ASRS 2026: ILUMIN-8 study shows real-world outcomes of aflibercept 8 mg in diabetic macular edema
Michael Klufas, MD, spoke with Ophthalmology 360 about his presentation at the American Society of Retina Specialists 2026 Annual Meeting on real-world use of aflibercept in patients with diabetic macular edema.
Michael Klufas, MD:
Hi, I’m Dr. Michael Klufas from the Retina Service of Wills Eye Hospital and Mid Atlantic Retina in Philadelphia, Pennsylvania. It’s my pleasure to be here today to discuss a study I presented at the ASRS Annual Meeting in Montreal, Canada.
This was on the real-world use of aflibercept 8 mg in patients with diabetic macular edema. This is also known as high-dose Eylea.
Just a little background on this study. This analysis, it was called the ILUMIN-8 study, aimed to describe the real-world outcomes in patients with diabetic macular edema or DME, in the American Academy of Ophthalmology IRIS Registry. These were patients who initially received aflibercept 8 mg or were previously treated with aflibercept 2 mg and were switched to aflibercept 8 mg.
It’s great to have 8-mg aflibercept in our treatment armamentarium. We want to see how the real-world use compares with clinical trials such as the PHOTON trial, which was the registry trial for the FDA.
A little background on the study design from the IRIS registry during the index period, which was from about September 2024 to September 2025, there were about 30,655 eligible diabetic macular edema patients. With our specific criteria, this was whittled down to about 585 treatment-naive patients and about 3,200 patients who were switched from aflibercept 2 mg.
Patients had to be followed for about 6 months and had to have had adequate follow-up to ascertain the vision. That’s what led to the whittling down of the numbers in this specific study.
If we looked at the overall demographics, there was a comparable number of males and females in each group. It was predominantly a Caucasian population, about 60%, 70%, but there were about 10% Hispanic or Latino and about 13% African-American or Black, and about 3% to 4% who are Asian or Pacific Islanders.
The number of patients with bilateral DME was about 90% as well. The number of eyes that were treated with aflibercept 8 mg in the fellow eye was about 30%.
If we look at the treatment exposure comparing treatment-naive and also switchers, we find that the follow-up duration was quite similar, approximately 66 weeks or so in each group, so they can be compared relatively well.
It’s also important to note that about 15% of the switch eyes received at least 3 doses of aflibercept 8 mg in the first 90 days. This contrasts with about 50% of treatment-naive patients receiving the full loading doses. This is important to real-world treatment because, often in treatment-naive patients, we are performing the full-loading doses, although not every provider in this real-world study did. This may be less likely in our switch population, especially when there are longer treatment intervals present.
It’s important to note that the eyes in the switch population in this study had to have an interval of 6 weeks or longer to represent that extended durability in the real world.
What did we find? With regard to the treatment-naive patients 6 months after initiating aflibercept 8 mg, we found that the injection intervals were approximately 12 weeks after initiating aflibercept 8 mg. I also like to look at the lower quartile, which was closer to 9 weeks, and the upper quartile, which was up to 17 weeks. The mean change in visual acuity was about 5 letters in patients with vision 20/50 or worse and unchanged for patients with vision better than 20/50 at the index date. This makes sense. In many diabetic macular edema trials, vision has to be worse than 20/30 or 20/40 to show an adequate gain of vision.
With regard to patients who received the 3 monthly injections of aflibercept that loading rather than earlier extension, the findings were very similar to the main analysis. The median injection interval in these patients was approximately 11 weeks, and the mean vision change was actually plus-9 letters in those that were visual acuity 20/50 or worse, and the visual acuity was unchanged in those that were 20/50 or better.
This just highlights that some doctors in the real world may allow earlier extension than the loading doses, and we achieve a very similar ultimate treatment at all about 11 or 12 weeks, regardless of whether the patients were loaded with the monthly injections.
Then, moving on to the switch patients. If we looked at the patients who switched from 2-mg to 8-mg aflibercept in this ILUMIN-8 study, we found that injection intervals were extended by about 2 weeks, and the visual acuity was maintained when patients were switched to 8 mg.
A sensitivity analysis was also performed here, on those that were switched to 7 weeks or longer. The whole cohort of the switches had to have been 6 weeks or longer, but if we looked at those that were 7 weeks or longer, the results were not meaningfully different. Patients were actually extended by a little bit longer, 2.9 weeks instead of the average of 2 weeks.
I think it’s important to know some limitations of this study. This is obviously a database study with electronic health records, so this may not reflect a complete medical and ocular history. Also, we have to remember in clinical trials we’re using ETDRS letters. This was routine clinical visual acuity. In the real world, sometimes doctors may switch or patients may switch insurances, and so they may switch on or off aflibercept 8 mg, but the patients in this study had to have consistent treatment for 6 months. These patients, they may have switched or discontinued or not reflected in the current analysis.
There may have been other patients in the real world that may switch from other anti-VEGF agents, but in this current study, patients had to be switched from 2 mg to 8 mg to be included in analysis to allow contextualization of the results. But for instance, this study wouldn’t apply if someone switched from faricimab to aflibercept 8 mg, so that may represent a more common real-world scenario.
In conclusion, in this real-world analysis of the IRIS registry after 6 months, treatment-naive patients with DME achieved an injection interval of 12 weeks, with visual acuity gains and those with vision less than 20/50 at the index date. Patients who were switched to 8 mg previously from 2 mg achieved extensions of at least 2 weeks and up to 3 weeks in some subsets, with a median follow-up of 66 weeks.
We’re looking forward to performing additional analyses to assess the long-term effectiveness and durability of aflibercept 8 mg in treatment-naive and previously treated patients with DME in the real-world setting. Thank you very much for your attention.
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