Sir,

We thank Dan Călugăru and Mihai Călugăru for their insight into our publication; however, we disagree with several of the points they made.

There is no clear data showing the greater efficacy of switching to steroids versus aflibercept in cases of chronic DME refractory to bevacizumab/ranibizumab therapy (Table 1). In addition, steroids are known to cause complications such as elevated IOP as well as cataracts which is a limitation to their use particularly in phakic patients. The exact timing of this switch is particularly important because as suggested by the FAME study, chronic edema is estimated to begin 1.73 years post the start of edema.1 Patients treated with steroids in the FAME study who had edema <3 years failed to show anatomic or visual gains compared with the sham group. Only patients who had edema >3 years responded significantly. If we were to consider the definition suggested, patients are expected to have received at least 19 prior injections before steroids would be a valid option. In the study by Rahimy et al2 patients had a previous median of 13 injections which would fall within the predicted margin of non-chronic edema. Therefore, it is important to have a clear definition for chronic and refractory edema because the two are not mutually exclusive. It would be expected that steroids would not be as effective in early switching. With regards to late switching, its superiority should be assessed using a randomized control trial, with the understanding that before such a trial clear definitions have to be pre-determined.

Table 1 Summary of the major studies that looked at switching between intravitreal drugs in diabetic macular edema
Full size table

Although it is tempting to class all anti-VEGFs together and that they are all fairly interchangeable, recent data from protocol T has demonstrated significant anatomical differences between aflibercept, ranibizumab, and bevacizumab during the first year especially for patients with baseline VA <20/40 (6/12).3 The exact reason for this difference although speculative cannot be disregarded (CFT <250 microns in 70% of cases treated with aflibercept compared with 60% for ranibizumab and 50% for bevacizumab). It also highlights the anatomic effectiveness of aflibercept in resolving edema, especially in patients with high volumes of residual fluid.4

With regards to switching, the study by Rahimy et al showed that 25% of patients achieved dryness, whereas 56% showed improvement.2 Wood et al showed that 80% of eyes showed some improvement in anatomy.5 This anatomic improvement in a significant percentage of patients is worth exploring before switching to steroids, which has been shown in the switch studies to cause increased IOP in ~20–25% of cases with many patients requiring re-treatments (Table 1).

Finally, switching in DME has not been extensively studied; AMD has over 40 publications that have tackled switching to aflibercept compared with only 3 in DME.5, 6, 7 This issue warrants more studies and more data before reaching a definitive conclusion regarding the efficacy and timing of switching. However, it remains a valid first option in non-responsive cases before steroid switch.