We appreciate the interest of Drs Călugăru in our recently published COMRADE-C trial comparing the clinical efficacy and safety of ranibizumab vs dexamethasone in macular edema secondary to central retinal vein occlusion (CRVO).

We acknowledge that the HORIZON study showed a 4.2-letter loss in the CRVO group. However, compared with baseline there was still a 12-letter increase, which is superior compared with the natural course in CRVO. Consideration should also be given to the small number of patients followed in the HORIZON study compared with the original CRUISE trial. In conclusion, the given letter reduction between months 12 and 24 in this subgroup of the original trial cohort with an unknown selection bias cannot be judged as a significant visual loss in a heterogenous disease such as CRVO with a possibility of conversion to ischemia in 34% within 3 years.

Thirty-two patients with CRVO were included in the RETAIN study and data were available for 28 patients 4 years after the CRUISE baseline study. A total of 53.1% of these patients treated with ranibizumab gained 15 letters or more, which in our opinion is excellent. A detailed analysis of the 6 patients with functional worsening compared with the CRUISE baseline study is provided in the RETAIN paper. Four of these patients were graded as nonresponders, resulting in a central scar formation, 1 converting to ischemia and another to an epiretinal membrane.

We are of the opinion that intravitreal anti-VEGF treatments provide good long-term outcomes in a high percentage of CRVO patients. However, a subgroup of CRVO patients who do not respond to anti-VEGF treatment could benefit from an early switch to intraocular steroids. We do not agree with the authors’ assumption that ischemic eyes shouldn’t be treated with anti-VEGF drugs. Campochiaro and associates showed that under ranibizumab treatment the nonperfused areas in RVO patients were reduced compared with control.

Earlier retreatment in the dexamethasone implant group could have improved the visual acuity results at month 6, but we believe adverse effects would have occurred more often. However, the study was designed to treat patients according to their specific European Summaries of Product Characteristics. We believe that our COMRADE-C trial results are of importance, since no monthly data about the efficacy of the dexamethasone implant in the GENEVA study are available. Our study provides the first direct comparison between both intravitreal drugs on a monthly basis with regard to anatomic and functional response over 6 months of treatment.

Our study achieved superior visual outcomes in the ranibizumab group compared with other pivotal trials. Most probably the exclusion of CRVO patients with a disease duration longer than 3 months in our study was one of the main reasons for the beneficial results. The fact that, despite a higher percentage of ischemic patients than in the CRUISE trial, the presented visual results are better herein are in accordance with the findings of the CRYSTAL study.

A thorough subanalysis of COMRADE-C and B focusing on retinal ischemia is currently underway. Preliminary data will be presented at the Club Jules Gonin meeting in July 2016.