- MeSH
- apolipoproteiny E genetika škodlivé účinky MeSH
- epigeneze genetická fyziologie genetika MeSH
- geny * fyziologie genetika MeSH
- komplement - faktor H genetika škodlivé účinky MeSH
- lidé MeSH
- makulární degenerace * genetika patofyziologie MeSH
- retinální drúzy patologie MeSH
- riziko MeSH
- životní styl MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- Bruchova membrána patologie MeSH
- fagocytóza MeSH
- lidé MeSH
- lipofuscin biosyntéza fyziologie škodlivé účinky MeSH
- macula lutea * patologie MeSH
- makulární degenerace * imunologie patofyziologie patologie MeSH
- neovaskularizace choroidey patofyziologie MeSH
- oxidační stres fyziologie MeSH
- proliferace buněk fyziologie MeSH
- retinální drúzy patologie MeSH
- retinální pigmentový epitel cytologie patologie MeSH
- stárnutí fyziologie MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
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. Trial Registration: ClinicalTrials.gov Identifier: NCT03150589.
- MeSH
- biosimilární léčivé přípravky škodlivé účinky farmakokinetika terapeutické užití MeSH
- časové faktory MeSH
- dvojitá slepá metoda MeSH
- inhibitory angiogeneze škodlivé účinky farmakokinetika terapeutické užití MeSH
- injekce intravitreální MeSH
- lidé středního věku MeSH
- lidé MeSH
- makulární degenerace diagnóza farmakoterapie patofyziologie MeSH
- neovaskularizace choroidey diagnóza farmakoterapie patofyziologie MeSH
- obnova funkce MeSH
- ranibizumab škodlivé účinky farmakokinetika terapeutické užití MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- terapeutická ekvivalence MeSH
- vaskulární endoteliální růstový faktor A antagonisté a inhibitory MeSH
- výsledek terapie MeSH
- zrak účinky léků MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- hodnocení ekvivalence MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Backgroung. Age-related macular degeneration (AMD) is a disease of the macula, which significantly affects the eyesight and leads to irreversible central vision loss. The etiopathogenesis of AMD is still not absolutely clear. It is thought that age-related macular degeneration has a multifactorial etiology, the development of which may be caused by interrelation of environmental with innate factors, while genetic factors also have an impact. Macular degenerative changes occur due to the formation of drusen, about 40% of which is lipids. As the CYP2J2 gene is involved in the metabolism of lipids, it was selected for investigation in this study.PURPOSE: To determine the relation between early stage and exudative AMD and CYP2J2 (-76G>T) gene rs890293 polymorphism in a Lithuanian population. METHODS: The study enrolled 204 patients with early AMD, 197 patients with exudative AMD and 198 healthy controls. Samples of DNA from peripheral white blood cells were purified using commercial kits. The genotyping was carried out using a real-time PCR method. RESULTS: The CYP2J2 (-76G>T) rs890293 TT genotype in patients with early AMD was statistically significantly less frequent than in the control group: 0% vs. 2.5% (P=0.028). There were no significant differences in rs890293 gene polymorphisms between the exudative AMD and control groups. Also, the CYP2J2 (-76G>T) rs890293 TT genotype was statistically significantly less frequent in older early AMD patients (≥65 years) compared to control group persons (≥65 years): 0% vs. 5.4% (P=0.03). CONCLUSION: The CYP2J2 (-76G>T) TT genotype may be associated with reduced manifestation of early stage AMD; therefore, a larger sample size is required for further analysis.
- MeSH
- genetická predispozice k nemoci * MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- makulární degenerace genetika patofyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- systém (enzymů) cytochromů P-450 genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Litva MeSH
INTRODUCTION: Combinatory strategies using pharmacology and stem cell therapy have emerged due to their potential in the treatment of retinal pigment epithelium (RPE) cell related diseases, and a variety of different stem cell sources have been evaluated both in animal models and in humans. RPE cells derived from human embryonic stem cells (hESCs) and human induced pluripotent cells (hiPSCs) are already in clinical trials, holding great promise for the treatment of age-related macular disease (AMD) and hereditary RPE-related retinal dystrophies. Highly efficient protocol for RPE generations have been developed, but they are still time-consuming and laborious. Areas covered: The authors review RPE related diseases, as well as the known functions of RPE cells in retinal homeostasis. The authors also discuss small molecules that target RPE in vivo as well as in vitro to aid RPE differentiation from pluripotent stem cells clinically. The authors base this review on literature searches performed through PubMed. Expert opinion: Using high-throughput systems, technology will provide the possibility of identifying and optimizing molecules/drugs that could lead to faster and simpler protocols for RPE differentiation. This could be crucial in moving forward to create safer and more efficient RPE-based personalized therapies.
