We conducted a systematic review to evaluate whether the existing evidence justifies the intravit... more We conducted a systematic review to evaluate whether the existing evidence justifies the intravitreal use of bevacizumab in comparison to ranibizumab in age-related macular degeneration. Compared with photodynamic therapy, bevacizumab shows a relative improvement in visual acuity that is of similar size as in the comparison of ranibizumab with photodynamic therapy (relative improvement from 30 to 35%). However, this finding is based on one randomized controlled trial including less than 50 patients treated with bevacizumab. Also, nothing is known about long-term (>12 months) improvements in visual acuity and optimal treatment intervals for bevacizumab.Regarding safety, the published literature indicates that ocular and systemic adverse effects are less frequent under bevacizumab than ranibizumab treatment. But the validity of this finding is strongly limited by inadequate reporting, an unsystematic evaluation of adverse effects and short follow-up times in studies evaluating bevacizumab. Given the lack of controlled data, the widespread off-label use of bevacizumab is not justified in clinical practice. On the other hand, a major challenge in the management of patients who require repeated antivascular endothelial growth factor injections is the high cost of ranibizumab. This dilemma underlines the need for head-to-head studies comparing both vascular endothelial growth factor antibodies, or, at least, well conducted randomized controlled trials evaluating intravitreal bevacizumab.
ABSTRACT Purpose To measure the level of VEGF protein in serum and breast milk after intravitreal... more ABSTRACT Purpose To measure the level of VEGF protein in serum and breast milk after intravitreal injection of bevacizumab and ranibizumab.Methods Serum and breast milk samples before and after repeated intravitreal injections of bevacizumab and ranibizumab were collected from a 35-year old female who was treated for CNV secondary to a chorioretinal scar and who was nursing her 4-month old son. Samples were analysed for the level of VEGF protein via ELISA.Results VEGF protein in the serum was reduced significantly to non-detectable levels after intravitreal injection of bevacizumab and started to recover only after 6 weeks. After intravitreal injection of ranibizumab, however, only a temporary dip 3 days after injection could be detected. VEGF in breast milk was reduced by approximately one third directly after injection of bevacizumab. After injection of ranibizumab, the level of VEGF protein remained unaltered.Conclusion Use of intravitreal VEGF inhibitors should be avoided during pregnancy or while nursing a baby. However, if necessary, ranibizumab seems to have a lower effect on VEGF in the serum or breast milk an should therefore be used.
To compare the complication spectrum and rate of 23-G and 20-G vitrectomy for macular surgery. Th... more To compare the complication spectrum and rate of 23-G and 20-G vitrectomy for macular surgery. This was a retrospective comparative analysis of 20-G and 23-G vitrectomy (introduced in 2007) for macular surgery due to macular pucker or macular hole performed between 2006 and 2010 in 61 and 59 eyes, respectively, by 2 experienced surgeons and 2 trainees. We assessed the adjusted hazard ratio for vitrectomy 23-G vs 20-G with a Cox proportional hazard model. We counted retinal detachment, vitreous hemorrhage, endophthalmitis (as early postoperative complications), or cataract progression (as late postoperative complication) as endpoint. We adjusted for indication, surgeon, retinopexy method, and the endotamponade. Follow-up averaged 712 days. Median time to first event was 385 days in the 23-G group and 342 days in the 20-G group. Cox proportional hazard analysis showed no significant difference between vitrectomy 23-G vs 20-G with regard to postoperative complications (hazard ratio 0.7...
Although anti-VEGF therapy of exudative AMD with bevacizumab and ranibizumab proved efficacious i... more Although anti-VEGF therapy of exudative AMD with bevacizumab and ranibizumab proved efficacious in the majority of patients, CNV activity does not respond to continued treatment after repeated injections in a considerable amount of patients. These are referred to as nonresponders. A change of the drug to bevacizumab or ranibizumab could possibly offer an alternative option for the treatment of nonresponding exudative AMD. A total of 138 nonresponders who switched therapy from bevacizumab to ranibizumab (n=114) or vice versa (n=24) were included in a retrospective study. Visual acuity (VA) and foveal thickness before and after the switch of therapy were compared. By means of linear regression analysis, we analyzed possible prognostic factors associated with a favorable outcome for visual acuity. Linear regression analysis revealed a statistically significant benefit for nonresponders when treatment was changed to a different anti-VEGF drug (bevacizumab or ranibizumab). VA at the time of the switch was positively correlated with a beneficial development of VA after changing the drug. There was no significant correlation with age, macular thickness, number of injections before the switch, or the development of VA under treatment before the switch. Both patients switching to Avastin and Lucentis benefitted without statistically significant differences. An exchange of bevacizumab with ranibizumab or vice versa should be considered in nonresponders in the treatment of exudative AMD. Further prognostic factors may help to identify patients who might benefit from a switch. These factors should be investigated in further studies.
