Author Response: Functional and Anatomic Outcomes in Patients With Serous Retinal Detachment in Diabetic Macular Edema Treated With Ranibizumab

We appreciate the interest of Ashraf¹ in our recent publication of outcomes from the Ophthalmology Department of Avicenne Hospital in France, entitled “Functional and anatomical outcomes in patients with serous retinal detachment in diabetic macular edema treated with ranibizumab.”² 

We agree with several of his assertions, but we would like to clarify some points that we developed in our discussion. 

We agree that the post hoc analysis of the RISE and RIDE studies³ on the impact of subretinal detachment (SRD) in diabetic macular edema (DME) showed that patients with SRD treated monthly with ranibizumab were more likely to achieve a final visual acuity (VA) of >20/40 in contrast with patients with SRD in the sham group, who were more likely to achieve a low final VA of <20/100. We did not dispute these results. However, our study found the same visual gain in both groups (with or without SRD), which is why we carefully concluded that “SRD does not seem to be a good prognostic factor during DME treatment with ranibizumab with a PRN regimen and in a real-life setting.” Also, we would like to insist on the fact that we used a PRN regimen based on VA in a real-life setting, involving, as Ashraf¹ suggested, a potential undertreatment of our patients (between 5.2 and 5.5 injections over 1 year) versus 12 injections in RISE and RIDE studies.⁴ However, our number of intravitreal injections over the first year, although low, is consistent with those reported in previous real-life studies (5.4⁵–7.2⁶ injections over the first year). Like Ashraf,¹ we are convinced that SRD could be a good visual outcome prognostic indicator under monthly ranibizumab therapy, and a poor prognostic factor resulting in severe visual loss in patients who do not receive anti-VEGF^3,7 or any DME treatment, and our patients with SRD probably would have needed more injections to significantly improve their VA compared to patients with DME without SRD. 

Regarding our results, Ashraf¹ considered our SRD+ group as undertreated before inclusion, because the eyes received less laser photocoagulation. However, we only performed focal photocoagulation in case of extracentral macular edema with vision loss threat in these eyes (no grid), before they experienced central edema with vision loss, or 6 months after initiation of intravitreal treatment if the extracentral edema still was present. So, we considered that if patients received less laser in the SRD+ group, this means that they would have less needed laser, and this is not undertreatment but a lower need for treatment in this case. Also, for more accuracy about the type of edema, we would like to specify that all our eyes included had central cystoid macular edema associated or not with SRD, and not diffuse edema, and, thus, both groups were homogeneous regarding this parameter. 

Another major interesting point highlighted by Ashraf¹ is that our retreatment criteria were based only on VA and if we had used a protocol based on visual and anatomic parameters to guide retreatment, SRD would have been associated with better visual outcomes. However, at the time of the study we followed the European guidelines⁸ based on the results of the RESTORE study,⁹ recommending retreatment based on VA outcomes. We agree on this point with Ashraf¹ and our results support it, with still 26.5% of SRD persisting after 1 year of follow-up despite treatment, for which a more aggressive treatment would have been beneficial. 

Finally, our study was retrospective and not a prospective randomized controlled trial. This design has some limitations and we were not able to match our patients on anatomic predictive factors, such as disorganization of inner retinal layers (DRIL).¹⁰ However, the regression of the DRIL size correlated with a better visual improvement, and we focused on baseline predictive factors rather than on evolving factors, such as DRIL. Moreover, we agree that since no large prospective studies assessing predictive factors of response to anti-VEGF in DME are available, but only retrospective studies or post hoc analyses, and since there is no real consensus on the subject, prospective studies taking into account the need to control important anatomical parameters, such as DRIL for instance, are needed.