Ziv-aflibercept in macular disease

Abstract

Background/aimsAflibercept is an approved therapy for neovascular age-related macular degeneration (AMD) and diabetic macular oedema (DME). In vitro and in vivo studies did not detect toxicity to the retinal pigment epithelium cells using the approved cancer protein, ziv-aflibercept. Our purpose is to determine if ziv-aflibercept can be used in AMD and DME without ocular toxicity, to test the stability of ziv-aflibercept, and to do a cost analysis.MethodsProspectively, consecutive patients with AMD or DME and poor vision underwent one intravitreal injection of 0.05 mL of fresh filtered ziv-aflibercept (1.25 mg). Monitoring of best-corrected visual acuity, intraocular inflammation, cataract progression, and retinal structure by spectral domain optical coherence tomography was done at 1 day and 1 week after injection. Ziv-aflibercept activity over 4 weeks was measured by capturing vascular endothelial growth factor by ELISA.ResultsThere were no signs of retinal toxicity, intraocular inflammation or change in lens status in four eyes with AMD and two eyes with DME. Visual acuity improved (p=0.05) and central foveal thickness decreased in all patients (p=0.05). Ziv-aflibercept had no loss of anti-VEGF activity when kept at 4°C in polycarbonate syringes over 4 weeks. Similar to bevacizumab, compounded ziv-aflibercept would yield a tremendous saving compared with aflibercept or ranibizumab.ConclusionsOff-label use of ziv-aflibercept improves visual acuity without ocular toxicity and may offer a cheaper alternative to the same molecule aflibercept.Trial registration numberNCT02173873.

Viability of Primary Human Pigment Epithelium Cells and Muller-Glia Cells after Intravitreal Ziv-Aflibercept and Aflibercept

“…In a prospective noncomparative case series of 6 patients (4 with AMD and 2 with refractory diabetic macular edema), intravitreal ziv-aflibercept improved the visual acuity and decreased the central macular thickness. However, the follow-up was only 4 weeks [9] .…”

“…Ziv-aflibercept is a similar fusion protein and has shown promising results in the short term [8,9,11] . In our previous study of intravitreal ziv-aflibercept for diabetic macular edema, all patients experienced improvement in BCVA and decrease in CRT from baseline till 24 weeks of follow-up [11] .…”

“…Even after this in vitro study, consecutive clinical studies had been published demonstrating the safety and efficacy of ziv-aflibercept in the treatment of macular diseases [8][9][10] . For instance, de Andrade et al [10] showed good results in the treatment of diabetic macular edema with ziv-aflibercept resulting in improvement in best corrected visual acuity (BCVA) and reduction in central retinal thickness (CRT) and no signs of ocular or systemic toxicity in all treated patients.…”

Short-Term Safety Profile of Intravitreal Ziv-Aflibercept

“…Some investigators contend that intravitreal injections of ziv-aflibercept solution may be toxic to the retina or uveal tract, but others believe that it might be safe and, therefore, useful against chorioretinal vascular conditions. 15 We believe that intravitreal ziv-aflibercept may be safe and effective when used in human eyes with neovascular AMD, and herein, we present a detailed safety evaluation using sequential clinical evaluations and electroretinographic (ERG) testing after single intravitreal injections.…”

Effect of Intravitreal Ziv-Aflibercept on Choroidal Neovascularization Membrane Secondary to Post Traumatic Choroidal Rupture

“…Clinical trial conducted by Malik et al [3] to address the safety issue of ziv-aflibercept in vivo and in vitro and concluded that there is non-significant RPE toxicity where, Mansour et al [4] has studied the safety of intravitreal Ziv-aflibercept in six patients and all patients, and the results didn't show any signs of retinal, ocular toxicity or inflammation and suggested that the 0.05 ml Ziv-aflibercept is diluted in 4 ml of vitreous when intravitreally injected, thus it is 80 times diluted which means the final osmolarity of 312 mOsm/kg after intravitreal injection of 0.05 ml Ziv-aflibercept, Masnour et al [5] also studied the safety and efficacy of intravitreal ziv-aflibercept in wet age related macular degeneration and concluded that intravitreal ziv-aflibercept can be safe and effective without causing any ocular toxicity. …”