INTRODUCTION: AZURE was a 76-week, randomized, open-label, parallel-group, phase IIIb noninferiority study comparing the efficacy and safety of intravitreal aflibercept (IVT-AFL) in a treat-and-extend (T&E) regimen with fixed dosing in patients with neovascular age-related macular degeneration (nAMD) previously receiving IVT-AFL for ≥ 1 year. METHODS: Patients were aged ≥ 51 years and had completed ≥ 1 year of IVT-AFL treatment prior to enrollment (IVT-AFL once per month [- 1 or + 2 weeks] for 3 months followed by IVT-AFL every 2 months [6-12 weeks]). Patients were randomly assigned (1:1) to receive IVT-AFL 2 mg in either a T&E (minimum treatment interval of 8 weeks with no upper limit, adjusted according to functional and anatomic outcomes, as assessed by the investigator; n = 168), or a fixed dosing regimen (treatment every 8 weeks [± 3 days]; n = 168). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline to week (W) 52. The key secondary endpoint was the proportion of patients maintaining vision (< 15-letter loss) at W52. RESULTS: The full analysis set comprised 332 patients (T&E: n = 165; fixed dosing: n = 167). Mean BCVA change (baseline to W52) was - 0.3 ± 7.5 vs. - 0.5 ± 8.4 letters (T&E vs. fixed dosing; least-squares mean difference [95% CI]: 0.22 [- 1.51 to 1.96] letters; P < 0.0001 for noninferiority test [5-letter margin]). From baseline to W52, 95.2% (T&E) and 94.0% (fixed dosing) of patients maintained vision. Mean central subfield thickness change from baseline to W52 was - 24 ± 55 (T&E) and - 33 ± 47 (fixed dosing) μm. Last treatment interval to W76 was ≥ 12 weeks for 37.0% of T&E patients. No new safety signals were identified. CONCLUSION: IVT-AFL T&E can achieve similar functional and anatomic outcomes to fixed dosing every 8 weeks over 52 weeks in patients with nAMD who have completed ≥ 1 year of treatment, while reducing treatment burden. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02540954.

• MeSH
• injekce intravitreální MeSH
• lidé středního věku MeSH
• lidé MeSH
• makulární degenerace * farmakoterapie   MeSH
• receptory vaskulárního endoteliálního růstového faktoru * terapeutické užití   MeSH
• rekombinantní fúzní proteiny * terapeutické užití   MeSH
• senioři MeSH
• výsledek terapie MeSH
• zraková ostrost MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• hodnocení ekvivalence MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH

BACKGROUND/AIMS: To evaluate efficacy, safety, pharmacokinetics (PK) and immunogenicity of SB15 versus reference aflibercept (AFL), and switching from AFL to SB15 in neovascular age-related macular degeneration (nAMD). DESIGN: Prospective, double-masked, randomised, phase 3 trial. METHODS: Participants with nAMD were randomised 1:1 to receive SB15 (N=224 participants) or AFL (N=225). At week 32, participants either continued on SB15 (SB15/SB15, N=219) or AFL (AFL/AFL, N=108), or switched from AFL to SB15 (AFL/SB15, N=111). This manuscript reports 1-year and switching results of secondary efficacy endpoints such as changes from baseline to week 56 in best-corrected visual acuity (BCVA), central subfield thickness (CST, from internal limiting membrane (ILM) to retinal pigment epithelium), and total retinal thickness (TRT, from ILM to Bruch's membrane). Additional endpoints included safety, PK and immunogenicity. RESULTS: Efficacy results were comparable between groups. The least squares mean (LSmean) change in BCVA from baseline to week 56 was 7.4 letters for SB15/SB15 and 7.0 letters for AFL/AFL (difference (95% CI)=0.4 (-2.5 to 3.2)). The LSmean changes from baseline to week 56 in CST and TRT were -119.2 μm and -132.4 μm for SB15/SB15 and -126.6 μm and -136.3 μm for AFL/AFL, respectively (CST: difference (95% CI)=7.4 μm (-6.11 to 20.96); TRT: difference (95% CI)=3.9 μm (-18.35 to 26.10)). Switched and non-switched participants showed similar LSmean changes in BCVA from baseline to week 56 (AFL/SB15, 7.9 letters vs AFL/AFL, 7.8 letters; difference (95% CI)=0.0 (-2.8 to 2.8)). Safety, PK and immunogenicity were comparable between groups. CONCLUSIONS: Efficacy, safety, PK and immunogenicity were comparable between SB15 and AFL and between switched and non-switched participants.