ABSTRACT Purpose EphrinB2 is predominantly expressed in arteries, while its ligand EphB4 is predo... more ABSTRACT Purpose EphrinB2 is predominantly expressed in arteries, while its ligand EphB4 is predominantly expressed in veins. Activation of ephrinB2 and EphB4 by receptor dimers have been shown to enhance neovascularization, whereas inhibition of EphB4 reduced neovascularization both in vitro and in vivo in a mouse model of oxygen-induced retinopathy (OIR). These data suggest a role of the ephrinB2-EphB4 system in retinal neovascularization. We looked for expression of these membrane-bound factors in a mouse model of OIR.Methods Heterogenic EphB4lacZ+/- mice were examined in a well-established mouse model of oxygen-induced retinopathy. Mice were kept in 75% oxygen for postnatal days P7-P12. Returned to room air, they underwent a relative hypoxia and developed a proliferative retinopathy within the next 5-7 days. Eyes were enucleated on P17-P19 during the peak of vascular proliferation, stained for LacZ, and embedded in paraffin. Sections were investigated for LacZ staining.Results Sections show a strong expression of EphB4 in preretinal neovascularization both in small and larger vessels. EphB4 is also mildly expressed in vessels in the inner plexiform layer and in the ganglion cell layer.Conclusion The expression pattern suggests a role of EphB4 in preretinal neovascularization in a mouse model of OIR. Further studies of the intracellular localisation of EphB4 are needed to add to understanding the role of the ephrin system in OIR.
We conducted a systematic review to evaluate whether the existing evidence justifies the intravit... more We conducted a systematic review to evaluate whether the existing evidence justifies the intravitreal use of bevacizumab in comparison to ranibizumab in age-related macular degeneration. Compared with photodynamic therapy, bevacizumab shows a relative improvement in visual acuity that is of similar size as in the comparison of ranibizumab with photodynamic therapy (relative improvement from 30 to 35%). However, this finding is based on one randomized controlled trial including less than 50 patients treated with bevacizumab. Also, nothing is known about long-term (>12 months) improvements in visual acuity and optimal treatment intervals for bevacizumab.Regarding safety, the published literature indicates that ocular and systemic adverse effects are less frequent under bevacizumab than ranibizumab treatment. But the validity of this finding is strongly limited by inadequate reporting, an unsystematic evaluation of adverse effects and short follow-up times in studies evaluating bevacizumab. Given the lack of controlled data, the widespread off-label use of bevacizumab is not justified in clinical practice. On the other hand, a major challenge in the management of patients who require repeated antivascular endothelial growth factor injections is the high cost of ranibizumab. This dilemma underlines the need for head-to-head studies comparing both vascular endothelial growth factor antibodies, or, at least, well conducted randomized controlled trials evaluating intravitreal bevacizumab.
ABSTRACT Purpose To measure the level of VEGF protein in serum and breast milk after intravitreal... more ABSTRACT Purpose To measure the level of VEGF protein in serum and breast milk after intravitreal injection of bevacizumab and ranibizumab.Methods Serum and breast milk samples before and after repeated intravitreal injections of bevacizumab and ranibizumab were collected from a 35-year old female who was treated for CNV secondary to a chorioretinal scar and who was nursing her 4-month old son. Samples were analysed for the level of VEGF protein via ELISA.Results VEGF protein in the serum was reduced significantly to non-detectable levels after intravitreal injection of bevacizumab and started to recover only after 6 weeks. After intravitreal injection of ranibizumab, however, only a temporary dip 3 days after injection could be detected. VEGF in breast milk was reduced by approximately one third directly after injection of bevacizumab. After injection of ranibizumab, the level of VEGF protein remained unaltered.Conclusion Use of intravitreal VEGF inhibitors should be avoided during pregnancy or while nursing a baby. However, if necessary, ranibizumab seems to have a lower effect on VEGF in the serum or breast milk an should therefore be used.
