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    A multicenter study adds evidence that intravitreal ziv-aflibercept, a low-cost formulation of aflibercept originally developed as a systemic chemotherapy agent, is safe for treatment of retinal diseases.

    Study design

    Investigators from 3 centers enrolled 60 consecutive patients (65 eyes) with neovascular AMD, DME, CME associated with CRVO, or pseudophakic CME. Subjects received 6 or more injections of 0.05 mL ziv-aflibercept and were followed a minimum of 6 months. Treatment patterns adhered to each center’s protocol for the respective disease entity.


    The study found significant improvements in central macular thickness (CMT) and BCVA after treatment with ziv-aflibercept at the 6-month (65 eyes) and 9-month (19 eyes) visits. Although there was not a statistically significant difference in mean vision and CMT at 12 months, there was a very small sample size at this time point (7 eyes). No adverse systemic effects were found. The only adverse effect noted during the study was a single episode of transient iritis noted in a patient after their 4th injection; they experienced no recurrent iritis after further doses.

    There were previous concerns about using ziv-aflibercept due to the use of sucrose in the buffer solution, resulting in a high osmolarity (1000 mOsm/kg) that is toxic to most cells. However, the effect of injecting 0.05ml of ziv-aflibercept only increases the osmolarity in the vitreous cavity by 4%, which is theoretically within a safe range. No retinal toxicity was noted in this study.


    While the results are encouraging, studies with larger cohorts and longer follow-up are needed to establish ziv-aflibercept as a safe and effective anti-VEGF option. Longitudinal electroretinogram testing in patients receiving ziv-aflibercept injections would provide more comprehensive support for the drug’s safety profile.  

    Clinical significance

    The cost of branded intravitreal anti-VEGF medications is significant and often prohibitive for patients without insurance coverage or those in developing nations. Having another generic anti-VEGF medication would be helpful to reduce medical cost and increase patients’ access to treatment.