• MeSH
• biosimilární léčivé přípravky * terapeutické užití   MeSH
• inhibitory angiogeneze terapeutické užití   MeSH
• injekce intravitreální MeSH
• lidé MeSH
• makulární degenerace * farmakoterapie   MeSH
• prospektivní studie MeSH
• zraková ostrost MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

BACKGROUND/AIMS: To 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). METHODS: Setting: 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. RESULTS: Baseline 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. CONCLUSIONS: Longer-term results of this study further support the biosimilarity established between SB11 and RBZ.

• MeSH
• biosimilární léčivé přípravky * terapeutické užití   MeSH
• inhibitory angiogeneze terapeutické užití   MeSH
• injekce intravitreální MeSH
• lidé středního věku MeSH
• lidé MeSH
• makulární degenerace * farmakoterapie   MeSH
• ranibizumab terapeutické užití   MeSH
• vaskulární endoteliální růstový faktor A MeSH
• vlhká makulární degenerace * diagnóza   farmakoterapie   MeSH
• výsledek terapie MeSH
• zraková ostrost MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

IMPORTANCE: Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy. OBJECTIVE: To establish equivalence in efficacy and similarity in safety, pharmacokinetics, and immunogenicity of SB15 and reference aflibercept (AFL) in neovascular age-related macular degeneration (nAMD). DESIGN, SETTING, AND PARTICIPANTS: This was a randomized double-masked parallel group phase 3 trial conducted at 56 centers in 10 countries from June 2020 to March 2022, including follow-up through 56 weeks. Of 549 screened participants, 449 participants 50 years and older with treatment-naive nAMD were included and randomly assigned to SB15 (n = 224) or AFL (n = 225). Key exclusion criteria included considerable scarring, fibrosis, atrophy, and hemorrhage. This report includes results up to the end of the parallel group period at week 32. Of the 449 randomized participants, 438 (97.6%) completed week 32 follow-up. INTERVENTION: Participants were randomized 1:1 to receive 2 mg of SB15 or AFL every 4 weeks for the first 12 weeks (3 injections), followed by dosing every 8 weeks up to week 48, with final assessments at week 56. MAIN OUTCOMES AND MEASURES: The primary end point was the change in best-corrected visual acuity (BCVA) from baseline to week 8 with predefined equivalence margins of -3 letters to 3 letters. Other key end points were changes in BCVA and central subfield thickness up to week 32, safety, pharmacokinetics, and immunogenicity. RESULTS: The mean (SD) age among the 449 included participants was 74.0 (8.1) years, and 250 participants (55.7%) were female. Baseline demographic characteristics and most disease characteristics were comparable between treatment groups. The least squares mean change in BCVA from baseline to week 8 in the SB15 group was equivalent to that in the AFL group (6.7 letters vs 6.6 letters, respectively; difference, 0.1 letters; 95% CI, -1.3 to 1.4). Comparable efficacy between treatment groups was maintained up to week 32 (least squares mean change from baseline in BCVA: SB15, 7.6 letters vs AFL, 6.5 letters; least squares mean change from baseline in central subfield thickness: SB15, -110.4 μm vs AFL, -115.7 μm). No clinically relevant differences were observed in the incidence of treatment-emergent adverse events (TEAEs) (SB15, 107/224 [47.8%] vs AFL, 98/224 [43.8%]) and ocular TEAEs in the study eye (SB15, 41/224 [18.3%] vs AFL, 28/224 [12.5%]). The serum concentration profiles and cumulative incidences of overall antidrug antibody positive participants were comparable. CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, SB15 and AFL showed equivalent efficacy and comparable safety, pharmacokinetics, and immunogenicity in participants with nAMD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04450329.

