The results of the current paper have shown that DEX implant may be a valuable option for treating patients with DME who have not completed the standard anti-VEGF loading dose regimen.
COVID-19 has posed a global public health threat due to the severity of its contagion and associated morbidity and mortality [16, 17]. In fact, the volume of outpatient and surgical procedures has significantly decreased during the pandemic . In most ophthalmic centers, provision of care was restricted to urgent or emergency cases .
Anti-VEGF intravitreal injections are currently considered the standard of care for patients with DME . However, since unintentional treatment interruptions can result in severe adverse visual sequelae [22, 23], evaluation of alternative longer-term therapy is crucial for achieving optimal clinical outcomes among patients with DME . The positive effect of switching to DEX implant in eyes with persistent DME unresponsive to anti-VEGF therapy has been previously reported [17,18,19,20]. Switching to DEX implant has also been shown to result in better anatomical outcomes over those of continued anti-VEGF therapy [24,25,26]. In the current study, the indication for switching was not due to lack of efficacy, but rather the patient’s inability to comply with a routine monthly anti-VEGF therapy.
Although, when comparing to those eyes that underwent the standard anti-VEGF therapeutic regimen, switching to DEX implant did not lead better BCVA improvement or CRT reduction, it is noteworthy that one DEX implant significantly improved both functional and anatomic clinical outcomes in those eyes that did not complete anti-VEGF loading dose.
In the DEX group median BCVA improvement between pre- and post-anti-VEGF therapy was not statistically significant (Hodges–Lehmann median difference 5.0 letters, 95% CI − 0.6 to 9.5 letters, p = 0.097). Nevertheless, there was significant reduction in CRT after anti-VEGF injections (Hodges–Lehmann median difference 117.3 µm, 95% CI 44.0 to 191.0 µm, p = 0.002).
Moreover, after adjustment for age, previous laser, and baseline BCVA, mean BCVA improvement was greater in those eyes that were switched to DEX than in those who underwent anti-VEGF loading dose (mean difference 1.99 letters, 95% CI − 8.85 to 12.83), although such a difference was not statistically significant (p = 0.712). However, the power to detect significant differences with the observed values was 7%. Similarly, after adjustment for age, previous laser, and baseline CRT, there were no significant differences in mean CRT reduction between DEX and anti-VEGF groups (mean difference 62.0, 95% CI − 39.6 to 163.6, p = 0.224); however, as happened with BCVA, our study was underpowered to detect such a difference (24%).
Regarding safety, there were no unexpected adverse events and there were no differences between groups in either incidence of ocular hypertension or cataract/lens opacification or loss of BCVA.
According to the European Society of Retina Specialists (EURETINA) guidelines , anti-VEGF treatment should be initiated early on with monthly injections, and in those patients who experience positive anatomic and/or functional outcomes, continuing with monthly injections until visual acuity and/or OCT stability is reached. This raises the question of whether anti-VEGF treatment can be continued or should it be restarted? In any case, this would require monthly visits, which during the pandemic would not be possible. Therefore, having a therapeutic alternative, like DEX implant, which provides good anatomical and functional outcomes in both treatment naïve and anti-VEGF refractory patients with DME may be considered as a valuable alternative [12, 20, 27].
The most important limitations of the current study are its retrospective design and small sample size. Selection bias and confounding factors are inherent to retrospective studies; nevertheless, strict inclusion/exclusion criteria aimed to minimized such issues. Additionally, our small sample size also limits the power of the analysis. In fact, with the observed pooled standard deviation and the number of eyes included in each group, the power to detect a mean BCVA improvement of 5 ETDRS letters or a CRT reduction of 25 µm between DEX and anti-VEGF groups, with an alpha error of 0.05 in a bilateral contrast, would be 14% and 8%, respectively. Therefore, further investigations with a larger number of recruited patients would be needed. It should be mentioned that our study did not evaluate the role of OCT biomarkers, which may provide valuable information about the predictive capacity of DEX response. Different OCT biomarkers, such as disorganization of retinal inner layers  or ellipsoid zone integrity [29, 30], may predict anatomic and functional outcomes after treatment with DEX implants. This information may be extremely useful, particularly in these times, when the pandemic limits our consultation capacity and it is crucial for optimizing our resources.