Sir,

We thank Dr Calugaru for his comments regarding our recently published article on ‘Aflibercept in persistent neovascular AMD: comparison of different treatment strategies in switching therapy’.1 The comments of Călugăru et al2 deserve additional clarifications.

In our study, we decided to retrospectively evaluate and report the types of the CNV and the presence of PED that are both, in our opinion, fundamental in the characterization of the neovascular lesions included in the analysis. No patients presented hemorrhagic serous detachment or disciform scars (this latter represents one of our exclusion criteria as we supposed that there are no active lesions still). As reported, only patients with persistent intraretinal cysts and/or serous detachment of the neurosensory retina have been switched to aflibercept and included in the analysis.

We are aware that the baseline characteristics of our patients present many differences. However, only the baseline OCT CRT values were significantly higher in the fixed in comparison with the PRN group. All the other baseline characteristics were not statistically different (age, gender distribution, number of injections, time between CNV diagnosis and the first aflibercept, CNV type, proportion of PED, and BCVA).

We underlined in the Discussion section that the current study was not designed to compare the efficacy of the two treatment regimens in a randomized trial. However, we believe that our data are of value because they represent the result of an exploratory analysis on the effects of a PRN regimen as an alternative to a Fixed Regimen in eyes with persistent CNV activity despite multiple ranibizumab injections in a real setting. In addition, the involvement of two separate retina departments, even if currently taking part in clinical trials, and the separate enrollment of patients in each center, could introduce other biases.

Currently there is no agreement on which outcomes, among the morphological and the functional ones, could be considered the best in the assessment of the results of a treatment, mostly in previously treated eyes.

However, we agree that, specifically in this population, the evaluation of the outcomes could be guided primarily by the anatomical data as the functional ones might be influenced by additional factors (disease duration, number of treatments, characteristics of the lesion, and so on).

Regarding our anatomical findings and the differences in the final median CRT values, we considered the mean change in CRT from the baseline a good indicator of the response, to avoid the influence of the mean baseline value, which was higher for the fixed than in the PRN group (480 vs 346 μM). In fact, we found that the CRT mean change by month 12 was similar (P=0.20) in the PRN (median −66.5; 95% CI −111/−20) as well as the Fixed Regimen group (median −81; 95% CI −146/−40). In addition, even if the absolute CRT reduction was higher in the Fixed Regimen group (148 vs 94 μM), the proportion of the thickness reduction was similar in the two groups (−30.8% in Fixed and −27.2% in PRN regimen) (P=0.20).

We can not conclude from our data, considering only the final CRT values, that patients treated with the fixed regimen had unresolved macular edema and the disease process was still active.

Moreover, we agree that PRN determined a greater proportion of dry macula in comparison with the fixed regimen, but despite this difference, the proportion of dry patients between groups was not statistically significant at the end of follow-up (P=0.23).

We also agree that PRN determined a greater number of complete PED flattening, however, on the other hand, a greater reduction in the median subfoveal PED height was achieved at the 12-month visit in the Fixed Regimen (186 vs 90 μM, 52% reduction) in comparison with the PRN regimen (262 vs 174 μM, 31.9% reduction).

For all these reasons, we reported in our conclusions that at 12 months of follow-up, both treatment strategies determined an overall stabilization of visual acuity and an improvement in the morphological findings. We agree that the PRN regimen demonstrated to be also a good choice in the management of switched eyes.