• MeSH
• biosimilární léčivé přípravky * škodlivé účinky   MeSH
• inhibitory angiogeneze škodlivé účinky   MeSH
• injekce intravitreální MeSH
• lidé MeSH
• makulární degenerace * farmakoterapie   MeSH
• ranibizumab terapeutické užití   MeSH
• receptory vaskulárního endoteliálního růstového faktoru terapeutické užití   MeSH
• rekombinantní fúzní proteiny škodlivé účinky   MeSH
• senioři MeSH
• vlhká makulární degenerace * diagnóza   farmakoterapie   chemicky indukované   MeSH
• výsledek terapie MeSH
• zraková ostrost MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

• MeSH
• dítě MeSH
• injekce intravitreální metody   MeSH
• lidé MeSH
• mladiství MeSH
• myopie komplikace   MeSH
• neovaskularizace sítnice * diagnóza   etiologie   farmakoterapie   klasifikace   MeSH
• optická koherentní tomografie metody   MeSH
• poruchy zraku etiologie   klasifikace   prevence a kontrola   MeSH
• vaskulární endoteliální růstové faktory * antagonisté a inhibitory   aplikace a dávkování   terapeutické užití   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Cieľ: Kazuistika záchytu choroidálnej neovaskularizácie (CNV) u pacienta v ranom detstve liečeného pre obojstranný retinoblastóm. Materiál a metodika: Pacient v 1,5 roku života liečený na endofytický retinoblastóm 4. štádia (podľa Reese-Ellsworthovej klasifikácie) obojstranne, s pozitívnou mutáciou v Rb1 géne. Po 3-násobnom absolvovaní obojstranného laserového ošetrenia sietnice a 6-tich cykloch systémovej chemoterapie zostal tumor bez aktivity a iných komplikácii. V 14-tich rokoch sa u chlapca objavilo zhoršenie videnia na ľavom oku s prítomnými metamorfopsiami. Na základe lokálneho nálezu a ďalších pomocných vyšetrení mu bola diagnostikovaná CNV v makulárnej oblasti na rozhraní jazvy po tumore a zdravej sietnice ľavého oka. Výsledky: Po troch podaniach anti-VEGF(antibodies blocking vascular endothelial growth factor) preparátu intravitreálne (bevacizumab 1,2 mg) došlo k redukcii CNV a tiež k zlepšeniu zrakových funkcii. Záver: Vitreoretinálne komplikácie po liečbe retinoblastómu nie sú časté, avšak môžu sa vyskytnúť ako dôsledok lokálnej a celkovej liečby tumoru. U nášho pacienta sa jednalo o raritnú komplikáciu so vznikom CNV v dlhšom časovom odstupe od liečby s dobrou reakciou na intravitreálne podanie anti-VEGF preparátu.

Aim: Case report of choroidal neovascularization (CNV) detection in patient who was treated for bilateral retinoblastoma in early childhood. Material and methods: Patient at 1.5 years of age treated for endophytic retinoblastoma stage 4 (according to the Reese-Ellsworth classification) bilaterally, with a positive mutation in the Rb1 gene. After undergoing bilateral retinal laser treatment and 6 cycles of systemic chemotherapy, the tumor remained inactive without other complications. At the age of 14, the boy developed visual impairment in his left eye with metamorphosis. Based on a local finding and other auxiliary examinations, he was diagnosed with CNV in the macular area at the interface of the tumor scar and the healthy retina of the left eye. Results: After three applications of anti-VEGF (antibodies blocking vascular endothelial growth factor) substance intravitreally (bevacizumab 1.2 mg), there was a reduction in CNV and also an improvement in visual function.

