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AIM: The main aim of this study is to evaluate the anatomical and functional results of pars plana vitrectomy (PPV) with peeling of the internal limiting membrane (ILM), membrane blue staining and subsequent expansile gas tamponade (perfluoropropane) in the treatment of idiopathic macular hole (IMH). MATERIAL AND METHODS: The retrospective analysis consisted of 100 eyes of a total of 100 patients (61 women and 39 men) with IMH, operated on at the Department of Ophthalmology of the Slovak Medical University and University Hospital Bratislava from 1 January 2021 to 1 January 2024, using 25-gauge PPV with ILM peeling and perfluoropropane tamponade (C3F8) of 15% concentration. After surgery, the patients were required to remain in a face-down position for at least one week. Best corrected visual acuity (BCVA), minimal linear diameter (MLD) on optic coherence tomography, macular hole closure type and occurrence of complications were evaluated. The obtained results were expressed with the use of arithmetic averages and displayed in graphs. RESULTS: Primary closure of macular hole was achieved in 93 patients (93%). The most frequently occurring type of closure was 1A. After surgery, the BCVA of all patients improved, from an average value of 0.101 preoperatively to 0.300 one year after surgery. In all groups of patients (regardless of the size of the macular hole before surgery), during the one-year follow-up period there was a gradual increase in BCVA with its stabilization by 6 months. The main factors that influenced postoperative BCVA were the preoperative values of MLD and BCVA. CONCLUSION: PPV with ILM peeling and perfluoropropane tamponade is an effective treatment for idiopathic macular holes with a success rate of more than 90%. This surgical procedure, associated with a relatively low number of complications, brings patients a definite improvement of BCVA.
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Fluorocarbonos , Perfurações Retinianas , Acuidade Visual , Vitrectomia , Humanos , Vitrectomia/métodos , Perfurações Retinianas/cirurgia , Perfurações Retinianas/fisiopatologia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Fluorocarbonos/administração & dosagem , Resultado do TratamentoRESUMO
This article presents an overview of treatment regimens of drugs containing antivascular endothelial growth factor for the treatment of neovascular form of age-related macular degeneration. Currently, drugs containing antivascular endothelial growth factor are the only effective treatment for this chronic and progressive disease. The treatment regimens for this disease in the last two decades have seen a shift from a simple endeavor to stabilize the disease to achieving maximum improvement of visual acuity and its maintenance, with improvement of the patient's quality of life and a minimal treatment burden on patients and their families. Other goals of the alternative dosing regimens that have replaced the original fixed regimens were greater individualization of the dosing regimen, better patient cooperation, saving financial costs and reducing the burden on application centers. Age-related macular degeneration, whether dry form or wet form, represents a serious health and socioeconomic problem, as the disease is one of the most common causes of severe and irreversible central visual acuity disorders up to the degree of practical blindness of one or both eyes in people over 50 years of age in developed industrialized countries. The most important issue is to ensure early diagnosis of this disease, followed by prompt and continuous treatment with an individualized proactive treatment regimen, with the aim of stabilizing and improving anatomical and functional results.
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Inibidores da Angiogênese , Degeneração Macular , Humanos , Inibidores da Angiogênese/administração & dosagem , Degeneração Macular/tratamento farmacológico , Degeneração Macular/diagnóstico , Degeneração Macular/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Bevacizumab/administração & dosagem , Bevacizumab/uso terapêuticoRESUMO
BACKGROUND: Age-related macular degeneration (AMD) is one of the major causes of vision loss in individuals aged ≥ 65 years in developed countries. This study aimed to determine the associations between modifiable risk factors and AMD. This is the first study describing the relationship between lifestyle factors and AMD in the Czech Republic. METHODS: In this cross-sectional case-control study, 93 AMD cases and 58 controls without AMD and cataract were included. All participants were examined by Optical coherence tomography at the Clinic of Eye Treatment at the University Hospital Brno. Data were collected using a pre-tested self-report questionnaire in a face-to-face interview. RESULTS: We found significant associations between those who were living in the city (OR 95% CI: 2.19 (1.0-4.6); p = 0,039), with a positive family history of AMD (OR 95% CI: 12.75 (1.6-98.6); p = 0,015), exposure to cigarette smoke (OR 95% CI: 2.72 (1.4-5.4); p = 0,004), and daily exposure to passive smoking (OR 95% CI: 2.29 (1.0-5.1); p = 0,045) and AMD. In men, we found significant associations between daily sunlight exposure (OR 95% CI: 2.98 (1.0-8.5); p = 0,041), short or long sleep duration (OR 95% CI: 3.98 (1.2-13.2); p = 0,024) and AMD. Men daily exposed to sunlight were at a 2.98 times higher risk of AMD than men with less than daily sunlight exposure. Men with short or long sleep duration (< 6 and > 8â h) were at a 3.98 times higher risk of AMD than men with recommended sleep duration of 6-8â h. CONCLUSIONS: An increased risk of AMD was observed for living in the city, family history of AMD, exposure to cigarette smoke, and daily exposure to passive smoking. Increased risk of AMD was observed for daily sunlight exposure and short or long sleep duration; however, only in men.
