Real-World Study Finds Stable Vision After Switch to Ranibizumab Biosimilar

A growing share of people receiving long-term anti–vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (nAMD) face an ongoing challenge: maintaining durable disease control while managing the cumulative cost and burden of chronic intravitreal injections.¹ As biosimilars enter ophthalmic practice, clinicians and payers are increasingly focused on whether switching stable patients can preserve outcomes without disrupting disease control.²

Switching from aflibercept to ranibizumab biosimilars maintains stability in nAMD treatment, offering a cost-effective solution for long-term management. | Image credit: 61766578 - stock.adobe.com

Researchers in Japan addressed this question in a prospective observational analysis evaluating outcomes after switching from intravitreal aflibercept to a ranibizumab biosimilar in people with well-controlled nAMD.³ The investigators examined both clinical end points and aqueous humor cytokine levels to assess whether the transition maintained stability at the functional, anatomic, and molecular levels.

The study included 38 eyes from 38 adults with nAMD treated at an academic center between July 2022 and May 2024. All participants had been receiving aflibercept under a treat-and-extend regimen and were considered stable, defined as maintaining injection intervals of 16 weeks or longer for more than 1 year. The mean age was 76.5 years, and 71.1% of eyes belonged to male patients. Polypoidal choroidal vasculopathy was the most common nAMD subtype (57.9%), followed by type 1 macular neovascularization (23.7%), type 2 (15.8%), and type 3 (2.6%). On average, patients had received anti-VEGF therapy for just over 60 months before the switch.

At the time of transition, injection intervals were shortened to 12 weeks to reduce the risk of disease reactivation, then gradually extended based on optical coherence tomography findings. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured before switching, shortly afterward, and again at 12 months. In addition, aqueous humor samples were collected before and after switching to evaluate changes in VEGF-A, placental growth factor (PlGF), and angiopoietin-2 (Ang-2). Eight eyes from individuals undergoing cataract surgery served as controls for cytokine comparisons.

Short-term outcomes showed minimal change after the switch. Mean BCVA remained stable, with no statistically significant difference from baseline, and CRT values were nearly identical before and after the transition. The proportion of eyes with a dry macula decreased slightly, from 94.7% before switching to 89.5% afterward, but most eyes maintained anatomic disease control.

At 1 year, 35 eyes were available for evaluation. Two eyes (5.7%) required a switch back to aflibercept because persistent exudative changes could not be controlled at extended dosing intervals. Among the remaining eyes, disease activity remained controlled in more than 94% of cases. Mean BCVA and CRT did not differ significantly from baseline, and no eye experienced a vision loss greater than 0.3 logMAR. Injection intervals were extended back to a mean of 16 weeks by the end of follow-up, suggesting that treatment burden was not increased after the switch.

Cytokine analyses provided insight into the biologic effects of transitioning therapies. Ang-2 levels did not change significantly after switching and were not statistically different from control eyes. PlGF concentrations also remained stable, though they were consistently higher in eyes with nAMD than in controls both before and after the switch. VEGF-A levels increased significantly following the transition from aflibercept to the ranibizumab biosimilar, reflecting known pharmacologic differences between agents. Despite this increase, VEGF-A concentrations remained lower than those observed in control eyes and were not associated with worsening clinical outcomes.

Summarizing the overall findings, the authors concluded that “switching from aflibercept to ranibizumab BS effectively maintained disease stability and cytokine balance in eyes with nAMD,” supporting the biosimilar as “a viable and cost-effective alternative for long-term treatment.” The investigators also noted that strong VEGF suppression may be most critical during induction therapy, whereas less intensive suppression could be sufficient during the maintenance phase in stable disease.

The study had several limitations. The sample size was relatively small, and all participants were treated at a single center, which may limit generalizability. The control group for cytokine analysis included only 8 eyes, reducing statistical power for biomarker comparisons. Additionally, the cohort consisted exclusively of people with long-standing, stable nAMD receiving extended-interval aflibercept, so the findings may not apply to individuals with more active disease or shorter treatment intervals.

Even with these constraints, the results add to a growing body of real-world evidence suggesting that ophthalmic biosimilars can be integrated into maintenance therapy without compromising outcomes in carefully selected patients.

References

1. Jeremias S. Swiss analysis shows biosimilars cut costs but longer-interval options lead savings. The Center for Biosimilars^®. December 4, 2025. Accessed January 7, 2026. https://www.centerforbiosimilars.com/view/swiss-analysis-shows-biosimilars-cut-costs-but-longer-interval-options-lead-savings

2. Jeremias S. Seeing eye to eye: FDA's Dr Sarah Yim discusses efforts to increase confidence in ophthalmology biosimilars. The Center for Biosimilars. January 29, 2023. Accessed January 7, 2025. https://www.centerforbiosimilars.com/view/seeing-eye-to-eye-fda-s-dr-sarah-yim-discusses-efforts-to-increase-confidence-in-ophthalmology-biosimilars

3. Ota H, Takeuchi J, Nonogaki R, Tamura K, Kaneko H, Nishiguchi KM. Efficacy of switching from existing anti-vascular endothelial growth factor drugs to ranibizumab biosimilar in neovascular age-related macular degeneration. Jpn J Ophthalmol. 2025;69(6):886-893. doi:10.1007/s10384-025-01224-0