Michael Singer, MD: Today I have the honor of interviewing my dear friend, Baruch D. "Barry" Kuppermann, MD, who is chairman of ophthalmology at the Gavin Herbert Eye Institute, University of California at Irvine School of Medicine. Dr. Kuppermann, you recently presented fascinating data from the ERYLDEX study. Can you explain it to our readers?
Baruch D. Kuppermann, MD, PhD: Thanks for the invitation, Dr. Singer. ERYLDEX was a retrospective study of 167 patients at 7 clinics in the United States. Like most others, I use anti-VEGF as first-line therapy for diabetic macular edema (DME), but there is a subset of a quarter to a third or even more of patients who have a suboptimal to no response, which is quite frustrating for us and our patients. The concept behind ERLYDEX was to look in a retrospective fashion at the outcomes of patients who were switched to the dexamethasone intravitreal implant (Ozdurex; AbbVie), or DEX-I, after a suboptimal response vs those that were maintained on anti-VEGF therapy. We looked specifically at best recorded visual acuity at weeks 4 and 12, rather than BCVA.
A suboptimal response was defined as having less than 5 letters gained and less than 20% central subfield thickness (CST) improvement on anti-VEGF. Not surprisingly, we saw that those who were switched to DEX-I improved their vision by 8 letters or so, whereas those that were maintained on anti-VEGF therapy did not have any vision gain. Patients who were switched to DEX-I also had a significant improvement in CST by more than 100 µm—120 µm by week 12—whereas those who were maintained on anti-VEGF therapy had a modest decrease in CST.
At week 12, more patients (50%) gained 10 letters if they switched to DEX-I vs 6% of patients who maintained anti-VEGF therapy. More patients (25%) also gained 15 letters if they were switched to DEX-I compared with 4% of patients on anti-VEGF, and fewer patients lost 10 or 15 letters if they switched. No patients on DEX-I lost 10 letters or more at week 12, compared with 10% of patients who were treated with anti-VEGF. Further, no patients in the implant group lost 15 or more letters at week 12, but 8.5% of patients on anti-VEGF lost 15 letters or more.
Again, this was a retrospective study, so it had associated limitations, but it did reconfirm that when you encounter patients with a suboptimal response to anti-VEGF therapy, it is a reasonable strategy to switch them over to the DEX implant.
Dr. Singer: What anti-VEGFs did the patients have? What were they on when they started the trial?
Dr. Kuppermann: Patients were on a wide range of therapies, from bevacizumab (Avastin; Genentech) to ranibizumab (Lucentis; Genentech) to aflibercept (Eylea; Regeneron). They may have gone through step therapy, or whatever was mandated. This was a classic real-world study, which presented limitations and possible selection bias regarding phakic status or risk of cataract and increased IOP, but I would argue that these are great candidates to switch if there is a suboptimal response to anti-VEGF. The strength of the evidence is compelling in terms of drying up the retina, improving vision, and minimizing vision loss.
Dr. Singer: Do we have any incident levels of worsening cataracts or IOP?
Dr. Kuppermann: We do not have that evidence yet.
Dr. Singer: How do these results change or, in your situation, reinforce your point of view of how to treat these patients?
Dr. Kuppermann: They corroborate what I thought before the trial. These results are a reminder to get an OCT at every visit, whatever you use for your definition of suboptimal response, so you can track what is happening to patients’ CST and macular edema. These data also remind me that even though I, like many physicians, delay a switch to the DEX implant to around 6 injections of anti-VEGF, I now think I should be switching patients to DEX-I after 3 injections or so because there is not enough benefit to delay the switch from anti-VEGF therapy.
Dr. Singer: Thank you so much, Dr. Kuppermann. This is valuable data that reinforces, as you said, switching earlier because patients have a chance of getting better vision. Repeated dosing with anti-VEGF does not seem to increase the chance of patients with DME keeping vision over time, so when you run into a wall of not getting improvement with anti-VEGF, we can consider switching earlier.
Dr. Kuppermann: That is exactly right. By switching to the implant after you have made a determination of suboptimal response, you will likely get vision gains and decreased CST, and you can avoid vision loss. It is an important consideration when you take into account that these patients risk losing vision by staying on anti-VEGF therapy. RP