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Estilo de Vida , Degeneração Macular , Tomografia de Coerência Óptica , Humanos , Masculino , Feminino , Idoso , Estudos de Casos e Controles , Fatores de Risco , Estudos Transversais , Degeneração Macular/epidemiologia , Degeneração Macular/etiologia , Inquéritos e Questionários , Idoso de 80 Anos ou mais , República Tcheca/epidemiologia , Pessoa de Meia-Idade , Poluição por Fumaça de Tabaco/efeitos adversos , Fumar/efeitos adversos , Fumar/epidemiologiaRESUMO
BACKGROUND: Recently, trabeculectomy with mitomycin C (MMC) where MMC is applied by injection into the Tenon layer has attracted close attention. However, the data on efficacy and safety of this technique is still limited and more clinical studies are needed. Therefore, the work is aimed at comprehensive evaluation of the effectiveness of trabeculectomy using MMC applied by intra-Tenon injection. METHODS: A set of 50 eyes in 50 patients underwent trabeculectomy using MMC at concentration of 0.4 mg/ml in a total volume of 0.05 ml. The primary end point was to control intraocular pressure (IOP) on postoperative days 1, 8, 30 and 90 and subsequently at 6 and 12 months after surgery. The secondary end point was to evaluate the changes in various corneal parameters prior to and 90 days after surgical procedure. RESULTS: The mean preoperative IOP was 32.34 ± 9.45 mmHg. After surgery, the mean IOP significantly decreased to 17.52 ± 4.58 mmHg at the 90-day follow-up, and to 18.14 ± 3.74 and 19.30 ± 3.82 mmHg at 6 and 12 months after the procedure, respectively. The mean BCVA values remained unchanged compared to baseline (0.77 ± 0.23) to the 90-day follow-up (0.80 ± 0.23). The mean number of anti-glaucoma medications significantly reduced from 3.50 ± 0.74 to 0.58 ± 1.03 postoperatively. Similarly, the mean corneal hysteresis and ACD of the eye as well as CECD were significantly changed postoperatively. CONCLUSIONS: Trabeculectomy using MMC applied by injection is a safe and effective surgical method for the treatment of primary and secondary forms of open-angle glaucoma. It has a significant hypotonising effect and allows a complete discontinuation of antiglaucoma drugs (Tab. 3, Fig. 3, Ref. 58).
