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Biomedical subjects

K U Bartz-Schmidt

Publications and source records attributed to K U Bartz-Schmidt.

At least 19 recordsLinked to original sources

Intravitreal bevacizumab (Avastin) for occult choroidal neovascularization in age-related macular degeneration.

BACKGROUND: The purpose of the study is to report data on short-term safety of intravitreal bevacizumab treatment and its effect on visual function, central retinal thickness, and angiographical changes of occult choroidal neovascularization due to age-related macular degeneration. METHODS: A consecutive interventional case series of 30 patients with active subfoveal occult choroidal neovascularization secondary to age-related macular degeneration was followed after one intravitreal injection of 1.25 mg bevacizumab at baseline and subsequent injections following standardized criteria. At baseline and follow-up visits patients had visual acuity assessment, intraocular pressure measurement, fluorescein angiography, and optical coherence tomography imaging. RESULTS: No serious ocular or systemic adverse events were identified. A significant increase of intraocular pressure or signs of retinal toxicity or endophthalmitis were not detected in any patient. Optical coherence tomography revealed significant decrease (p < 0.001) in central retinal thickness after 1 week, 4 weeks, and 12 weeks, respectively. Fluorescein leakage decreased within 1 week and improvement was maintained at week 12 in the majority of patients. Visual acuity improved or remained stable in 29 of 30 patients; improvement of 3 or more lines was seen in 14 of 30 patients; one patients showed improvement of 6 lines. No patient had severe vision loss of 6 lines or more; moderate vision loss of 3 lines was seen in one patient. Re-injections of bevacizumab according to standard criteria were performed one to two times during the follow-up period of 12 weeks with a re-injection interval of 4 to 18 weeks (median 8 weeks). CONCLUSIONS: Short-term results suggest that intravitreal injection of bevacizumab is well tolerated and for the majority of patients with occult choroidal neovascularization in AMD results in improvement of visual acuity, decrease in central retina thickness, and reduction of angiographic leakage of the lesion. Bevacizumab as intravitreal treatment may provide a novel therapeutic option for selected patients with exudative AMD. Randomized prospective multicenter trials seem justified to further evaluate long term effects and impact of intravitreal bevacizumab on different subtypes of AMD compared to established therapies.

Aged↗

Effects of bevacizumab on retinal function in isolated vertebrate retina.

BACKGROUND: Bevacizumab (Avastin) is a recombinant protein that targets vascular endothelial growth factor (VEGF). In vitro, bevacizumab inhibits VEGF induced cell proliferation and tissue factor production. Abnormal angiogenesis involving VEGF is a central event during the development of choroidal neovascularisation (CNV). The present study was designed to evaluate the short term toxic effects of bevacizumab on retinal function for a therapeutic intraocular application. METHODS: Isolated bovine retinas were perfused with an oxygen pre-incubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using silver/silver chloride electrodes. Bevacizumab was added in different concentrations to the nutrient solution for 45 minutes. Thereafter the retina was reperfused for 60 minutes with normal nutrient solution. The percentage of a-wave and b-wave reduction during the application of bevacizumab was calculated and compared to control recordings. RESULTS: During the application of three different concentrations of bevacizumab (0.08 mg/ml, 0.25 mg/ml, 0.8 mg/ml) no significant reduction of the a-wave and b-wave amplitude was observed. During the washout, the ERG amplitudes were unchanged. CONCLUSION: The present study suggests that an intraocular application of 0.25 mg/ml bevacizumab for the treatment of CNV is reasonable. No significant short term effects of bevacizumab on retinal function were detected, but long term effects cannot be excluded.

Angiogenesis Inhibitors↗

Antiproliferative and cytotoxic properties of bevacizumab on different ocular cells.

