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IMPORTANCE Neovascular age-related macular degeneration is the leading cause of blindness in individuals 50 years or older. The availability of a ranibizumab biosimilar product (SB11) may facilitate access to an effective alternative to this treatment. OBJECTIVE To demonstrate equivalence of efficacy, similar safety, and similar immunogenicity of SB11 compared with the reference ranibizumab. DESIGN, SETTING, AND PARTICIPANTS This randomized, double-masked, parallel-group phase 3 equivalence study was conducted in 75 centers in 9 countries from March 14, 2018, to December 9, 2019, among 705 participants 50 years or older with neovascular age-related macular degeneration with active subfoveal choroidal neovascularization lesions. Analysis was performed on an intent-to-treat basis. INTERVENTIONS Intravitreous injection of SB11 or ranibizumab, 0.5 mg, every 4 weeks through week 48. MAIN OUTCOMES AND MEASURES Preplanned interim analysis after all participants completed the week 24 assessment of primary efficacy end points at week 8 for change from baseline in best-corrected visual acuity (BCVA) and week 4 for central subfield thickness (CST), with predefined equivalence margins for adjusted treatment differences of −3 letters to 3 letters for BCVA and −36 μm to 36 μm for CST. RESULTS Baseline and disease characteristics among 705 randomized participants (403 women [57.2%]; mean [SD] age, 74.1 [8.5] years) were comparable between treatment groups (SB11, 351; ranibizumab, 354). Least-squares mean (SE) changes in BCVA from baseline at week 8 were 6.2 (0.5) letters in the SB11 group vs 7.0 (0.5) letters in the ranibizumab group, with an adjusted treatment difference of −0.8 letter (90% CI, −1.8 to 0.2 letters). Least-squares mean (SE) changes in CST from baseline at week 4 were −108 (5) μm in the SB11 group vs −100 (5) μm in the ranibizumab group, with an adjusted treatment difference of −8 μm (95% CI, −19 to 3 μm). Incidences of treatment-emergent adverse events (231 of 350 [66.0%] vs 237 of 354 [66.9%]), including serious treatment-emergent adverse events (44 of 350 [12.6%] vs 44 of 354 [12.4%]) and treatment-emergent adverse events leading to study drug discontinuation (8 of 350 [2.3%] vs 5 of 354 [1.4%]), were similar in the SB11 and ranibizumab groups. Immunogenicity was low, with a cumulative incidence of antidrug antibodies up to week 24 of 3.0% (10 of 330) in the SB11 group and 3.1% (10 of 327) in the ranibizumab group. CONCLUSIONS AND RELEVANCE These findings of equivalent efficacy and similar safety and immunogenicity profiles compared with ranibizumab support the use of SB11 for patients with neovascular age-related macular degeneration.

Anterior chamber measurements were significantly deeper with AS-OCT than with US immersion A-scan. Repeatability of ACD measurements was better with AS-OCT than with immersion US, and reproducibility was equal with the 2 methods.

In phakic eyes, ACD measured with the Pentacam and with US was the same. However, in pseudophakic eyes, the difference was significantly lower when the ACD was measured with the Pentacam. Therefore, in pseudophakic patients, further evaluation of ACD data with the Scheimpflug-based system is necessary.

ABSTRACT.Purpose: Failure of retinal pigment epithelial (RPE) cells and macrophages to engulf different dying cells in the retina may result in accumulation of debris and development of age-related macular degeneration (AMD). The dynamics and influence of different treatments on this clearance process can be studied in vitro using human ARPE-19 cells and macrophages as phagocytes modelling dry and wet type of AMD, respectively.Methods: Death through extracellular matrix detachment using polyHEMA-coated surfaces (anoikis) and UV irradiation (apoptosis) was induced in ARPE-19 cells. Twocoloured phagocytic assays were performed to quantify the amount of dying cells phagocytes engulfed (flow cytometry) and for visualization (fluorescent and scanning electron microscopy). The effect of phosphatidylserine inhibition with recombinant annexin-V and glucocorticoid (triamcinolone) treatment on the phagocytic process was tested.Results: The clearance of anoikic and apoptotic cells by nondying ARPE-19 cells over 8 hr of co-incubation increased over time (at 8 hr, over 53% and 35% of the phagocytes contained engulfed dying cells, respectively). The human macrophages engulfed the anoikic and apoptotic ARPE-19 cells with seven and four times lower capacity, respectively. Phosphatidylserine appearance on the dying cells did not affect, but triamcinolone treatment enhanced the phagocytosis of the dying cells by macrophages.Conclusions: ARPE-19 cells are more efficient in clearing anoikic than UV-induced apoptotic cells. Macrophages are less efficient in the clearance process than ARPE-19 cells. The present model can be used for studying both dry and wet type of AMD in vitro and for testing different pharmacological aspects affecting this disease.

Background/AimsTo provide longer-term data on efficacy, safety, immunogenicity and pharmacokinetics (PK) of ranibizumab biosimilar SB11 compared with the reference ranibizumab (RBZ) in patients with neovascular age-related macular degeneration (nAMD).MethodsSetting: Multicentre. Design: Randomised, double-masked, parallel-group, phase III equivalence study. Patient population: ≥50 years old participants with nAMD (n=705), one ‘study eye’. Intervention: 1:1 randomisation to monthly intravitreal injection of 0.5 mg SB11 or RBZ. Main outcome measures: Visual efficacy endpoints, safety, immunogenicity and PK up to 52 weeks.ResultsBaseline and disease characteristics were comparable between treatment groups. Of 705 randomised participants (SB11: n=351; RBZ: n=354), 634 participants (89.9%; SB11: n=307; RBZ: n=327) completed the study until week 52. Previously reported equivalence in primary efficacy remained stable up to week 52 and were comparable between SB11 and RBZ. The adjusted treatment difference between SB11 and RBZ in full analysis set at week 52 of change from baseline in best-corrected visual acuity was −0.6 letters (90% CI −2.1 to 0.9) and of change from baseline in central subfield thickness was −14.9 µm (95% CI –25.3 to –4.5). The incidence of ocular treatment-emergent adverse events (TEAEs) (SB11: 32.0% vs RBZ: 29.7%) and serious ocular TEAE (SB11: 2.9% vs RBZ: 2.3%) appeared comparable between treatment groups, and no new safety concerns were observed. The PK and immunogenicity profiles were comparable, with a 4.2% and 5.5% cumulative incidence of antidrug antibodies up to week 52 for SB11 and RBZ, respectively.ConclusionsLonger-term results of this study further support the biosimilarity established between SB11 and RBZ.

The Pentacam HR provided reliable K measurements in clinical practice in comparison with an automated keratometer and a corneal topographer. Based on the results, for patient follow-up, one keratometry device is recommended.

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