Chhablani, Jay

AbstractZiv‐aflibercept (Zaltrap®), a recombinant fusion protein that binds diffusible vascular endothelial growth factor (VEGF), is approved for the treatment of metastatic colorectal carcinoma. Its molecular structure is the same as aflibercept (Eylea®), thus making it an attractive option for the off‐label treatment of chorioretinal vascular conditions. Ziv‐aflibercept is distributed in 4 and 8 ml vials for intravenous use, and its cost after compounding is similar to bevacizumab. Studies with retinal pigment epithelium cytotoxicity, animal histologic sections and electroretinography have demonstrated its safety, and mathematical modelling combined with over four dozen clinical publications from different ophthalmic centres throughout the world attest to its efficacy. No appreciable differences in visual or anatomic outcomes between 1.25 mg (0.05 ml) and 2.5 mg (1.0 ml) doses have been noted. The long duration of action combined with the low cost make ziv‐aflibercept an attractive anti‐VEGF treatment option, especially in low‐ and middle‐income countries where its popularity is increasing.

Purpose: To evaluate the safety of single intravitreal 2 mg ziv-aflibercept (0.08 mL) injections for the treatment of choroidal neovascular membranes (CNVM). Methods: Eyes with choroidal neovascular membranes because of several conditions each received single intravitreal injections of 2 mg ziv-aflibercept (0.08 mL). Comprehensive ophthalmic examinations and detailed systemic evaluations were performed at baseline and Days 1, 7, and 30 after injections. Standard electroretinography was performed at baseline and Day 30. Primary outcome measures consisted of safety assessments (signs of clinical toxicity and electroretinographic abnormalities). Secondary outcome measures included changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) of the macula. Results: Twenty-one eyes of 20 patients (12 males) received injections. Etiologies responsible for the choroidal neovascular membranes included age-related macular degeneration (14), polypoidal choroidal vasculopathy (PCV) (3), myopia (2), and idiopathic juxtafoveal telangiectasia (2). None of the patients complained of worsening vision or pain after the intravitreal injections and no intraocular inflammation was seen. No significant changes in the electroretinographic b/a ratio from baseline to 1 month were measured (scotopic: P = 0.89; photopic: P = 0.13) and mean intraocular pressures were unchanged (14.2 ± 3.6 vs. 13.7 ± 3.0 mmHg; P = 0.62). Mean best-corrected visual acuity did not change significantly from baseline to 1 month (0.66 ± 0.37 logMAR [Snellen equivalent: 20/100] vs. 0.61 ± 0.35 logMAR [Snellen equivalent: 20/80]; P = 0.72) but significant improvements in central subfield thickness were seen (343 ± 177 vs. 210 ± 133 μ m; P = 0.01). Conclusion: Single intravitreal injections of 2 mg ziv-aflibercept (0.08 mL) appear to be safe through 1 month.

Purpose: To report flattening of a treatment-resistant retinal pigment epithelial detachment (PED) due to neovascular age-related macular degeneration after a single intravitreal injection of ziv-aflibercept (Zaltrap). Methods: A 67-year-old woman with a neovascular age-related macular degeneration–related PED was treated with intravitreal injections of bevacizumab and ranibizumab, and in combination with verteporfin photodynamic therapy, before receiving a single intravitreal injection of ziv-aflibercept (1.25 mg/0.05 mL). Results: The patient presented with a visual acuity of 20/30 in the right eye, a PED height of 581 μm, and a central macular thickness of 381 μm. She received eight intravitreal injections of bevacizumab and ranibizumab, one in combination with photodynamic therapy. The height of the PED and the central macular thickness varied over time, but 3 years later, they measured 382 μm and 418 μm, respectively. A single intravitreal injection of ziv-aflibercept resulted in a dramatic reduction in PED height to 140 μm, which was maintained 2 months later. The visual acuity remained stable, and there were no clinical signs of toxicity. Conclusion: Intravitreal ziv-aflibercept safely and effectively improved a treatment-resistant PED. Intravitreal ziv-aflibercept could become a treatment option for neovascular age-related macular degeneration in countries where aflibercept (Eylea) is not available or its cost is prohibitive, but further studies are necessary to establish efficacy and safety.