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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.

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.

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Usher syndrome (USH) is the most common form of monogenic deaf-blindness. Loss of vision is untreatable and there are no suitable animal models for testing therapeutic strategies of the ocular constituent of USH, so far. By introducing a human mutation into the harmonin-encoding USH1C gene in pigs, we generated the first translational animal model for USH type 1 with characteristic hearing defect, vestibular dysfunction, and visual impairment. Changes in photoreceptor architecture, quantitative motion analysis, and electroretinography were characteristics of the reduced retinal virtue in USH1C pigs. Fibroblasts from USH1C pigs or USH1C patients showed significantly elongated primary cilia, confirming USH as a true and general ciliopathy. Primary cells also proved their capacity for assessing the therapeutic potential of CRISPR/Cas-mediated gene repair or gene therapy in vitro. AAV-based delivery of harmonin into the eye of USH1C pigs indicated therapeutic efficacy in vivo.

Usher syndrome (USH) is the most common form of monogenic deaf-blindness. Loss of vision is untreatable and, so far, there are no suitable animal models for testing therapeutic strategies. By introducing a human mutation into the harmonin-encoding USH1C gene in pigs, we generated the first translational animal model for USH type 1 with characteristic hearing defect, vestibular dysfunction and visual impairment. Changes in photoreceptor architecture, quantitative motion analysis and electroretinography were characteristics of the reduced retinal virtue in USH1C pigs. Primary cells from those animals and USH1C patients showed significantly elongated primary cilia, compared to wild-type, confirming the nature of USH as a true and general ciliopathy and proving the therapeutic capacity of gene supplementation and gene repair approaches.

Purpose. To compare the effect of different types of intraocular tamponade and different types of postoperative positioning on the closure of idiopathic macular hole (IMH). Methods. Prospective randomized clinical trial enrolling 104 eyes of 100 patients (age, 57–87 years) undergoing MH surgery. All patients were operated on by an experienced surgeon using 25-gauge pars plana vitrectomy (PPV) and internal limiting membrane (ILM) peeling. Patients were randomized according to the type of intraocular tamponade and postoperative positioning into the following four groups: SF6 + nonsupine reading position (n = 26) (group 1), air + nonsupine reading position (n = 25) (group 2), air + prone position (n = 26) (group 3), or SF6 + prone position (n = 27) (group 4). The follow-up period was 6 months. Results. MH closure was achieved in 87 eyes (83.7 %) in the overall sample after the first surgery, with closure rates of 100%, 56%, 84.6%, and 92.6% in groups 1, 2, 3, and 4, respectively. The group 2 was significantly less successful compared to the other three groups ( p  < 0.05). MH of sizes ≤400 µm was closed in 97.2% of cases after the first surgery, with no significant differences between groups ( p  = 0.219). MH with sizes over 400 µm was closed in 70.9% of cases after the first surgery, with both groups with air tamponade being significantly less successful than group 1. The nonsupine reading position was subjected to a better subjective evaluation in terms of postoperative comfort and quality of sleep, with no differences between air and SF6 tamponade tolerance. Conclusion. PPV with ILM peeling, intraocular tamponade, and positioning remains the basic surgical approach in the treatment of IMH. For MH ≤ 400 µm, a high closure rate can be achieved by combining air tamponade and nonsupine reading position. For macular holes >400 µm, the greatest anatomical success can be achieved by using the SF6 tamponade in combination with the nonsupine reading position.

Aims. To evaluate the anatomical and functional results in patients with rhegmatogenous retinal detachment (RRD) who underwent 25-gauge pars plana vitrectomy (PPV) with gas tamponade. Materials and Methods. A retrospective evaluation of 126 eyes of 126 patients (79 men, 47 women) with RRD who underwent 25-gauge PPV with gas tamponade (13% C3F8 in 87 eyes, 20% SF6 in 39 eyes). 113 patients (89.7%), were operated on under local anaesthesia, 13 patients (10.3%) under general anaesthesia. Macula was detached in 85 eyes (67.5%). 53 eyes had pseudophakic RRD, 73 eyes were phakic. Anatomical success of the primary intervention, change in best corrected visual acuity (BCVA) and incidence of complications were assessed. An average follow-up period is 7.2 months (6-15). Results. With single operation, retinal attachment was achieved in 125 eyes (99.2%); the final anatomical success was 100%. The initial mean BCVA was 0.89 logMar (2.00 to 0.00); at the end of the follow-up period, it improved to 0.23logMAR (1.00 to -0.10), P < 0,0001. During the first post-intervention day, hypotony of the eye below 10 mmHg was observed in 1 patient (0.8%); on the contrary, intraocular pressure was temporarily increased to 25 mmHg and more in 36 patients (28.6%). Conclusion. The surgical treatment of RRD using 25-gauge PPV with expansive gas tamponade renders excellent anatomical results and improvement in BCVA. The incidence of complications and necessity of sclerotomy suturing are low.