• MeSH
• injekce intravitreální MeSH
• lidé MeSH
• mladiství MeSH
• neovaskularizace choroidey diagnóza   farmakoterapie   komplikace   MeSH
• retinoblastom * komplikace   terapie   MeSH
• vaskulární endoteliální růstový faktor A terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• biosimilární léčivé přípravky klasifikace   terapeutické užití   MeSH
• humanizované monoklonální protilátky aplikace a dávkování   klasifikace   škodlivé účinky   MeSH
• injekce intravitreální ošetřování   MeSH
• klinická studie jako téma MeSH
• laserová terapie s nízkou intenzitou světla MeSH
• lidé MeSH
• makulární degenerace * farmakoterapie   terapie   MeSH
• neovaskularizace choroidey diagnóza   patologie   MeSH
• nežádoucí účinky léčiv epidemiologie   klasifikace   MeSH
• ranibizumab aplikace a dávkování   MeSH
• vaskulární endoteliální růstové faktory antagonisté a inhibitory   fyziologie   klasifikace   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• geografická atrofie epidemiologie   etiologie   MeSH
• injekce intravitreální škodlivé účinky   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• makulární degenerace * farmakoterapie   MeSH
• neovaskularizace choroidey etiologie   patologie   MeSH
• nežádoucí účinky léčiv MeSH
• nitrooční tlak účinky léků   MeSH
• rizikové faktory MeSH
• vaskulární endoteliální růstové faktory antagonisté a inhibitory   MeSH
• Check Tag
• lidé MeSH

Cíl: Cílem studie bylo porovnat účinek třech počátečních dávek anti-VEGF ranibizumabu a afliberceptu na serózní ablaci retinálního pigmentového epitelu (PED), subretinální tekutinu (SRF) a intraretinální tekutinu (IRF) v makule u pacientů s neléčenou neovaskulární věkem podmíněnou makulární degenerací (nvAMD). Materiál a metody: Soubor tvoří 148 pacientů, z toho 74 pacientů bylo léčených ranibizumabem (51 žen a 23 mužů) a 74 afliberceptem (46 žen a 28 mužů). Údaje se zaznamenávaly prospektivně od okamžiku diagnózy a počátku léčby po dobu 3 měsíců. V okamžiku diagnózy a o 3 měsíce později bylo provedeno OCT vyšetření. OCT vyšetření zahrnovalo makulární sken s 25 skeny. Pomocí softwaru OCT přístroje jsme změřili maximální elevaci serózní PED, maximální výšku SRF a největší průměr intraretinální cystické tekutiny. Výsledky: Úplná regrese PED, SRF a IRF se vyskytla u 3 (4,1 %), 25 (39 %) a 20 (51 %) pacientů léčených ranibizumabem a u 5 (7,9 %, p = 0,470), 28 (47 %, p = 0,470) a 25 (57 %, p = 0,827) pacientů léčených afliberceptem. Průměrná regrese PED, SRF a IRF byla -60,4 μm (medián -37,5 μm), -84,3 μm (medián -85 μm) a -109,3 μm (medián -81 μm) u pacientů léčených ranibizumabem a -46,3 μm (medián -30 μm, p = 0,389), -127,7 μm (medián -104 μm, p = 0,096) a -204,4 μm (medián -163 μm, p = 0,005) u pacientů léčených afliberceptem. Mezi skupinami s ranibizumabem a afliberceptem jsme neprokázali statisticky významný rozdíl v míře regrese PED, SRF a IRF (u pacientů s IRF po úpravě vyšších vstupních hodnot IRF u pacientů léčených afliberceptem, p = 0,891). Závěr: Naše výsledky ukazují, že ranibizumab a aflibercept mají stejný účinek na serózní PED, SRF a IRF v makule u pacientů s dosud neléčenou nvAMD během úvodní fáze terapie.

