients. Of course, reimbursement remains a practical barrier.
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 four 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 datasets 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 over a decade and now we have prospective, head-to-head data against anti-VEGF 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
