One-year treatment outcomes of ziv-aflibercept for treatment-naïve macular oedema in branch retinal vein occlusion.

Abstract

Intravitreal ziv-aflibercept (Zaltrap; Regeneron, Eastview, New York, USA), an FDA-approved chemotherapeutic agent for metastatic colorectal cancer, has previously demonstrated therapeutic efficacy in the management of neovascular age-related macular degeneration (AMD) (de Oliveira Dias et al. 2016) and diabetic macular oedema (DME) (Andrade et al. 2016; de Andrade et al. 2017; Ashraf et al. 2016, 2017). To the best of our knowledge, only one report has described the use of ziv-aflibercept in treatment-naïve branch retinal vein occlusion (BRVO)-associated macular oedema, demonstrating favourable structural and functional outcomes (Andrade et al. 2016; de Andrade et al. 2017). However, its longer-term efficacy and safety data is currently lacking. We conducted a prospective pilot study involving 11 treatment-naïve patients (11 eyes) with BRVO-associated macular oedema. All eyes were treated with 0.05 ml ziv-aflibercept (1.25 mg) on a pro re nata (PRN) regimen from the first injection, for 12 months. Monthly monitoring visits were scheduled. At each visit, Snellen visual acuity (VA) assessment, slit-lamp and dilated fundus examinations, tonometry, and optical coherence tomography imaging were conducted. Retreatment indication was based on persistence or recurrence of macular oedema, increase in central macular thickness (CMT) by >50 μm, or worsening of VA by Snellen equivalent of 0.1 logMAR (i.e. five letters). The primary endpoints were VA and CMT at the 12-month visit. The secondary endpoints included total number of injections, change in intraocular pressure (IOP), and incidence of systemic and ocular adverse effects. Our cohort (seven males and four females; all Caucasian) had an average age of 58.6 ± 9.4 years (range, 42–77). At baseline, the average logMAR VA was 0.62 ± 0.22 (Snellen ≈ 20/80), and CMT was 586.0 ± 162.3 μm. Twelve months later, logMAR VA improved by 0.33 ± 0.22 to 0.29 ± 0.21 (Snellen ≈ 20/40) (p < 0.001), equivalent to a gain of +16.5 ETDRS letters. Also, CMT decreased by 271.9 ± 101.8 μm to 231.3 ± 48.4 μm (p < 0.001). The average number of injections through 12 months was 3.3 ± 1.6 (range, 2–7). No systemic or ocular adverse effects were noted, and IOP remained unchanged over 12 months (Table 1). As some cases of BRVO macular oedema pursue a self-resolving course, a PRN rather than fixed-dosing schedule may be sufficient to achieve favourable visual outcomes and minimize treatment burden. Importantly, our results were largely similar to that in the VIBRANT trial (Clark et al. 2016), in which BRVO cases treated with fixed-dosing aflibercept monthly for 6 months, followed by bimonthly for the next 6 months, had VA gains of +17 letters, and CMT decrease by 283.9 μm. The outcomes with ziv-aflibercept also compare well with that of PRN bevacizumab and ranibizumab for centre-involving macular oedema in BRVO in the MARVEL study (Narayanan et al. 2016). At 12 months, ranibizumab and bevacizumab achieved VA gains of +18.9 and +16.1 letters, and CMT reductions of 165.7 and 184.8 μm, respectively. The number of ziv-aflibercept injections for ranibizumab and bevacizumab were 3.5 and 3.3, respectively. Interestingly, the reduction in CMT with a PRN ziv-aflibercept regime was higher than that achieved by PRN ranibizumab and bevacizumab in MARVEL. In previous reports, electroretinography (ERG) testing in AMD and DME patients treated with ziv-aflibercept found no evidence of retinal toxicity through 6 months (Andrade et al. 2016; de Andrade et al. 2017; de Oliveira Dias et al. 2016). While ERG was not employed in our cases, we observed no ocular adverse events of inflammation or ocular hypertension. In summary, our results support the use of PRN ziv-aflibercept for macular oedema secondary to BRVO. As ziv-aflibercept is considerably more affordable than aflibercept, there is vast potential for it to significantly impact visual loss from BRVO, especially in resource-poor countries. A Phase 1 study based on a larger cohort should be conducted to further investigate dose ranges and confirm its safety profile.