Comment on: ‘central retinal vein occlusion: modifying current treatment protocols’

SIR, In their interesting article, Ashraf _et al_1 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 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 With regard to the adequate dose of ranibizumab used, Ashraf _et al_1 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 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 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 We do not

agree with the assertion made by Ashraf _et al_1 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 The benefits of switching to aflibercept have not been

clinically proved. Most of the study cited by Ashraf _et al_1 included a small number of patients, and the largest study quoted (Papakostas _et al_7) 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). In conclusion, central/hemicentral RVO has to be considered an ophthalmic emergency. Therefore,

therapy with anti-VEGF agents has to be promptly applied as soon as possible after RVO onset. Regardless of the anti-VEGF agents used (ranibizumab/aflibercept/bevacizumab), and regardless of

the treatment approaches chosen (TAE/pro re nata algorithm), the efficacy of therapy depends primarily on the precociousness of the therapy after RVO diagnosis. AUTHOR CONTRIBUTIONS Both

authors (DC and MC) were involved in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the

manuscript. REFERENCES * Ashraf M, Souka SSR, Singh RP . Central retinal vein occlusion: modifying current treatment protocols. _Eye_ 2016; 30: 505–514. Article  CAS  Google Scholar  * Wang

MD, Jeng-Miller KW, Fend HL, Prenner JL, Fine HF, Shah SP . Retina specialists treating cystoid macular oedema secondary to retinal vein occlusion recommend different treatments for patients

than they could choose for themselves. _Br J Ophthalmol_. e-pub ahead of print 30 December 2016; doi:10.1136/bjopthalmol-2015-307849. * Călugăru D, Călugăru M . Intravitreal bevacizumab in

acute central/hemicentral retinal vein occlusions: three-year results of a prospective clinical study. _J Ocul Pharmacol Ther_ 2015; 31 (2): 78–86. Article  Google Scholar  * Campochiaro PA,

Hafiz G, Mir TA, Scott AW, Solomon S, Zimmer-Galler I _et al_. Scatter photocoagulation does not reduce macular edema or treatment burden in patients with retinal vein occlusion. The Relate

trial. _Ophthalmology_ 2015; 122 (7): 1426–1437. Article  Google Scholar  * Ogura Y, Roider J, Korobelnik JF, Holtz FG, SImader C, Schmidt-Erfurth U _et al_. Intravitreal aflibercept for

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Korobelnik JF, Holz FG, Roider J, Ogura Y, Simader C, Schmidt-Erfurth U _et al_. Intravitreal Aflibercept Injection for macular Edema Resulting from Central Retinal Vein Occlusion: One-Year

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Article  CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Ophthalmology, University of Medicine, Cluj-Napoca, Romania D Călugăru & M

Călugăru Authors * D Călugăru View author publications You can also search for this author inPubMed Google Scholar * M Călugăru View author publications You can also search for this author

inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to M Călugăru. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. RIGHTS AND PERMISSIONS

Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Călugăru, D., Călugăru, M. Comment on: ‘Central retinal vein occlusion: modifying current treatment protocols’. _Eye_ 30,

1395–1396 (2016). https://doi.org/10.1038/eye.2016.83 Download citation * Published: 22 April 2016 * Issue Date: October 2016 * DOI: https://doi.org/10.1038/eye.2016.83 SHARE THIS ARTICLE

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