To compare the complication spectrum and rate of 23-G and 20-G vitrectomy for macular surgery. Th... more To compare the complication spectrum and rate of 23-G and 20-G vitrectomy for macular surgery. This was a retrospective comparative analysis of 20-G and 23-G vitrectomy (introduced in 2007) for macular surgery due to macular pucker or macular hole performed between 2006 and 2010 in 61 and 59 eyes, respectively, by 2 experienced surgeons and 2 trainees. We assessed the adjusted hazard ratio for vitrectomy 23-G vs 20-G with a Cox proportional hazard model. We counted retinal detachment, vitreous hemorrhage, endophthalmitis (as early postoperative complications), or cataract progression (as late postoperative complication) as endpoint. We adjusted for indication, surgeon, retinopexy method, and the endotamponade. Follow-up averaged 712 days. Median time to first event was 385 days in the 23-G group and 342 days in the 20-G group. Cox proportional hazard analysis showed no significant difference between vitrectomy 23-G vs 20-G with regard to postoperative complications (hazard ratio 0.7...
Although anti-VEGF therapy of exudative AMD with bevacizumab and ranibizumab proved efficacious i... more Although anti-VEGF therapy of exudative AMD with bevacizumab and ranibizumab proved efficacious in the majority of patients, CNV activity does not respond to continued treatment after repeated injections in a considerable amount of patients. These are referred to as nonresponders. A change of the drug to bevacizumab or ranibizumab could possibly offer an alternative option for the treatment of nonresponding exudative AMD. A total of 138 nonresponders who switched therapy from bevacizumab to ranibizumab (n=114) or vice versa (n=24) were included in a retrospective study. Visual acuity (VA) and foveal thickness before and after the switch of therapy were compared. By means of linear regression analysis, we analyzed possible prognostic factors associated with a favorable outcome for visual acuity. Linear regression analysis revealed a statistically significant benefit for nonresponders when treatment was changed to a different anti-VEGF drug (bevacizumab or ranibizumab). VA at the time of the switch was positively correlated with a beneficial development of VA after changing the drug. There was no significant correlation with age, macular thickness, number of injections before the switch, or the development of VA under treatment before the switch. Both patients switching to Avastin and Lucentis benefitted without statistically significant differences. An exchange of bevacizumab with ranibizumab or vice versa should be considered in nonresponders in the treatment of exudative AMD. Further prognostic factors may help to identify patients who might benefit from a switch. These factors should be investigated in further studies.
ABSTRACT Purpose EphrinB2 is predominantly expressed in arteries, while its ligand EphB4 is predo... more ABSTRACT Purpose EphrinB2 is predominantly expressed in arteries, while its ligand EphB4 is predominantly expressed in veins. Activation of ephrinB2 and EphB4 by receptor dimers have been shown to enhance neovascularization, whereas inhibition of EphB4 reduced neovascularization both in vitro and in vivo in a mouse model of oxygen-induced retinopathy (OIR). These data suggest a role of the ephrinB2-EphB4 system in retinal neovascularization. We looked for expression of these membrane-bound factors in a mouse model of OIR.Methods Heterogenic EphB4lacZ+/- mice were examined in a well-established mouse model of oxygen-induced retinopathy. Mice were kept in 75% oxygen for postnatal days P7-P12. Returned to room air, they underwent a relative hypoxia and developed a proliferative retinopathy within the next 5-7 days. Eyes were enucleated on P17-P19 during the peak of vascular proliferation, stained for LacZ, and embedded in paraffin. Sections were investigated for LacZ staining.Results Sections show a strong expression of EphB4 in preretinal neovascularization both in small and larger vessels. EphB4 is also mildly expressed in vessels in the inner plexiform layer and in the ganglion cell layer.Conclusion The expression pattern suggests a role of EphB4 in preretinal neovascularization in a mouse model of OIR. Further studies of the intracellular localisation of EphB4 are needed to add to understanding the role of the ephrin system in OIR.
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Papers by Christoph Ehlken