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Bin Chen - One of the best experts on this subject based on the ideXlab platform.
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Combination of Verteporfin-PDT and PI3K inhibitors enhances cell growth inhibition and apoptosis in endothelial cells
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXV, 2016Co-Authors: Daniel Kraus, Bin ChenAbstract:Vascular targeted photodynamic therapy is a promising cancer treatment modality by ablating tumor vasculature. The effectiveness of this treatment is often compromised by regrowth of endothelial cells, which causes tumor recurrence. In this preliminary report, we showed that activated PI3K signaling was involved in endothelial cell regrowth after PDT with Verteporfin and combination between Verteporfin-PDT and PI3K pathway inhibitor BEZ235 induced more cell apoptosis and greater inhibition in cell proliferation. These results suggest that rational combination of Verteporfin-PDT and PI3K inhibitors result in enhanced treatment outcomes.
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Abstract 3800: Targeting PI3K signaling pathway for therapeutic enhancement of Verteporfin-mediated photodynamic therapy
Molecular and Cellular Biology, 2015Co-Authors: Daniel Kraus, Pratheeba Palasuberniam, Bin ChenAbstract:Photodynamic therapy (PDT) induces cell injury and death through generation of reactive oxygen species (ROS) after light activation. Verteporfin is a photosensitizer that has been approved for the treatment of age-related macular degeneration and is under investigation for targeting tumor vasculature for therapy. Being primarily localized in mitochondria, Verteporfin-mediated PDT induced a rapid apoptotic cell death in SVEC mouse endothelial cells by activating mitochondria-initiated cell death pathways. However, activation of phosphatidylinositol 3-kinase (PI3K) signaling pathway was also observed after Verteporfin-PDT, especially at a sub-lethal dose. Furthermore, activation of PI3K signaling was correlated with cell growth after PDT. Thus, the goal of this study is to test the hypothesis that therapeutic outcome of Verteporfin-PDT can be enhanced by targeting PDT-induced pro-survival PI3K signaling pathway. We found that PI3K-mTOR pathway inhibitor NVP-BEZ235 (BEZ235) significantly inhibited PDT-induced PI3K signaling activation and combination of BEZ235 and Verteporfin-PDT resulted in more cell apoptosis and greater inhibition in cell proliferation in SVEC cells. The combination therapy led to significantly more tumor growth inhibition than each individual treatment in the PC-3 prostate tumor model. Examination of tumor samples for PI3K signaling activity and functional vasculature revealed that the combination treatment caused more inhibition in PI3K signaling and reduction in functional blood vessels than Verteporfin-PDT or BEZ235 treatment alone. These results indicate that targeting pro-survival PI3K signaling pathway is an effective approach for enhancing tumor response to Verteporfin-PDT. Citation Format: Daniel E. Kraus, Pratheeba Palasuberniam, Bin Chen. Targeting PI3K signaling pathway for therapeutic enhancement of Verteporfin-mediated photodynamic therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3800. doi:10.1158/1538-7445.AM2015-3800
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Abstract B53: Targeting PI3K signaling pathway for therapeutic enhancement of Verteporfin-mediated photodynamic therapy
Other Topics, 2015Co-Authors: Daniel Kraus, Bin ChenAbstract:Photodynamic therapy (PDT) induces cell injury and death through generation of reactive oxygen species (ROS) after light activation. Verteporfin is a photosensitizer that has been approved for the treatment of age-related macular degeneration and is under investigation for targeting tumor vasculature for therapy. Being primarily localized in mitochondria, Verteporfin-mediated PDT induced a rapid apoptotic cell death in SVEC mouse endothelial cells by activating mitochondria-initiated cell death pathways. However, activation of phosphatidylinositol 3-kinase (PI3K) signaling pathway was also observed after Verteporfin-PDT, especially at a sub-lethal dose. Furthermore, activation of PI3K signaling was correlated with cell growth after PDT. Thus, the goal of this study is to test the hypothesis that therapeutic outcome of Verteporfin-PDT can be enhanced by targeting PDT-induced pro-survival PI3K signaling pathway. We found that PI3K-mTOR pathway inhibitor NVP-BEZ235 (BEZ235) significantly inhibited PDT-induced PI3K signaling activation and combination of BEZ235 and Verteporfin-PDT resulted in more cell apoptosis and greater inhibition in cell proliferation in SVEC cells. The combination therapy led to significantly more tumor growth inhibition than each individual treatment in the PC-3 prostate tumor model. Examination of tumor samples for PI3K signaling activity and functional vasculature revealed that the combination treatment caused more inhibition in PI3K signaling and reduction in functional blood vessels than Verteporfin-PDT or BEZ235 treatment alone. These results indicate that targeting pro-survival PI3K signaling pathway is an effective approach for enhancing tumor response to Verteporfin-PDT. Citation Format: Daniel Kraus, Bin Chen. Targeting PI3K signaling pathway for therapeutic enhancement of Verteporfin-mediated photodynamic therapy. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr B53.
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Effects of Verteporfin-mediated photodynamic therapy on endothelial cells
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXIV, 2015Co-Authors: Daniel Kraus, Bin ChenAbstract:Photodynamic therapy (PDT) is a treatment modality in which cytotoxic reactive oxygen species are generated from oxygen and other biological molecules when a photosensitizer is activated by light. PDT has been approved for the treatment of cancers and age-related macular degeneration (AMD) due to its effectiveness in cell killing and manageable normal tissue complications. In this study, we characterized the effects of Verteporfin-PDT on SVEC mouse endothelial cells and determined its underlying cell death mechanisms. We found that Verteporfin was primarily localized in mitochondria and endoplasmic reticulum (ER) in SVEC cells. Light treatment of photosensitized SVEC cells induced a rapid onset of cell apoptosis. In addition to significant structural damages to mitochondria and ER, Verteporfin-PDT caused substantial degradation of ER signaling molecules, suggesting ER stress. These results demonstrate that Verteporfin-PDT triggered SVEC cell apoptosis by both mitochondrial and ER stress pathways. Results from this study may lead to novel therapeutic approaches to enhance PDT outcome.
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Comparison between endothelial and tumor cells in the response to Verteporfin-photodynamic therapy and a PI3K pathway inhibitor
Photodiagnosis and photodynamic therapy, 2015Co-Authors: B. A. Fateye, Aaron Wan, Xue Yang, Kenneth A. Myers, Bin ChenAbstract:Abstract Background Photodynamic therapy (PDT) is an established cancer treatment. Molecular-targeted agents targeting phosphatidylinositol 3-kinase (PI3K) pathway is showing great promise as anticancer drugs. This study compared SVEC mouse endothelial and PC-3 human prostate tumor cells in the response to Verteporfin-mediated photodynamic therapy (PDT) and a pan-PI3K pathway inhibitor LY294002. Methods Verteporfin cellular uptake and intracellular localization was determined by spectrofluorometry and confocal fluorescence microscopy, respectively, in the SVEC and PC-3 cells. Cytotoxicity induced by LY294002 and Verteporfin-PDT was assessed by the MTS assay. Effects of treatments on cell survival and death signaling were examined by Western blot analysis. Results PC-3 cells had a higher cellular uptake of Verteporfin than SVEC cells at 15 min after incubation with Verteporfin. Verteporfin was mainly localized in mitochondria in both SVEC and PC-3 cells. Verteporfin-PDT alone as well as PDT in combination with LY294002 induced more apoptosis and caused more reduction in cell viability in SVEC cells than in PC-3 cells. PC-3 cells exhibited a higher level of anti-apoptotic Bcl-2 family proteins than SVEC cells. Conclusions SVEC cells were more responsive to Verteporfin-PDT and PI3K pathway inhibitor LY294002 than PC-3 cells. Such differences in response were likely due to differences in Bcl-2 family protein level. These results support tumor vascular targeting by Verteporfin-PDT and its therapeutic enhancement by PI3K pathway inhibition.
Neil M. Bressler - One of the best experts on this subject based on the ideXlab platform.
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Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: meta-analysis of 2-year safety results in three randomized clinical trials: Treatment Of Age-Related Macular Degeneration With Photodynamic Therapy and
Retina (Philadelphia Pa.), 2004Co-Authors: Mohammad Azab, Kevin J Blinder, Susan B Bressler, Evangelos S. Gragoudas, Mustapha Benchaboune, Neil M. Bressler, Gary E. Fish, Yong Hao, Laurie Haynes, Jennifer I. LimAbstract:PURPOSE We sought to evaluate the detailed safety profile of photodynamic therapy with Verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (ARMD) from the combined analysis of three multicenter, double-masked, placebo-controlled, randomized 24-month clinical trials of similar design (TAP Investigation Studies A and B and the VIP ARMD Trial), and to clarify the adverse reaction information in the current Verteporfin product prescription information approved in the United States. METHODS Nine hundred forty-eight patients were randomly assigned to Verteporfin or placebo. Treatment was administered as described in previous reports. All general entry criteria were similar, so systemic safety results were combined for this analysis. Entry criteria for CNV lesion composition and visual acuity in the two TAP Investigation trials was different from those used in the VIP ARMD trial, so ocular safety results for the treated eye were not combined. RESULTS The percentage of patients who experienced at least one ocular or nonocular adverse event, regardless of relationship to therapy, was similar between the Verteporfin and placebo groups (92.3 and 89.1%, respectively, P = 0.114). The overall incidence of study eye adverse events was not significantly different between Verteporfin and placebo. The only clinically relevant ocular adverse events reported with higher incidence after Verteporfin compared with placebo were visual disturbances (22.1 versus 15.5% in TAP [P = 0.054] and 41.7 and 22.8% in VIP [P < 0.001]). Acute severe visual acuity decrease (defined as a visual acuity letter score decrease of at least 20, equivalent to at least four-line decrease, within 7 days of therapy) occurred in 3 patients treated with Verteporfin in the TAP Investigation (0.7%) and 11 in the VIP ARMD trial (4.9%). Systemic adverse events with increased incidence after Verteporfin compared with placebo, most of which were transient and mild or moderate, were injection site reactions (13.1 versus 5.6%; P < 0.001), photosensitivity reactions (2.4 versus 0.3%; P = 0.016), and infusion-related back pain (2.4 versus 0%; P = 0.004). No clinically relevant difference was observed between the Verteporfin and placebo groups in any other adverse event. CONCLUSION In 948 ARMD patients, Verteporfin therapy had an overall safety profile similar to that for placebo, with a few exceptions. Visual disturbances, including acute severe visual acuity decrease, did not affect the net vision outcome benefits associated with treatment that has been reported previously. This detailed safety profile of Verteporfin therapy clarifies the adverse reaction information in the current Verteporfin product prescription information.
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Large submacular hemorrhages after Verteporfin therapy
American journal of ophthalmology, 2004Co-Authors: Diana V., Neil M. Bressler, Susan B BresslerAbstract:Abstract Purpose To report the occurrence of large submacular hemorrhages after photodynamic therapy with Verteporfin in age-related macular degeneration patients with subfoveal choroidal neovascularization (CNV) composed of occult with no classic CNV in whom the hemorrhage precluded determining if additional therapy should be given within 3 months after initiation of treatment. Design Retrospective, noncomparative case series. Methods The records of all age-related macular degeneration patients who received Verteporfin therapy for subfoveal lesions composed of occult with no classic CNV between February and July 2001 at The Wilmer Eye Institute were reviewed. Subjects who reported either having undergone a procedure to remove intraocular blood before a month 3 follow-up visit, or who had submacular hemorrhage at the month 3 visit that was severe enough to preclude determining if additional Verteporfin therapy should be given were identified. Results Fifty-five eyes of 52 patients were reviewed. Five eyes (9% [95% confidence interval, 1.4%–16.6%]) developed submacular hemorrhage that precluded determining if additional Verteporfin therapy should be given. Visual acuity 3 months after documentation of the hemorrhage decreased a median of 8.5 lines compared with pretreatment acuity. Conclusions Even in the absence of acute severe visual acuity decrease, submacular hemorrhage after Verteporfin therapy can be associated with severe vision loss and preclude determining if additional therapy should be given.
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Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia 2 year results of a randomized clinical trial vip report no 3
Ophthalmology, 2003Co-Authors: Kevin J Blinder, Susan B Bressler, G Donati, Ugo Menchini, Joan W Miller, Neil M. Bressler, Mark S Blumenkranz, Hilel Lewis, Jordi Mones, Michael J PotterAbstract:PURPOSE: To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with Verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia. DESIGN AND SETTING: Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North America. PARTICIPANTS: Patients with subfoveal choroidal neovascular lesions caused by pathologic myopia measuring no more than 5400 micro m and best-corrected visual acuity (approximate Snellen equivalent) of 20/100 or better. METHODS: Similar to methods described for 1-year results with follow-up examinations beyond 1 year, continuing every 3 months (except Photograph Reading Center evaluations only at the month 24 examination). During the second year, the same regimen (with Verteporfin or placebo as applied at baseline) was used if angiography showed fluorescein leakage from CNV. MAIN OUTCOME MEASURES: The primary outcome was the proportion of eyes with fewer than 8 letters (approximately 1.5 lines) of visual acuity loss at the month 24 examination, adhering to an intent-to-treat analysis and using the last observation carried forward method to impute for any missing data. RESULTS: Seventy-seven of 81 patients (95%) in the Verteporfin group, compared with 36 of 39 patients (92%) in the placebo group, completed the month 24 examination. At this time point, 29 of 81 Verteporfin-treated patients (36%) compared with 20 of 39 placebo-treated patients (51%) lost at least 8 letters (P = 0.11). The distribution of change in visual acuity at the month 24 examination was in favor of a benefit for the cases assigned to Verteporfin (P = 0.05). This included improvement by at least 5 letters (equivalent to at least 1 line) in 32 Verteporfin-treated cases [40%] vs. five placebo-treated cases (13%) and improvement by at least 15 letters (equivalent to at least 3 lines) in 10 Verteporfin-treated cases (12%) vs. zero placebo-treated cases. No additional photosensitivity adverse reactions or injection site adverse events were associated with Verteporfin therapy in the second year of follow-up. CONCLUSIONS: Verteporfin therapy for subfoveal CNV caused by pathologic myopia safely maintained a visual benefit compared with a placebo therapy through 2 years of follow-up. Although the primary outcome was not statistically significantly in favor of Verteporfin therapy at 2 years as it had been at 1 year of follow-up, the distribution of change in visual acuity at the month 24 examination was in favor of the Verteporfin-treated group and showed that this group was more likely to have improved visual acuity through the month 24 examination. The VIP Study Group recommends Verteporfin therapy for subfoveal CNV resulting from pathologic myopia based on both the 1- and 2-year results of this randomized clinical trial.
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Photodynamic therapy with Verteporfin for subfoveal choroidal neovascularization in children
American journal of ophthalmology, 2003Co-Authors: Karin Mimouni, Susan B Bressler, Neil M. BresslerAbstract:Abstract Purpose To report the safety of photodynamic therapy with Verteporfin in three children. Design Retrospective interventional noncomparative case series. Methods Children identified from all patients treated with Verteporfin therapy at a university-based practice had records reviewed for adverse retinal or systemic events. Results Patients aged 11, 11, and 13 years, with subfoveal idiopathic choroidal neovascularization (CNV) received Verteporfin therapy with no ocular complications recognized either immediately after the procedure or during the follow-up from 7 to 12 months. Treatment resulted in cessation of fluorescence leakage from CNV by the last follow-up visit in two patients and reduced leakage from the lesion in one. The visual acuity change was + 4, +7, and 0 lines. Conclusion Verteporfin therapy in three children with subfoveal CNV was associated with stable or improved vision during short-term follow-up in the absence of serious ocular or systemic adverse events.
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effects of Verteporfin therapy on contrast sensitivity results from the treatment of age related macular degeneration with photodynamic therapy tap investigation tap report no 4
Retina-the Journal of Retinal and Vitreous Diseases, 2002Co-Authors: Gary S Rubin, Neil M. BresslerAbstract:Background: In the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) investigation, Verteporfin therapy reduced the risk of at least moderate vision loss (defined as a loss of at least 15 letters of visual acuity) in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (ARMD). This report presents detailed analyses of 24-month contrast sensitivity outcomes in these patients. Methods: The patients included in the TAP investigation had subfoveal CNV secondary to ARMD and received Verteporfin therapy (n = 402) or placebo (n = 207) at the first visit, with retreatment at each 3-month follow-up visit if angiography revealed fluorescein leakage from CNV. Contrast sensitivity was determined at each visit using a Pelli-Robson chart. Results: At the month 24 examination, Verteporfin-treated patients were less likely to lose at least 6 or 15 letters of contrast sensitivity than placebo-treated patients (86 [21%] versus 94 [45%] , and 27 [7%] versus 24 [12%] , respectively; P < 0.05 for both comparisons). The superiority of Verteporfin therapy over placebo was greater in patients with predominantly classic CNV at baseline, although Verteporfin-treated patients with minimally classic CNV also had better contrast sensitivity outcomes. Conclusions: Consistent with visual acuity outcomes, Verteporfin therapy reduced the risk of a clinically relevant loss of contrast sensitivity in the total study population, with the greatest effect in patients with predominantly classic subfoveal CNV secondary to ARMD. Verteporfin-treated patients with minimally classic CNV also had better contrast sensitivity outcomes than patients who received placebo. Given the association between contrast sensitivity and visual disability, the beneficial effects of Verteporfin therapy on contrast sensitivity outcomes are expected to have a favorable impact on patients' daily activities.
Susan B Bressler - One of the best experts on this subject based on the ideXlab platform.
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Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: meta-analysis of 2-year safety results in three randomized clinical trials: Treatment Of Age-Related Macular Degeneration With Photodynamic Therapy and
Retina (Philadelphia Pa.), 2004Co-Authors: Mohammad Azab, Kevin J Blinder, Susan B Bressler, Evangelos S. Gragoudas, Mustapha Benchaboune, Neil M. Bressler, Gary E. Fish, Yong Hao, Laurie Haynes, Jennifer I. LimAbstract:PURPOSE We sought to evaluate the detailed safety profile of photodynamic therapy with Verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (ARMD) from the combined analysis of three multicenter, double-masked, placebo-controlled, randomized 24-month clinical trials of similar design (TAP Investigation Studies A and B and the VIP ARMD Trial), and to clarify the adverse reaction information in the current Verteporfin product prescription information approved in the United States. METHODS Nine hundred forty-eight patients were randomly assigned to Verteporfin or placebo. Treatment was administered as described in previous reports. All general entry criteria were similar, so systemic safety results were combined for this analysis. Entry criteria for CNV lesion composition and visual acuity in the two TAP Investigation trials was different from those used in the VIP ARMD trial, so ocular safety results for the treated eye were not combined. RESULTS The percentage of patients who experienced at least one ocular or nonocular adverse event, regardless of relationship to therapy, was similar between the Verteporfin and placebo groups (92.3 and 89.1%, respectively, P = 0.114). The overall incidence of study eye adverse events was not significantly different between Verteporfin and placebo. The only clinically relevant ocular adverse events reported with higher incidence after Verteporfin compared with placebo were visual disturbances (22.1 versus 15.5% in TAP [P = 0.054] and 41.7 and 22.8% in VIP [P < 0.001]). Acute severe visual acuity decrease (defined as a visual acuity letter score decrease of at least 20, equivalent to at least four-line decrease, within 7 days of therapy) occurred in 3 patients treated with Verteporfin in the TAP Investigation (0.7%) and 11 in the VIP ARMD trial (4.9%). Systemic adverse events with increased incidence after Verteporfin compared with placebo, most of which were transient and mild or moderate, were injection site reactions (13.1 versus 5.6%; P < 0.001), photosensitivity reactions (2.4 versus 0.3%; P = 0.016), and infusion-related back pain (2.4 versus 0%; P = 0.004). No clinically relevant difference was observed between the Verteporfin and placebo groups in any other adverse event. CONCLUSION In 948 ARMD patients, Verteporfin therapy had an overall safety profile similar to that for placebo, with a few exceptions. Visual disturbances, including acute severe visual acuity decrease, did not affect the net vision outcome benefits associated with treatment that has been reported previously. This detailed safety profile of Verteporfin therapy clarifies the adverse reaction information in the current Verteporfin product prescription information.
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Large submacular hemorrhages after Verteporfin therapy
American journal of ophthalmology, 2004Co-Authors: Diana V., Neil M. Bressler, Susan B BresslerAbstract:Abstract Purpose To report the occurrence of large submacular hemorrhages after photodynamic therapy with Verteporfin in age-related macular degeneration patients with subfoveal choroidal neovascularization (CNV) composed of occult with no classic CNV in whom the hemorrhage precluded determining if additional therapy should be given within 3 months after initiation of treatment. Design Retrospective, noncomparative case series. Methods The records of all age-related macular degeneration patients who received Verteporfin therapy for subfoveal lesions composed of occult with no classic CNV between February and July 2001 at The Wilmer Eye Institute were reviewed. Subjects who reported either having undergone a procedure to remove intraocular blood before a month 3 follow-up visit, or who had submacular hemorrhage at the month 3 visit that was severe enough to preclude determining if additional Verteporfin therapy should be given were identified. Results Fifty-five eyes of 52 patients were reviewed. Five eyes (9% [95% confidence interval, 1.4%–16.6%]) developed submacular hemorrhage that precluded determining if additional Verteporfin therapy should be given. Visual acuity 3 months after documentation of the hemorrhage decreased a median of 8.5 lines compared with pretreatment acuity. Conclusions Even in the absence of acute severe visual acuity decrease, submacular hemorrhage after Verteporfin therapy can be associated with severe vision loss and preclude determining if additional therapy should be given.
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effect of lesion size visual acuity and lesion composition on visual acuity change with and without Verteporfin therapy for choroidal neovascularization secondary to age related macular degeneration tap and vip report no 1
American Journal of Ophthalmology, 2003Co-Authors: Kevin J Blinder, S Bradley, N M Bressler, Susan B Bressler, G Donati, Ugo Menchini, Joan W Miller, Michael J Potter, Constantin J Pournaras, Al ReavesAbstract:PURPOSE: To determine whether differences in baseline lesion size and visual acuity might explain differing results found in three different lesion compositions (predominantly classic, minimally classic, and occult with no classic) among three placebo-controlled, randomized clinical trials evaluating photodynamic therapy with Verteporfin (Visudyne, Novartis AG), also termed Verteporfin therapy, in patients with subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS: Exploratory analyses were conducted in patients with predominantly classic or minimally classic lesions at enrollment in the Treatment of AMD with Photodynamic Therapy (TAP) Investigation and in AMD patients with occult with no classic CNV in the Verteporfin In Photodynamic Therapy (VIP) Trial. Baseline characteristics of patients among these three lesion compositions were compared. In addition, multiple linear regression modeling was used to explore the effect of baseline lesion size, visual acuity, and lesion composition on mean change in visual acuity from baseline to 24 months. RESULTS: At baseline, the mean size of predominantly classic lesions (3.4 disk areas) was smaller than that of minimally classic (4.7 disk areas) and occult with no classic lesions (4.3 disk areas). In the multiple linear regression model of individual lesion compositions, there was a significant treatment-by-lesion-size interaction for minimally classic and occult with no classic lesions, but not for predominantly classic lesions. Interaction between treatment and baseline visual acuity was not significant for any lesion composition. Small Verteporfin-treated lesions lost less vision than large Verteporfin-treated lesions in each lesion composition. In the multiple linear regression model that included all lesion compositions, lesion size was a more significant predictive factor for the magnitude of treatment benefit than either lesion composition or visual acuity. Smaller (4.0 disk areas or less) minimally classic and occult with no classic lesions had similar visual acuity outcomes to those observed in predominantly classic lesions. CONCLUSIONS: Based on exploratory analyses, lesion size in the TAP Investigation and VIP Trial was an important predictor of the magnitude of treatment benefit with Verteporfin therapy in occult with no classic and minimally classic lesion compositions. In patients with AMD, treating smaller rather than larger neovascular lesions, regardless of lesion composition, likely will result in a better level of visual acuity.
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Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia 2 year results of a randomized clinical trial vip report no 3
Ophthalmology, 2003Co-Authors: Kevin J Blinder, Susan B Bressler, G Donati, Ugo Menchini, Joan W Miller, Neil M. Bressler, Mark S Blumenkranz, Hilel Lewis, Jordi Mones, Michael J PotterAbstract:PURPOSE: To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with Verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia. DESIGN AND SETTING: Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North America. PARTICIPANTS: Patients with subfoveal choroidal neovascular lesions caused by pathologic myopia measuring no more than 5400 micro m and best-corrected visual acuity (approximate Snellen equivalent) of 20/100 or better. METHODS: Similar to methods described for 1-year results with follow-up examinations beyond 1 year, continuing every 3 months (except Photograph Reading Center evaluations only at the month 24 examination). During the second year, the same regimen (with Verteporfin or placebo as applied at baseline) was used if angiography showed fluorescein leakage from CNV. MAIN OUTCOME MEASURES: The primary outcome was the proportion of eyes with fewer than 8 letters (approximately 1.5 lines) of visual acuity loss at the month 24 examination, adhering to an intent-to-treat analysis and using the last observation carried forward method to impute for any missing data. RESULTS: Seventy-seven of 81 patients (95%) in the Verteporfin group, compared with 36 of 39 patients (92%) in the placebo group, completed the month 24 examination. At this time point, 29 of 81 Verteporfin-treated patients (36%) compared with 20 of 39 placebo-treated patients (51%) lost at least 8 letters (P = 0.11). The distribution of change in visual acuity at the month 24 examination was in favor of a benefit for the cases assigned to Verteporfin (P = 0.05). This included improvement by at least 5 letters (equivalent to at least 1 line) in 32 Verteporfin-treated cases [40%] vs. five placebo-treated cases (13%) and improvement by at least 15 letters (equivalent to at least 3 lines) in 10 Verteporfin-treated cases (12%) vs. zero placebo-treated cases. No additional photosensitivity adverse reactions or injection site adverse events were associated with Verteporfin therapy in the second year of follow-up. CONCLUSIONS: Verteporfin therapy for subfoveal CNV caused by pathologic myopia safely maintained a visual benefit compared with a placebo therapy through 2 years of follow-up. Although the primary outcome was not statistically significantly in favor of Verteporfin therapy at 2 years as it had been at 1 year of follow-up, the distribution of change in visual acuity at the month 24 examination was in favor of the Verteporfin-treated group and showed that this group was more likely to have improved visual acuity through the month 24 examination. The VIP Study Group recommends Verteporfin therapy for subfoveal CNV resulting from pathologic myopia based on both the 1- and 2-year results of this randomized clinical trial.
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Photodynamic therapy with Verteporfin for subfoveal choroidal neovascularization in children
American journal of ophthalmology, 2003Co-Authors: Karin Mimouni, Susan B Bressler, Neil M. BresslerAbstract:Abstract Purpose To report the safety of photodynamic therapy with Verteporfin in three children. Design Retrospective interventional noncomparative case series. Methods Children identified from all patients treated with Verteporfin therapy at a university-based practice had records reviewed for adverse retinal or systemic events. Results Patients aged 11, 11, and 13 years, with subfoveal idiopathic choroidal neovascularization (CNV) received Verteporfin therapy with no ocular complications recognized either immediately after the procedure or during the follow-up from 7 to 12 months. Treatment resulted in cessation of fluorescence leakage from CNV by the last follow-up visit in two patients and reduced leakage from the lesion in one. The visual acuity change was + 4, +7, and 0 lines. Conclusion Verteporfin therapy in three children with subfoveal CNV was associated with stable or improved vision during short-term follow-up in the absence of serious ocular or systemic adverse events.
Monique P. Curran - One of the best experts on this subject based on the ideXlab platform.
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Spotlight on Verteporfin in Subfoveal Choroidal Neovascularisation
Drugs & Aging, 2004Co-Authors: Susan J. Keam, Lesley J. Scott, Monique P. CurranAbstract:Verteporfin (Visudyne®) therapy (photodynamic therapy with intravenous liposomal Verteporfin) is the first treatment to effectively prevent the loss of visual acuity in patients with subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD), pathological myopia or presumed ocular histoplasmosis syndrome (POHS). In adult patients with classic subfoveal CNV or occult with no classic subfoveal CNV secondary to AMD, or subfoveal CNV secondary to pathological myopia or POHS, Verteporfin therapy slows or prevents loss of visual acuity. In well designed clinical trials, Verteporfin therapy was superior to placebo in patients with subfoveal classic-containing CNV and occult with no classic CNV secondary to AMD at 12 and/or 24 months (Treatment of Age-related macular degeneration with Photodynamic therapy [TAP] Investigation and Verteporfin In Photodynamic therapy [VIP-AMD] trial) and in patients with pathological myopia at 12 months (Verteporfin In Photodynamic therapy [VIP-PM] trial). Limited data suggest that Verteporfin therapy also prevents loss of visual acuity in patients with subfoveal CNV secondary to POHS. Verteporfin therapy was generally well tolerated in clinical trials; most adverse events were mild to moderate in intensity and transient. The most frequently reported Verteporfin therapy-related adverse events (incidence >2%) were visual disturbance, injection-site reactions, photosensitivity reactions and infusion-related back pain. Approximately 5% of patients with occult with no classic subfoveal CNV secondary to AMD reported severe vision decrease within 7 days of treatment in clinical trials; 3 months later, several patients had recovered some of this loss. Conclusion: Photodynamic therapy with Verteporfin, the first photosensitiser approved for the treatment of subfoveal CNV, is a well tolerated treatment that stabilises or slows visual acuity loss in adult patients with predominantly classic or occult with no classic subfoveal CNV secondary to AMD, and subfoveal CNV secondary to pathological myopia or POHS. Thus, Verteporfin therapy provides a valuable option for the management of these patients for whom treatment options are few, and should be considered as a first-line therapy in these difficult-to-manage conditions.
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Spotlight on Verteporfin in Subfoveal Choroidal Neovascularisation
Drugs & aging, 2004Co-Authors: Susan J. Keam, Lesley J. Scott, Monique P. CurranAbstract:Verteporfin (Visudyne®) therapy (photodynamic therapy with intravenous liposomal Verteporfin) is the first treatment to effectively prevent the loss of visual acuity in patients with subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD), pathological myopia or presumed ocular histoplasmosis syndrome (POHS).
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Verteporfin : a review of its use in the management of subfoveal choroidal neovascularisation.
Drugs, 2003Co-Authors: Susan J. Keam, Lesley J. Scott, Monique P. CurranAbstract:UNLABELLED Verteporfin (Visudyne) therapy (photodynamic therapy with intravenous liposomal Verteporfin) is the first treatment to effectively prevent the loss of visual acuity in patients with subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD), pathological myopia or presumed ocular histoplasmosis syndrome (POHS). In adult patients with classic subfoveal CNV or occult with no classic subfoveal CNV secondary to AMD, or subfoveal CNV secondary to pathological myopia or POHS, Verteporfin therapy slows or prevents loss of visual acuity. In well designed clinical trials, Verteporfin therapy was superior to placebo in patients with subfoveal classic-containing CNV and occult with no classic CNV secondary to AMD at 12 and/or 24 months (Treatment of Age-related macular degeneration with Photodynamic therapy [TAP] Investigation and Verteporfin In Photodynamic therapy [VIP-AMD] trial) and in patients with pathological myopia at 12 months (Verteporfin In Photodynamic therapy [VIP-PM] trial). Limited data suggest that Verteporfin therapy also prevents loss of visual acuity in patients with subfoveal CNV secondary to POHS. Verteporfin therapy was generally well tolerated in clinical trials; most adverse events were mild to moderate in intensity and transient. The most frequently reported Verteporfin therapy-related adverse events (incidence >2%) were visual disturbance, injection-site reactions, photosensitivity reactions and infusion-related back pain. Approximately 5% of patients with occult with no classic subfoveal CNV secondary to AMD reported severe vision decrease within 7 days of treatment in clinical trials; 3 months later, several patients had recovered some of this loss. CONCLUSION Photodynamic therapy with Verteporfin, the first photosensitiser approved for the treatment of subfoveal CNV, is a well tolerated treatment that stabilises or slows visual acuity loss in adult patients with predominantly classic or occult with no classic subfoveal CNV secondary to AMD, and subfoveal CNV secondary to pathological myopia or POHS. Thus, Verteporfin therapy provides a valuable option for the management of these patients for whom treatment options are few, and should be considered as a first-line therapy in these difficult-to-manage conditions.
Lesley J. Scott - One of the best experts on this subject based on the ideXlab platform.
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Spotlight on Verteporfin in Subfoveal Choroidal Neovascularisation
Drugs & Aging, 2004Co-Authors: Susan J. Keam, Lesley J. Scott, Monique P. CurranAbstract:Verteporfin (Visudyne®) therapy (photodynamic therapy with intravenous liposomal Verteporfin) is the first treatment to effectively prevent the loss of visual acuity in patients with subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD), pathological myopia or presumed ocular histoplasmosis syndrome (POHS). In adult patients with classic subfoveal CNV or occult with no classic subfoveal CNV secondary to AMD, or subfoveal CNV secondary to pathological myopia or POHS, Verteporfin therapy slows or prevents loss of visual acuity. In well designed clinical trials, Verteporfin therapy was superior to placebo in patients with subfoveal classic-containing CNV and occult with no classic CNV secondary to AMD at 12 and/or 24 months (Treatment of Age-related macular degeneration with Photodynamic therapy [TAP] Investigation and Verteporfin In Photodynamic therapy [VIP-AMD] trial) and in patients with pathological myopia at 12 months (Verteporfin In Photodynamic therapy [VIP-PM] trial). Limited data suggest that Verteporfin therapy also prevents loss of visual acuity in patients with subfoveal CNV secondary to POHS. Verteporfin therapy was generally well tolerated in clinical trials; most adverse events were mild to moderate in intensity and transient. The most frequently reported Verteporfin therapy-related adverse events (incidence >2%) were visual disturbance, injection-site reactions, photosensitivity reactions and infusion-related back pain. Approximately 5% of patients with occult with no classic subfoveal CNV secondary to AMD reported severe vision decrease within 7 days of treatment in clinical trials; 3 months later, several patients had recovered some of this loss. Conclusion: Photodynamic therapy with Verteporfin, the first photosensitiser approved for the treatment of subfoveal CNV, is a well tolerated treatment that stabilises or slows visual acuity loss in adult patients with predominantly classic or occult with no classic subfoveal CNV secondary to AMD, and subfoveal CNV secondary to pathological myopia or POHS. Thus, Verteporfin therapy provides a valuable option for the management of these patients for whom treatment options are few, and should be considered as a first-line therapy in these difficult-to-manage conditions.
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Spotlight on Verteporfin in Subfoveal Choroidal Neovascularisation
Drugs & aging, 2004Co-Authors: Susan J. Keam, Lesley J. Scott, Monique P. CurranAbstract:Verteporfin (Visudyne®) therapy (photodynamic therapy with intravenous liposomal Verteporfin) is the first treatment to effectively prevent the loss of visual acuity in patients with subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD), pathological myopia or presumed ocular histoplasmosis syndrome (POHS).
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Verteporfin : a review of its use in the management of subfoveal choroidal neovascularisation.
Drugs, 2003Co-Authors: Susan J. Keam, Lesley J. Scott, Monique P. CurranAbstract:UNLABELLED Verteporfin (Visudyne) therapy (photodynamic therapy with intravenous liposomal Verteporfin) is the first treatment to effectively prevent the loss of visual acuity in patients with subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD), pathological myopia or presumed ocular histoplasmosis syndrome (POHS). In adult patients with classic subfoveal CNV or occult with no classic subfoveal CNV secondary to AMD, or subfoveal CNV secondary to pathological myopia or POHS, Verteporfin therapy slows or prevents loss of visual acuity. In well designed clinical trials, Verteporfin therapy was superior to placebo in patients with subfoveal classic-containing CNV and occult with no classic CNV secondary to AMD at 12 and/or 24 months (Treatment of Age-related macular degeneration with Photodynamic therapy [TAP] Investigation and Verteporfin In Photodynamic therapy [VIP-AMD] trial) and in patients with pathological myopia at 12 months (Verteporfin In Photodynamic therapy [VIP-PM] trial). Limited data suggest that Verteporfin therapy also prevents loss of visual acuity in patients with subfoveal CNV secondary to POHS. Verteporfin therapy was generally well tolerated in clinical trials; most adverse events were mild to moderate in intensity and transient. The most frequently reported Verteporfin therapy-related adverse events (incidence >2%) were visual disturbance, injection-site reactions, photosensitivity reactions and infusion-related back pain. Approximately 5% of patients with occult with no classic subfoveal CNV secondary to AMD reported severe vision decrease within 7 days of treatment in clinical trials; 3 months later, several patients had recovered some of this loss. CONCLUSION Photodynamic therapy with Verteporfin, the first photosensitiser approved for the treatment of subfoveal CNV, is a well tolerated treatment that stabilises or slows visual acuity loss in adult patients with predominantly classic or occult with no classic subfoveal CNV secondary to AMD, and subfoveal CNV secondary to pathological myopia or POHS. Thus, Verteporfin therapy provides a valuable option for the management of these patients for whom treatment options are few, and should be considered as a first-line therapy in these difficult-to-manage conditions.
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Verteporfin
Drugs & Aging, 2000Co-Authors: Lesley J. ScottAbstract:▲ Verteporfin, a benzoporphyrin derivative monoacid ring A, is a photosensitising drug for photodynamic therapy (PDT) activated by low-intensity, nonheat-generating light of 689nm wavelength. Activation generates cytotoxic oxygen free radicals. ▲ The specificity and uptake of Verteporfin for target cells with a high expression of low density lipoprotein (LDL) receptors, such as tumour and neovascular endothelial cells, is enhanced by the use of a liposomal formulation and its rapid uptake by plasma LDL. ▲ Verteporfin therapy (at light doses < 150 J/cm^2) selectively damages neovascular endothelial cells leading to thrombus formation and specific occlusion of choroidal neovascular vessels in subfoveal lesions in patients with age-related macular degeneration (AMD). ▲ Repeated applications of Verteporfin therapy 6 mg/m^2 improved or maintained visual acuity in the majority of patients with some classic subfoveal choroidal neovascularisation (CNV) secondary to AMD at 1 year’s follow-up in 2 large multicentre, placebocontrolled, double-blind trials. ▲ Furthermore, in a subgroup of these patients with predominantly classic CNV secondary to AMD, there was a significantly more marked visual acuity (VA) benefit with 67.3% of Verteporfin-treated eyes experiencing less than a 15-letter loss of VA versus 39.3% with placebo treatment. ▲ Multiple applications of Verteporfin therapy were well tolerated in patients with subfoveal CNV secondary to AMD. The most common adverse events were visual disturbances, injection site reactions, photosensitivity reactions and infusion-related back pain.