AIM: To evaluate the antiproliferative and cytotoxic properties of bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), on human retinal pigment epithelium (ARPE19) cells, rat retinal ganglion cells (RGC5), and pig choroidal endothelial cells (CEC). METHODS: Monolayer cultures of ARPE19, RGC5, and CEC were used. Bevacizumab (0.008-2.5 mg/ml), diluted in culture medium, was added to cells that were growing on cell culture dishes. Cellular proliferative activity was monitored by 5'-bromo-2'-deoxyuridine (BrdU) incorporation into cellular DNA and the morphology assessed microscopically. For cytotoxicity assays ARPE19, RGC5, and CEC cells were grown to confluence and then cultured in a serum depleted medium to ensure a static milieu. The MTT test was performed after 1 day. The "Live/Dead" viability/cytotoxicity assay was performed and analysed by fluorescence microscopy after 6, 12, 18, 24, 30, 36, and 48 hours of incubation. Expression of VEGF, VEGF receptors (VEGFR1 and VEGFR2) and von Willebrand factor was analysed by immunohistochemistry. RESULTS: No cytotoxicity of bevacizumab on RGC5, CEC, and ARPE19 cells could be observed after 1 day. However, after 2 days at a bevacizumab concentration of 2.5 mg/ml a moderate decrease in ARPE19 cell numbers and cell viability was observed. Bevacizumab caused a dose dependent suppression of DNA synthesis in CEC as a result of a moderate antiproliferative activity (maximum reduction 36.8%). No relevant antiproliferative effect of bevacizumab on RGC5 and ARPE19 cells could be observed when used at a concentration of 0.8 mg/ml or lower. CEC and ARPE 19 cells stained positively for VEGF, VEGFR1, and VEGFR2. More than 95% of the CEC were positive for von Willebrand factor. CONCLUSIONS: These experimental findings support the safety of intravitreal bevacizumab when used at the currently applied concentration of about 0.25 mg/ml. Bevacizumab exerts a moderate growth inhibition on CEC when used in concentrations of at least 0.025 mg/ml. However, at higher doses (2.5 mg/ml) bevacizumab may be harmful to the retinal pigment epithelium.

Angiogenesis Inhibitors↗

Verteporfin photodynamic therapy induced apoptosis in choroidal neovascular membranes.

AIM: To evaluate the impact of verteporfin photodynamic therapy (PDT) on the induction of apoptosis in choroidal neovascular membranes (CNV) secondary to age related macular degeneration. METHODS: Retrospective review of 22 surgically excised CNV. 12 of these patients had been treated with PDT 3-146 days previously. Apoptotic cells were detected with the TUNEL technique and compared to the expression of CD34 (endothelial cells, EC), CD105 (activated endothelial cells), Ki-67 (proliferation marker), and cytokeratin18 (retinal pigment epithelial cells, RPE). RESULTS: CNV excised 3 days after PDT were characterised both by collapsed and patent vessels. The EC displayed a statistical significant positive TUNEL reaction when compared to the remaining treated CNV (p < 0.001) and untreated CNV (P = 0.002). The proliferative activity was reduced. CNV excised 1-5 months after PDT displayed a patent vascularisation and high proliferative activity. All membranes either treated or untreated disclosed only sporadic TUNEL positive cells within the stroma and the RPE. CONCLUSIONS: Verteporfin PDT leads to selective and effective damage of EC within CNV. Both patent and occluded vessels were lined by apoptotic EC. This finding and the increased expression of proliferation marker at later time points suggest that revascularisation after PDT is caused by angiogenesis rather than recanalisation.

Aged↗

[Intravitreal bevacizumab for neovascular age-related macular degeneration].

The efficacy and safety of the therapeutic anti-VEGF concept has already been demonstrated for pegaptanib and ranibizumab. Bevacizumab acts as an antibody against all VEGF-A isoforms and has been developed for oncological indications with intravenous application. Initial reports on intravitreal administration in patients with neovascular age-related macular disease (AMD) have shown beneficial morphological and functional effects. In the meantime, bevacizumab has been used off-label in thousands of patients with AMD. However, data from prospective, controlled, randomized trials on both safety and efficacy are lacking. Herein recent experiences with bevacizumab are summarized and discussed. Furthermore, a web-based platform for online data registration and pooled analyses is presented.

Angiogenesis Inhibitors↗

[(Side) effects of VEGF inhibition].

