AIM: To report the efficacy of intravitreal ziv-aflibercept injections in eyes with macular edema due to retinal vein occlusions (RVOs).
METHODS: Consecutive patients with persistent or recurrent macular edema (central macula thickness >250 μm) due to RVO were enrolled in this prospective study. Study eyes received intravitreal injections of ziv-aflibercept (1.25 mg/0.05 mL) at baseline. Patients were reassessed monthly for 4 months and given additional injections pro re nata for worsening best-corrected visual acuity (BCVA), intraretinal edema or subretinal fluid seen on spectral domain optical coherence tomography, or central macular thickness (CMT) measurements >250 μm. The primary endpoint was improvement in mean CMT at 4 months. Secondary endpoints included improvement in mean BCVA, and ocular and systemic safety signals.
RESULTS: Nine eyes (five central and four branch RVOs) of nine patients were enrolled. The mean ± standard deviation CMT decreased from 604±199 μm at baseline to 319±115 μm (P=0.001) at 1 month and to 351±205 μm (P=0.026) at 4 months. The mean BCVA did not improve significantly from baseline (1.00 LogMAR) to the 1-month (0.74 LogMAR; P=0.2) and 4-month (0.71 LogMAR; P=0.13) visits. No safety signals were noted.
CONCLUSION: In this small prospective study, intravitreal ziv-aflibercept significantly improved mean CMT in eyes with persistent or recurrent macular edema due to RVOs. Prospective, randomized trials comparing ziv-aflibercept with standard pharmacotherapy are needed to better define efficacy and safety.
Strengths
The Methods describe a prospective two-center study with IRB approval, written informed consent, monthly follow-up, and clinical trial registration. This gives the case series more procedural transparency than a retrospective report.
↳ Methods, first paragraph; Clinical Evaluations and Treatments
The Results report a substantial decrease in mean CMT at 1 and 4 months with P-values, while also reporting that BCVA did not improve significantly. This separates the anatomic signal from the weaker functional outcome.
↳ Results, Visual Acuity; Results, Macular Thickness
The Discussion explains why aflibercept access is limited in some countries and compares the per-vial costs of ziv-aflibercept, aflibercept, and bevacizumab. That creates a clear real-world motivation for studying the intervention.
↳ Discussion, affordability paragraphs
Limitations
The study has no comparator arm and includes only nine eyes, so the observed CMT improvement cannot be separated from regression to the mean, natural disease fluctuation, or residual effects of prior therapies.
↳ Methods, study design; Results, Baseline Characteristics
The cohort pools five CRVO and four BRVO eyes despite different disease characteristics, and prior injections ranged from 2 to 24 with last treatment 1 to 63 months before enrollment. This limits attribution of response to ziv-aflibercept and weakens subgroup inference.
↳ Results, Baseline Characteristics; Discussion, strengths and weaknesses paragraph
The Discussion says the data support use in selected RVO patients, but the paper itself acknowledges the small cohort, mixed composition, and brief endpoint. That phrasing is stronger than the evidence can sustain.
↳ Discussion, final paragraph
The score is driven by a clear but modest contribution: a prospective pilot of ziv-aflibercept in previously treated RVO eyes with a tangible cost-access rationale. The methods are reasonably transparent for a case series, including explicit retreatment criteria, monthly visits, OCT measurement handling, and paired nonparametric testing. The largest constraint is inferential rather than reporting-related: nine eyes, no control arm, pooled CRVO/BRVO disease, heterogeneous prior treatment exposure, and a four-month endpoint leave efficacy uncertain. The impact score is held below the quality score because the practical problem is real, but the evidence is still far from implementation-ready.
Nabu’s assessment, alongside the field’s view.
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Sound3.1
Confidence mediumThe study makes a modest but real contribution by providing prospective, registered, two-center pilot data on ziv-aflibercept for RVO-associated macular edema. The contribution is limited by the small, uncontrolled design and should be read as hypothesis-generating rather than practice-changing.
first prospective study to evaluate the safety and efficacy
The methods include explicit eligibility criteria, monthly follow-up, PRN retreatment criteria, defined endpoints, OCT harmonisation across devices, and a simple nonparametric analysis suited to the small sample. Interpretive craft is constrained by nine eyes, no comparator, pooled CRVO/BRVO analysis, heterogeneous prior treatment history, and a four-month endpoint.
small cohort prevents us from detecting statistically significant visual acuity changes
The paper clearly states the intervention, endpoints, follow-up schedule, and main anatomic and visual results. The Discussion acknowledges major limitations, although some phrasing moves from pilot signal toward clinical-use support.
Prospective, randomized trials comparing ziv-aflibercept with standard pharmacotherapy are needed
The paper situates the study within anti-VEGF evidence for RVO, prior aflibercept trials, SCORE-2, and emerging ziv-aflibercept safety reports. It also identifies the affordability and regulatory-access rationale, though that practical framing is stronger than the direct efficacy evidence provided by the pilot.
Aflibercept use in developing countries is limited due to its high cost
Caveats4 of 4 checks
The main numerical results are broadly coherent, with only a trivial abstract/results CMT rounding difference. The Discussion includes efficacy-supportive language that exceeds what a small single-arm heterogeneous pilot can establish.
The paper declares IRB approval at two institutions, Declaration of Helsinki adherence, written informed consent, and trial registration. No data/code availability statement or visible conflict-of-interest statement is reported in the supplied text.
Flags: 2 declared / 5 total
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Where this paper’s evidence sits on the path from initial observation to real-world use.
The findings are early clinical proof-of-concept: prospective and patient-based, but not comparative or long-term. The anatomic signal and short-term safety observations require controlled validation before translation into routine practice.
Larger, multicenter, prospective, controlled studies are needed
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