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Glaucoma de Ângulo Aberto , Glaucoma , Trabeculectomia , Humanos , Trabeculectomia/métodos , Mitomicina/uso terapêutico , Glaucoma/cirurgia , Glaucoma de Ângulo Aberto/cirurgia , Glaucoma de Ângulo Aberto/tratamento farmacológico , Resultado do Tratamento , Pressão Intraocular , SeguimentosRESUMO
BACKGROUND: Gait disturbance accompanies many neurodegenerative diseases; it is characteristic for Parkinson's disease (PD). Treatment of advanced PD often includes deep brain stimulation (DBS) of the subthalamic nucleus. Regarding gait, previous studies have reported non-significant or conflicting results, possibly related to methodological limitations. OBJECTIVE: The objective of this prospective study was to assess the effects of DBS on biomechanical parameters of gait in patients with PD. METHODS: Twenty-one patients with advanced PD participated in this prospective study. Gait was examined in all patients using the Zebris FDM-T pressure-sensitive treadmill (Isny, Germany) before DBS implantation and after surgery immediately, further immediately after the start of neurostimulation, and 3 months after neurostimulator activation. We assessed spontaneous gait on a moving treadmill at different speeds. Step length, stance phase of both lower limbs, double-stance phase, and cadence were evaluated. RESULTS: In this study, step length increased, allowing the cadence to decrease. Double-stance phase duration, that is, the most sensitive parameter of gait quality and unsteadiness, was reduced, in gait at a speed of 4.5 km/h and in the narrow-based gaits at 1 km/h (tandem gait), which demonstrates improvement. CONCLUSION: This study suggests positive effects of DBS treatment on gait in PD patients. Improvement was observed in several biomechanical parameters of gait.
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BACKGROUND: To evaluate the efficacy and safety of two individualized ranibizumab retreatment schemes in neovascular age-related macular degeneration. METHODS: Patients (N = 671) were randomized (1:1) to receive three initial monthly ranibizumab 0.5 mg injections, then retreatment guided by either best-corrected visual acuity (BCVA) loss (Group I) or BCVA loss and/or signs of disease activity on optical coherence tomography (OCT; Group II). The study was terminated prematurely and the decision to discontinue the study was made by the sponsor. Efficacy analyses were performed on patients who completed 12 months of the originally planned 24-month study. Safety analyses are presented for all safety analyzable patients. RESULTS: Of 671 randomized patients, 305 completed 12 months of the study. For the 12-month completers, baseline mean (standard deviation) BCVA and reading-center evaluated central subfield thickness (CSFT) were comparable [Group I: 60.9 (13.10) letters and 517.7(201.79) µm; Group II: 60.2 (12.21) letters and 515.3 (198.37) µm]. The change from baseline at Month 12 in BCVA was 6.7 (13.48) letters in Group I and 8.3 (13.53) letters in Group II and the change in CSFT was - 161.3 (163.48) µm and - 175.3 (170.45) µm, respectively. The mean number of ranibizumab injections was 8.2 in Group I and 8.4 in Group II. CONCLUSION: Ranibizumab treatment resulted in visual and anatomic gains at 12 months for both retreatment strategies, with a trend in favor of OCT-guided vs BCVA loss guided retreatment. No new safety signals were seen. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT01780935). Registered 31 January 2013.
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Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Ranibizumab/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Ranibizumab/efeitos adversos , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/fisiopatologiaRESUMO
PURPOSE: To evaluate the effect of intravitreal aflibercept injections in treatment-naive type 3 neovascularization using a fixed treatment regime during the first year of therapy. METHODS: Fourteen eyes of 14 patients diagnosed with type 3 neovascularization were studied. All patients were treated with intravitreal aflibercept injections using a fixed treatment regime of 3 consecutive monthly dosages followed by 2-month interval injections. Results were assessed after a 12-month follow-up period. Changes of best corrected visual acuity (BCVA), central retinal thickness (CRT), central macular volume (CMV), and retinal pigment epithelium (RPE) atrophy at fundus autofluorescence and infrared reflectance images were recorded and analyzed. RESULTS: BCVA improved from 60.3 ± 11.7 ETDRS letters at the baseline to 70.9 ± 10.3 ETDRS letters at 12-months follow-up (p = 0.036). Also, CRT and CMV statistically improved after the treatment (from 425 ± 117 to 308 ± 117 µm [p = 0.031] and from 9.52 ± 1.90 to 8.29 ± 0.95 mm3 [p = 0.073], respectively). In 4 patients, development and progression of RPE atrophy were observed, and it was associated with the presence of serous pigment epithelium detachment at the baseline. Furthermore, the development of a fibrotic lesion eccentric to the fovea was observed in 5 patients, without significant impairment of BCVA (p = 0.290). CONCLUSION: Intravitreal aflibercept administered in a fixed treatment regime during the first year of therapy may be effective for the improvement and stabilization of BCVA in eyes with type 3 neovascularization. However, RPE atrophy and subretinal/intraretinal fibrosis can develop during the treatment.
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Macula Lutea/patologia , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Epitélio Pigmentado da Retina/patologia , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Estudos Retrospectivos , Tomografia de Coerência Óptica , Degeneração Macular Exsudativa/diagnósticoRESUMO
BACKGROUND: The wet form of age-related macular degeneration (AMD) is characterized by pathological vascularization of the outer retinal layers. The condition responds to treatment with antibodies against vascular endothelial growth factor (VEGF), but the patients receiving such anti-VEGF therapy sometimes show undesirable acute short-term increases in the intraocular pressure (IOP). The cause of this adverse effect is unknown, and here, we are testing a hypothesis that it is related to CD36 gene polymorphisms. MATERIALS AND METHODS: A group of 134 patients with AMD were given three therapeutic doses of anti-VEGF antibody (ranibizumab) at monthly intervals. Their IOP was measured immediately before and 30 min after each injection. Patients' DNA was analyzed, and the changes in IOP were matched against seven polymorphisms of the CD36 gene. RESULTS: Three polymorphisms were found to be associated with increases in IOP: rs1049673 (p = 0.006), rs3211931 (p = 0.01), and rs1761667 (p = 0.043) at the time of the third injection only. Pronounced elevations (IOP > 25 mmHg) were associated with rs1049673 polymorphism: GC genotype (p < 0.01) and CC genotype (p < 0.05); both increasing the risk 2.6-fold, the presence of C-allele conferring a 1.5-fold greater risk and with rs3211931 polymorphism: AG genotype (p < 0.01) and GG genotype (p < 0.05); increasing the risk 2.6-fold (AG) and 2.7-fold (GG). CONCLUSIONS: CD36 receptor may be involved in mediating the effects of VEGF on IOP. The findings will help to identify the patients at risk of acutely elevated IOP following the anti-VEGF therapy.
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Inibidores da Angiogênese/uso terapêutico , Antígenos CD36/genética , Pressão Intraocular/genética , Hipertensão Ocular/genética , Polimorfismo de Nucleotídeo Único , Ranibizumab/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Feminino , Humanos , Injeções Intravítreas , Masculino , Reação em Cadeia da Polimerase , Tonometria Ocular , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/genéticaRESUMO
Highly macroporous semisynthetic cryogel microcarriers can be synthesized for culturing stem cells and neuronal type cells. Growth factors loaded to heparin-containing microcarriers show near zero-order release kinetics and cell-loaded microcarriers can be injected through a fine gauge cannula without negative effect on the cells. These carriers can be applied for cell transplantation applications.
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Anoikis/efeitos dos fármacos , Transplante de Células , Criogéis/farmacologia , Microesferas , Neurônios/citologia , Células-Tronco/citologia , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Injeções , Neurônios/efeitos dos fármacos , Células PC12 , Ratos , Ratos Transgênicos , Células-Tronco/efeitos dos fármacosRESUMO
AIMS: The aim of this communication was to evaluate ranibizumab in the treatment of wet age-related macular degeneration. METHODS: Anonymised data on treatment efficacy and safety were consecutively entered into the Czech national database. From 01/09/2008 to 25/10/2011, 671 patients/685 eyes treated with ranibizumab monotherapy were entered in the registry. 454 ranibizumab treated eyes and 444 patients were monitored for 12-months. The dependent variable used to monitor disease progression and treatment results was change in visual acuity in the ETDRS (Early Treatment Diabetic Retinopathy Study) chart over time. RESULTS: After 12 months of treatment, a loss of < 15 letters in the ETDRS chart was found in 81.5% of eyes treated with ranibizumab. A gain of ≥ 15 letters was found in 9.7% of eyes on ranibizumab. The results for our patients treated in clinical practice with ranibizumab were poorer than those in the SUSTAIN (Ranibizumab in Patients With Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration) study. A rationale for this was sought in a sub-analysis. CONCLUSIONS: Sub-analysis demonstrated that treatment naive CNV (choroidal neovascularization), occult CNV and lower height of the macular oedema at the outset of the disease may be positive prognostic factors for final visual acuity in anti-VEGF (vascular endothelial growth factor) treated patients.
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Degeneração Macular/tratamento farmacológico , Ranibizumab/uso terapêutico , Sistema de Registros , Idoso , Inibidores da Angiogênese/uso terapêutico , República Tcheca/epidemiologia , Feminino , Humanos , Incidência , Degeneração Macular/diagnóstico , Degeneração Macular/epidemiologia , Masculino , Estudos Retrospectivos , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade VisualRESUMO
Retinal vein occlusion (RVO) is a major cause of vision loss. Of the two main types of RVO, branch retinal vein occlusion (BRVO) is 4 to 6 times more prevalent than central retinal vein occlusion (CRVO). A basic risk factor for RVO is advancing age. Further risk factors include systemic conditions like hypertension, arteriosclerosis, diabetes mellitus, hyperlipidemia, vascular cerebral stroke, blood hyperviscosity, and thrombophilia. A strong risk factor for RVO is the metabolic syndrome (hypertension, diabetes mellitus, and hyperlipidemia). Individuals with end-organ damage caused by diabetes mellitus and hypertension have greatly increased risk for RVO. Socioeconomic status seems to be a risk factor too. American blacks are more often diagnosed with RVO than non-Hispanic whites. Females are, according to some studies, at lower risk than men. The role of thrombophilic risk factors in RVO is still controversial. Congenital thrombophilic diseases like factor V Leiden mutation, hyperhomocysteinemia and anticardiolipin antibodies increase the risk of RVO. Cigarette smoking also increases the risk of RVO as do systemic inflammatory conditions like vasculitis and Behcet disease. Ophthalmic risk factors for RVO are ocular hypertension and glaucoma, higher ocular perfusion pressure, and changes in the retinal arteries.
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PURPOSE: To evaluate the safety, tolerability and bioactivity of ascending doses of MP0112, a designed ankyrin repeat protein (DARPin) that binds with high affinity to vascular endothelial growth factor-A (VEGF-A), in treatment-naive patients with exudative age-related macular degeneration (AMD). DESIGN: Phase I/II, open-label, multicenter, dose-escalation study. METHODS: Patients were to receive a single intravitreal injection of MP0112 at doses ranging from 0.04 to 3.6 mg and be monitored for 16 weeks for safety, efficacy, pharmacokinetics, and dose response. RESULTS: Altogether, 32 patients received a single injection of MP0112. The maximum tolerated dose was 1.0 mg because of a case of endophthalmitis in the 2.0 mg cohort. Drug-related adverse events were reported by 13 (41%) of 32 patients; they included ocular inflammation in 11 patients (7 mild, 4 moderate in severity). Visual acuity scores were stable or improved compared with baseline for ≥4 weeks following injection; both retinal thickness and fluorescein angiography leakage decreased in a dose-dependent manner. Rescue therapy was administered to 20 (91%) of 22 patients who received 0.04-0.4 mg MP0112 compared with 4 of 10 (40%) patients who received 1.0 or 2.0 mg. Of patients in the higher-dose cohorts who did not require rescue treatment, 83% (5/6) maintained reductions in central retinal thickness through week 16. CONCLUSIONS: A single injection of 1.0 or 2.0 mg MP0112 resulted in mean decreases in retinal thickness and leakage area despite ocular inflammation. Larger-scale studies are warranted to confirm these observations.
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Repetição de Anquirina , Peptídeos/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/metabolismo , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Disponibilidade Biológica , Relação Dose-Resposta a Droga , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Masculino , Dose Máxima Tolerável , Peptídeos/efeitos adversos , Peptídeos/metabolismo , Peptídeos/farmacocinética , Ligação Proteica , Distribuição Tecidual , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/metabolismoRESUMO
High resolution imaging of biological structures and changes induced by various agents such as drugs and toxins is commonly performed by fluorescence and electron microscopy (EM). Although high-resolution imaging is possible with EM, the requirements for fixation and staining of samples for image contrast severely limits the study of living organisms. Atomic force microscopy (AFM), on the other hand, is capable of simultaneous nanometer spatial resolution and piconewton force detection, allowing detailed study of cell surface morphology and monitoring cytomechanical information. We present a method that images and studies mechanically characterized cells using AFM. We used a HeLa cell line (cervix carcinoma cell), which is sensitive to photodynamic treatment (PDT); growth media as a scanning surrounding; atomic force microscopy NT-MDT Aura for cytomechanical measurement; and scanning electron microscope Hitachi Su 6600 for control images of the cells. The modulus of elasticity for intact and photodynamically damaged cells can indicate mechanical changes to the main properties of cells. Cell elasticity changes can provide information on the degree or value of cell damage, for example after PDT. Measurements were carried out on approximately sixty cells, including three independent experiments on a control group and on sixty cells in a photodamaged group. Cells before PDT show higher elasticity: the median of Young´s modulus on the nucleus was 35.283 kPa and outside of the nucleus 107.442 kPa. After PDT, the median of Young's modulus on the nucleus was 61.144 kPa and outside of the nucleus was 193.605 kPa.
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Fotoquimioterapia , Fenômenos Biomecânicos , Módulo de Elasticidade/efeitos dos fármacos , Módulo de Elasticidade/efeitos da radiação , Células HeLa , Humanos , Microscopia de Força Atômica , Microscopia Eletrônica de VarreduraRESUMO
PURPOSE: Evaluation of the cost and effectiveness of therapy for patients with the wet form of age-related macular degeneration (AMD) in routine clinical practice. METHODS: A retrospective multicentre evaluation of changes in the best-corrected visual acuity in applied kinds of therapy and a comparison with the cost of individual therapeutic procedures. RESULTS: An overall total of 788 eyes of 763 patients with an average age of 73.2 ± 8.6 years was evaluated for a 1-year minimum period. In the ranibizumab and pegaptanib therapy groups, a reduction of 1.3 letters (p = 0.303) and 1.4 letters (p = 0.197) was found, respectively. In the group of photodynamic therapy (PDT) with verteporfin, a reduction of 5.2 letters was achieved (p < 0.001). Under the conditions of routine practice in the Czech Republic, the annual cost is highest (EUR 5,467.63/patient) in patients with pegaptanib therapy. The annual cost in patients with ranibizumab therapy is lower by EUR 1,220.16. The cost is nearly half (EUR 2,783.65) in the group treated with PDT with verteporfin. CONCLUSION: An initiation of AMD therapy by ranibizumab is cost-effective as compared to pegaptanib. Both ranibizumab and pegaptanib are significantly more efficient as compared to PDT with verteporfin. Therapy with ranibizumab and pegaptanib, as compared to PDT with verteporfin, prevents the loss of 1 line of vision on the ETDRS chart for EUR 1,225.98 and 2,286.18, respectively.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Aptâmeros de Nucleotídeos/uso terapêutico , Custos de Cuidados de Saúde/estatística & dados numéricos , Porfirinas/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/economia , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Aptâmeros de Nucleotídeos/economia , Análise Custo-Benefício , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia/economia , Fármacos Fotossensibilizantes/economia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/economia , Ranibizumab , Estudos Retrospectivos , Resultado do Tratamento , Verteporfina , Acuidade VisualRESUMO
Photodynamic therapy is a modality of treatment for tumors. The photochemical interactions of sensitizer, light and molecular oxygen produce reactive oxygen species (ROS) such as singlet oxygen, peroxide, hydroxyl radical and superoxide ion. The tumor is destroyed either by the formation of highly reactive singlet oxygen (type II mechanism) or by the formation of radical products (type 1 mechanism) generated in an energy transfer reaction. The resulting damage to organelles within malignant cells leads to tumor ablation. The cellular effects include membrane damage, mitochondrial damage and DNA damage. A new treatment modality called sonodynamic therapy has been developed, in which the ultrasound-induced cytotoxicity of sonochemical sensitizers inhibits tumor growth. In this study, the promising new generation of sensitizers - phthalocyanines - were used to induce the photodamage. In addition, we applied an ultrasound treatment to support the photodynamic effect. We report on the production of ROS in G361 melanoma cells. Light-emitting diodes were used to evoke the photodynamic effect. Changes in cells were evaluated using fluorescence microscope and atomic force microscopy. The quantitative ROS production changes in relation to sensitizer concentration, irradiation doses and ultrasound intensity were proved by a fluororeader. Our results showed the highest generation of ROS within G361 melanoma cells was achieved at an irradiation dose of 15 Jcm(-2) followed by ultrasound treatment at intensity of 2 Wcm(-2) and frequency of 1 MHz in the presence of 100 muM chloroaluminum phthalocyanine disulfonate (ClAlPcS2). These results suggest that ClAlPcS2 is a potential photosensitizer and sonosensitizer for sonodynamic or photodynamic treatment of cancer.
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Indóis/uso terapêutico , Melanoma/terapia , Compostos Organometálicos/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Cutâneas/terapia , Terapia por Ultrassom/métodos , Linhagem Celular Tumoral , Terapia Combinada/métodos , Relação Dose-Resposta a Droga , Fluorometria , Humanos , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Microscopia de Força Atômica , Microscopia de Fluorescência , Espécies Reativas de Oxigênio/análise , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Resultado do TratamentoRESUMO
The basic fibroblast growth factor (bFGF) is considered to be one of the candidate genes in the processes of tumour growth and angiogenesis. The aim of the present investigation was to find possible association of new polymorphisms in bFGF with proliferative diabetic retinopathy (PDR) and determine the plasma level in PDR. Allele, genotype and haplotype frequencies were determined in the association study comprising three groups of Caucasian subjects (n=488) (diabetics with/ PDR/ and without retinopathy/ non-PDR/ and non-diabetics/ non-DM/) in order to identify genetic marker for PDR. The plasma level of the bFGF protein was analysed by ELISA method. Significantly higher frequencies of 754C allele of the new 754C/G polymorphisms was found between PDR and non-DM group (p=0.05, OR=1.38). The comparison of plasma level of the bFGF showed statistically significant difference among studied groups (p=0.001). The bFGF plasma level in PDR group was significantly higher than in the groups of non-PDR and non-DM (p=0.017, p=0.001, respectively) and was significantly higher for CC and GC genotypes of 754C/G polymorphism in PDR group (p=0.006). Increased plasma level of the bFGF confirmed the importance of this candidate gene in the formation of PDR. However, the regulatory mechanisms of the bFGF level need further examinations.
Assuntos
Retinopatia Diabética/genética , Fator 2 de Crescimento de Fibroblastos/sangue , Fator 2 de Crescimento de Fibroblastos/genética , Variação Genética , Polimorfismo de Nucleotídeo Único , Polimorfismo Conformacional de Fita Simples , Idoso , Retinopatia Diabética/sangue , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/genética , Reação em Cadeia da PolimeraseRESUMO
Von Willebrand factor, a multimeric glycoprotein synthesized mainly by endothelial cells, is involved in platelet adhesion and aggregation and has an important role in the process of angiogenesis. Increased levels of von Willebrand factor, reflecting activation or damage of endothelial cells, have been described in association with proliferative diabetic retinopathy (PDR). We investigated the relationships of two polymorphisms (-1793G/C and Thr789Ala) in the von Willebrand factor gene with PDR. Genotypes were detected by polymerase chain reactions with subsequent restrictions with specific endonucleases. Allele frequencies were determined in an association study (n = 371) comprising three groups of subjects (diabetics with and without retinopathy and nondiabetics). Allele frequencies of the -1793G/C and Thr789Ala did not differ between the non-insulin-dependent diabetes mellitus (NIDDM) + PDR and the NIDDM non-PDR groups (p > 0.05). However, a statistically significant difference in allele and genotype frequencies of the -1793G/C was proved between all NIDDM versus nondiabetic subjects (p = 0.024 and 0.0065, respectively) with allele G and genotype GG being significantly more frequent in the NIDDM group. Calculated odds ratio for the GG genotype was 1.20 (95% CI, 0.77-1.86). Although significantly higher plasma von Willebrand factor antigen levels in NIDDM patients with PDR have been described in several studies, our findings indicate that no association exists between the two polymorphisms and PDR. However, the -1793G/C polymorphism might affect the risk of NIDDM.