Vascular endothelial growth factor (VEGF) plays a pivotal role for embryo- and organogenesis. By regulating haemodynamics, (lymphoid) vessel architecture, haematopoiesis and immune system, endocrinology and reparative processes in adults, inhibited VEGF can cause multiple adverse events. Although the intravitreal administration of smaller doses can drastically reduce the systemic exposure, possible local side effects on retinal perfusion and survival of neuronal tissue must be taken into consideration. Before experience has been gained with VEGF inhibitors for longer than several years, individual discussion before the use, extensive informed consent and careful follow-up are necessary. From the ethical point of view, the available drugs should not be used without hesitation despite the clear benefit. First experiences with bevacizumab (Avastin), the first available (off-label) drug in Germany, are reported. In future, direct comparison of the different available drugs has to assess possible differences in the risk-benefit profile.

Angiogenesis Inhibitors↗

[Bevacizumab for treatment of macular edema secondary to retinal vein occlusion].

Application of VEGF inhibitors represents a treatment option for macular edema secondary to retinal vein occlusion that targets the disease at the causal molecular level. First reports on intravitreal injections of bevacizumab show promising morphological and functional effects and demonstrate that bevacizumab is a potent antiedematous agent in this context. A significant reduction of the central retinal thickness followed by a rapid improvement of visual acuity may be achieved within days. In a pilot study with a review period of 3 months, we found a significant improvement of one or more lines in 93% and four or more lines in 27% of eyes. This was associated with a concomitant significant reduction in central retinal thickness, which, however, was not sustained by a single injection (64% reduction after 1 month and 28% after 3 months). No relevant adverse events were noted. The duration of action after intravitreal bevacizumab administration is currently unknown. Reinjections will be necessary to maintain a lasting beneficial effect. Prospective, controlled long-term studies are mandatory to develop standardized treatment protocols that allow a safe and effective application of this off-label therapy.

Angiogenesis Inhibitors↗

[Current strategies for macular hole surgery in Germany, Austria and Switzerland].

BACKGROUND: Main aim of this study was to determine how macular hole surgery is currently being performed in Germany, Austria and Switzerland. METHODS: A questionnaire concerning the different aspects of surgery for stage 3 macular hole was developed and sent out to the 380 members of the German Retina Society. RESULTS: This analysis is based on 129 returned questionnaires from colleagues who perform macular hole surgery. A total of 95% (n=123) of the surgeons routinely perform vitrectomy with posterior vitreous detachment, peeling of epiretinal tissue and internal limiting membrane (ILM) peeling. Some 86% (n=106) stain the ILM, with 80% of these (n=85) using indocyanine green (ICG) in concentrations ranging from 0.005% up to 10%. Fourteen percent of ICG users perform a fluid-air exchange before applying the dye. Platelet concentrate is used by 8% of the surgeons with 97% (n=125) performing a gas tamponade using SF6 (53%), C3F8 (22%), C2F6 (16%) or just air (5%) (multiple answers: 4%). Simultaneous cataract surgery is routinely performed by 8%; by 73% only if there is significant cataract. CONCLUSIONS: There is common consent on the basic surgical steps, but several surgical details, e.g. ILM staining, are performed in substantially different ways.

Austria↗

[Injector implantation of a scleral-fixated intraocular lens].

BACKGROUND: In this pilot study, a new injector technique for small-incision implantation of scleral-fixated intraocular lenses (IOLs) was evaluated for IOL stability and visual rehabilitation. PATIENTS AND METHODS: Secondary lens implantation was performed in 18 aphakic eyes using a new small incision technique with injector implantation. This allowed for haptic suturing with the lens body inside the cartridge. All patients were followed-up for best-corrected visual acuity, refraction, IOL evaluation and ultrasound biomicroscopy. RESULTS: In all eyes the IOL was stable without tilt or torque. Best-corrected visual acuity improved 2.2 ETDRS lines after 1 week and 3.1 lines after a mean follow-up time of 7.9+/-2.8 months. Two eyes were complicated with small, peripheral transillumination defects (n=2), but no pigmentary glaucoma occurred. CONCLUSION: By using a self-sealing tunnel incision and injector technique, significant fluid egress and consecutive transient hypotony is minimized throughout the whole procedure. The technique shows a high IOL stability without tilt and assures rapid visual rehabilitation.

