Sir,

In their interesting article, Ashraf et al1 presented a modifying of the current treatment protocols for central retinal vein occlusion (CRVO). We want to address some issues directly related to the intravitreal therapy with anti-vascular endothelial growth factor (VEGF) agents in patients with CRVOs. The article has several shortcomings that prevent the validation of their results and that can be specifically summarized as follows:

  1. 1

    Nothing was stated regarding the long-term outcomes of the intravitreal therapy with bevacizumab (Avastin, Genentech, Inc., South San Francisco, CA, USA). Even if bevacizumab is unlicensed, it is still currently recommended in CRVO-related macular edema by a majority of retina specialists (56.7%) over ranibizumab (Lucentis, Genentech, Inc.) (22.2%) and aflibercept (Eylea, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA) (15.1%; P<0.0001).2 In 2015, we conducted a prospective clinical study3 on the 3-year results of bevacizumab treatment in patients with acute (≤1 month after the occlusion was diagnosed) central/hemicentral retinal vein occlusions (central/hemicentral RVOs). The results of this study were the first evidence suggesting that the 3-year intravitreal bevacizumab provided sustained vision and anatomic gains in most phakic patients with acute central/hemicentral RVOs.

  2. 2

    With regard to the adequate dose of ranibizumab used, Ashraf et al1 have considered that patients with CRVO respond equally well to the 0.3, 0.5, and 2 mg doses of ranibizumab. Importantly, the Relate study4 reported that visual outcomes were no better after 24 weeks of injections of 2.0 mg ranibizumab every 4 weeks compared with injections every 4 weeks of 0.5 mg ranibizumab. However, 90% of the patients in the 2.0 mg ranibizumab group had central subfield thickness of 320 μm or less compared with 52.6% of the patients in the 0.5 mg group (P=0.03). Considering that the presence of macular edema is mainly guided by anatomical measure data with visual changes as a secondary guide, we believe that the significant difference between the two percentages of patients emphasizes the significantly greater effectiveness of the 2.0 mg dose of ranibizumab in comparison with the 0.5 mg dose in patients with CRVO-related macular edema.

  3. 3

    There were no data on the treat-and-extend (TAE) regimens with intravitreal anti-VEGF agents used in RVOs to reduce burden of treatment on patients and physicians while maintaining effectiveness in the treatment.

  4. 4

    The article by Ogura et al,5 which reported the 18-month results of the Galileo study, was not included in the reference list, although the content of this article was erroneously encompassed in the paper by Korobelnik et al,6 which reported the 1-year results of the Galileo study.

  5. 5

    We do not agree with the assertion made by Ashraf et al1 that aflibercept is the only anti-VEGF agent tested in ischemic CRVO patients in randomized clinical trials. Of note, the Galileo and Copernicus trials, which were thoroughly presented by Ashraf et al,1 and where aflibercept was used, included a very small percentage of ischemic occlusions, that is, 8.2% and 15.5%, respectively. On the other hand, our prospective study published in 20153 included 50% patients with ischemic occlusions. Based on the evidence, we concluded for the first time that bevacizumab was more effective in patients with ischemic occlusions who still required a significantly higher number of injections.

  6. 6

    The benefits of switching to aflibercept have not been clinically proved. Most of the study cited by Ashraf et al1 included a small number of patients, and the largest study quoted (Papakostas et al7) was retrospectively conducted with a possible existence of a bias and reported poor visual and anatomic results (a gain of approximately five letters in visual acuity; persistent macular edema in 45% of cases; and significant thinning of the retina (macular fibrosis? epiretinal membrane formation?) in 16.6% of cases).

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