Polypoidal choroidal vasculopathy (PCV) is usually regarded as a subtype of choroidal neovascularization (CNV) that is secondary to age-related macular degeneration (AMD) characterized by choroidal vessel branching, ending in polypoidal lesions. Despite their close association, PCV and neovascular AMD have shown differences, especially regarding patients’ treatment response. Currently, antivascular endothelial growth factor (anti-VEGF) drugs, such as ranibizumab, bevacizumab and aflibercept, have demonstrated their efficacy in CNV patients. However, in PCV, anti-VEGF treatments have shown inconclusive results. Many genetic polymorphisms have been associated with a variable response in exudative/wet AMD patients. Thus, the aim of this study is to explore the genetic variants affecting anti-VEGF drug response in PCV patients. In this regard, we performed a systematic review and meta-analysis. We found four variants (CFH I62V, CFH Y402H, ARMS2 A69S, and HTRA1-62A/G) that have been significantly related to response. Among them, the ARMS2 A69S variant is assessed in our meta-analysis. In conclusion, in order to implement anti-VEGF pharmacogenetics in clinical routines, further studies should be performed, distinguishing physio-pathogenic circumstances between PCV and exudative AMD and the combined effect on treatment response of different genetic variants.
High myopia is an ophthalmic pathology that affects half of the young adults in the United States and Europe and it is predicted that a third of the world’s population could be nearsighted at the end of this decade. It is characterized by at least 6 diopters or axial length > 26 mm and, choroidal neovascularization (CNV) in 5 to 11% of cases. Ranibizumab is a recombinant humanized monoclonal antibody fragment. It is an anti-vascular endothelial growth factor (anti-VEGF) drug used in the treatment of CNV. Many genetic polymorphisms have been associated with interindividual differences in the response to ranibizumab, but these associations were not yet assessed among patients with high myopia and CNV. We performed a retrospective study assessing the association of genetic polymorphisms with response to ranibizumab in patients with CNV secondary to high myopia (mCNV). We included genetic polymorphisms previously associated with the response to drugs used in CNV patients (bevacizumab, ranibizumab, aflibercept, and photodynamic therapy (PDT)). We also included genetic variants in the VEGFA gene. Based on our results, ARMS2 (rs10490924) and CFH (rs1061170) are associated with response to ranibizumab in high myopia patients; and, included VEGFA genetic polymorphisms are not associated with ranibizumab response in our population but might be related to a higher risk of CNV.
A severe form of myopia defined as pathologic/high myopia is the main cause of visual impairment and one of the most frequent causes of blindness worldwide. It is characterized by at least 6 diopters or axial length (AL) of eyeball >26 mm and choroidal neovascularization (CNV) in 5 to 10% of cases. Ranibizumab is a humanized recombinant monoclonal antibody fragment targeted against human vascular endothelial growth factor A (VEGF-A) used in the treatment of CNV. It acts by preventing VEGF-A from interacting with its receptors (VEGFR-1 and -2) encoded by the FLT1 and KDR genes. Several studies found that the KDR and FLT1 genotypes may represent predictive determinants of efficacy in ranibizumab-treated neovascular age-related macular degeneration (nAMD) patients. We performed a retrospective study to evaluate the association of single nucleotide polymorphisms (SNPs) in VEGFR coding genes with the response rate to ranibizumab in patients with high myopia and CNV. In the association study of genotypes in FLT1 with the response to ranibizumab, we found a significant association between two FLT1 variants (rs9582036, rs7993418) with ranibizumab efficacy at the 12-month follow-up. About the KDR gene, we found that two KDR variants (rs2305948, rs2071559) are associated with best-corrected visual acuity (BCVA) improvement and KDR (rs2239702) is associated with lower rates of BCVA worsening considering a 12-month follow-up period.
BackgroundCD69 receptor is a C lectin transmembrane protein expressed by T cells, natural killer (NK) cells and active B cells. This receptor is involved in the production and regulation of T cells, B cells and NK cells, and these are involved in interleukin 6 (IL-6) production. IL-6 is a multifunctional glycoprotein involved in the immune response, inflammation and bone metabolism; IL-6 makes significant contributions to autoimmune and inflammatory diseases such as rheumatoid arthritis (RA). Tocilizumab is a humanised monoclonal antibody inhibitor of IL-6 receptor, indicated in combination with methotrexate in the treatment of RA in patients with inadequate response or intolerance to prior therapies.PurposeThe aim of this study was evaluate the role of the CD69 A>G (rs11052877) genetic polymorphism on the response to tocilizumab in RA patients.Material and methodsThe CD69 A>G (rs11052877) genetic polymorphism was genotyped using predesigned TaqMan genotyping assay technology and analysed on a ViiA7 real time PCR system. Clinical response was evaluated at 3, 6, 9 and 12 months after the first infusion of the drug, using the 28 joint disease activity score criteria (DAS28), and good responders were classified according to EULAR criteria. EULAR good response was defined as a change in DAS28 >1.2 and DAS28 ≤3.2. Statistical analysis was performed using SPSS V.20.ResultsClinical data from 140 tocilizumab treated patients were obtained. The patients were aged (mean±SD) 53.25±12.42 years and 79% were women. Even though we found a greater proportion of good responders among CD69 GG carriers than among A/G or A/A carriers at 3 months (60% vs 43.27%), 6 months (72.73% vs 59.17%), 9 months (76.19% vs 65.66%) and 12 months (90% vs 73.95%), these results were not statistically significant (p=0.17, p=0.22, p=0.34 and p=0.09)ConclusionThese results show that the CD69 A>G (rs11052877) genetic polymorphism by itself is not useful as a predictor of tocilizumab response in RA patients but its influence should be studied further.No conflict of interest
Background Hospitals are putting in place more systems to improve the use of medicines. Since 2010, the Pharmacy Service has regularly been using a Medicines Reconciliation (MR) System at admission to the General Surgery, Urology and Orthopaedic Surgery wards. Purpose To assess the level of satisfaction of specialist and nurses with the MR System at hospital admission. Materials and methods An anonymous satisfaction survey with four questions was designed with the intention of identifying the subjects’ opinion about the following: the daily presence of the pharmacist on the ward; the extent to which MR may improve patients’ safety and clinical condition. Finally, the subjects were asked to evaluate the MR system as a whole. We used a Likert scale from 1 = full disagreement to 5 = full agreement. The head of each Service and the nurse supervisor were informed about the aims of the survey, and later on the services themselves were in charge of handing out the survey to their staff from March to May 2012. Results 100 surveys were filled in. 68.5% of specialists and 60% of nurses participated in this project. 92.3% of nurses fully agreed with the daily presence of the pharmacist in the ward, whereas only 52.5% of specialists did. Regarding the patients’ clinical condition the survey showed that 50% of specialists and 92.3% of nurses fully agreed with the positive effect of MR. 71.8% of nurses and 62.3% of specialists fully agreed that the patient’s safety improved due to MR. The overall assessment concluded that 40% of specialists gave the system full marks (5 out of 5); 15.4% of nurses were in agreement and 84.6% in full agreement. Conclusions In general, a high degree of satisfaction with MR was detected in the Surgery Services, more particularly among nurses. No conflict of interest.
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