We would like to address several challenges arising from the interesting study by Hoerauf and associates, which can be specifically summarized as follows:

We do not agree with the assertion made by the authors that the Horizon and Retain studies have highlighted maintenance of the visual gains in central retinal vein occlusion (CRVO) over a period of 4 years. Thus, in the Horizon study, which was a 12-month extension of the Cruise study, there was a decrease in the best-corrected visual acuity (BCVA) score, with -4.2, -5.2, and -4.1 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the 3 groups of patients, namely, sham/0.5 mg of ranibizumab (Lucentis; Genentech, Inc, South San Francisco, California, USA) or 0.3 mg and 0.5 mg of ranibizumab, respectively. At the end of the Retain study, which extended the follow-up to 51.4 months after the Cruise baseline, 56% of patients had reduced visual potential, with 6 patients experiencing a reduction in the BCVA score of -33, -18, -11, -4, -3, and -3 ETDRS letters.

Regarding the treatments applied to the 2 study groups, there was a bias that favored patients treated with ranibizumab. These patients were treated with an aggressiveness ranked as approximately one half of the standard aggressiveness definitely set by the level 1 evidence of the pivotal Cruise study (eg, a mean of 4.52 injections including the mandatory 3 monthly injections). In comparison, patients in the dexamethasone (Ozurdex; Allergan, Inc, Irvine, California, USA) group were insufficiently treated, receiving only a single implant, and thus being impeded from achieving maximally visual benefits. Importantly, the currently valid recommendations, that the duration of ≥3-line visual improvement after dexamethasone implant is typically 2–3 months, and that reinjections generally will be performed after 4–5 months, have not been taken into account. If these assertions had been considered, the design and outcomes of the present study would have been completely different.

The visual results of ranibizumab therapy in the present study were better than those in the Cruise study (larger proportions of patients who gained ≥15 ETDRS letters, higher BCVA improvements), although the percentage of patients with retinal ischemia at baseline was greater in the present study (18.2% vs 1.5%) while applying a less aggressive treatment with a smaller number of injections (4.52 vs 5.5). Interestingly, the results of this study highlighted better visual improvements than those in the Cruise study using a less aggressive therapy. These changes could be explained by the shorter duration of time from CRVO diagnosis to initiation of the therapy, namely, ≤6 months before screening in the ranibizumab group and ≤12 months in the Cruise study.

Altogether, this study brought relevant arguments to support the currently available concepts, namely, the median time of 98 days to achieve significant visual gains; a great number of dropouts (39.5%) because of treatment failure at visits 5, 6, and 7 carried out monthly at the end of the follow-up; and a decline of dexamethasone efficacy substantiated in terms of decreasing visual improvements and increasing central subfield retinal thickness after implantation from month 3 onwards.