We thank Drs Dan and Mihai Călugăru for their interest and comments regarding our recent publication titled “Conversion to aflibercept after prior anti-VEGF therapy for persistent diabetic macular edema.”
As a point of clarification to the authors’ correspondence, it is incorrect to state that “56% of the eyes [were] lost over 4.6 months of subsequent follow-up.” The objective of the current study was to report our initial short-term clinical experiences with aflibercept in a subpopulation of patients with persistent diabetic macular edema (DME) largely unresponsive to previous, approximately monthly anti-VEGF therapy. Patients in this study were not lost to follow-up. Rather, their duration of follow-up was directly dependent on when the decision was reached to switch therapy and the number of aflibercept injections that were administered thereafter until the time the data were gathered. Many of these patients have continued to receive injections through the present day. We do agree with the authors that the follow-up data were limited in length after transition, and we fully discussed the possibility of tachyphylaxis or tolerance developing in response to the aflibercept. Longer-term follow-up will help elucidate whether that is the case or whether these improvements will be sustained or potentially even further advanced upon.
To address the optical coherence tomography (OCT)-related comments, we elected not to discuss the anatomic subtypes of macular edema present within the manuscript owing to the low overall numbers in this series. That being said, at the visit where therapy was switched to aflibercept, 6 of the 50 eyes (12%) had persistent subretinal fluid. After they had received the second injection of aflibercept, the subretinal fluid had resolved in all of these eyes and, furthermore, did not develop in any other study eyes during the remaining duration of follow-up. With respect to the percentage of eyes with central macular thickness (CMT) ≤320 μm, 6 eyes (12%) were at or below this threshold prior to aflibercept conversion. After the second aflibercept injection, 22 of the 50 eyes (44%) had achieved this level.
Although we did see significant morphologic improvements on OCT imaging, this did not translate into a significant visual benefit, at least during the short course of follow-up, as the authors duly noted. The most likely explanation for this disparity, as we proposed, is some degree of irreversible functional damage caused by long-standing DME. As discussed in our paper, we emphasized that the eyes included in this study had received a mean of 13.7 injections of bevacizumab/ranibizumab prior to transitioning over to aflibercept and had chronic exudation. Interestingly, however, we did observe that in the subset of 22 eyes that received at least 4 aflibercept injections after conversion, a visually significant improvement in mean logarithm of the minimal angle of resolution visual acuity was observed compared to the pre-switch vision (0.65 vs 0.80, P = .003). In this regard, it is possible that the short-term follow-up available was not sufficient to uncover a delayed-onset recovery in vision, or “function lagging behind form.”
As the authors stated, and we fully agree, these points highlight the necessity of early detection of DME and prompt institution of therapy, as delays in treatment can lead to less-than-optimal functional outcomes. However, one must be cognizant of the fact that some patients are noncompliant or delay seeking appropriate care, which can affect “real-world” outcomes. We are currently in the process of analyzing 1-year outcomes in this cohort, which we hope to submit for publication in the near future.