- MeSH
- buněčná diferenciace fyziologie MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- makulární degenerace patofyziologie terapie MeSH
- nemoci retiny patofyziologie terapie MeSH
- pluripotentní kmenové buňky cytologie MeSH
- retinální pigmentový epitel cytologie MeSH
- rychlé screeningové testy MeSH
- transplantace kmenových buněk metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
x
x
- Klíčová slova
- aflibercept,
- MeSH
- inhibitory angiogeneze terapeutické užití MeSH
- injekce intravitreální MeSH
- lidé MeSH
- makulární degenerace * diagnóza patofyziologie terapie MeSH
- ranibizumab terapeutické užití MeSH
- receptory vaskulárního endoteliálního růstového faktoru terapeutické užití MeSH
- rekombinantní fúzní proteiny terapeutické užití MeSH
- rizikové faktory MeSH
- vaskulární endoteliální růstový faktor A antagonisté a inhibitory terapeutické užití MeSH
- Check Tag
- lidé MeSH
PURPOSE: The implantation of an intraocular telescope increases life quality in patients with end-stage age-related macular degeneration (AMD). The present study monitored changes in electrophysiological markers of visual processing before and during seventeen months after a novel mirror telescope implantation in two patients (OV-male 90 years, MZ-female 70 years) with the final-stage form of AMD. METHODS: Visual evoked potentials were recorded to high-contrast pattern-reversal (PR-VEP for check size 40' and 10'), low-contrast motion-onset stimuli (in visual periphery M-VEP M20°, and in central part M-VEP C8°), and event-related potentials (ERPs) in the oddball visual paradigm. RESULTS: MZ's more systematic responses showed attenuation and prolongation of the M-VEP M20° and the PR-VEP 40' immediately after the telescope implantation with a slow amplitude recovery with unchanged prolonged latency. The implantation completely eradicated the M-VEP C8° without any restoration. The PR-VEP 10' were not readable. Only a part of OV's PR-VEP 40' and M-VEP M20' were of a repeatable and expected morphology. These OV's VEPs were consistent with MZ's findings. The ERPs did not show any effect of implantation in both patients. Post-implantation visual acuity and reaction time overcame the pre-implantation levels. CONCLUSIONS: The mirror telescope preserved peripheral vision in contrast to classic telescopes; however, the telescope concurrently reduced the luminance of the magnified retinal image, which was likely responsible for the prolongation of the VEP latencies.
- MeSH
- čočky * MeSH
- lidé MeSH
- makulární degenerace * patofyziologie rehabilitace MeSH
- rozpoznávání obrazu fyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- teleskopy * MeSH
- zraková ostrost MeSH
- zraková percepce fyziologie MeSH
- zrakové evokované potenciály * MeSH
- zrakové protézy * normy MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- MeSH
- lidé MeSH
- makulární degenerace * diagnóza farmakoterapie patofyziologie MeSH
- optická koherentní tomografie MeSH
- receptory vaskulárního endoteliálního růstového faktoru * aplikace a dávkování terapeutické užití MeSH
- rekombinantní fúzní proteiny * aplikace a dávkování terapeutické užití MeSH
- retina účinky léků MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vaskulární endoteliální růstové faktory antagonisté a inhibitory aplikace a dávkování terapeutické užití MeSH
- vlhká makulární degenerace farmakoterapie MeSH
- výsledek terapie MeSH
- zraková ostrost účinky léků MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- diferenciální diagnóza MeSH
- lidé MeSH
- makulární degenerace * komplikace patofyziologie MeSH
- nemoci retiny * etiologie patofyziologie MeSH
- neovaskularizace choroidey komplikace MeSH
- optická koherentní tomografie MeSH
- retinální pigmentový epitel patologie MeSH
- rizikové faktory MeSH
- vaskulární endoteliální růstové faktory antagonisté a inhibitory MeSH
- vlhká makulární degenerace komplikace patofyziologie MeSH
- Check Tag
- lidé MeSH