Purpose: The aim of the study was to compare the effect of three initial doses of the anti-VEGF ranibizumab and aflibercept medication on serous pigment epithelial detachment (PED), subretinal fluid (SRF) and intraretinal fluid (IRF) in the macula of treatment naive neovascular AMD (nvAMD) patients. Material and Methods: The cohort consists of 148 patients, of which 74 patients were treated with ranibizumab (51 females and 23 males) and 74 with aflibercept (46 females and 28 males). The data was recorded prospectively from the moment of diagnosis and start of treatment for a period of 3 months. At the moment of diagnosis and 3 months later, an OCT examination (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany) was performed. The OCT examination included a macular scan with 25 scans. Using the OCT instrument software, we measured the maximum anterior-posterior elevation of serous PED, the highest thickness of SRF and the largest diameter of the intraretinal cystic space. The statistical significance of differences between groups was evaluated using the t-test for continuous data and the Fisher exact test for categorical data. Changes in values of continuous variables over time were evaluated using the Wilcoxon paired test. Paired comparisons of binary parameters were determined by the McNemar test. Results: Full regression of PED, SRF and IRF occurred in 3 (4.1%), 25 (39%) and 20 (51%) patients treated with ranibizumab, and in 5 (7.9%, p = 0.470), 28 (47%, p = 0.470) and 25 (57%, p = 0.827) patients treated with aflibercept, respectively. The average regression of PED, SRF and IRF was -60.4 μm (median -37.5 μm), -84.3 μm (median -85 μm) and -109.3 μm (median -81 μm) in patients treated with ranibizumab, and -46.3 μm (median -30 μm, p = 0.389), -127.7 μm (median -104 μm, p = 0.096) and -204.4 μm (median -163 μm, p = 0.005) in patients treated with aflibercept, respectively. We did not show a statistically significant difference in the regression rates of PED, SRF and IRF between the ranibizumab and aflibercept groups. (in patients with IRF after adjustment of the higher baseline IRF volumes in patients treated with aflibercept, p = 0.891). Conclusion: We are convinced that ranibizumab and aflibercept have the same effect on serous PED, SRF and IRF in the macula in patients with treatment naive nvAMD during the initial loading phase.

• MeSH
• inhibitory angiogeneze farmakologie   terapeutické užití   MeSH
• injekce intravitreální MeSH
• lidé MeSH
• odchlípení sítnice diagnóza   MeSH
• optická koherentní tomografie MeSH
• ranibizumab * terapeutické užití   MeSH
• receptory vaskulárního endoteliálního růstového faktoru MeSH
• rekombinantní fúzní proteiny terapeutické užití   MeSH
• retinální pigmenty terapeutické užití   MeSH
• retrospektivní studie MeSH
• vaskulární endoteliální růstový faktor A MeSH
• vlhká makulární degenerace * diagnóza   farmakoterapie   MeSH
• zraková ostrost MeSH
• Check Tag
• lidé MeSH

Aim: This study aimed to determine the effects of a single intravitreal ranibizumab injection in rabbits induced with retinoblastoma (RB). Material and Methods: RB was induced in six New Zealand white rabbits by subretinal injection of a cultured WERI-RBb-1 cell line into the right eye. After six weeks, Group A (n = 3) was given intravitreal ranibizumab injection (0.3mg in 0.03ml) and Group B (n = 3) was the control. Baseline and serial clinical examinations were performed on days 1, 3, 6, 12, 15, 18 and 21. The right eyes were enucleated for both groups on day 21 for histopathological examination. Results: The rabbits in both groups developed intraocular lesions which was detectable clinically at one-week post-tumor inoculation. The tumor grew slowly without spontaneous regression. After the animals in Group A were given an intravitreal ranibizumab injection, regression of the tumor was detected clinically, while the tumor in Group B continued to grow slowly. Histopathological findings confirmed the presence of a tumor that closely resembled features of poorly differentiated human RB cells. At the end of 21 days, the size of the tumor was larger in Group B in comparison to Group A. However, the treated group also developed a focal area of retinal hyperplasia. There was no significant side effect of ranibizumab injection except temporary high intraocular pressure immediately post-injection, which was relieved after paracentesis. Conclusions: Intravitreal ranibizumab is a potential treatment for RB. It is an effective therapy with a tolerable safety profile in this animal experimental study.

• MeSH
• inhibitory angiogeneze farmakologie   MeSH
• injekce intravitreální MeSH
• králíci MeSH
• modely nemocí na zvířatech MeSH
• nádory sítnice chemicky indukované   farmakoterapie   MeSH
• ranibizumab * terapeutické užití   MeSH
• retinoblastom * chemicky indukované   farmakoterapie   MeSH
• vaskulární endoteliální růstový faktor A MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH