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Sample records for single intravitreal bevacizumab

  1. Quality of bevacizumab (Avastin®) repacked in single-use glass vials for intravitreal administration.

    Science.gov (United States)

    Sugimoto, Michelle A A; Toledo, Vicente de Paulo Coelho Peixoto de; Cunha, Mariem Rodrigues Ribeiro; Carregal, Virginia M; Jorge, Rodrigo; Leão, Pedro; Fialho, Sílvia Ligorio; Silva-Cunha, Armando

    2017-01-01

    Avastin® (bevacizumab) is an anti-vascular endothelial growth factor (VEGF) monoclonal antibody given as an off-label drug by intravitreal administration for treatment of ocular diseases. The drug's clinical application and its cost-benefit profile has generated demand for its division into single-use vials to meet the low volume and low-cost doses necessary for intraocular administration. However, the safety of compounding the drug in single-use vials is still under discussion. In this study, the stability and efficacy of Avastin® repacked in individual single-use glass vials and glass ampoules by external compounding pharmacies were evaluated. Polyacrylamide gel electrophoresis (PAGE), size-exclusion chromatography (SEC), dynamic light scattering (DLS), and turbidimetry were selected to detect the formation of aggregates of various sizes. Changes in bevacizumab biological efficacy were investigated by using an enzyme-linked immunosorbent assay (ELISA). Repacked and reference bevacizumab showed similar results when analyzed by PAGE. By SEC, a slight increase in high molecular weight aggregates and a reduction in bevacizumab monomers were observed in the products of the three compounding pharmacies relative to those in the reference bevacizumab. A comparison of repacked and reference SEC chromatograms showed that the mean monomer loss was ≤1% for all compounding pharmacies. Protein aggregates in the nanometer- and micrometer-size ranges were not detected by DLS and turbidimetry. In the efficacy assay, the biological function of repacked bevacizumab was preserved, with <3% loss of VEGF binding capacity relative to that of the reference. The results showed that bevacizumab remained stable after compounding in ampoules and single-use glass vials; no significant aggregation, fragmentation, or loss of biological activity was observed.

  2. Intravitreal bevacizumab (avastin for circumscribed choroidal hemangioma

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    Subrata Mandal

    2011-01-01

    Full Text Available Circumscribed choroidal hemangiomas are rare ophthalmic entities that cause diminution in vision due to accumulation of subretinal and/or intraretinal fluid in the macular area. Various treatment options ranging from conventional laser to photodynamic therapy have been employed to destroy the tumor and reduce the exudation; however, either the inability to penetrate through the exudative fluid or the collateral retinal damage induced by these treatment modalities make them unsuitable for lesions within the macula. We evaluated the role of intravitreal bevacizumab, a pan-vascular endothelial growth factor (VEGF inhibitor, in reducing the sub- and intraretinal fluid in three patients with circumscribed choroidal hemangiomas. All the patients had complete resolution of the serous retinal detachment that was maintained till at least 12 months after the first injection. Intravitreal bevacizumab may be used in combination with thermal laser or photodynamic therapy in treating circumscribed choroidal hemangiomas with subretinal fluid.

  3. Acute anterior uveitis following intravitreal bevacizumab but not subsequent ranibizumab

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    Antonopoulos C

    2011-11-01

    Full Text Available Christina Antonopoulos1, Maxwell Stem2, Grant M Comer21Department of Ophthalmology, Boston University, Boston, MA, USA; 2WK Kellogg Eye Center, Department of Ophthalmology, University of Michigan, Ann Arbor, MI, USAPurpose: Previous reports have identified noninfectious uveitis as a potential sequela following both intravitreal bevacizumab and ranibizumab injections. We present two unique cases of acute anterior uveitis following intravitreal bevacizumab that did not occur with subsequent ranibizumab injections.Methods: Case report.Conclusion: These cases may reflect differences in the etiology of anterior uveitis following intravitreal bevacizumab and ranibizumab. Given these differences, it may be reasonable to offer ranibizumab to patients who have experienced presumed bevacizumab-induced anterior uveitis.Keywords: adverse effect, age-related macular degeneration, anterior uveitis, bevacizumab, ranibizumab, uveitis

  4. Isolated sixth nerve palsy after intravitreal bevacizumab injection.

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    Cakmak, Hasan Basri; Toklu, Yasin; Yorgun, Mücella Arikan; Simşek, Saban

    2010-03-01

    To report a case of sixth nerve palsy after intravitreal bevacuzimab injection. After intravitreal bevacizumab injection in a 64-year-old man, the patient admitted to our clinic with the complaint of diplopia. A complete ophthalmologic examination was done to clear the symptomatology of patient. Examination of ductions revealed marked limitation of abduction of the right eye and full ductions of the left eye, consistent with right lateral rectus paralysis. Although intravitreal bevacizumab injections are generally well tolerated, it is possible that some serious systemic adverse events may occur. For this reason, patients must be closely monitored following these injections.

  5. Acute sterile endophthalmitis following intravitreal bevacizumab: case series

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    Orozco-Hernández, Axel; Ortega-Larrocea, Ximena; Sánchez-Bermúdez, Gustavo; García-Aguirre, Gerardo; Cantón, Virgilio Morales; Velez-Montoya, Raul

    2014-01-01

    Background Since the ophthalmological community adopted the use of intravitreal bevacizumab as an accepted off-label treatment for neovascular diseases, the amount of knowledge regarding its effects and properties has been increasing continually. In the last few years, there have been an increasing number of reports about sterile intraocular inflammation and intraocular pressure elevations after intravitreal bevacizumab. In the following case series, we describe the clinical presentation and outcomes of ten consecutive cases of patients developing mild-to-severe sterile intraocular inflammation after intravitreal bevacizumab and their management. Methods This report presents a retrospective case series. We reviewed the medical records of ten consecutive patients from a group of 46, in whom repackaged bevacizumab in individual aliquots from two vials from the same batch were used. All surgical procedures were performed using standard sterile techniques in the operating room. At each follow-up visit, patients underwent a complete ophthalmological examination including visual acuity assessment, intraocular pressure, biomicroscopy, and posterior fundus examination. Results Ten patients presented sterile endophthalmitis with an onset time of 3.5±1.95 days. The clinical characteristics were mild pain, slight visual loss, conjunctival hyperemia, and various degrees of intraocular inflammation with microhypopyon. All cultures were negative. All patients were managed with topical steroids and antibiotics, except two, in whom, due to severe vitreous cells, intravitreal antibiotics were used. Three patients showed a transient elevation of intraocular pressure. Only 50% of the patients regained a visual acuity equal or better to the baseline visual acuity on file. Conclusion The increasing number of intravitreal injections of bevacizumab applied every day, due to its widespread acceptance, might be one reason why the number of cases of sterile endophthalmitis is rising. Fast

  6. Pharmacokinetics of intravitreal bevacizumab (Avastin® in rabbits

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    Sinapis C

    2011-05-01

    Full Text Available Christos I Sinapis1,*, John G Routsias2,*, Angelos I Sinapis1,*, Dimitrios I Sinapis1,*, George D Agrogiannis3, Alkistis Pantopoulou1, Stamatis E Theocharis4, Stefanos Baltatzis5, Efstratios Patsouris3, Despoina Perrea11Laboratory for Experimental Surgery and Surgical Research 'N.S.Christeas', 2Laboratory of Pathophysiology, 3Laboratory of Pathology, 4Laboratory of Forensic Medicine and Toxicology, 5Department of Ophthalmology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece *Contributed equally to the studyPurpose: To describe the pharmacokinetics of intravitreal bevacizumab (Avastin® in rabbits.Methods: The right eye of 20 rabbits was injected intravitreally with 1.25 mg/0.05 mL bevacizumab. Both eyes of four rabbits each time were enucleated at days 1, 3, 8, 15, and 29. Bevacizumab concentrations were measured in serum, aqueous humor, and vitreous.Results: Maximum vitreous (406.25 µg/mL and aqueous humor (5.83 µg/mL concentrations of bevacizumab in the right eye were measured at day 1. Serum bevacizumab concentration peaked at day 8 (0.413 µg/mL and declined to 0.032 µg/mL at 4 weeks. Half-life values in right vitreous, right aqueous humor, and serum were 6.61, 6.51, and 5.87 days, respectively. Concentration of bevacizumab in the vitreous of the noninjected eye peaked at day 8 (0.335 ng/mL and declined to 0.218 ng/mL at 4 weeks. In the aqueous humor of the noninjected eye, maximum concentration of bevacizumab was achieved at day 8 (1.6125 ng/mL and declined (to 0.11 ng/mL at 4 weeks.Conclusion: The vitreous half-life of 1.25 mg/0.05 mL intravitreal bevacizumab was 6.61 days in this rabbit model. Maximum concentrations of bevacizumab were reached at day 1 in both vitreous and aqueous humor of the right eye and at day 8 in the serum. Very low concentrations of bevacizumab were measured in the fellow noninjected eye.Keywords: bevacizumab, pharmacokinetics, rabbits, intravitreal

  7. [The results of intravitreal bevacizumab in high myopic subretinal neovascularisation].

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    Branisteanu, D; Moraru, Andreea

    2013-01-01

    To asses the anatomical and functional results after intravitreal bevacizumab administration in choroidal neovascularization secondary to pathologic myopia; To asses the safety and results stability; Prospective, interventional case study of 18 eyes with choroidal neovascularization secondary to pathologic myopia treated with 1.25 mg. intravitreal bevacizumab (AVASTIN). Intravitreal injection was repeated, if needed, at 4-6 weeks until leakage stopped. In all cases fluorescein angiograms and Spectral 3D OCTs were performed. Visual acuity was measured with ETDRS optotype. Cases were followed-up at least 6 months. Statistical analysis was performed using ANOVA and Wilcoxon tests. Mean age of patients in the study was 43.86%--6.32 years (ranging 24-62 years). The mean number of intravitreal injections was 2.62%--0.53 (ranging between 1 - 4 injections). Mean visual acuity improved in all cases. An increase of more than 15 letters was noted in 44.44.% of the cases. OCT confirmed a reduced depth of lesion and also a reduced lesion volume after treatment. No major local or systemic side-effects were noted. At 6 months follow-up the choroidal neovascularization reappeared in 5 cases (27.77%) requiring additional treatment. These results confirm the efficacy and safety of intravitreal bevacizumab in controlling the choroidal neovascularization secondary to pathologic myopia. More than 40% of the cases regained at least 3 lines in ETDRS chart but a recurrence was noted in 27.77% of the cases at 6 months.

  8. Acute sterile endophthalmitis following intravitreal bevacizumab: case series

    Directory of Open Access Journals (Sweden)

    Orozco-Hernández A

    2014-09-01

    Full Text Available Axel Orozco-Hernández,1 Ximena Ortega-Larrocea,1 Gustavo Sánchez-Bermúdez,1 Gerardo García-Aguirre,1 Virgilio Morales Cantón,1 Raul Velez-Montoya2 1Retina Department, Asociación para Evitar la Ceguera en México IAP, Mexico City, Mexico; 2Department of Ophthalmology, University of Colorado School of Medicine, Rocky Mountain Lions Eye Institute, Aurora, CO, USA Background: Since the ophthalmological community adopted the use of intravitreal bevacizumab as an accepted off-label treatment for neovascular diseases, the amount of knowledge regarding its effects and properties has been increasing continually. In the last few years, there have been an increasing number of reports about sterile intraocular inflammation and intraocular pressure elevations after intravitreal bevacizumab. In the following case series, we describe the clinical presentation and outcomes of ten consecutive cases of patients developing mild-to-severe sterile intraocular inflammation after intravitreal bevacizumab and their management. Methods: This report presents a retrospective case series. We reviewed the medical records of ten consecutive patients from a group of 46, in whom repackaged bevacizumab in individual aliquots from two vials from the same batch were used. All surgical procedures were performed using standard sterile techniques in the operating room. At each follow-up visit, patients underwent a complete ophthalmological examination including visual acuity assessment, intraocular pressure, biomicroscopy, and posterior fundus examination. Results: Ten patients presented sterile endophthalmitis with an onset time of 3.5±1.95 days. The clinical characteristics were mild pain, slight visual loss, conjunctival hyperemia, and various degrees of intraocular inflammation with microhypopyon. All cultures were negative. All patients were managed with topical steroids and antibiotics, except two, in whom, due to severe vitreous cells, intravitreal antibiotics were

  9. Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity

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    Mintz-Hittner, Helen A.; Kennedy, Kathleen A.; Chuang, Alice Z.

    2011-01-01

    BACKGROUND Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity. METHODS We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks’ postmenstrual age. RESULTS We enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks’ postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P = 0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P = 0.003) but not for zone II disease (P = 0.27). CONCLUSIONS Intravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety. PMID:21323540

  10. Intravitreal bevacizumab (Avastin in choroidal neovascular membrane in angioid streaks

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    Sachdev Nishant

    2007-01-01

    Full Text Available Angioid streaks are crack-like dehiscences in the Bruch′s membrane, which predispose to the development of a choroidal neovascular membrane (CNVM that carries a poor visual outcome. We report successful treatment in a 25-year-old woman with bilateral angioid streaks and subfoveal CNVM in the left eye who received two doses of intravitreal bevacizumab (1.25 mg injections six weeks apart, resulting in rapid regression of the CNVM.

  11. Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture

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    Arevalo, J. Fernando; Sanchez, Juan G.; Lasave, Andres F.; Wu, Lihteh; Maia, Mauricio; Bonafonte, Sergio; Brito, Miguel; Alezzandrini, Arturo A.; Restrepo, Natalia; Berrocal, Maria H.; Saravia, Mario; Farah, Michel Eid; Fromow-Guerra, Jans; Morales-Canton, Virgilio

    2011-01-01

    This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy. PMID:21584260

  12. Indications and Treatment Outcomes of Intravitreal Bevacizumab ...

    African Journals Online (AJOL)

    angiogenesis, reduces vascular permeability and licensed for use in neovascular macular degeneration. However, its use is on the decline.[11]. The study was conducted to determine the indications and treatment outcomes in the use of intravitreal antiVEGF in a group of patients presenting to a tertiary hospital in Southern.

  13. Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes

    OpenAIRE

    Moisseiev, Elad; Waisbourd, Michael; Ben-Artsi, Elad; Levinger, Eliya; Barak, Adiel; Daniels, Tad; Csaky, Karl; Loewenstein, Anat; Barequet, Irina S.

    2013-01-01

    Background Topical bevacizumab is a potential treatment modality for corneal neovascularization, and several recent studies have demonstrated its efficacy. No previous study of the pharmacokinetics of topical bevacizumab has been performed in human eyes. The purpose of this study is to investigate the pharmacokinetics of topical administration of bevacizumab in human eyes, and also to compare the pharmacokinetics of intravitreal bevacizumab injections with previously reported data. Methods Tw...

  14. Intravitreal bevacizumab therapy for idiophatic juxtafoveolar retinal telangiectasis associated with serous macular detachment

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    Paulo Escarião

    2014-01-01

    Full Text Available The authors describe a 50-year-old woman with group 2 juxtafoveolar retinal telangiectasis and macular detachment treated with a single-dose of intravitreous bevacizumab injection. There was an improvement in her visual acuity, with a decrease in retinal thickness showed by the optical coherence tomography and fluorescein leakage in the angiography on follow-up visits. No adverse events were observed as a result of the treatment used. After one year of follow-up, the vision remained stable and macular detachment did not recur.

  15. Comparison of endophthalmitis rates following intravitreal injection of compounded bevacizumab, ranibizumab, and aflibercept.

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    Forooghian, Farzin; Albiani, David A; Kirker, Andrew W; Merkur, Andrew B

    2017-12-01

    Whereas the incidence of endophthalmitis after compounded intravitreal bevacizumab is known to be low, the rates of endophthalmitis after intravitreal injection of compounded ranibizumab and aflibercept are not known. The purpose of this study was to determine the incidence of endophthalmitis after treatment with compounded intravitreal ranibizumab and aflibercept and to compare this to the incidence with compounded intravitreal bevacizumab. Retrospective chart review. All patients with post-injection endophthalmitis who were seen over a 6.5-year period at a tertiary retina referral practice. We identified all cases of endophthalmitis by searching for patients who received intravitreal antibiotics and had antecedent intravitreal injection of bevacizumab, ranibizumab, or aflibercept. A total of 54,101 injections of bevacizumab, 5,614 injections of ranibizumab, and 3,468 injections of aflibercept were performed. The incidence of suspected endophthalmitis was 0.041% (95% CI: 0.026-0.062) for bevacizumab, 0.036% (95% CI: 0.0043-0.13) for ranibizumab, and 0.06% (95% CI: 0.007-0.2) for aflibercept. For culture-positive cases, the incidence was 0.017% (95% CI: 0.0076-0.032) for bevacizumab, 0.02% (95% CI: 0.0005-0.1) for ranibizumab, and 0.03% (95% CI: 0.0007-0.2) for aflibercept. There was no statistically significant difference in endophthalmitis rate between the 3 different compounded drugs with respect to both overall suspected endophthalmitis rate and culture-positive endophthalmitis rate (p = 0.87). Compounding of ranibizumab and aflibercept for intravitreal use appears to be safe because the endophthalmitis rate does not appear to be different from that of intravitreal bevacizumab. Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  16. Quantitative evaluation of hard exudates in diabetic macular edema after short-term intravitreal triamcinolone, dexamethasone implant or bevacizumab injections.

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    Shin, Yong Un; Hong, Eun Hee; Lim, Han Woong; Kang, Min Ho; Seong, Mincheol; Cho, Heeyoon

    2017-10-03

    To quantitatively compare short-term hard exudates (HEs) alteration in patients with diabetic macular edema (DME) after intravitreal triamcinolone, dexamethasone implant or bevacizumab injections. This retrospective study enrolled DME eyes with HEs that underwent a single-dose intravitreal injection of triamcinolone (25 eyes), dexamethasone implant (20 eyes), or three monthly injections of bevacizumab (25 eyes) and completed at least three months of follow-up. All patients were examined before and after 1, 2 and 3 months of injections. Using color fundus photographs, the amount of HEs was quantified by two masked graders. The difference in HEs area between baseline and each follow-up visit was compared among the three groups. After three months, HEs area was reduced to 52.9 ± 4.21% (P bevacizumab group. A significant reduction in HEs appeared at one month in the triamcinolone group (53.5 ± 4.91%, P bevacizumab does not. Therefore, intravitreal steroids may be useful in DME with HEs in the fovea.

  17. Systemic Biodistribution and Intravitreal Pharmacokinetic Properties of Bevacizumab, Ranibizumab, and Aflibercept in a Nonhuman Primate Model.

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    Christoforidis, John Byron; Briley, Karen; Binzel, Katherine; Bhatia, Prayna; Wei, Lai; Kumar, Krishan; Knopp, Michael Vinzenz

    2017-11-01

    To determine the intravitreal pharmacokinetic properties and to study the systemic biodistribution characteristics of I-124-labeled bevacizumab, ranibizumab, and aflibercept with positron emission tomography-computed tomography (PET/CT) imaging in a nonhuman primate model. Three groups with four owl monkeys per group underwent intravitreal injection with 1.25 mg/0.05 mL I-124 bevacizumab, 0.5 mg/0.05 mL I-124 ranibizumab, or 2.0 mg/0.05 mL I-124 aflibercept in the right eye of each subject. All subjects were imaged using PET/CT on days 0, 1, 2, 4, 8, 14, 21, 28, and 35. Serum blood draws were performed at hours 1, 2, 4, 8, 12 and days 1, 2, 4, 8, 14, 21, 28, and 35. Radioactivity emission measurements were used to determine the intravitreal half-lives of each agent and to study the differences of radioactivity uptake in nonocular organs. The intravitreal half-lives were 3.60 days for I-124 bevacizumab, 2.73 days for I-124 ranibizumab, and 2.44 days for I-124 aflibercept. Serum levels were highest and most prolonged for bevacizumab as compared to both ranibizumab and aflibercept. All agents were primarily excreted through the renal and mononuclear phagocyte systems. However, bevacizumab was also found in significantly higher levels in the liver, heart, and distal femur bones. Among the three anti-VEGF agents used in clinical practice, bevacizumab demonstrated the longest intravitreal retention time and aflibercept the shortest. Significantly higher and prolonged levels of bevacizumab were found in the serum as well as in the heart, liver, and distal bones. These differences may be considered by clinicians when formulating treatment algorithms for intravitreal therapies with these agents.

  18. Optical coherence tomography and vessel diameter changes after intravitreal bevacizumab in diabetic macular oedema

    DEFF Research Database (Denmark)

    Soliman, W.; Vinten, M.; Sander, B.

    2008-01-01

    Purpose: To assess the effect of intravitreal bevacizumab on diabetic macular oedema (DMO) and retinal vessel calibres. Methods: We performed a consecutive case series study in which 10 consecutive eyes with diffuse DMO, two of which had not previously been treated, received an intravitreal...... injection of bevacizumab 1 mg, which was followed by two more injections at 6-week intervals. Fundus photography and optical coherence tomography (OCT) were carried out at baseline immediately before injection and at 1, 2.5 and 4 months after the first injection. Outcome measures were best corrected visual...... acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters, macular volume, foveal subfield thickness and vessel diameter measurement. Results: Intravitreal administration of bevacizumab was followed by a mean increase in BCVA of 7.3 +/- 17 (mean +/- standard deviation) letters between baseline...

  19. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration in treatment-naive patients

    DEFF Research Database (Denmark)

    Pedersen, Karen Bjerg; Sjølie, Anne Katrin; Møller, Flemming

    2008-01-01

    Abstract. Purpose: To report the effects of intravitreal bevacizumab (Avastin((R))) in treatment-naive patients with exudative age-related macular degeneration (ARMD) assessed by visual acuity (VA), optical coherence tomography (OCT) and contrast sensitivity. Methods: A prospective, uncontrolled......, pilot study of 26 eyes of 26 patients, all previously treatment-naive to photodynamic therapy, argon laser or anti-vascular endothelial growth factor (VEGF), were treated with one or more intravitreal injections of 1.25 mg bevacizumab. Of the 26 patients, 15 (57.7%) had occult choroidal...... points. The results indicate that 1.25 mg intravitreal bevacizumab is associated with functional as well as morphological improvement among treatment-naive ARMD patients....

  20. Serial Intravitreal Bevacizumab Injections Slow the Progression of Radiation Maculopathy Following Iodine-125 Plaque Radiotherapy.

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    Stacey, Andrew W; Demirci, Hakan

    2016-01-01

    To assess the outcomes of intravitreal bevacizumab injection in the management of radiation maculopathy secondary to plaque radiotherapy, and to identify optimal treatment strategies. A retrospective review of all choroidal melanoma patients at one referral center who were treated with plaque radiotherapy, subsequently developed radiation maculopathy, and received intravitreal bevacizumab. A total of 31 patients were identified. The mean visual acuity decreased three Snellen lines in the year leading up to the first bevacizumab injection. After initiating injection therapy, the mean visual acuity remained stable for 9 months. The change in visual acuity of patients who received injections within 90 days of previous injections was significantly better than the visual acuity of those who received injections more than 90 days apart (p=0.0003). Patients who demonstrated late-phase macular leakage on fluorescein angiography at the time of the first bevacizumab injection had better long-term visual acuity outcomes than patients who had no evidence of macular leakage (average of one line improvement of vision vs. ten line loss of vision, p=0.03). Intravitreal bevacizumab injection was effective in stabilizing visual acuity in patients with radiation maculopathy. Patients benefited most from injections administered every 90 days or sooner. Fluorescein angiography can help identify patients who will respond favorably to treatment.

  1. Assessment of patient pain experience during intravitreal 27-gauge bevacizumab and 30-gauge ranibizumab injection.

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    Güler, Mete; Bilgin, Burak; Çapkın, Musa; Şimşek, Ali; Bilak, Şemsettin

    2015-06-01

    To compare pain scores of patients during intravitreal 27-gauge bevacizumab and 30-gauge ranibizumab injection procedures. Seventy eyes of 70 patients who had not previously undergone intravitreal anti-vascular endothelial growth factor therapy were included in this study. Thirty-five patients received ranibizumab and 35 patients received bevacizumab. The diagnoses of the patients were: 27 age related macular degeneration, 15 diabetic macular edema, 9 diabetic vitreous hemorrhage, 6 central retinal vein occlusion, 11 branch retinal vein occlusion and 2 central serous chorioretinopathy. Bevacizumab (1.25 mg/0.05 mL) was injected into the vitreous cavity using a 27-gauge needle, and ranibizumab (0.5 mg/0.05 mL) was injected with 30-gauge needle. Patients were asked just after the injection to rate their perceived pain during the injection using the visual analogue scale (VAS) of 0 (no pain) to 10 (unbearable/worst pain). The average of these scores was used as the primary outcome. The VAS pain scores in the ranibizumab and bevacizumab groups were 1.06 ± 0.91 (range, 0 to 3) and 1.94 ± 1.55 (range, 0 to 7), respectively, a significant difference (p = 0.005). Patients gauge intravitreal injection is more comfortable than 27-gauge injection. Injection of bevacizumab with 30-gauge needle syringes may be more tolerable for patients.

  2. Intravitreal bevacizumab in refractory neovascular glaucoma: a prospective, observational case series.

    Science.gov (United States)

    Kotecha, Aachal; Spratt, Alexander; Ogunbowale, Lola; dell'Omo, Roberto; Kulkarni, Avinash; Bunce, Catey; Franks, Wendy A

    2011-02-01

    To examine the efficacy of intravitreal bevacizumab for pain relief in eyes with refractory neovascular glaucoma. In this prospective case series, 52 eyes with neovascular glaucoma were administered intravitreal bevacizumab, 1.25 mg, and monitored for 6 months. The primary outcome measure was change in subjective pain score. Intraocular pressure and iris neovascularization were evaluated at each visit. Surgical intervention for control of intraocular pressure was performed according to clinical need. Forty-two patients (44 eyes) completed the 6-month follow-up. Subjective pain score was reduced significantly 1 week after intravitreal bevacizumab injection and lasted throughout the follow-up period (median [interquartile range]: baseline, 3 [0-6]; week 1, 1 [0-3]; month 1, 0 [0-1]; month 3, 0 [0-1]; and month 6, 0 [0-0]; Kruskal-Wallis χ(2) 31.03; P < .001). A rapid, yet relatively transient, reduction in iris neovascularization was also noted (iris neovascularization grade at baseline, 4.0 [3-4]; week 1, 2.5 [1-4]; month 1, 2.0 [1-4]; month 3, 3.0 [2-4]; and month 6, 3.0 [2-4], χ(2) 23.33; P < .001). Four eyes (8%) required more than 1 injection to facilitate further intraocular surgery. Intravitreal bevacizumab is a useful adjunct in the management of refractory neovascular glaucoma, producing rapid relief of pain. However, we found no evidence to suggest that intravitreal bevacizumab lowers intraocular pressure in eyes with angle closure; conventional medical, laser, and surgical treatment are still needed in these eyes.

  3. INTRAVITREAL DEXAMETHASONE IMPLANT AS ADJUVANT TREATMENT FOR BEVACIZUMAB- AND RANIBIZUMAB-RESISTANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Prospective Pilot Study.

    Science.gov (United States)

    Barikian, Anita; Salti, Haytham; Safar, Ammar; Mahfoud, Ziyad R; Bashshur, Ziad F

    2017-07-01

    To study the benefit of intravitreal dexamethasone implant in the management of neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. Patients with persistent macular fluid on optical coherence tomography despite monthly treatment with at least three consecutive bevacizumab injections followed by at least three ranibizumab injections were prospectively enrolled. A single dexamethasone implant was administered followed by intravitreal ranibizumab 1 week later. Ranibizumab was continued afterward on an as-needed basis. Main outcomes were improvement in central retinal thickness and best-corrected visual acuity. Nineteen patients (19 eyes) were enrolled. There was no significant change in best-corrected visual acuity over 6 months. Greatest reduction in mean central retinal thickness, from 295.2 μm to 236.2 μm, occurred 1 month after dexamethasone implant (P macular intraretinal fluid in eyes with neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. However, this treatment had a limited duration.

  4. Indications and treatment outcomes of intravitreal bevacizumab and ...

    African Journals Online (AJOL)

    Background: The emergence of intravitreal antivascular endothelial growth factors (antiVEGF) has revolutionalised the treatment and prognosis of many retinal diseases. Aim: To determine the indications and treatment outcomes for use of intravitreal antiVEGF agents in retinal diseases among patients in a tertiary hospital ...

  5. Mortality in patients treated with intravitreal bevacizumab for age-related macular degeneration.

    Science.gov (United States)

    Hanhart, Joel; Comaneshter, Doron S; Freier Dror, Yossi; Vinker, Shlomo

    2017-10-10

    The aim of this study is to analyze mortality in patients treated with bevacizumab for wet AMD. We conducted a retrospective case-control study between patients who received intravitreal injections of bevacizumab as the sole treatment for exudative AMD between September 2008 and October 2014 (n = 5385) and age and gender matched controls (n = 10,756). All individuals included in the study were reviewed for sociodemographic data and comorbidities. Survival analysis was performed using adjusted Cox regression, using relevant adjusted variables. During follow-up (maximum: 73 months), 1063 (19.7%) individuals after bevacizumab died compared with 1298 (12.1%) in the control group (P bevacizumab compared to a same age and gender group without wet AMD.

  6. The effect of intravitreal bevacizumab and transpupillary thermotherapy on choroidal metastases and literature review

    Directory of Open Access Journals (Sweden)

    Chun-Ju Lin

    2015-01-01

    Full Text Available Aims : To represent the effects of transpupillary thermotherapy (TTT and intravitreal bevacizumab on choroidal metastases and review the literature. Settings and Design : A retrospective, interventional, noncomparative case series. Materials and Methods : A retrospective, interventional, noncomparative case series of five eyes in three patients with choroidal metastases was conducted. Fundus findings of choroidal metastases were divided into two types: Solitary or diffuse type. The size of the tumor was termed small (15 mm diameter. All eyes received one session of TTT followed by 3 weekly intravitreal bevacizumab injections as an adjuvant therapy. The parameters of treatment for TTT were 1.2-3 mm spot size, 150-300 mW, 60 s with the whole lesion covered confluently. The changes in preoperative and postoperative best-corrected visual acuity (BCVA were recorded. Serial color fundus photography and optical coherent tomography were performed to measure the treatment efficacy. Results : All eight choroidal metastases were solitary type. The size of six tumors was small, the size of one tumor was medium, and the size of one tumor was large. All five eyes of the three patients had improvement of BCVA after treatment. Fundus photos revealed tumor shrinkage and the mean shrinkage percentage was 61.27 ± 21.71%. Optical coherence tomography revealed complete resolution of serous retinal detachment. There was no recurrence after 6 months follow-up. Conclusions : TTT combined with intravitreal bevacizumab injections brought about beneficial effects in reducing tumor size and improving vision in all five eyes of the three patients. Despite the retrospective nature of our study, the absence of control group and the size limitation that, of course, limit the statistical power, TTT combined with intravitreal bevacizumab seems to be efficient in providing another cost-reducing and time-saving treatment option for patients with choroidal metastases. The

  7. Intravitreal Bevacizumab injection combined duplex technique in treatment of neovascular glaucoma

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    Zheng-Jun Hu

    2015-05-01

    Full Text Available AIM: To observe the clinical curative effect of intravitreal Bevacizumab injection combined duplex technique in treatment of neovascular glaucoma(NVG.METHODS:Totally 25 eyes of 25 patients with NVG who underwent intravitreal Bevacizumab injection of 1.0mg(0.05mL, after the regression of iris neovascularization, 5 eyes with anterior chamber paracentesis fluid auxiliary controlled intraocular pressure. After 2wk, patients were treated by trabeculectomy and phacomulsification(9 eyes were implanted intraocular lens. The changes and complications of intraocular pressure, visual acuity, corneas and neovessels were observed after surgery, and followed up 12mo.RESULTS:After injection Bevacizumab in 25 eyes, iris neovascularization of 20 eyes subsided in 3~5d, and 5 eyes subsided in 7d. After controlling intraocular pressure, count of the corneal endothelial cell were 1 629±226mm2, and none suffered decompensation of corneal endothelium after two-surgery of trabeculectomy and phacomulsification. After followed up 12mo, intraocular pressure of 20 eyes were controlled in normal range; 2 eyes could control in normal range after treated by a kind of anti-glaucoma medicine and 3 eyes was 34~38mmHg after treated by anti-glaucoma medicine. 9 eyes had improved vision after implanted intraocular lens.CONCLUSION:Intravitreal Bevacizumab injection can subside iris and anterior chamber angle neovascularization effectively in a short time and reduce intraocular pressure. It can also reduce the risk of bleeding during operation or after operation. Intravitreal Bevacizumab injection combined with two-surgery of trabeculectomy and phacomulsification can treat neovascular glaucoma effectively.

  8. Advanced Coats’ disease treated with intravitreal bevacizumab combined with laser vascular ablation

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    Villegas VM

    2014-05-01

    Full Text Available Victor M Villegas,1 Aaron S Gold,1 Audina M Berrocal,2 Timothy G Murray11Ocular Oncology and Retina, Miami, FL, USA; 2Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL, USAPurpose: To evaluate the impact of intravitreal bevacizumab combined with laser vascular ablation in the management of advanced Coats’ disease presenting with exudative retinal detachment.Methods: This was a retrospective review of 24 children that presented with exudative retinal detachments associated with advanced Coats’ disease. Mean patient age was 62 months (range 9–160 months. Presenting signs included retinal detachment in 24 children (100%, vascular telangiectasia in 24 children (100%, and retinal ischemia in 24 children (100%. Twenty of 24 children presented with elevated, vascular leakage in the fovea (83%. Two children presented with sub-retinal fibrosis associated with presumed long-standing retinal detachment without evidence of rhegmatogenous retinal detachment. Ten patients exhibited vascular alterations in the periphery of the second eye without clinical evidence of exudation. All 24 children were treated with a large-spot-size diode laser directly to areas of abnormal telangiectatic vasculature. All 24 children received intravitreal bevacizumab injection. Results: All 24 children had resolution of exudative retinal detachment, ablation of vascular telangiectasia, and anatomic improvement of the retina. No child exhibited progressive retinal detachment and no eye required enucleation. No cases of neovascular glaucoma were seen. Fellow eyes with peripheral vascular alterations showed no progression to exudative vasculopathy during the observation period. Intravitreal bevacizumab injection was not associated with endophthalmitis or systemically-observed complications.Conclusion: Repetitive intravitreal bevacizumab combined with laser vascular ablation may be utilized effectively

  9. [The results of intravitreal bevacizumab in subretinal neovascularisation in angioid streaks].

    Science.gov (United States)

    Brănişteanu, D; Moraru, Andreea

    2014-01-01

    To assess the anatomical and functional results after intravitreal bevacizumab administration in choroidal neovascularization (CNV) due to angioid streaks; To assess the safety and results stability; Prospective, nonrandomized, interventional case study on choroidal neovascularization due to angioid streaks treated with intravitreal bevacizumab (AVASTIN). Intravitreal injection was repeated, if needed, at 4-6 weeks until leakage stopped. In all cases fluorescein angiograms and Spectral 3D OCTs were performed. Visual acuity was measured with ETDRS optotype. Cases were followed-up at least 6 months. Statistical analysis was performed using ANOVA and Wilcoxon tests. 8 cases with CNV associated to angioid streaks were evaluated between January 2007 and January 2013. Mean age of patients in the study was 52,36 +/- 4,33 years (ranging 42-64 years). The mean number of intravitreal injections was 4.64 +/- 0,42 (ranging between 3-8 injections). Mean visual acuity improved significantly in all cases after 3 intravitreal injections with a gain of more than 15 letters in 6 out of 8 cases (75%). OCT confirmed reduced depth of lesion and also a reduced lesion volume after treatment. No major local or systemic side-effects were noted. At 6 months follow-up the CNV reoccurred in 5 out of 8 cases (62.5%) requiring additional treatment. 3 out of 8 cases finally lost more than 5 letters due to subretinal fibrosis. These results confirm the efficacy and safety of intravitreal bevacizumab in controlling the CNV due to angioid streaks. High recurrence rate and quick lesion progression to subretinal fibrosis might be responsible for long-term poor functional results in this type of CNVs. More cases are needed for validation.

  10. Real-world evidence of safety profile of intravitreal bevacizumab (Avastin) in an Indian scenario.

    Science.gov (United States)

    Jain, Prashant; Sheth, Jay; Anantharaman, Giridhar; Gopalakrishnan, Mahesh

    2017-07-01

    The purpose of this study was to evaluate the safety profile of intravitreal bevacizumab (Avastin) as an off-label pharmacotherapeutic agent for various ocular conditions. Retrospective analysis was carried out on 3806 injections of 1761 patients that were administered with intravitreal bevacizumab injection at a tertiary eye care center in India. The injections were administered on a pro re nata basis for various indications such as age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). The mean age of the patients was 61.8 ± 11.59 years. A total of 59.2% of the patients were men and 40.8% women. The most common indications for which the injection was administered were DME (27.5%), AMD (26%), and branch RVO (12.3%). Among the ocular side effects, endophthalmitis was seen in three eyes (0.08%), retinal breaks in none of the eyes whereas 35 eyes had a rise in intraocular pressure (IOP) >21 mmHg (0.9%). Preexisting glaucoma was present in four eyes while remaining 31 eyes did not have any history of glaucoma. IOP rise was significantly more in eyes with preexisting glaucoma as compared to nonglaucomatous eyes (P = 0.04). No systemic adverse events were noted in our study population. Our study provides real-world evidence regarding the safety profile of intravitreal bevacizumab (Avastin). These data suggest that bevacizumab is a safe and economical pharmacotherapeutic agent that can be administered for a variety of ocular disorders. Analyzing the safety of bevacizumab is necessary for a developing country like India as the majority of the population cannot afford the costly ranibizumab as compared to bevacizumab for ocular healthcare.

  11. Fellow Eye Macular Edema Improvement after Intravitreal Bevacizumab for Radiation Retinopathy

    Directory of Open Access Journals (Sweden)

    Isis A. S. Brito

    2015-01-01

    Full Text Available Radiation retinopathy (RR is a progressive, chronic condition directly related to the amount of radiation administered to the retina. We report a 37-year-old patient with medulloblastoma that was treated with external beam radiation and presented to us with bilateral cystoid macular edema. He was treated with monthly bevacizumab injections only in his worst seeing eye. There was a significant improvement in his fellow eye, with marked retinal thickness reduction. Therefore, we present clinical evidence of systemic absorption and fellow eye activity of the drug (bevacizumab. One must be aware of distant side effects after intravitreal injections.

  12. The effect of intravitreal bevacizumab injection on the corneal endothelial cells

    Directory of Open Access Journals (Sweden)

    Akbar Derakhshan

    2016-04-01

    Full Text Available Introduction:Bevacizumab (Avastin, as an effectiveness treatment modality, is currently used in patients with various ocular disease. However the results have been promising, the use of bevacizumab in the treatment of ocular disease is an off-label application. Hence, the aim of this study was to systematically review the effectiveness of intravitreal injection of bevacizumab on various ocular tissues, especially corneal endothelial cells. Methods: The articles related to the effect of application of Avastin in the treatment of ophthalmic diseases and especially its effect on corneal endothelial cells were collected and reviewed. We searched PubMed, Google scholar, and Scopus databases and used Avastin, ocular diseases and corneal endothelial cells as search keywords.Result: Of all 55 articles found in all databases, only 10 were relevant to the purpose of this study, and 45 articles were excluded in several step by step process of article selection according to the inclusion/exclusion criteria. The results revealed that intracameral bevacizumab injection caused no changes in specular microscopy and corneal pachymetry. Moreover, it had no significant toxicity on corneal endothelial cells.Discussion: Effectiveness of bevacizumab as a new modality in the treatment of different ophthalmic diseases have been suggested. Recent data on both human and animal models showed that intravitreal injection of bevacizumab resulted in no significant toxicity on various ocular cells, and it could be considered as a suitable therapeutic approach in clinical use.Conclusion: According to the results of included documents, bevacizumab was not toxic to corneal endothelial cells at various clinically relevant doses.

  13. Intravitreal bevacizumab for macular edema due to branch retinal vein occlusion: 12-month results

    OpenAIRE

    Demir M; Oba E; Gulkilik G; Odabasi M; Ozdal E

    2011-01-01

    Mehmet Demir, Ersin Oba, Gökhan Gulkilik, Mahmut Odabasi, Erhan OzdalSisli Etfal Training and Research Hospital, Eye Clinic, Sisli, Istanbul, TurkeyPurpose: To present the functional and anatomic changes after intravitreal bevacizumab in eyes with macular edema (ME) due to branch retinal vein occlusion (BRVO).Design: The study was a retrospective study.Materials and methods: The study included 31 patients with ME due to BRVO. We compared the examination findings of patients with ME b...

  14. Intravitreal bevacizumab (Avastin treatment of diffuse diabetic macular edema in an Indian population

    Directory of Open Access Journals (Sweden)

    Kumar Atul

    2007-01-01

    Full Text Available Background: To report the anatomic and visual acuity response after intravitreal bevacizumab (Avastin in patients with diffuse diabetic macular edema. Design: Prospective, interventional case series study. Materials and Methods: This study included 20 eyes of metabolically stable diabetes mellitus with diffuse diabetic macular edema with a mean age of 59 years who were treated with two intravitreal injections of bevacizumab 1.25 mg in 0.05 ml six weeks apart. Main outcome measures were 1 early treatment diabetic retinopathy study visual acuity, 2 central macular thickness by optical coherence tomography imaging. Each was evaluated at baseline and follow-up visits. Results: All the eyes had received some form of laser photocoagulation before (not less than six months ago, but all of these patients had persistent diffuse macular edema with no improvement in visual acuity. All the patients received two injections of bevacizumab at an interval of six weeks per eye. No adverse events were observed, including endophthalmitis, inflammation and increased intraocular pressure or thromboembolic events in any patient. The mean baseline acuity was 20/494 (log Mar=1.338±0.455 and the mean acuity at three months following the second intravitreal injection was 20/295 (log Mar=1.094±0.254, a difference that was highly significant ( P =0.008. The mean central macular thickness at baseline was 492 µm which decreased to 369 µm ( P =0.001 at the end of six months. Conclusions: Initial treatment results of patients with diffuse diabetic macular edema not responding to previous photocoagulation did not reveal any short-term safety concerns. Intravitreal bevacizumab resulted in a significant decrease in macular thickness and improvement in visual acuity at three months but the effect was somewhat blunted, though still statistically significant at the end of six months.

  15. Long-Term Follow-Up of Intravitreal Bevacizumab in Retinal Arterial Macroaneurysm: A Case Report

    Directory of Open Access Journals (Sweden)

    Shani Golan

    2011-12-01

    Full Text Available Purpose: To present the long-term effect of intravitreal bevacizumab (Avastin® therapy in a patient suffering from retinal arterial macroaneurysm. Methods: Case report of a 72-year-old female diagnosed with retinal macroaneurysm in the superior temporal artery leading to macular edema. Functional and morphological data at baseline, 4 weeks, 2 months, and 13 months following treatment with two consecutive intravitreal bevacizumab injections are presented. Results: Best-corrected visual acuity improved from 20/160 at baseline to 20/20 at the3-months follow-up and remained stable through 13 months of follow-up. Central retinal thickness measured by optical coherence tomography decreased from 364 µm at baseline to 248 µm at the 13-months follow-up. No ocular or systemic side effects were detected. Conclusions: Intravitreal bevacizumab therapy may lead to resolution of macular edema associated with retinal macroaneurysm and consequently visual improvement. This treatment may promise a long-lasting effect but warrant further investigation in larger series.

  16. Predictive factors for functional improvement following intravitreal bevacizumab injections after central retinal vein occlusion.

    Science.gov (United States)

    Januschowski, Kai; Feltgen, Nicolas; Pielen, Amelie; Spitzer, Bernhard; Rehak, Matus; Spital, Georg; Dimopoulos, Spyridon; Meyer, Carsten H; Szurman, Gesine B

    2017-03-01

    Vision loss in central retinal vein occlusion (CRVO) is mostly caused by macular edema (ME) and can be treated with intravitreal bevacizumab injections. The goal of this study was to identify predictive factors for improvement in visual acuity. Three hundred and sixteen eyes of six centres having received intravitreal bevacizumab for ME due to CRVO were enrolled in this multicentre, retrospective, interventional case series. The follow-up time was 24 to 48 weeks. Investigated patient characteristics were pretreatment, duration of CRVO prior to the first injection, initial best-corrected visual acuity (BCVA), baseline central retinal thickness as measured by optical coherence tomography, gender, eye, age, comorbidity with glaucoma, systemic hypertension, or diabetes mellitus. Multiple regression analysis confirmed the following baseline predictive factors for an increase in visual acuity: low BCVA (p  0.1). Intravitreal injections of bevacizumab in a routine clinical setting effectively improved and stabilized BCVA in CRVO. Our large multicenter study identified initial BCVA, baseline CRT, and pre-treatment as prognostic factors for visual improvement.

  17. Intravitreal bevacizumab for neovascular glaucoma in uveal melanoma treated by proton beam therapy.

    Science.gov (United States)

    Mahdjoubi, Amir; Najean, Marie; Lemaitre, Stéphanie; Dureau, Sylvain; Dendale, Rémi; Levy, Christine; Rouic, Livia Lumbroso-Le; Desjardins, Laurence; Cassoux, Nathalie

    2018-02-01

    To evaluate the efficacy of bevacizumab on reduction of the enucleation rate and control of intraocular pressure (IOP) in neovascular glaucoma (NVG)-complicating proton beam therapy for UM and to identify the determinants of the efficacy of bevacizumab. Retrospective comparative study of patients with rubeosis following proton therapy for uveal melanoma. Patients were divided into two groups: a bevacizumab group and a control group which comprised two subgroups: panretinal photocoagulation (PRP)/cryotherapy and observation subgroups. Bevacizumab was administered by three intravitreal injections at 1-month intervals. A second series of injections was administered when necessary. Data concerning IOP and the secondary enucleation rate were collected and compared between the two groups. Univariate and multivariate analyses were performed to determine predictive factors of response to bevacizumab. A total of 169 patients who developed rubeosis following proton therapy between 2006 and 2016 were included: 44 patients in the bevacizumab group and 125 in the control group (38 in the PRP/cryotherapy subgroup and 87 in the observation subgroup). The two groups presented the same baseline characteristics apart from hypertension, retro-equatorial site, and proximity of the optic disk, which were more frequent in the control group, while initial retinal detachment and larger tumor volume were more frequent in the bevacizumab group. After a mean follow-up of 31 months, IOP was less than 21 mmHg in 54.54% of patients after IVB versus 72.7% before treatment (p = 0.06). Statistical analysis did not reveal any statistically significant reduction of the enucleation rate in the bevacizumab group compared to the observational group, whereas the PRP/cryotherapy group showed better eye retention rate (p = 0.15). No enucleation was performed when IOP was bevacizumab. Despite the improvement of IOP level, intravitreal bevacizumab (IVB) did not reduce the overall enucleation rate in

  18. Comparison of intravitreal ranibizumab and bevacizumab treatment for retinopathy of prematurity

    Directory of Open Access Journals (Sweden)

    Muhammet Kazim Erol

    2015-12-01

    Full Text Available ABSTRACT Purpose: To compare the efficacy of intravitreal ranibizumab and bevacizumab treatment for type 1 retinopathy of prematurity (ROP. Methods: 36 eyes of 20 patients with type 1 ROP who received anti-vascular endothelial growth factor (anti-VEGF intravitreal injections between August 2011 and February 2013 were retrospectively evaluated. Fifteen eyes of 8 patients received 0.25 mg ranibizumab (group 1, and 21 eyes of 12 patients received 0.625 mg bevacizumab (group 2. Eyes were examined by indirect ophthalmoscopy on the first day, third day, first week, and first month and as required after injections. Laser photocoagulation was performed in cases with progression of ROP. Results: The mean gestation time was 26.2 ± 2.7 weeks in group 1 patients and 27.1 ± 2.5 weeks in group 2 patients. No statistical difference in the time of gestation was observed between the two groups. The mean follow-up period was 20 ± 4.5 months. Laser photocoagulation was performed in 6 of 15 eyes from group 1 and 2 of 21 eyes from group 2. No eyes developed retinal detachment during the follow-up period. Conclusion: Ranibizumab and bevacizumab showed an efficacy in the treatment of type 1 ROP. The incidence of disease relapse was higher in eyes which received ranibizumab. Further randomized, controlled clinical trials are required to compare the efficacy of ranibizumab and bevacizumab.

  19. Intravitreal Diclofenac plus Bevacizumab versus Bevacizumab alone in treatment-naive diabetic macular edema: a randomized double-blind clinical trial.

    Science.gov (United States)

    Ghanbari, Heshmatollah; Kianersi, Farzan; Sonbolestan, Seyed Ali; Abtahi, Mohammad-Ali; Akbari, Mojataba; Abtahi, Zahra-Alsadat; Abtahi, Seyed-Hossein

    2017-08-01

    The aim of this study is to evaluate the short-term effects of a single intravitreal injection of 1.25 mg Bevacizumab combined with 300 lg/0.1 mL Diclofenac (IVB/D) versus 1.25 mg intravitreal Bevacizumab (IVB) alone in the treatment of naive diabetic macular edema (DME). In this prospective, randomized clinical trial, 80 eyes were included in the final analysis; 42 and 38 of which in the IVB and IVB/D groups, respectively. The primary outcome measure was a change in best-corrected visual acuity (BCVA) in logMAR at week 4. The secondary outcomes included changes in central macular thickness (CMT), macular volume, and potential injection-related complications. Significant improvement of BCVA was demonstrated in both study arms (mean reductions in LogMAR: -0.088 ± 0.278, -0.228 ± 0.330 for IVB and IVB/D, respectively). The difference in BCVA changes was in favor of IVB/D; however, not to a statistically significant level (P = 0.160). Significant reduction of CMT was documented in both study arms (mean reductions: 82.43 ± 160.09 and 153.26 ± 163.85 for IVB and IVB + IVD, respectively). Comparison of CMT changes between groups showed that IVB/D reduced CMT more than that of IVB (P = 0.04). Effects on macular volume corresponded to those of CMT. No injection-related complications or significant alterations in intraocular pressure were observed in any of the study arms. In treatment-naive DME, superiority of IVB/D combination therapy over IVB monotherapy may exist; especially as regards anatomical features. In our therapeutic arsenal for DME, IVD can be added as an adjunct to Bevacizumab.

  20. MACULAR CHOROIDAL VOLUME CHANGES AFTER INTRAVITREAL BEVACIZUMAB FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    Palkovits, Stefan; Seidel, Gerald; Pertl, Laura; Malle, Eva M; Hausberger, Silke; Makk, Johanna; Singer, Christoph; Osterholt, Julia; Herzog, Sereina A; Haas, Anton; Weger, Martin

    2017-12-01

    To evaluate the effect of intravitreal bevacizumab on the macular choroidal volume and the subfoveal choroidal thickness in treatment naïve eyes with exudative age-related macular degeneration. The macular choroidal volume and the subfoveal choroidal thickness were measured using enhanced depth imaging optical coherence tomography. After a screening examination, each patient received 3 monthly intravitreal injections of 1.25 mg bevacizumab. One month after the third injection was a final assessment. Forty-seven patients with a mean age of 80 ± 6.4 years were included. The macular choroidal volume decreased significantly from median 4.1 mm (interquartile range 3.4-5.9) to median 3.9 mm (interquartile range 3.1-5.6) between the baseline and final examination (difference -0.46 mm, 95% confidence interval: -0.57 to 0.35, P macular choroidal volume at baseline and subfoveal choroidal thickness at baseline were not associated with the response to treatment. The macular choroidal volume and the subfoveal choroidal thickness decreased significantly after 3 monthly bevacizumab injections for exudative age-related macular degeneration.

  1. Pneumatic displacement and intravitreal bevacizumab: A new approach for management of submacular hemorrhage in choroidal neovascular membrane

    Directory of Open Access Journals (Sweden)

    Chawla Shobhit

    2009-01-01

    Full Text Available Choroidal neovascular membrane (CNVM is one of the most common causes of submacular hemorrhage (SMH. Conventional treatment involves management of the SMH with pneumatic displacement with or without tissue plasminogen activator (TPA followed by intravitreal injection of bevacizumab in a second sitting. We decided to assess the efficacy of treating SMH secondary to CNVM with pneumatic displacement using sulphur hexafluoride (SF6 gas and intravitreal bevacizumab. Four patients with SMH secondary to CNVM were included in this study. Intravitreal bevacizumab, 0.05 ml, along with 0.5 ml of SF6 was injected through the pars plana into the vitreous cavity. Postoperative best corrected visual acuity improved in all eyes with complete or partial displacement of SMH out of the foveal area.

  2. Change in macular thickness in a case of refractory diabetic macular edema with dexamethasone intravitreal implant in comparison to intravitreal bevacizumab: A case report

    Directory of Open Access Journals (Sweden)

    Ashish Sharma

    2012-01-01

    Full Text Available We report on the significant improvement of central macular thickness in a case of clinically significant macular edema after dexamethasone 0.7 mg sustained-release intravitreal implant (Ozurdex®; Allergan, Inc, Irvine, CA, USA. Patient presented to us with persistent clinically significant macular edema (CSME in both eyes. Right eye received dexamethasone implant and left eye received two intravitreal bevacizumab injections 1.25 mg/0.05 mL (Avastin®; Genentech Inc., South San Francisco, CA, USA with an interval of four weeks. After six weeks of follow-up, dexamethasone implant in the right eye showed normal macular thickness whereas persistent macular edema (ME was found even after second intravitreal bevacizumab injection in the left eye.

  3. Effect of intravitreal injection of bevacizumab-chitosan nanoparticles on retina of diabetic rats

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    Yan Lu

    2014-02-01

    Full Text Available AIM:To investigate the effects of intravitreal injection of bevacizumab-chitosan nanoparticles on pathological morphology of retina and the expression of vascular endothelial growth factor (VEGF protein and VEGF mRNA in the retina of diabetic rats.METHODS: Seventy-two 3-month aged diabetic rats were randomly divided into 3 groups, each containing 24 animals and 48 eyes. Both eyes of the rats in group A were injected into the vitreous at the pars plana with 3μL of physiological saline, while in groups B and C were injected with 3μL (75μg of bevacizumab and 3μL of bevacizumab-chitosan nanoparticles (containing 75μg of bevacizumab, respectively. Immunohistochemistry was used to assess retinal angiogenesis, real-time PCR assay was used to analyse the expression of VEGF mRNA, and light microscopy was used to evaluate the morphology of retinal capillaries.RESULTS:Real-time PCR assay revealed that the VEGF mRNA expression in the retina before injection was similar to 1 week after injection in group A (P>0.05, while theVEGF mRNA expression before injection significantly differed from those 4 and 8 weeks after injection (P<0.05. Retinal expression of VEGF protein and VEGF mRNA was inhibited 1 week and 4 weeks after injection (P<0.05 in group B, and the expression of VEGF protein and VEGF mRNA was obviously inhibited until 8 weeks after injection (P<0.05 in group C. Using multiple comparisons among group A, group B, and group C, the VEGF expression before injection was higher than at 1, 4 and 8 weeks after injection (P<0.05. The amount of VEGF expression was higher 8 weeks after injection than 1 week or 4 weeks after injection, and also higher 1 week after injection compared with 4 weeks after injection (P<0.05. No toxic effect on SD rats was observed with bevacizumab-chitosan nanoparticles injection alone.CONCLUSION: The results offer a new approach for inhibiting angiogenesis of diabetic retinopathy and indicate that the intravitreal injection of

  4. Effect of intravitreal bevacizumab on diabetic macular edema with hard exudates

    Science.gov (United States)

    Jeon, Sohee; Lee, Won Ki

    2014-01-01

    Background We evaluated the efficacy of intravitreal bevacizumab on diabetic macular edema with subfoveal and perifoveal hard exudates. Materials and methods Eleven eyes (11 patients) exhibiting diabetic macular edema with subfoveal and perifoveal hard exudates were included in this prospective, nonrandomized interventional pilot study. All patients were treated with monthly scheduled intravitreal bevacizumab injections for 6 months. Changes in the Early Treatment Diabetic Retinopathy Study best corrected visual acuity, amount of hard exudates on fundus photography, and macular edema detected by central subfield thickness on spectral domain optical coherence tomography after six serial injections, were assessed. The amount of hard exudates at each visit was evaluated as pixels in fundus photography, using an Adobe Photoshop program. Results Ten of 11 patients completed follow-up. The mean Early Treatment Diabetic Retinopathy Study best corrected visual acuity was 59.9±5.7 letters (Snellen equivalent, 20/63) at baseline evaluation. The best corrected visual acuity exhibited no significant difference at month 6 compared with at baseline (57.9±6.0 letters or 20/70 at month 6; P=0.085). At month 6, mean central subfield thickness decreased from 370.4±56.5 to 334.6±65.0 μm (P=0.009). The mean amount of hard exudates increased from 4467.1±2736.1 to 6592.4±2498.3 pixels at month 6 (P=0.022). No serious adverse events occurred. Conclusion Continuous intravitreal bevacizumab was found to have no benefit in visual acuity and amount of hard exudates, despite the improvement of macular edema at 6 months. PMID:25143708

  5. Phacoemulsification with intravitreal bevacizumab injection in diabetic patients with macular edema and cataract.

    Science.gov (United States)

    Akinci, Arsen; Batman, Cosar; Ozkilic, Ersel; Altinsoy, Ali

    2009-01-01

    The purpose of this study was to evaluate the results of phacoemulsification with intravitreal bevacizumab injection in patients with diabetic clinically significant macular edema and cataract. The records of 31 patients with diabetic clinically significant macular edema and cataract, which would interfere with macular laser photocoagulation, who have undergone phacoemulsification with intravitreal injection of 1.25 mg bevacizumab were retrospectively evaluated. All patients had undergone focal or modified grid laser photocoagulation 1 month after the surgery. All patients were evaluated by spectral optical coherence tomography/optical coherence tomography SLO before and 1 and 3 months after the surgery beyond complete ophthalmologic examination. The best-corrected visual acuity (BCVA) levels and central macular thickness (CMT) recorded at the first and third months after the surgery were compared with the initial values. Paired samples t test was used for statistical analysis. The mean initial BCVA was 0.10 +/- 0.04 (range, 0.05-0.2). The mean BCVA at the first and third months after the surgery were 0.47 +/- 0.16 (standard deviation) (range, 0.2-0.5) and 0.51 +/- 0.12 (standard deviation) (range, 0.3-0.6), respectively. The BCVA level recorded at the first and third months after the surgery were significantly higher than the initial BCVA (P = 0.004). The mean initial CMT was 387.5 +/- 109.5 microm. The mean CMT at the first and third months after the surgery were 292.7 +/- 57.2 and 275.5 +/- 40.3. The CMT recorded at the first and third months after the surgery were significantly lower than the initial CMT (P < 0.001, P < 0.001). Phacoemulsification with intravitreal injection of bevacizumab provides improvement in clinically significant macular edema with a gain in BCVA in patients with diabetes with clinically significant macular edema and cataract.

  6. Results of the treatment with intravitreal bevacizumab injection in branch retinal vein occlusion

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    Osman Sayýn

    2017-06-01

    Material and Method: The files of patients who had macular edema caused by branch retinal vein occlusion and who were applied intravitreal bevacizumab injection were studied retrospectively. Visual acuity (logMAR in follow-ups of the patients before and after the injection and the macular thickness values of the quadrant of the occlusion were recorded and the effect of intravitreal bevacizumab on these parameters were analyzed. Results: 24 eyes of 24 patients, 17 of which are male and 7 of which are female, were included in the study. The mean age of the patients were 59.1±7.7. The mean visual acuity prior to the injection was determined to be 0.7±0.5 logMAR, and the mean macular thickness value 489.7±129.6 μm. The mean injection number applied was 1.5±0.7. The mean follow-up time after the injection was 3.5±2.7 months. The mean macular thickness was determined to be 393.1±5.7 μm and mean visual acuity was 0.5±0.1 logMAR in the 1st month. In the last follow-ups of the patients, the mean visual acuity was 0.26±0.28 logMAR and the mean macular thickness value was 317.4±71.5 μm. The increase in visual acuity and decrease in macular thickness between first and last control after the injection was found statistically significant. (p<0.001. Conclusion: The intravitreal bevacizumab injection used in macular edema secondary to BRVO increases visual acuity and decreases macular thickness. [J Contemp Med 2017; 7(2.000: 143-148

  7. Juxtapapillary neovascular membrane secondary to idiopathic intracranial hypertension treated with intravitreal bevacizumab: A case report.

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    Hernández-Ortega, V; Soler-Sanchís, M I; Jiménez-Escribano, R M; Sanz-López, A M

    2016-05-01

    A 48 year-old woman with visual acuity loss in left eye (0.3). Funduscopic examination showed papillary oedema and neovascular membrane in the left eye. All neurological tests were normal, except the lumbar puncture with opening pressure of 35cmH2O, being diagnosed with idiopathic intracranial hypertension (IIH). After four doses of bevacizumab, the visual acuity of the left eye has not improved and is counting fingers. Pathogenesis of the juxtapapillary neovascular membrane associated with IIH is not well known. An effect was observed after the anti-VEGF treatment. In our case, there was no improvement after four doses of intravitreal bevacizumab. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  8. Posterior capsule opacification and neovascularization treated with intravitreal bevacizumab and Nd:YAG capsulotomy

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    Sánchez-Castro, Grimelda Yuriana; Hitos-Fájer, Alejandra; Mendoza-Schuster, Erick; Velez-Montoya, Raul; Velasco-Barona, Cecilio Francisco

    2008-01-01

    We reported a 75-year-old diabetic man, who developed opacification and neovascularization of the posterior capsule after extracapsular cataract extraction and posterior chamber intraocular lens implantation. The patient was treated with two injections of 2.5 mg of intravitreal bevacizumab. The treatment produced an important regression of the posterior capsular new vessels, allowing us to perform a successful Nd:YAG capsulotomy, clearing the visual axis and improving the visualization of the posterior pole. Even though, best corrected visual acuity was 20/200 due to diabetic macular edema. PMID:19668770

  9. The effect of intravitreal bevacizumab and ranibizumab on cutaneous tensile strength during wound healing

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    Christoforidis JB

    2013-01-01

    Full Text Available John B Christoforidis,1 Jillian Wang,2 Angela Jiang,2 James Willard,5 Cedric Pratt,2 Mahmoud Abdel-Rasoul,3 Sashwati Roy,4 Heather Powell51Department of Ophthalmology and Vision Science, College of Medicine, The University of Arizona, Tucson, AZ, USA; 2Department of Ophthalmology, College of Medicine, The Ohio State University, Columbus, OH, USA; 3Center for Biostatistics, The Ohio State University, Columbus, OH, USA; 4Center Surgery, The Ohio State University, Columbus, OH, USA; 5Department of Materials Science, College of Engineering, The Ohio State University, Columbus, OH, USAPurpose: To investigate the effect of intravitreal bevacizumab and ranibizumab on wound tension and by histopathology during cutaneous wound healing in a rabbit model and to compare this effect to placebo intravitreal saline controls 1 and 2 weeks following intravitreal injection.Methods: A total of 120 New Zealand white rabbits were randomly assigned to one of three treatment groups each consisting of 40 rabbits. Each group received intravitreal injections of bevacizumab, ranibizumab, or normal saline. Immediately afterwards, each rabbit underwent four 6 mm full-thickness dermatologic punch biopsies. Twenty rabbits from each agent group underwent wound harvesting on day 7 or day 14. The skin samples were stained for CD34 for vascular endothelial cells on day 7, and maximal wound tensile load was measured on days 7 and 14. Quantitative assessment of mean neovascularization (MNV scores was obtained from 10 contiguous biopsy margin 400× fields of CD34-stained sections by two independent observers.Results: Wound tension reading means (N with standard error and adjusted P-values on day 7 were: saline placebos, 7.46 ± 0.87; bevacizumab, 4.50 ± 0.88 (P = 0.041; and ranibizumab, 4.67 ± 0.84 (P = 0.025. On day 14 these were: saline placebos, 7.34 ± 0.55; bevacizumab, 6.05 ± 0.54 (P = 0.18; and ranibizumab 7.99 ± 0.54 (P = 0.40. MNV scores in CD34 stained sections were

  10. Posterior capsule opacification and neovascularization treated with intravitreal bevacizumab and Nd:YAG capsulotomy

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    Grimelda Yuriana Sánchez-Castro

    2008-10-01

    Full Text Available Grimelda Yuriana Sánchez-Castro1, Alejandra Hitos-Fájer1, Erick Mendoza-Schuster1, Raul Velez-Montoya2, Cecilio Francisco Velasco-Barona11Asociación para Evitar la Ceguera en México. Hospital “Dr. Luis Sánchez Bulnes”, México, D.F. Ophthalmology Department – Anterior Segment; 2Asociación para Evitar la Ceguera en México. Hospital “Dr. Luis Sánchez Bulnes”, México, D.F. Ophthalmology Department – Retina departmentAbstract: We reported a 75-year-old diabetic man, who developed opacification and neovascularization of the posterior capsule after extracapsular cataract extraction and posterior chamber intraocular lens implantation. The patient was treated with two injections of 2.5 mg of intravitreal bevacizumab. The treatment produced an important regression of the posterior capsular new vessels, allowing us to perform a successful Nd:YAG capsulotomy, clearing the visual axis and improving the visualization of the posterior pole. Even though, best corrected visual acuity was 20/200 due to diabetic macular edema.Keywords: posterior capsule opacification, posterior capsule neovascularization, cataract surgery, postoperative complications, intravitreal bevacizumab

  11. Intravitreal bevacizumab combined with plaque brachytherapy reduces melanoma tumor volume and enhances resolution of exudative detachment

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    Houston SK

    2013-01-01

    Full Text Available Samuel K Houston,1 Nisha V Shah,1 Christina Decatur,1 Marcela Lonngi,1 William Feuer,1 Arnold M Markoe,2 Timothy G Murray1–31Department of Ophthalmology, 2Department of Radiation Oncology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, 3Murray Ocular Oncology and Retina, Miami, FL, USABackground: The purpose of this study was to evaluate intravitreal bevacizumab as an adjuvant treatment to plaque brachytherapy in the treatment of choroidal melanoma.Methods: This was a retrospective, consecutive study of 124 patients treated from 2007 to 2009 for choroidal melanoma with plaque brachytherapy. Patients were treated with I-125 plaque brachytherapy with 2 mm margins and 85 Gy to the tumor apex. Consecutive patients were injected intravitreally with 2.5 mg/0.1 mL bevacizumab at a site away from the primary tumor and immediately following plaque removal. Choroidal melanomas were observed using indirect ophthalmoscopy, wide-angle photography, and ultrasound. The main outcome measures were tumor volume, resolution of exudative retinal detachment, and visual acuity.Results: One hundred and twenty-four patients met our inclusion criteria and were included in the analysis. The mean patient age was 65.7 years, and the mean apical tumor height was 4.0 ± 2.7 mm and basal diameter was 12.7 ± 3.0 mm. Mean follow-up was 24 months. Prior to treatment, 100% of tumors had exudative retinal detachment, and pretreatment visual acuity was 20/55 (median 20/40. Tumor control was 100%, metastasis was 0% at last follow-up, and 89.8% had complete resolution of exudative retinal detachment, with a mean time to resolution of 3.36 months. At one month, 43% had complete resolution of exudative retinal detachment, which increased to 73% at 4 months. Visual acuity was 20/62 (median 20/40 at 4 months, with stabilization to 20/57 (median 20/40 at 8 months, 20/56 (median 20/30 at 12 months, and 20/68 (median 20/50 at 24 months. Tumor

  12. Intravitreal bevacizumab as a treatment for choroidal neovascularisation secondary to myopia: 4-year study results.

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    Peiretti, Enrico; Vinci, Michela; Fossarello, Maurizio

    2012-02-01

    To report long-term follow-up results from intravitreal bevacizumab (IVB) treatment of choroidal neovascularisation (CNV) secondary to pathologic myopia (PM). The study was designed as a retrospective analysis of consecutive patients presenting with PM. Twenty-one eyes were examined from 20 different patients. The study was designed as a retrospective, consecutive, nonrandomised, interventional case series. Twenty-one eyes from 20 patients with CNV secondary to PM who were treated with bevacizumab were followed for a maximum of 52 months. Best-corrected visual acuity (BCVA), optical coherence tomography, and fluorescein and indocyanine green angiography were performed on each patient at baseline presentation and every 3 months thereafter for the entire follow-up period. The continuation therapy was based on dosing as needed regimen (PRN) for treatment assessment. Overall, 15 (71.4%) of the 21 eyes studied demonstrated an improvement of ≥ 1 line on the Snellen chart. A total of 3 (14.3%) eyes showed no change with this analysis, and 3 (14.3%) eyes lost 1 line of discrimination. After the 4-year study period, fluorescein angiography suggested absence of angiographic leakage or fibrotic lesions in 15 eyes, and 3 eyes showed partial regression of myopic CNV. The remaining 3 eyes demonstrated total regression of CNV. Intravitreal bevacizumab appears to be an effective therapy for myopic CNV and its benefit may persist in a long-term follow-up, on the basis of PRN treatment compared to the natural history of the disease. Copyright © 2012 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  13. The effects of intravitreal bevacizumab in infectious and noninfectious uveitic macular edema.

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    Al-Dhibi, Hassan; Hamade, Issam H; Al-Halafi, Ali; Barry, Maan; Chacra, Charbel Bou; Gupta, Vishali; Tabbara, Khalid F

    2014-01-01

    Background/Aims. To assess the effect of intravitreal bevacizumab injection (IVBI) for the treatment of macular edema due to infectious and noninfectious uveitides. Design. Retrospective interventional case series. Methods. A chart review was performed on all the patients who were diagnosed with uveitic macular edema (UME) and received 1.25 mg of IVBI at two referral centers in Riyadh, Saudi Arabia. All included patients had their visual acuity and macular thickness analyzed at baseline and at 1 and 3 months following IVBI and any sign of reactivation was noted. Results. The mean age of patients was 41 ± 16 years with a mean followup of 4 ± 1 months. Ten patients had idiopathic intermediate uveitis, 9 patients had Behcet's disease, 10 had idiopathic panuveitis, and twelve patients had presumed ocular tuberculosis uveitis. Following IVBI, the mean LogMAR visual acuity improved from 0.8 ± 0.8 at baseline to 0.4 ± 0.5 at 1 month and 0.3 ± 0.5 at 3 months (P < 0.002, at 3 months). The mean macular thickness was 430 ± 132 μm at baseline. Following IVBI macular thickness improved to 286 ± 93 μm at 1 month and to 265 ± 88 μm at 3 months of followup (P < 0.001, at 3 months). Conclusion. Bevacizumab was effective in the management of UME associated with both infectious and noninfectious uveitides. Intravitreal bevacizumab induced remission of UME with infectious uveitis and had no immunosuppressive effect against infectious agents.

  14. The Effects of Intravitreal Bevacizumab in Infectious and Noninfectious Uveitic Macular Edema

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    Hassan Al-Dhibi

    2014-01-01

    Full Text Available Background/Aims. To assess the effect of intravitreal bevacizumab injection (IVBI for the treatment of macular edema due to infectious and noninfectious uveitides. Design. Retrospective interventional case series. Methods. A chart review was performed on all the patients who were diagnosed with uveitic macular edema (UME and received 1.25 mg of IVBI at two referral centers in Riyadh, Saudi Arabia. All included patients had their visual acuity and macular thickness analyzed at baseline and at 1 and 3 months following IVBI and any sign of reactivation was noted. Results. The mean age of patients was 41±16 years with a mean followup of 4±1 months. Ten patients had idiopathic intermediate uveitis, 9 patients had Behcet’s disease, 10 had idiopathic panuveitis, and twelve patients had presumed ocular tuberculosis uveitis. Following IVBI, the mean LogMAR visual acuity improved from 0.8±0.8 at baseline to 0.4±0.5 at 1 month and 0.3±0.5 at 3 months (P<0.002, at 3 months. The mean macular thickness was 430±132 μm at baseline. Following IVBI macular thickness improved to 286±93 μm at 1 month and to 265±88 μm at 3 months of followup (P<0.001, at 3 months. Conclusion. Bevacizumab was effective in the management of UME associated with both infectious and noninfectious uveitides. Intravitreal bevacizumab induced remission of UME with infectious uveitis and had no immunosuppressive effect against infectious agents.

  15. Progression of choroidal metastasis of ovarian serous cystoadenocarcinoma after intravitreal bevacizumab treatment

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    Victor E. Reviglio

    2013-02-01

    Full Text Available A 57-year-old woman presented to her ophthalmologist because of rapid deterioration in vision. Dilated funduscopic examination of the right eye showed an elevated, yellow-orange choroidal mass temporal to the fovea; a complete retinal detachment was present in the left eye. The patient was referred to an oncologist. Computerized tomography of the brain, thorax, abdomen, and pelvis were obtained. They revealed an 11-mm mass in the right parietal lobe, a 30-mm mass in the left temporal lobe, 23-mm mass in the right kidney, and multiple nodules in both lungs. Supported by published experience with intravitreal bevacizumab for choroidal metastasis, the patient was injected into the vitreous through the pars plana of the left eye. The tumor mass did not show signs of regression and the visual acuity was unchanged. The patient suffered from end-state complications tumor metastasis and expired one month after the invitreal injection.

  16. Intravitreal bevacizumab for treatment of choroidal neovascularization associated with osteogenesis imperfecta

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    Pukhraj Rishi

    2012-01-01

    Full Text Available A 12-year-old girl, diagnosed of osteogenesis imperfecta, presented with sudden visual loss in the left eye. Investigations revealed an active choroidal neovascular membrane. She underwent treatment with intravitreal Bevacizumab (1.25 mg/0.05 ml. Follow-up at 1 month revealed the development of lacquer crack running through the macula, underlying the fovea. The patient received two re-treatments at 1-month intervals, following which the choroidal neovascularization (CNV regressed completely. However, further progression of lacquer cracks was noted. At the last follow-up, 6 months following the last injection, the fundus remained stable and vision was maintained at 20/200. Considering the natural history of the disease and the increased risk of rupture of the Bruch′s membrane in such eyes, the possible complication of a lacquer crack developing must be borne in mind, before initiating treatment.

  17. Intravitreal bevacizumab associated with photodynamic therapy in a case of polypoidal choroidal vasculopathy associated with choroidal nevus: A case report.

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    Rangel, Carlos M; Villota, Eva; Fernández-Vega González, Álvaro; Sanchez-Avila, Ronald M

    2017-12-01

    Report the clinical findings and management of a case of polypoidal choroidal vasculopathy associated with choroidal nevus which received combination therapy. Decreased visual acuity in a woman with polypoidal choroidal vasculopathy and choroidal nevus. Polypoidal choroidal vasculopathy and choroidal nevus. The initial visual acuity was 0.5. After the first treatment with photodynamic therapy, exudation and bleeding appeared around the lesion. After this, the patient received 3 doses of intravitreal bevacizumab. After treatment with combination therapy, visual acuity, clinical and imaging findings improved, with no recurrence of exudation and bleeding. Intravitreal bevacizumab as an adjunctive treatment after photodynamic therapy is a good option for patients with polypoidal choroidal vasculopathy associated with choroidal nevus. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  18. Changes in aqueous concentrations of various cytokines after intravitreal bevacizumab and subtenon triamcinolone injection for diabetic macular edema.

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    Yu, Seung-Young; Nam, Dong Heun; Lee, Dae Yeong

    2018-01-01

    The purpose of this study was to compare the changes in the aqueous cytokine levels after intravitreal bevacizumab with those after combined intravitreal bevacizumab and subtenon triamcinolone injection in diabetic macular edema (DME). This study examined 24 eyes of 23 patients with DME. Each patient with DME received randomly either an intravitreal injection of bevacizumab (IVBe) or IVBe with a subtenon triamcinolone injection (IVBe + STTA). Best corrected visual acuity and foveal thickness were evaluated and aqueous samples were obtained before and 4 weeks after the injection. The aqueous concentrations of interleukin (IL)-6, IL-8, interferon-induced protein (IP)-10, monocyte chemotactic protein (MCP)-1, platelet-derived growth factor (PDGF)-AA, and vascular endothelial growth factor (VEGF) were measured using a multiplex bead assay. After the injection, the foveal thickness decreased more in the IVBe + STTA group than in the IVBe group (P = 0.042). The MCP-1, PDGF-AA, and VEGF levels decreased significantly in the IVBe + STTA group (p = 0.013, p = 0.004 and p = 0.018 respectively), but only the VEGF level decreased in the IVBe group (p = 0.001). IL-8 was significantly increased in the IVBe + STTA group (p = 0.003) but the changes in the VEGF levels were smaller than in the IVBe group (p = 0.025). Intravitreal bevacizumab and subtenon triamcinolone injection reduces the VEGF, MCP-1 and PDGF-AA levels and increases the IL-8 level in the plural cytokine profiles of patients with DME, which might explain the limited therapeutic effect of combination therapy.

  19. Efficacy of Intravitreal Bevacizumab in Treatment of Proliferative Type 2 Idiopathic Juxtafoveal Telangiectasia

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    Ökkeş Baz

    2017-06-01

    Full Text Available Objectives: To evaluate the effectiveness of intravitreal bevacizumab (IVB in patients with subretinal neovascularization secondary to type 2 juxtafoveal telangiectasia. Materials and Methods: Ten eyes of 10 patients were included in this retrospective study. All cases were treated with IVB (1.25 mg bevacizumab. Visual acuity and slit-lamp anterior and posterior segment examinations were performed at each visit. Central macular thickness (CMT and intraretinal/subretinal fluid were evaluated via spectral domain optical coherence tomography (OCT. Loss of a line in visual acuity chart and presence of fluid on OCT were defined as criteria for repeated treatment. Results: The mean age of patients was 66.0±7.0 years (56-75. The mean follow-up time was 54.7±16.0 month (24-72. The mean BCVA was 0.62±0.35 (0.00-1.00 logMAR at baseline and 0.54±0.35 (0.00-1.00 logMAR at final exam (p=0.03. The mean CMT was 251±25.4 µm at baseline and 239±39.3 µm at final exam (p=0.01. Patients received an average of 1.7±1.0 IVB injections during follow-up. At baseline, all cases had intraretinal/subretinal fluid. There was no fluid at final examination of all cases. Conclusion: IVB treatment may be effective in the treatment of subretinal neovascularization secondary to type 2 juxtafoveal telangiectasia.

  20. Effects of Vitrectomy on Recurrent Macular Edema due to Branch Retinal Vein Occlusion after Intravitreal Injection of Bevacizumab

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    Tatsuya Yunoki

    2013-01-01

    Full Text Available Purpose. To evaluate the effects of pars plana vitrectomy (PPV on recurrent macular edema due to branch retinal vein occlusion (BRVO after intravitreal injections of bevacizumab (IVB. Methods. This retrospective study included 22 eyes of 22 patients who underwent single or multiple IVB injections for macular edema due to BRVO and showed a recurrence of macular edema. All patients then underwent PPV and were followed up for more than 6 months after the surgery with examinations of best corrected visual acuity (BCVA and optical coherence tomography (OCT. OCT parameters were central macular thickness (CMT and average retinal thickness in a 1-mm-diameter circular region at the fovea (MRT. Results. Mean BCVA, CRT, and MRT were significantly improved from the baseline after PPV. Greater improvement of BCVA, CRT, and MRT was obtained after 1 month of IVB than after 6 months of PPV. No eyes showed worsening of macular edema after the surgery. Conclusion. PPV improved BCVA and recurrent macular edema due to BRVO, but PPV that was less effective than IVB had been in the same patients. PPV may be one of the treatment options for recurrent macular edema due to BRVO after IVB.

  1. Massive choroidal hemorrhage after intravitreal administration of bevacizumab (Avastin® for AMD followed by controlateral sympathetic ophthalmia

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    Dimitrios Brouzas

    2009-08-01

    Full Text Available Dimitrios Brouzas, Chryssanthi Koutsandrea, Marilita Moschos, Spiros Papadimitriou, Ioannis Ladas, Michael Apostolopoulos1st Eye Department , University of Athens, Athens, GreecePurpose: To report a severe ocular complication initiated ten days after intravitreal administration of bevacizumab (Avastin®, in a patient with exudative age-related macular degeneration (AMD.Patients and method: Case report.Results: Ten days after intravitreal injection of 1.25 mg Avastin®, the patient manifested acute loss of vision with excruciating pain. An extensive choroidal detachment was evident in close contact with the lens, which necessitated an emergency sclerotomy with reconstruction of the anterior chamber. Four months later, the eye proceeded to phthisis bulbi. Five months after the injection, the patient complained of mild pain, photophobia, and visual acuity deterioration from the fellow eye. The diagnosis of sympathetic ophthalmia was suggested and treated with intravitreal injections of triamcinolone acetonide every three months with good response, complicated by elevation of intraocular pressure which we managed with Ahmet valve implantation.Conclusion: Serious ocular complications after intravitreal of Avastin® can not be excluded, including massive choroidal hemorrhage and sympathetic ophthalmia of the fellow eye.Keywords: Avastin® complication, intravitreal injection, choroidal detachment, Phthisis bulbi, sympathetic ophthalmia

  2. Posterior vitreous detachment with microplasmin alters the retinal penetration of intravitreal bevacizumab (Avastin) in rabbit eyes.

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    Goldenberg, David T; Giblin, Frank J; Cheng, Mei; Chintala, Shravan K; Trese, Michael T; Drenser, Kimberly A; Ruby, Alan J

    2011-02-01

    Intravitreal bevacizumab (BV) (Avastin, Genentech Inc., South San Francisco, CA) is frequently used for the treatment of age-related macular degeneration. Previous studies have demonstrated full-thickness retinal penetration. Intravitreal recombinant microplasmin (MP) has been shown to successfully induce a posterior vitreous detachment (PVD) and vitreous liquefaction in animals. It has been suggested that a PVD may alter the retinal penetration of molecules in the vitreous cavity. The aim of this study was to compare BV retinal penetration in rabbit eyes with and without an MP-induced PVD. Twelve adult rabbits were injected with 0.1 mL (0.4 mg) of MP into the vitreous cavity of 1 eye. One week later, the rabbits were injected with 0.05 mL (1.25 mg) of BV into both eyes. Both eyes of 3 rabbits were harvested at 6 hours, 12 hours, 24 hours, and 72 hours after the BV injection. Frozen retinal cross sections were prepared, and BV retinal penetration was evaluated with immunohistochemistry using a fluorescence-labeled antibody against BV. Two eyes from one rabbit were not injected with either agent and used as controls to compare the background autofluorescence. Peripapillary retinal sections were recorded with a digital camera, and intraretinal BV fluorescence-labeled antibody was measured by qualitative photographic interpretation. Two additional rabbits received an intravitreal injection of 0.1 mL of MP in 1 eye. One week later, both eyes from each rabbit were enucleated, and frozen retinal sections were prepared and analyzed with light microscopy to evaluate histologic damage. Full-thickness BV retinal penetration was observed throughout the retina in both eyes of each rabbit. All the MP-injected eyes exhibited increased antibody labeling in retinas evaluated at 6 hours, 12 hours, and 24 hours after BV injection when compared with the contralateral non-MP-injected eyes. By 3 days after BV injection, all eyes demonstrated decreased antibody labeling compared with

  3. Reduced occurrence of programmed cell death and gliosis in the retinas of juvenile rabbits after shortterm treatment with intravitreous bevacizumab

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    Maria Alice Fusco

    2012-01-01

    Full Text Available OBJECTIVE: Bevacizumab has been widely used as a vascular endothelial growth factor antagonist in the treatment of retinal vasoproliferative disorders in adults and, more recently, in infants with retinopathy of prematurity. Recently, it has been proposed that vascular endothelial growth factor acts as a protective factor for neurons and glial cells, particularly in developing nervous tissue. The purpose of this study was to investigate the effects of bevacizumab on the developing retinas of juvenile rabbits. METHODS: Juvenile rabbits received bevacizumab intravitreously in one eye; the other eye acted as an untreated control. Slit-lamp and fundoscopic examinations were performed both prior to and seven days after treatment. At the same time, retina samples were analyzed using immunohistochemistry to detect autophagy and apoptosis as well as proliferation and glial reactivity. Morphometric analyses were performed, and the data were analyzed using the Mann-Whitney U test. RESULTS: No clinical abnormalities were observed in either treated or untreated eyes. However, immunohistochemical analyses revealed a reduction in the occurrence of programmed cell death and increases in both proliferation and reactivity in the bevacizumab-treated group compared with the untreated group. CONCLUSIONS: Bevacizumab appears to alter programmed cell death patterns and promote gliosis in the developing retinas of rabbits; therefore, it should be used with caution in developing eyes

  4. Macular Edema Formation and Deterioration of Retinal Function after Intravitreal Bevacizumab Injection for Proliferative Diabetic Retinopathy

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    Hisanori Imai

    2011-09-01

    Full Text Available Purpose: To report a case of proliferative diabetic retinopathy (PDR showing transient macular edema (ME and deteriorated retinal function after intravitreal bevacizumab injection (IVB. Methods and Results: A 53-year-old man received IVB (1.25 mg/0.05 ml in both eyes for the treatment of PDR. There was no treatment-related complication. However, he complained of photopsia in both eyes 6 h after the injection. Slit-lamp examination revealed mild cellular infiltrations (1+ in the anterior chamber in both eyes. Optical coherence tomography showed ME formation in the left eye. Both full-field and multifocal electroretinography (ERG revealed the deterioration of all parameters in both eyes compared with pretreatment. The inflammation in the anterior segment and ME disappeared 1 day after the injection. ERG parameters were improved 9 days after the injection, except for the N1 and P1 amplitude of multifocal ERG in the left eye. Conclusion: We propose that patients who undergo IVB should be carefully informed and followed up for possible complications including temporal ME formation and retinal function deterioration.

  5. Low fluence rate photodynamic therapy combined with intravitreal bevacizumab for neovascular age-related macular degeneration.

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    Costagliola, Ciro; Romano, Mario R; Rinaldi, Michele; dell'Omo, Roberto; Chiosi, Flavia; Menzione, Massimo; Semeraro, Francesco

    2010-02-01

    To report the efficacy and safety of intravitreal bevacizumab (IVB) alone versus IVB plus low-fluence photodynamic therapy (PDT) in age-related macular degeneration (AMD) patients and to verify the occurrence of a synergistic effect of the combined approach on visual acuity, size and morphology of lesion, as well as on the treatment rate. Prospective comparative interventional study on 85 patients with treatment-naive classic, or predominantly classic, subfoveal choroidal neovascularisation secondary to AMD. Patients were randomly assigned to group 1 (IVB injections) and group 2 (IVB plus low fluence PDT). In group 2, the PDT with verteporfin was delivered with a low fluence rate (300 mW/cm2 for 83 s, 25 J/cm2). The follow-up was scheduled at 1, 3, 6, 9 and 12 months. The eye without recurrence received a mean of 2.8 (group 1) versus 1.4 (group 2) IVB injections, whereas the eyes with recurrence received a mean of 3.2 (group 1) versus 2.2 (group 2) IVB injections. The difference in reinjection rate between the two groups was statistically significant (p=0.03, ANOVA test). Visual acuity improvement was not statistically significant between the two groups (p=0.31). The combination of IVB with low fluence PDT for the treatment of classic or predominantly classic neovascular AMD works in a synergistic fashion with a significant reduction in IVB reinjections rate.

  6. Posterior Pole Sparing Laser Photocoagulation Combined with Intravitreal Bevacizumab Injection in Posterior Retinopathy of Prematurity

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    Rebecca Kim

    2014-01-01

    Full Text Available Purpose. To report the results of the posterior pole sparing laser photocoagulation combined with intravitreal bevacizumab injection (IVB in retinopathy of prematurity (ROP. Methods. A retrospective chart review of premature babies with ROP, all of whom received laser photocoagulation with IVB. Eleven eyes of 6 infants with advanced zone I ROP underwent laser ablation sparing posterior pole with concurrent IVB. The results were compared with those of full-laser treatment combined with IVB to 8 eyes of 5 infants with advanced ROP without involvement of the posterior pole. Results. The posterior pole sparing laser with IVB was performed with zone I, stage 3+ ROP at the mean postmenstrual age of 36 weeks and 5 days. The plus sign decreased significantly at postoperative day 1, the neovascular proliferation regressed by postoperative week 1, and the normal vascularization started at postoperative day 32 on the average. Two months after treatment, vascularization of the spared avascular area was completed. There was no macular dragging, tractional retinal detachment, foveal destruction by laser scars, or any other adverse event. No significant anatomical differences were identified from those of full-laser ablation combined with IVB. Conclusions. Posterior pole sparing laser with IVB can give favorable results without destruction of posterior pole retina.

  7. Clinical and histological findings after intravitreal injection of bevacizumab (Avastin) in a porcine model of choroidal neovascularization

    DEFF Research Database (Denmark)

    Lassota, Nathan; Prause, Jan Ulrik; Scherfig, Erik

    2010-01-01

    PURPOSE: To examine the effect of intravitreally injected bevacizumab (Avastin) on the histological and angiographic morphology of choroidal neovascularization (CNV) in a masked and placebo-controlled animal study. METHODS: Choroidal neovascularization was induced surgically in 11 porcine eyes...... by perforating Bruch's membrane with a retinal perforator. After closure of the ports used for the vitrectomy, which was performed to facilitate the Bruch's membrane rupture, 0.05 ml of either bevacizumab or Ringer-Lactat (placebo) was injected into the vitreous cavity. Eyes were enucleated after 14 days. Fundus...... photographs and fluorescein angiograms (FAs) were obtained immediately prior to enucleation. Sections of formalin- and paraffin-embedded eyes were examined by light microscopy and by immunohistochemical staining. RESULTS: Placebo-injected eyes exhibited the highest propensity to leak, with five of six eyes...

  8. Photodynamic monotherapy or combination treatment with intravitreal triamcinolone acetonide, bevacizumab or ranibizumab for choroidal neovascularization associated with pathological myopia

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    Pukhraj Rishi

    2011-01-01

    Full Text Available This retrospective, interventional case series analyses treatment outcomes in eyes with choroidal neovascularization (CNV secondary to pathological myopia, managed with photodynamic therapy, (PDT, (Group 1, N = 11, PDT and intravitreal triamcinolone acetonide (4 mg/0.1ml (Group 2, N = 3, PDT and intravitreal anti-vascular endothelial growth factor (anti-VEGF bevacizumab 1.25 mg/0.05 ml, ranibizumab 0.5 mg/0.05 ml and reduced-fluence PDT and intravitreal ranibizumab 0.5 mg/0.05 ml (Group 3, N=12. All the patients underwent PDT. Intravitreal injections were repeated as required. SPSS 14 software was used to evaluate the data. Wilcoxon signed ranks test was used to evaluate pre- and post-treatment vision. The Kruskal-Wallis test was used for comparison between the groups. All the groups were statistically comparable. All the eyes showed complete regression of CNV, with a minimum follow-up of six months. All groups had visual improvement; significantly in Group 3 ( p = 0.003. Combination PDT with anti-VEGF agents appeared to be efficacious in eyes with myopic CNV. However, a larger study with a longer follow-up is required to validate these results.

  9. Clinical research on intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease.

    Science.gov (United States)

    Yan, Ying; Wang, Tao; Cao, Jing; Wang, Meng; Li, Fenghua

    2015-07-01

    This paper aimed to explore clinically curative effect of intravitreal injection of bevacizumab in the treatment of macula lutea and retinal edema of ocular fundus disease. The number of 300 patients (390 eyes) with ocular fundus diseases including retinal vein occlusion (RVO), diabetic retinopathy (DR), age-related macular degeneration (ARMD), central serous chorioretinopathy (CSC), choridal new vessel (CNV) received and cured in the hospital from February 2010 to February 2014 were given intravitreal injection of bevacizumab (1.5mg) with once per month and a total of 2-3 times. Results of patients' vision and fluorescence fundus angiography (FFA), optical coherence tomography (OCT) before and after treatment were compared and curative effects were evaluated. Vision of 349 eyes (89.49%) improved obviously with the average of more than 2 lines, patient's intraocular pressure (IOP) was normal and all indexes were clearly better; vision of 26 eyes (6.67%) was stable before the treatment and without any changes after the treatment, the situation of fundus got better without increased IOP; vision of 15 eyes (3.85%) decreased to some extent, and the symptoms eased slightly after symptomatic treatment. In the 1st day after intravitreal injection, best-corrected visual acuity increased to 0.239±0.175, best-corrected visual acuity in 1 m was 0.315±0.182, in 3m continuously climbed to 0.350±0.270, and in 6 m was 0.362±0.282. Compared with vision before injection, t value was t=3.184, t=7.213, t=9.274 and t=9.970 (P=0.002, P=0.000, P=0.000 and P=0.000) respectively, and all P were less than 0.01. Furthermore, the difference was significant if a=0.01, which could confirm that 1m best corrected visual acuity of patients after intravitreal injection improved clearly in combination with before injection and 3m and 6 m visions enhanced constantly after injection. To sum up, intravitreal injection of bevacizumab in treating ocular fundus disease improves patient's vision

  10. Buckling surgery and supplemental intravitreal bevacizumab or photocoagulation on stage 4 retinopathy of prematurity eyes.

    Science.gov (United States)

    Futamura, Yukiko; Asami, Tetsu; Nonobe, Norie; Kachi, Shu; Ito, Yasuki; Sato, Yoshiaki; Hayakawa, Masahiro; Terasaki, Hiroko

    2015-11-01

    To report the results of scleral buckling (SB) with or without photocoagulation (PC) and intravitreal bevacizumab (IVB) for stage 4 retinopathy of prematurity (ROP) eyes. Forty-two eyes of 28 patients with SB and/or PC or IVB were studied. Twenty-nine eyes had stage 4A and 13 eyes had stage 4B ROP. Seventeen eyes underwent SB combined with additional intraoperative or postoperative treatments (combined group). Twenty-five eyes underwent SB without additional therapy (non-combined group). The concentrations of vascular endothelial growth factor (VEGF) in the aqueous humor determined by enzyme-linked immunosorbent assay were compared between the two groups. The initial and final reattachment rates were also compared. The gestational age and birth weight were 25.0 ± 2.0 weeks and 786 ± 222 g in the combined group, and 25.5 ± 2.1 weeks and 899 ± 315 g in the non-combined group. The postmenstrual age at the time of initial surgery was 38.0 ± 1.9 in the combined and 44.1 ± 4.0 weeks in the non-combined group (P < 0.001). The initial reattachment rate was 92% in stage 4A and 75% in stage 4B of ROP eyes in the combined group, and the rate was 93% in stage 4A and 33% in stage 4B of ROP eyes in the non-combined group. The mean VEGF concentration in aqueous humor was 1923 ± 779 pg/ml in the combined group and 985 ± 303 pg/ml in the non-combined group (P < 0.05). Our results show that the retinal reattachment rate after combined therapy was comparable to that in the non-combined group. We conclude that combined therapy may be effective even in ROP eyes with high activity.

  11. Improvement of visual acuity based on optical coherence tomography patterns following intravitreal bevacizumab treatment in patients with diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Haider R. Cheema

    2014-04-01

    Full Text Available AIM:To report the visual outcome based on various patterns of optical coherence tomography (OCT morphology in diabetic macular edema (DME, following treatment with anti-VEGF intravitreal bevacizumab (IVB injection.METHODS:Sixty-seven consecutive subjects with centre involving DME underwent intravitreal injection of Bevacizumab (1.25 mg/0.05 mL in this retrospective, comparative, non randomized study. The DME was classified into one of four categories:focal, diffuse, focal cystoid and neurosensory detachment based on OCT. Best corrected visual acuity (BCVA, macular appearance, and OCT findings were used to decide whether the subject should have a repeat injection of intravitreal bevacizumab. Outcome measures were a change in mean BCVA (Snellen converted to logMAR and central macular thickness (CMT in each group during the six month follow-up period.RESULTS:The mean BCVA improved to logMAR 0.23 at final follow-up from a baseline of 0.32 logMAR (P=0.040 in the focal group, logMAR 0.80 at final follow-up from a baseline of 0.82 logMAR (P=0.838 in the diffuse group, worsened to logMAR 0.53 at final follow-up from a baseline of 0.43 logMAR (P=0.276 in the focal cystoid group, and improved to logMAR 0.79 at final follow-up from a baseline of 0.93 logMAR (P=0.490 in the neurosensory detachment group. The mean CMT before treatment were 298.8±25.03 μm in the focal group, 310.8±40.6 μm in the diffuse group, 397.15±31.05 μm in the focal cystoid group and 401.03±75.1 μm in the neurosensory detachment group. A mean of 2.05 (range:1-5 injections in the focal group, 1.32 (range:1-2 in the diffuse group, 2.6 (range:1-6 in the focal cystoid group and 2.6 (range:1-6 in the neurosensory detachment group were performed during the six month follow-up period. Following intravitreal bevacizumab treatment, vision improved, remained unchanged or worsened in 11, 7 and 2 subjects in focal group; 11, 9 and 8 in diffuse group; 0, 2 and 4 in focal cystoid group and 5

  12. Use of intravitreal bevacizumab or triamcinolone acetonide as a preoperative adjunct to vitrectomy for vitreous haemorrhage in diabetics

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    Daniel Araújo Ferraz

    2013-02-01

    Full Text Available PURPOSE: To evaluate the effect of preoperative intravitreal bevacizumab (IVB or triamcinolone (IVT on the rate of early postvitrectomy hemorrhage in proliferative diabetic retinopathy (PDR. METHODS: Eligible eyes were assigned randomly to 1 of 3 groups: the IVB group received 1.25 mg bevacizumab, the IVT group received 4,0mg triamcinolone and the control group underwent a sham procedure. The primary outcome measure was the incidence of early postvitrectomy hemorrhage. Secondary outcome measures included changes in visual acuity (BCVA and adverse events. RESULTS: Twenty and seven eyes, 9 in each group were randomized. The incidence of vitreous hemorrhage was lower in the IVB group (p=0.18. Postoperative vitreous hemorrhage at 1 month also was less in the IVB group compared with the control group (p > 0.05. The rate of bleeding immediately after surgery was higher in IVT group with 4 (44.4% cases. The overall mean visual acuity was 1.72 ± 0.37 logMAR preoperatively and 1.32 ± 0.73 logMAR in 6 months after surgery. Accessing visual acuity by group evidenced that the IVB group had initial mean logMAR VA of 1.87 and 1.57 logMAR VA at the six months (p = 0.84. In IVT group, initial mean VA was 1.75 logMAR and 0.96 logMAR VA at six months (p < 0.001. And in control group, the initial mean VA was 1.85 logMAR and 1.57 logMAR VA at six months (p= 0.34. CONCLUSION: Intravitreal injection of bevacizumab 1 week before vitrectomy seems to reduce the incidence of early postvitrectomy hemorrhage in diabetic patients. There was a better visual acuity outcome in the triamcinolone group.

  13. Combined photodynamic therapy and intravitreal bevacizumab for idiopathic polypoidal choroidal vasculopathy: one-year follow-up

    Directory of Open Access Journals (Sweden)

    Mario R Romano

    2010-10-01

    Full Text Available Mario R Romano1, Ugo Cipollone2, Francesco Semeraro3, Michele Rinaldi4, Ciro Costagliola11Dipartimento di Scienze per la Salute, Università degli Studi del Molise, Campobasso; 2Dipartimento di Oftalmologia, Ospedale G Vietri, Larino, Campobasso; 3Clinica Oculistica, Università degli Studi di Brescia, Brescia; 4Clinica Oculistica, II Università degli Studi di Napoli, Napoli, ItalyObjective: To report the efficacy and safety of combined photodynamic therapy (PDT and intravitreal bevacizumab (IVB injection in the treatment of idiopathic polypoidal choroidal vasculopathy (IPCV.Material and methods: A prospective case series of 10 eyes of 10 consecutive patients affected by IPCV with subfoveal involvement. PDT plus IVB (1.25 mg/0.05 mL injection two weeks later was performed in all patients. Two adjunctive injections of bevacizumab were scheduled at four and eight weeks after the initial treatment. Best-corrected visual acuity (BCVA, fluorescein and indocyanine green angiographies, and optical coherence tomography were obtained at baseline, and at one, three, six, nine, and 12 months.Results: The combined treatment led to an improvement of both neurosensory detachment and pigmented epithelial detachment in all eyes, with a decrease of exudation and regression of macular thickness, which remained stable to the end of follow-up. However, BCVA remained stable over the 12 months of follow-up.Conclusion: These findings demonstrate that PDT/IVB combined therapy is able to achieve morphologic stabilization of the IPCV lesion, through a rapid decrease of macular thickness and regression of the size of polypoidal vascular lesion.Keywords: combined treatment, idiopathic polypoidal choroidal vasculopathy, age-related macular degeneration, intravitreal bevacizumab, photodynamic therapy

  14. Effects of intravitreal bevacizumab injection on the clinical manifestations of nonproliferative diabetic retinopathy in patients with macular edema: a systematic review

    Directory of Open Access Journals (Sweden)

    Touka Banaee

    2016-04-01

    Full Text Available Introduction: Bevacizumab (Avastin is considered as an effective strategy in the treatment of various ocular diseases. As a vascular endothelial growth factor (VEGF inhibitor, Avastin is used to control macular edema in patients with nonproliferative diabetic retinopathy (NPDR. Therefore, in this study, we systematically reviewed the effects of intravitreal bevacizumab injections on nonproliferative stage of diabetic retinopathy. Methods: Scopus and PubMed were systematically searched to find articles in which the effect of Avastin (bevacizumab had been evaluated in nonproliferative stage of diabetic retinopathy. Literature search was performed using “Avastin OR bevacizumab”, “nonproliferative stage” and “diabetic retinopathy” as keyterms in the title, keywords, and abstract.Result: All 47 articles were found in all databases, two additional records were found through reference list screening, and only 10 articles were relevant to the purpose of this study. According to the inclusion/exclusion criteria, 39 articles were excluded in several step processes of article selection. The results revealed that intravitreal injection of bevacizumab could be safely used to treat various ocular disease, particularly NPDR stage of diabetic retinopathy with macular edema.Discussion: Bevacizumab is considered as a novel and effective modality in the treatment of various ocular diseases such as retinal neovascularization, neovascular glaucoma, macular edema, and other ocular complications. Findings also suggested that bevacizumab is a suitable therapeutic approach in clinical use.Conclusion: According to the results of included documents, intravitreal injection of bevacizumab could be considered as a promising treatment modality in the clinical management of NPDR stage of diabetic retinopathy.

  15. Comparison of intravitreal ranibizumab and bevacizumab for the treatment of macular edema secondary to retinal vein occlusion

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    Alex Yuan

    2014-02-01

    Full Text Available AIM:To compare the efficacy of ranibizumab and bevacizumab for macular edema due to retinal vein occlusion (RVO.METHODS:A retrospective study was conducted at a single academic institution. Eighty-one patients naïve to anti-VEGF therapy with RVO and macular edema were identified. Twenty-six eyes were treated with ranibizumab, 33 eyes with bevacizumab, and 22 eyes with bevacizumab then switched to ranibizumab (crossover. The main outcome was change in visual acuity at 3 months, 6 months, and final visit.RESULTS:The mean visual acuity improved from 20/80 to 20/40 in the ranibizumab (R group and from 20/125 to 20/60 in the bevacizumab (B group (P=0.66. The mean change in central subfield thickness (CST was -186 and -212µm, respectively (P=0.69. Mean time between injections was 94±21.1d in the R group and 103.8±10.5d in the B group (P=0.78. In the crossover group, mean initial visual acuity was 20/125, reached 20/60 at crossover, and remained 20/60 at conclusion (P=0.91.CONCLUSION:Both ranibizumab and bevacizumab are effective for the treatment of RVO and appear to have similar visual and anatomic outcomes. Changing treatments from bevacizumab to ranibizumab did not result in further gains in visual acuity.

  16. The effect of intravitreal bevacizumab (Avastin® on ocular pulse amplitude in neovascular age-related macular degeneration

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    Ehud Rechtman

    2011-01-01

    Full Text Available Ehud Rechtman1, Ingeborg Stalmans2, Joseph Glovinsky1, Christophe Breusegem2, Joseph Moisseiev1, Joachim Van Calster2, Alon Harris31Goldschleger Eye Institute, Sheba Medical Center, Ramat Gan, Israel; 2Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium; 3Department of Ophthalmology, Indiana University, Indianapolis, IN, USAPurpose: To evaluate the effect of intravitreal (IVT bevacizumab in neovascular age-related macular degeneration (AMD on global choroidal hemodynamics, as measured by ocular pulse amplitude (OPA.Methods: This was a two-center prospective study (Sheba Medical Center, Israel, and University Hospitals Leuven, Belgium. AMD patients who required IVT bevacizumab (1.25 mg/0.05 mL; first or repeated were examined three times: at days 0 (prior to injection, 7 (±3, and 28 (±7 postinjection. At each visit, OPAs of both eyes were measured using the Pascal dynamic contour tonometer (DCT. A paired t-test between preoperative and postoperative OPA was conducted. Pearson correlation was used to evaluate the influence of various measured parameters on DCT–OPA.Results: A total of 38 neovascular AMD patients were recruited, and 30 patients were included in the final analysis (18 females and 12 males; age 78.8 ± 5.82 years [mean ± standard deviation]. A good correlation was found throughout the study between the DCT–intraocular pressure (IOP and Goldmann IOP and between DCT–IOP and DCT–OPA. No change in OPA of bevacizumab-treated eyes was found between the visits (2.24 ± 0.73, 2.2 ± 0.86, and 2.23 ± 0.73 mm Hg at visits 1, 2, and 3, respectively; paired t-test: P = 0.77 between visits 1 and 2, P = 0.98 between visits 1 and 3. No correlations were found between DCT–OPA and age, heart rate, systemic blood pressure, axial length, keratometry readings, and central corneal thickness.Conclusions: OPA, an indirect measure of global choroidal hemodynamics, remains unchanged following IVT off-label bevacizumab. This

  17. The effect of intravitreal administration of bevacizumab on macular edema and visual acuity in age-related macular degeneration with subfoveolar choroidal neovascularisation

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    Ristić Dragana

    2013-01-01

    Full Text Available Background/Aim. Age-related macular degeneration (AMD is a leading cause of the loss of central visual acuity in population older than 70 years. We can distinguish wet and dry form of AMD. The aim of the study was to present our early results in treatment of the wet (neovascular form of AMD with intravitreal administration of bevacizumab. Methods. The study included 39 patients. Each patient underwent a complete ophthalmological examination, fluorescein angiography (FA and optical coherence tomography (OCT. All the patients received 1.25 mg of intravitreal bevacizumab (0.05 mL of commercial phial of Avastin®. The total of three doses was given with a one-month interval between doses. Results. Among 39 patients, 24 were women and 15 men. The average best corrected visual acuity (BCVA was improved from 0.09 before the therapy to 0.24 after the administration of all the three doses of bevacizumab (p < 0.001. The average central macular thickness (CMT measured by OCT was improved from 474 μm in the beginning to 341 μm after the administration of all the three doses of the drug (p < 0.001. There were no side effects. Conclusions. Our short-term experience indicates that intravitreal administration of three doses of bevacizumab in one-month intervals between the doses leads to a significant reduction of macular edema and improvement of BCVA in patients with neovascular AMD.

  18. Comparison of intravitreal bevacizumab with intravitreal triamcinolone acetonide for treatment of cystoid macular edema secondary to retinal vein occlusion: a Meta-analysis.

    Science.gov (United States)

    Sun, Yan; Qu, Yi

    2015-01-01

    To compare the effects of intravitreal injection of bevacizumab (IVB) with intravitreal triamcinolone acetonide (IVTA) on the treatment of cystoid macular edema (CME) secondary to retinal vein occlusion (RVO). A literature search was conducted using PubMed, the Cochrane Central Register of Controlled Trials, Web of Science and the Chinese Biomedical Database. The comparison was divided into two groups, group 1 conducted comparison in branch RVO (BRVO) or central RVO (CRVO), group 2 conducted comparison in ischemic-RVO or nonischemic-RVO. Pooled mean differences (MDs) for changes in visual acuity (VA), central macular thickness (CMT) and intraocular pressure (IOP) were calculated in groups at 4, 12 and 24wk after treatment respectively. Eight studies comparing the efficacy of IVB with IVTA were included in the Meta-analysis. In group 1, in BRVO, significant difference was shown on the comparison of CMT at 24wk (MD, -45.66; 95% CI, -76.03 to -15.28; P=0.003), IVB was effective on BRVO for at least 24wk; no significant differences were found in the comparison of VA at each time points (P>0.05 respectively). In CRVO, no significant differences were found in the comparison of VA or CMT between IVB and IVTA at each time points (P>0.05, respectively). In group 2, in ischemic-RVO, significant differences were shown in the comparison of VA (MD, -0.28; 95% CI, -0.42 to -0.14; Pcomparison of VA or CMT between IVB and IVTA at each time points (P>0.05, respectively). The occurrence of high IOP was much lower in IVB group. This Meta-analysis suggested that IVB was effective in decreasing CMT in BRVO for at least 24wk, IVB is more effective on improving VA and reducing CMT in ischemic-RVO. IVB is more promising on RVO than IVTA.

  19. Effect of laser photocoagulation and bevacizumab intravitreal in proliferative diabetic retinopathy: review on biomarkers of oxidative stress

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    Andi A. Victor

    2014-06-01

    Full Text Available Background: This study was aimed to compare the effect of laser photocoagulation (LF, intravitreal bevacizumab (IVB and combined treatments on biomarkers of oxidative stress such as aldehhyde dehidrogenase (ALDH, malondialdehyde (MDA level, superoxide dismutase (SOD activities, and vitreal vascular endothelial growth factor (VEGF on proliferative diabetic retinopathy (DR patients.Methods: In this single blind randomized clinical trial, 72 eyes from 69 cases of proliferative DR in Cipto Mangunkusumo Hospital between February 2011 - June 2013 were randomized into 4 groups : 1 control (n = 18; 2 LF pre-vitrectomy (n = 18; 3 IVB pre-vitrectomy (n = 18; and 4 combined IVB and LF pre-vitrectomy (n = 18. One-way ANOVA was used to compare oxidative stress parameters in the four groups.Results: There were no statistically significant differences in the average plasma ALDH activity (0.034 ± 0.02; 0.027 ± 0.02; 0.025 ± 0.02; 0.031 ± 0.11 IU/mg protein; p = 0.66, vitreal MDA level (1.661 ± 1.21; 1.557 ± 1.32; 1.717 ± 1.54; 1.501 ± 1.09 nmol/mL; p = 0.96 and SOD activity (0.403 ± 0.50; 0.210 ± 0.18; 0.399 ± 0.49; 0.273 ± 0.32 U/mL; p = 0.38 among these four groups, respectively. However, the VEGF vitreal level (pg/mL showed a statistically significant difference (0.356 ± 0.60; 0.393 ± 0.45; 0.150 ± 0.24; 0.069 ± 0.13; p = 0.05. The VEGF level in combination group was five times lower than the control group (p = 0.05.Conclusion: Combined treatments of DR by IVB and LF were correlated with lower vitreal MDA and plasma VEGF level, but did not have any effect on plasma ALDH and vitreal SOD in proliferative DR. Combined treatments with IVB and LF are recommended for the management of proliferative DR patients.  

  20. Efficacy of 12-month treatment of neovascular age-related macular degeneration with intravitreal bevacizumab based on individually determined injection strategies after three consecutive monthly injections.

    Science.gov (United States)

    Mekjavic, Polona Jaki; Kraut, Aleksandra; Urbancic, Mojca; Lenassi, Eva; Hawlina, Marko

    2011-11-01

    To report the results of intravitreal treatment with bevacizumab in neovascular age-related macular degeneration (AMD) after a loading dose (LD) of three monthly injections followed by an optical coherence tomography (OCT)-guided strategy, based on best-corrected visual acuity (VA) and number of injections required over 1 year. A series of consecutive cases of 149 eyes of 147 patients received three or more intravitreal injections of bevacizumab (1.25 mg) for neovascular AMD over a 1-year period. The patients underwent ophthalmological examinations: measurement of the VA, fluorescein angiography, dilated fundus examination at baseline; VA, OCT and dilated fundus examination at monthly follow-up visits. Repeated injections were given each month for the first 3 months (LD); thereafter, injections were only administered if leakage or macular oedema were present. Mean baseline VA was 51 ± 14 letters, which improved to 58 ± 15 letters (p injections per patient treated for 1 year was 5.1 (range 3-9). No systemic side-effects were noted. Treatment of neovascular AMD with intravitreal bevacizumab administered in LD of three monthly injections and followed by an OCT-guided strategy provides functional and anatomical improvements for up to 1 year. © 2009 The Authors. Journal compilation © 2009 Acta Ophthalmol.

  1. Intravitreal bevacizumab monotherapy for type-1 prethreshold, threshold, and aggressive posterior retinopathy of prematurity - 27 month follow-up results from Turkey.

    Science.gov (United States)

    Yetik, Huseyin; Gunay, Murat; Sirop, Sarkis; Salihoglu, Ziya

    2015-10-01

    To study the efficacy of intravitreal bevacizumab (IVB) injection as a single treatment for retinopathy of prematurity (ROP). This was a prospective interventional case series study performed in a clinical practice setting; a total of 122 patients including prethreshold (type 1) (n  = 79, 152 eyes, six unilateral), threshold (n = 12, 24 eyes), and aggressive posterior (APROP) (n = 31, 62 eyes); cases were included without any randomization or masking. A total of 253 IVB injections, 238 in the first session, 11 in the second session, and four in the third session were performed, and followed up for a mean of 89.155 ± 4.277 (range 82 to 105) weeks of postmenstrual age (PMA). Regression of ROP, maturation of the retina, and associated complications were evaluated. Total regression was achieved in 227/238 eyes (95.4 %) after the first dose injection. The remaining 11 received a second injection, after which an additional seven (234/238; 98.2 %) regressed; after the third injection, the remaining 4 (238/238; 100 %) regressed. Complete retinal vascular maturation was achieved without any significant complications in all of the cases. IVB injection as monotherapy seems to be a very effective treatment modality for ROP. Based on timely intervention, IVB as a single treatment modality can salvage almost all ROP cases before stage 4.

  2. Comparison of Intravitreal Bevacizumab, Intravitreal Ranibizumab and Laser Photocoagulation for Treatment of Type 1 Retinopathy of Prematurity in Turkish Preterm Children.

    Science.gov (United States)

    Kabataş, Emrah Utku; Kurtul, Bengi Ece; Altıaylık Özer, Pınar; Kabataş, Naciye

    2017-07-01

    To evaluate effectiveness of treatment modalities, major complications and refractive errors in children who were treated with intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR) or laser photocoagulation (LP) for type 1 retinopathy of prematurity (ROP). Premature infants who underwent IVB monotherapy (Group 1), IVR monotherapy (Group 2) or LP (Group 3) for type 1 ROP and infants with spontaneously regressed ROP (Group 4) were included for the study. Major complications, recurrence rate, recurrence time, total retinal vascularization time and refractive errors at 18 months of corrected age (CA) were determined. Groups 1, 2, 3 and 4 included 24 eyes of 12 patients, 12 eyes of six patients, 72 eyes of 36 patients and 148 eyes of 74 patients, respectively. Recurrence of the disease occurred in two eyes of one patient in Group 1 at 52 weeks of postmenstrual age (PMA) and two eyes of one patient at 48 weeks of PMA in Group 2. In Group 3, disease did not regress after the first treatment in 10 eyes of five patients. The mean vascularization time in Group 1 was 73 ± 10.1 weeks of PMA and 61.8 ± 6.6 weeks of PMA in Group 2 (p = 0.027). Macular ectopia was seen in two eyes of one patient and exudative retinal detachment (ERD) occurred in two eyes of one patient in Group 3. Mean spherical equivalent was 1.49 ± 3.04 diopters (D) in Group 1, -1.79 ± 2.87D in Group 2, -1.27 ± 2.8 D in Group 3 and 1.52 ± 1.07 D in Group 4 at 18 months of CA. There was no significant difference in astigmatism values in all groups. IVB, IVR and LP are options that can successfully treat ROP. Myopia was observed to be the main refractive error in all treatment groups. Vascularization of the retina was completed later in the IVB group than in the IVR group.

  3. Effect of intravitreal bevacizumab on serum, aqueous, and vitreous humor levels of erythropoietin in patients with proliferative diabetic retinopathy.

    Science.gov (United States)

    Cancarini, A; Costagliola, C; Dell'omo, R; Romano, M; Morescalchi, F; Agnifili, L; Ruggeri, G; Semeraro, F

    2014-12-01

    The aim of this study was to evaluate concentrations of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in serum, aqueous and vitreous humour of diabetic patients with proliferative retinopathy (PDR) and to verify their possible modifications induced by intravitreal injection of bevacizumab (IVB). This prospective observational study was performed on patients who underwent vitrectomy for proliferative diabetic retinopathy and macular hole or pucker. The study sample consisted of 33 patients with proliferative diabetic retinopathy and 20 non-diabetic patients with macular hole or pucker. EPO and VEGF levels in serum, aqueous and vitreous humour were measured in both groups. In diabetic patients measures were performed before and after IVB. EPO and VEGF levels in aqueous and vitreous humour were markedly increased in diabetic patients with PDR as compared with those recorded in the control group (P<0.001); contrarily, EPO serum levels were similar in both groups (p=not significant). IVB did not affect EPO levels (aqueous 39.1 ± 29.2 vs. 38.6 ± 26.1; vitreous 179.3 ± 88.3 vs. 131.6 ± 67.8; serum 9.2 ± 5.8 vs. 6.9 ± 3.7 mUI/mL); conversely, VEGF concentration significantly decreased 15 days after IVB in serum and ocular fluids (aqueous 141.6 ± 12.3 vs. 81.4 ± 5.4; vitreous 180.4 ± 45.8 vs. 95.8 ± 23.6; serum 113.9 ± 52.8 vs. 73.2 ± 65.6 mUI/mL). These findings demonstrate that the production of VEGF and EPO is regulated by different mechanisms. Intraocular levels of EPO in diabetic patients were significantly higher than those recorded in serum, suggesting a local production. In addition, bevacizumab does not influence intraocular levels of EPO.

  4. Management of recurrent inflammatory choroidal neovascular membrane secondary to Vogt-Koyanagi-Harada syndrome, using combined intravitreal injection of bevacizumab and triamcinolone acetate

    Directory of Open Access Journals (Sweden)

    Sivakami A Pai

    2012-01-01

    Full Text Available The purpose of this report is to evaluate the efficacy and safety of combined intravitreal injection of bevacizumab and intravitreal triamcinolone acetonide (IVTA for recurrent inflammatory choroidal neovascular membrane (CNVM. It was a prospective interventional study of a young female, who was a known case of Vogt-Koyanagi-Harada syndrome. She presented with an inflammatory choroidal neovascualar membrane and signs of panuveitis in the right eye. She underwent a complete ophthalmic examination. She was given intravitreal injection of bevacizumab and IVTA at different sites. There was complete regression of CNVM and ocular inflammation within a week. After six months, she had recurrence of CNVM in the same eye, which was treated similarly. There was a complete resolution of CNVM and ocular inflammation after the combination therapy and systemic steroids, until one year of follow-up. No serious systemic or ocular adverse events were noted. Combination therapy appears to be an effective and safe method in the management of recurrent inflammatory CNVM.

  5. First-Line XELOX Plus Bevacizumab Followed by XELOX Plus Bevacizumab or Single-Agent Bevacizumab as Maintenance Therapy in Patients with Metastatic Colorectal Cancer: The Phase III MACRO TTD Study

    Science.gov (United States)

    Gómez-España, Auxiliadora; Massutí, Bartomeu; Sastre, Javier; Abad, Albert; Valladares, Manuel; Rivera, Fernando; Safont, Maria J.; Martínez de Prado, Purificación; Gallén, Manuel; González, Encarnación; Marcuello, Eugenio; Benavides, Manuel; Fernández-Martos, Carlos; Losa, Ferrán; Escudero, Pilar; Arrivi, Antonio; Cervantes, Andrés; Dueñas, Rosario; López-Ladrón, Amelia; Lacasta, Adelaida; Llanos, Marta; Tabernero, Jose M.; Antón, Antonio; Aranda, Enrique

    2012-01-01

    Purpose. The aim of this phase III trial was to compare the efficacy and safety of bevacizumab alone with those of bevacizumab and capecitabine plus oxaliplatin (XELOX) as maintenance treatment following induction chemotherapy with XELOX plus bevacizumab in the first-line treatment of patients with metastatic colorectal cancer (mCRC). Patients and Methods. Patients were randomly assigned to receive six cycles of bevacizumab, capecitabine, and oxaliplatin every 3 weeks followed by XELOX plus bevacizumab or bevacizumab alone until progression. The primary endpoint was the progression-free survival (PFS) interval; secondary endpoints were the overall survival (OS) time, objective response rate (RR), time to response, duration of response, and safety. Results. The intent-to-treat population comprised 480 patients (XELOX plus bevacizumab, n = 239; bevacizumab, n = 241); there were no significant differences in baseline characteristics. The median follow-up was 29.0 months (range, 0–53.2 months). There were no statistically significant differences in the median PFS or OS times or in the RR between the two arms. The most common grade 3 or 4 toxicities in the XELOX plus bevacizumab versus bevacizumab arms were diarrhea, hand–foot syndrome, and neuropathy. Conclusion. Although the noninferiority of bevacizumab versus XELOX plus bevacizumab cannot be confirmed, we can reliably exclude a median PFS detriment >3 weeks. This study suggests that maintenance therapy with single-agent bevacizumab may be an appropriate option following induction XELOX plus bevacizumab in mCRC patients. PMID:22234633

  6. Intravitreal Bevacizumab Alone or Combined with Macular Laser Photocoagulation for Recurrent or Persistent Macular Edema Secondary to Branch Retinal Vein Occlusion

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    Takafumi Hirashima

    2014-01-01

    Full Text Available Background. To evaluate the efficacy of intravitreal bevacizumab (IVB injection with or without macular laser photocoagulation (MLP for recurrent or persistent macular edema (ME secondary to branch retinal vein occlusion (BRVO. Methods. Thirty-four eyes underwent IVB injection for ME secondary to BRVO as a primary treatment. Twenty of the 34 eyes experienced recurrent or persistent ME after the first IVB. Nine of the 20 eyes (Group 1 were retreated with IVB combined with MLP. The remaining 11 eyes (Group 2 were retreated with IVB alone. Results. In Group 1, the postoperative best corrected visual acuity (BCVA improved compared with the preoperative value at all follow-up visits, although no statistically significant improvement was observed at 6 months. In contrast, BCVA significantly improved from 0.53 to 0.40 at 6 months (P<0.05 in Group 2. Conclusion. Combined therapy tended to have a smaller effect on visual acuity compared with IVB monotherapy.

  7. A randomised, double-masked, controlled study of the efficacy and safety of intravitreal bevacizumab versus ranibizumab in the treatment of macular oedema due to branch retinal vein occlusion: MARVEL Report No. 1.

    Science.gov (United States)

    Narayanan, Raja; Panchal, Bhavik; Das, Taraprasad; Chhablani, Jay; Jalali, Subhadra; Ali, M Hasnat

    2015-07-01

    To assess the efficacy and safety of intravitreal bevacizumab (IVB) compared with ranibizumab (IVR) in the treatment of macular oedema due to branch retinal vein occlusion (BRVO). In this prospective, randomised, non-inferiority trial, 75 participants with macular oedema due to BRVO received intravitreal injections of ranibizumab or bevacizumab after 1:1 block randomisation. The primary outcome measure was the difference in mean changes in best-corrected visual acuity (BCVA) at 6 months. Secondary outcome measures included mean change in central retinal thickness (CRT), the proportion of patients improving by >15 letters and the proportion of patients developing neovascularisation. Participants received either IVR (n=37) or IVB (n=38). The mean BCVA at baseline was 52.8±14.4 letters (20/80) and 56.1±10.0 letters (20/80) (p=0.24) in the ranibizumab and bevacizumab groups, respectively. At 6 months, the mean gains in BCVA were +18.1 letters (p<0.0001; 95% CI, +12.8 to +22.6) in the ranibizumab group and +15.6 letters (p<0.0001; 95% CI +12.0 to +20.5) in the bevacizumab group. The difference between the mean visual gains of the treated groups (bevacizumab-ranibizumab) was -2.5 letters (95% CI -8.0 to +5.0; p=0.74). Mean reductions in CRT at 6 months were 177.1±122.3 µm in the ranibizumab group (p<0.0001) and 201.7±166.2 µm in the bevacizumab group (p<0.0001), with no significant difference between the two groups (p=0.48). The mean numbers of ranibizumab and bevacizumab injections were 3.2±1.5 and 3.0±1.4, respectively (p=0.55). Two serious adverse events occurred in the ranibizumab group and one in the bevacizumab group but both were unrelated to intravitreal injections. This study demonstrated significant gain in visual acuity in eyes with BRVO treated with either bevacizumab or ranibizumab. Pro-re-nata strategy was effective in maintaining the visual gain. http://www.ctri.nic.in/ CTRI/2012/01/003120. Published by the BMJ Publishing Group Limited

  8. A randomised, double-masked phase III/IV study of the efficacy and safety of Avastin® (Bevacizumab intravitreal injections compared to standard therapy in subjects with choroidal neovascularisation secondary to age-related macular degeneration: clinical trial design

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    Bunce Catey

    2008-10-01

    Full Text Available Abstract Background The management of neovascular age-related macular degeneration (nAMD has been transformed by the introduction of agents delivered by intravitreal injection which block the action of vascular endothelial growth factor-A (anti-VEGF agents. One such agent in widespread use is bevacizumab which was initially developed for use in oncology. Most of the evidence supporting the use of bevacizumab for nAMD has come from interventional case series and this clinical trial was initiated because of the increasing and widespread use of this agent in the treatment of nAMD (an off-label indication despite a lack of definitive unbiased safety and efficacy data. Methods and design The Avastin® (bevacizumab for choroidal neovascularisation (ABC trial is a double-masked randomised controlled trial comparing intravitreal bevacizumab injections to standard therapy in the treatment of nAMD. Patients are randomised to intravitreal bevacizumab or standard therapy available at the time of trial initiation (verteporfin photodynamic therapy, intravitreal pegaptanib or sham treatment. Ranibizumab treatment was not included in the control arm as it had not been licensed for use at the start of recruitment for this trial. The primary outcome is the proportion of patients gaining ≥ 15 letters of visual acuity at 1 year and secondary outcomes include the proportion of patients with stable vision and mean visual acuity change. Discussion The ABC Trial is the first double-masked randomised control trial to investigate the efficacy and safety of intravitreal bevacizumab in the treatment of nAMD. This trial fully recruited in November 2007 and results should be available in early 2009. Important design issues for this clinical trial include (a defining the control group (b use of gain in vision as primary efficacy end-point and (c use of pro re nata treatment using intravitreal bevacizumab rather than continuous therapy. Trial registration Current controlled

  9. Management of cataract with macular oedema due to diabetes mellitus Type-II and hypertension with grid laser prior to surgery and intra-vitreal bevacizumab (avastin) peroperatively

    International Nuclear Information System (INIS)

    Wahab, S.; Ahmed, J.

    2010-01-01

    To study the visual outcome in patients subjected to cataract extraction with prior grid laser and intraoperative intravitreal bevacizumab injection. Methods: This prospective case series comprised of 38 patients subjected to phacoemulsification and in the bag intraocular lens implantation at Al-Noor Eye Hospital and Sindh Govt Lyari General Hospital Karachi from January 2007 to December 2008. All the patients had prior macular grid treatment and intra-operative injection of intra-vitreal Avastin. Diabetes mellitus duration, preoperative glycosylated haemoglobin (HbA1c) level and other systemic and local complications of diabetes were recorded. The patients were clinically assessed with bio microscopic examination preoperatively, and postoperatively on day 1, week 1, and in months 1, 2, 3 and 6 respectively. Visual acuity and state of macular oedema was clinically assessed and documented. Results: Out of thirty-eight patients, eighteen were males and 20 were females. Mean duration of diabetes was 9.92 +- 5.5 years (Range 4-16) while that of hypertension was 7.87 +- 3.66 years (Range = 2-15). HbA1c level was 8.36% +- 1.93% (range 6.3 - 12.3). Thirty-one (81.5%) patients had HbA1c level 8.0% or above indicating a poor control. At 6 months of follow up best corrected distant visual acuity of 6/6 to 6/9 was achieved in 23(60.5 %), 6/12 in 11(28.9%) and 6/24 in 4(10.5%) cases while best corrected near acuity of N/6 was achieved in 22(57.8%) N/8 in 12(31.4%) and N/12 in 4(10.5%) cases. At 6 months follow up visual acuity declined in two cases because of uncontrolled diabetes and hypertension. Conclusion: Cataract surgery in diabetic patients with macular oedema and hypertension has a good visual outcome if prior macular grid laser is performed and intra-vitreal anti VEGF is injected during surgery. (author)

  10. The effect of intravitreal bevacizumab on ocular blood flow in diabetic retinopathy and branch retinal vein occlusion as measured by laser speckle flowgraphy

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    Nitta F

    2014-06-01

    Full Text Available Fumihiko Nitta,1 Hiroshi Kunikata,1,2 Naoko Aizawa,1 Kazuko Omodaka,1 Yukihiro Shiga,1 Masayuki Yasuda,1 Toru Nakazawa1–31Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai, Japan; 3Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, JapanBackground: This study evaluated the effect of intravitreal injection of bevacizumab (IVB on macular edema associated with diabetic retinopathy (DME or branch retinal vein occlusion (BRVOME using laser speckle flowgraphy.Methods: A comparative interventional study of 25 eyes from 22 patients with macular edema (DME group: 12 eyes; BRVOME group: 13 eyes who underwent IVB. Mean blur rate (MBR was measured in the retinal artery, retinal vein, optic nerve head (ONH, and choroid before and after IVB. Results: In the BRVOME group, there was no significant change in MBR in the retinal artery, retinal vein or ONH, but choroidal MBR decreased significantly (P=0.04. In the DME group, the MBR in the retinal artery, retinal vein, ONH, and choroid decreased significantly (P=0.02, P=0.04, P<0.001, and P=0.04, respectively. In the DME group, pre-IVB MBR in the ONH was significantly correlated with post-IVB foveal thickness (R= -0.71, P=0.002. There was no such correlation in the BRVOME group in the ONH.Conclusion: IVB had a suppressive effect on circulation in eyes with DME but not in those with BRVOME. This suggests that this noninvasive and objective biomarker may be a useful part of pre-IVB evaluations and decision-making in DME.Keywords: macular edema, mean blur rate, optic nerve head, biomarker, ocular circulation

  11. Combination of intravitreal bevacizumab and systemic therapy for choroidal metastases from lung cancer: report of two cases and a systematic review of literature.