Adult↗

[Four plus one].

Explore the source record for details and available documents.

Blindness↗

[Effect of timolol on central corneal thickness and endothelial cell density].

BACKGROUND: The measurement of corneal thickness plays an increasing role in glaucoma screening and diagnosis. The influence of a variety of drugs on corneal thickness is well established. Especially for antiglaucomateous drugs this effect seems to be important. However, little is known about the influence of beta receptor antagonists on corneal thickness. The aim of this study was to provide evidence of the effect of timolol on central corneal thickness and endothelial cell density. MATERIALS AND METHODS: Ten healthy volunteers (five women and five men) with a mean age of 29 years (range 25 to 56 years) were examined in a double-blind, prospective and randomised pilot study. Intraocular pressure, corneal thickness and endothelial cell density was estimated before as well as fifteen minutes, 24, 48, 72 and 96 hours after application of timolol 0.5 % eye drops twice daily. The partner eye received sodium hyaluronate eye drops twice daily and served as a control. RESULTS: The application of timolol showed a decrease of intraocular pressure from initially 12 mmHg to 9 mmHg after four days (p = 0,0188) as well as an increase of corneal thickness from 537 microm to 557 microm after four days (p = 0,0659). There was no change of intraocular pressure (p = 0,9935) or corneal thickness (p = 0,9998) in the control eyes. There was also no effect of timolol (p = 0,2782) or sodium hyaluronate (p = 0,1940) on endothelial cell density. CONCLUSIONS: The study provides evidence of the influence of beta receptor antagonists on corneal thickness. This effect may be caused by receptor mediated influences on corneal ion and fluid transport. Further studies are needed to show if the increase of corneal thickness after application of topical timolol has clinical importance.

Adult↗

[Protein kinase C isoforms in corneal epithelium and endothelium].

BACKGROUND: Protein kinase C (PKC) plays a key role in cell metabolism. Three subgroups and 12 isoforms have been isolated so far, catalysing specific functions in cell metabolism. The demonstration of PKC subtypes in corneal tissue has been inconsistent. The aim of this study was to verify the expression of several PKC subgroups and isoforms in human and bovine corneal epithelial and endothelial cells. MATERIALS AND METHODS: PKC subgroups and isoforms were studied using polyclonal antibodies. RESULTS: Antibodies to PKC-alpha, -delta, -epsilon and -zeta, representing all three PKC subgroups, bound in human and bovine corneal epithelium and endothelium. No binding was found for antibodies to PKC-beta2. CONCLUSIONS: For the first time the presence of all three PKC subgroups was demonstrated in human and bovine corneal epithelial and endothelial cells. Further studies are needed to show the role of these subgroups in cellular functions such as cell proliferation and differentiation.

Adult↗

["Do you have a remedy for macular degeneration?" A field study about the advice given on dietary supplementation in 60 German pharmacies].

PURPOSE: Since completion of the AREDS study, evidence has accumulated to suggest that some form of dietary supplementation may be of value in special individuals who are at risk of progressive age-related macular degeneration (ARMD). We wanted to find out which of the many supplements available are recommended in practice and which instructions, promises, and purchasing arguments are used by German pharmacies. METHODS: A blinded consultation following a standardized protocol was carried out in 60 pharmacies. RESULTS: In 36 pharmacies specific products for dietary supplementation were recommended, but the dosage never complied with the AREDS study, and in 24 pharmacies, the necessity for a medical examination or consultation with an ophthalmologist was not mentioned. Possible interactions with other drugs or side effects were generally excluded. CONCLUSIONS: Potential risks of supplement intake were underestimated. Medical knowledge of the most frequent cause of blindness in the Western world was insufficient. A clear policy of recommendations according to evidence-based criteria is needed.

Attitude of Health Personnel↗