    Science.gov (United States)

    Maturu, Venkata Nagarjuna; Singh, Navneet; Bansal, Pooja; Rai Mittal, Bhagwant; Gupta, Nalini; Behera, Digambar; Gupta, Amod

    2014-04-01

    Symptomatic choroidal metastasis (SCM) is an uncommon manifestation of lung cancer (LC). Treatment of SCM usually includes a combination of systemic therapy (chemotherapy and/or targeted therapy) for the primary tumor as well as local therapy (ocular radiation) for CM. Intravitreal bevacizumab (IV-Bev) is a newer modality being tried for local control of SCM. We describe here two patients with LC who presented with CM and were treated with IV-Bev. We performed a systematic literature review of previously reported patients with CM from LC who were treated with IV-Bev. Six reports (involving seven patients) in which IV-Bev was used as primary treatment modality for CM from LC were identified in the systematic literature review. A total of nine patients (seven previously reported and two index cases) were analyzed further. Along with individual case descriptions of index patients, pooled analysis of demographic profile, histology and outcomes with treatment (systemic and ocular) for the nine patients identified in this systematic review are described. A majority (n = 7) had non-small-cell lung cancer (NSCLC) histology, CM as presenting manifestation (n = 6) and unilateral ocular involvement (n = 8). IV-Bev was used in a dose of either 1.25 mg/cycle (n = 5) or 2.5 mg/cycle (n = 4) with number of cycles varying from 2 to 14 and duration between cycles varying from 2 to 8 weeks. Of the nine patients treated with IV-Bev as the primary ocular treatment modality, six (all non-squamous NSCLC) had favorable ocular response. No short-term ocular complications related to therapy were noted. We suggest that IV-Bev is a promising and safe alternative to ocular radiation for initial treatment of CM from non-squamous NSCLC. However, we recommend against using it for patients with small-cell lung cancer.

  12. Tratamento da retinopatia por radiação com injeção intravítrea de bevacizumab (Avastin®: relato de caso Treatment of radiation retinopathy with intravitreal injection of bevacizumab (Avastin®: case report

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    Marcelo Mendes Lavezzo

    2010-08-01

    Full Text Available OBJETIVO: Relatar tratamento de retinopatia por radiação em paciente submetido à radioterapia por linfoma em órbita direita com injeção intravítrea de bevacizumab (Avastin®. Paciente de 55 anos, diabético, com diagnóstico de linfoma MALT orbitário há três anos, tratado com radioterapia local (dose: 35Gy há dois anos, com queixa de redução da acuidade visual do olho direito há quatro meses. Ao exame oftalmológico, apresentava alterações sugestivas de retinopatia por radiação, bem como espessura macular à tomografia de coerência óptica de 480 µm. Paciente foi submetido à injeção intravítrea (0,05 ml de bevacizumab (Avastin® no olho direito, apresentando redução do edema macular, bem como melhora discreta da acuidade visual. Neste caso, o tratamento da retinopatia por radiação com injeção intravítrea de bevacizumab (Avastin® foi relativamente útil, com melhora discreta da acuidade visual, devido à regressão do edema macular.PURPOSE: To report a case of radiation retinopathy treatment with intravitreal injection of bevacizumab (Avastin® in a patient undergoing radiotherapy for lymphoma in the right orbit. Patient of 55 years-old male, diabetic, diagnosed with an orbital MALT lymphoma three years ago, treated with local radiotherapy (dose: 35Gy two years ago, complaining of reduced visual acuity of the right eye for about four months. During the ophthalmologic evaluation, he had an exam suggestive of radiation retinopathy. Macular thickness at the optical coherence tomography was 480 µm. Patient was referred to intravitreal injection (0.05 ml of bevacizumab (Avastin® in the right eye, showing reduction of macular edema and mild improvement of visual acuity. In this case, the treatment of radiation retinopathy with intravitreal injection of bevacizumab (Avastin® was relatively useful, with mild improvement of visual acuity due to the regression of macular edema.

  13. Aqueous humor levels of vascular endothelial growth factor before and after intravitreal bevacizumab in type 3 versus type 1 and 2 neovascularization. A prospective, case-control study.

    Science.gov (United States)

    dell'Omo, Roberto; Cassetta, Marilluccia; dell'Omo, Ermanno; di Salvatore, Angela; Hughes, John M; Aceto, Fabiana; Porcellini, Antonio; Costagliola, Ciro

    2012-01-01

    To determine the aqueous levels of vascular endothelial growth factor (VEGF) in patients with type 3 neovascularization (NV) secondary to age-related macular degeneration (AMD) and to compare the levels of those with type 1 and 2 NV secondary to AMD before and after administration of intravitreal bevacizumab (IVB). Prospective, case-control study. Aqueous samples were collected from 29 eyes of 29 patients with untreated wet AMD at baseline (day of the first IVB), month 1 (day of the second IVB), and month 2 (day of the third IVB). Among them, 10 eyes presented with type 1, 9 with type 2, and 10 with type 3 NV. A group of 14 aqueous samples from 14 patients who underwent cataract surgery without other ocular or systemic disease comprised the controls. Main outcome measures were concentration of VEGF at baseline and after IVB in the 3 NV groups; secondary outcome measures included best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes after IVB. Levels of VEGF were determined by commercially available enzyme-linked immunosorbent assay kits. VEGF concentrations in aqueous humor at baseline were higher in patients with type 3 NV when compared to controls (P = .0001) and type 1 and 2 NV patients (P = .002 and P = .0001 respectively). At month 1, levels of VEGF were significantly reduced compared to baseline (P < .05) and significantly lower compared to the controls (P < .005) in each NV group. These low levels were maintained at the 2-month interval. BCVA significantly improved in type 1 and 2 NV groups (P < .05). CMT significantly reduced in each NV group compared to baseline (P < .05). In eyes with untreated wet AMD, aqueous levels of VEGF are significantly higher in type 3 NV than in type 1 or 2 NV. Regardless of the type of NV, aqueous VEGF levels significantly reduce 1 month after IVB as compared to both the baseline measurements and the values recorded in age-matched controls. These decreases are maintained at 2 months after administering

  14. The effectiveness of bevacizumab in radionecrosis after radiosurgery of a single brain metastasis

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    Durim Delishaj

    2015-12-01

    Full Text Available Radionecrosis (RN of brain tissue is a serious late complication of brain irradiation and historically has been treated with corticosteroid therapy and alternatively surgical decompression. Recently, bevacizumab has been suggested for treatment of cerebral radiation necrosis. We present a case of a 73-years-old women affected by a primary non-small cell lung cancer with a single brain metastasis treated with radiosurgery. Two years after radiosurgery the patient referred neurological symptoms and a brain magnetic resonance confirmed the presence of RN. The patient refused surgical decompression so underwent at the treatment with bevacizumab 7.5 mg/kg/2 weeks for a total of 4 cycles. After two months of treatment the patient reported strumental and clinical improvement. Ten months after bevacizumab discontinuation the patient experienced a recurrence of RN with evident clinical manifestation and confirmed by radiological imaging. A new treatment with bevacizumab was not performed due to the systemic progression disease and the worsening of clinical status. Despite limited to only one clinical case, our study suggests the efficacy of bevacizumab to treat RN. Future studies are needed to confirm its mechanism and to properly define the optimal scheduling, dosage and duration of therapy.

  15. Initial Experience with Bevacizumab (Avastin ) in the Treatment of ...

    African Journals Online (AJOL)

    PROF SABE NWOSU

    Objective: To report on the early experience with the treatment of neovascular AMD with intravitreal injection of bevacizumab. (Avastin) in Nigeria. Materials and Methods: Eight eyes (7 patients) with neovascular. AMD who met the inclusion criteria were treated with intravitreal 1.25mg bevacizumab between September 2008 ...

  16. Initial Experience with Bevacizumab (Avastin TM ) in the Treatment ...

    African Journals Online (AJOL)

    Objective: To report on the early experience with the treatment of neovascular AMD with intravitreal injection of bevacizumab (Avastin) in Nigeria. Materials and Methods: Eight eyes (7 patients) with neovascular AMD who met the inclusion criteria were treated with intravitreal 1.25mg bevacizumab between September 2008 ...

  17. Sterile Endophthalmitis after Intravitreal Injections

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    Joaquín Marticorena

    2012-01-01

    Full Text Available Sterile endophthalmitis appears as an infrequent complication of intravitreal injections and seems to develop mainly in the context of the off-label use of drugs that have not been conceived for intravitreous administration. The aetiology of sterile endophthalmitis, independently of the administered drug, remains uncertain and a multifactorial origin cannot be discarded. Sterile inflammation secondary both to intravitreal triamcinolone acetonide and to intravitreal bevacizumab share many characteristics such as the acute and painless vision loss present in the big majority of the cases. Dense vitreous opacity is a common factor, while anterior segment inflammation appears to be mild to moderate. In eyes with sterile endophthalmitis, visual acuity improves progressively as the intraocular inflammation reduces without any specific treatment. If by any chance the ophthalmologist is not convinced by the sterile origin of the inflammation, this complication must be treated as an acute endophthalmitis because of the devastating visual prognosis of this intraocular infection in the absence of therapy.

  18. A phase II trial of single-agent bevacizumab in patients with recurrent anaplastic glioma.

    Science.gov (United States)

    Kreisl, Teri N; Zhang, Weiting; Odia, Yazmin; Shih, Joanna H; Butman, John A; Hammoud, Dima; Iwamoto, Fabio M; Sul, Joohee; Fine, Howard A

    2011-10-01

    The purpose of this study was to evaluate the activity of single-agent bevacizumab in patients with recurrent anaplastic glioma and assess correlative advanced imaging parameters. Patients with recurrent anaplastic glioma were treated with bevacizumab 10 mg/kg every 2 weeks. Complete patient evaluations were repeated every 4 weeks. Correlative dynamic contrast-enhanced MR and (18)fluorodeoxyglucose PET imaging studies were obtained to evaluate physiologic changes in tumor and tumor vasculature at time points including baseline, 96 h after the first dose, and after the first 4 weeks of therapy. Median overall survival was 12 months (95% confidence interval [CI]: 6.08-22.8). Median progression-free survival was 2.93 months (95% CI: 2.01-4.93), and 6-month progression-free survival was 20.9% (95% CI: 10.3%-42.5%). Thirteen (43%) patients achieved a partial response. The most common grade ≥ 3 treatment-related toxicities were hypertension, hypophosphatemia, and thromboembolism. Single-agent bevacizumab produces significant radiographic response in patients with recurrent anaplastic glioma but did not meet the 6-month progression-free survival endpoint. Early change in enhancing tumor volume at 4 days after start of therapy was the most significant prognostic factor for overall and progression-free survival.

  19. A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of biosimilar ABP 215 and bevacizumab in healthy adult men.

    Science.gov (United States)

    Markus, Richard; Chow, Vincent; Pan, Zhiying; Hanes, Vladimir

    2017-10-01

    This study compared the pharmacokinetic (PK) profiles of the proposed biosimilar ABP 215 with bevacizumab in healthy males. In this randomized, single-blind, single-dose, three-arm, parallel-group study, healthy subjects were randomized to receive ABP 215 (n = 68), bevacizumab (US) (n = 67), or bevacizumab (EU) (n = 67) 3 mg/kg intravenously. Primary endpoints were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC inf ) and the maximum observed concentration (C max ). Secondary endpoints included safety and immunogenicity. AUC inf and C max were similar across the three groups. Geometric means ratio (GMR) for C max and AUC inf , respectively, was 0.98 and 0.99 for ABP 215 versus bevacizumab (US); 1.03 and 0.96 for ABP 215 versus bevacizumab (EU); and 1.05 and 0.97 for bevacizumab (US) versus bevacizumab (EU). The 90% confidence intervals for the GMRs of AUC inf and C max were within the prespecified standard PK bioequivalence criteria of 0.80 to 1.25. The incidence of adverse events (AEs) was 47.1, 32.8, and 61.2% in the ABP 215, bevacizumab (US) and bevacizumab (EU) groups, respectively. When analyzed by investigational site, the incidence and severity of AEs were comparable in the ABP 215 and bevacizumab groups. There were no AEs leading to study discontinuation. No binding or neutralizing anti-drug anti-bodies was detected. This study demonstrated the PK similarity of ABP 215 to both bevacizumab (US) and bevacizumab (EU), and of bevacizumab (US) to bevacizumab (EU). Safety and tolerability were comparable between treatments and no subject developed binding or neutralizing anti-drug anti-bodies.

  20. Intravitreal bevacizumab injection alone or combined with triamcinolone versus macular photocoagulation in bilateral diabetic macular edema; application of bivariate generalized linear mixed model with asymmetric random effects in a subgroup of a clinical trial.

    Science.gov (United States)

    Yaseri, Mehdi; Zeraati, Hojjat; Mohammad, Kazem; Soheilian, Masoud; Ramezani, Alireza; Eslani, Medi; Peyman, Gholam A

    2014-01-01

    To compare the efficacy of intravitreal bevacizumab (IVB) injection alone or with intravitreal triamcinolone acetonide (IVB/IVT) versus macular photocoagulation (MPC) in bilateral diabetic macular edema (DME). In this study we revisited data from a subset of subjects previously enrolled in a randomized clinical trial. The original study included 150 eyes randomized to three treatment arms: 1.25 mg IVB alone, combined injection of 1.25 mg IVB and 2 mg IVT, and focal or modified grid MPC. To eliminate the possible effects of systemic confounders, we selected fellow eyes of bilaterally treated subjects who had undergone different treatments; eventually 30 eyes of 15 patients were re-evaluated at baseline, 6, 12, 18, and 24 months. Using mixed model analysis, we compared the treatment protocols regarding visual acuity (VA) and central macular thickness (CMT). Improvement in VA in the IVB group was significantly greater compared to MPC at months 6 and 12 (P = 0.037 and P = 0.035, respectively) but this difference did not persist thereafter up to 24 months. Other levels of VA were comparable at different follow-up intervals (all P > 0.05). The only significant difference in CMT was observed in favor of the IVB group as compared to IVB/IVT group at 24 months (P = 0.048). Overall VA was superior in IVB group as compared to MPC up to 12 months. Although the IVB group showed superiority regarding CMT reduction over 24 months as compared to IVB/IVT group, it was comparable to the MPC group through the same period of follow up.

  1. Aqueous humor levels of vascular endothelial growth factor and adiponectin in patients with type 2 diabetes before and after intravitreal bevacizumab injection.

    Science.gov (United States)

    Costagliola, Ciro; Daniele, Aurora; dell'Omo, Roberto; Romano, Mario R; Aceto, Fabiana; Agnifili, Luca; Semeraro, Francesco; Porcellini, Antonio

    2013-05-01

    To determine the levels of vascular endothelial growth factor (VEGF) and adiponectin (APN) in the aqueous humor of patients with type 2 diabetes before and after injection of bevacizumab (IVB). Twenty eyes of twenty consecutive patients with type 2 diabetes with PDR and clinically significant macular edema were enrolled in this study. Aqueous samples were collected at baseline and one month after IVB to evaluate VEGF and APN levels. Twenty age-matched patients undergoing cataract surgery were used as control. Best-corrected visual acuity (BCVA) and foveal thickness (FT) changes after IVB were also measured. Safety was assessed by recording the incidence of ocular and non-ocular adverse events. At baseline APN and VEGF levels were significantly lower in controls than in PDR patients (APN: 3.6 ± 1.1 vs 18.7 ± 4.5 ng/ml; VEGF: 22.6 ± 16.1 vs 146.2 ± 38.71 pg/ml). After IVB, both compounds significantly decreased. FT and BCVA at baseline were significantly different between controls and patients (FT: 215.6 ± 34.8 vs 532.7 ± 112.4 μm; BCVA: 23.6 ± 4.2 vs 18.4 ± 7.3 letters). After IVB a significant decrease of FT with a concomitant improvement of BCVA occurred. Neither ocular nor systemic adverse events were reported. Our findings demonstrate that patients with type 2 diabetes, PDR and macular edema show VEGF and APN levels in aqueous humor higher than those found in control subjects. IVB significantly reduced the levels of both compounds, which remained anyway at concentrations higher than those recorded in control subjects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Bevacizumab Injection

    Science.gov (United States)

    Bevacizumab is used with chemotherapy to treat cancer of the colon (large intestine) or rectum that has spread to other parts of the body. Bevacizumab is also used with chemotherapy to treat certain ...

  3. Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1 year after a single intravitreal injection of dobesilate

    Science.gov (United States)

    Cuevas, P; Outeiriño, L A; Azanza, C; Giménez-Gallego, G

    2013-01-01

    Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate. PMID:24225910

  4. Use of intravitreal bevacizumab or triamcinolone acetonide as a preoperative adjunct to vitrectomy for vitreous haemorrhage in diabetics Injeção intravítrea de bevacizumabe ou triancinolona como adjuvantes da vitrectomia posterior no tratamento da hemorragia vítrea em diabéticos

    Directory of Open Access Journals (Sweden)

    Daniel Araújo Ferraz

    2013-02-01

    Full Text Available PURPOSE: To evaluate the effect of preoperative intravitreal bevacizumab (IVB or triamcinolone (IVT on the rate of early postvitrectomy hemorrhage in proliferative diabetic retinopathy (PDR. METHODS: Eligible eyes were assigned randomly to 1 of 3 groups: the IVB group received 1.25 mg bevacizumab, the IVT group received 4,0mg triamcinolone and the control group underwent a sham procedure. The primary outcome measure was the incidence of early postvitrectomy hemorrhage. Secondary outcome measures included changes in visual acuity (BCVA and adverse events. RESULTS: Twenty and seven eyes, 9 in each group were randomized. The incidence of vitreous hemorrhage was lower in the IVB group (p=0.18. Postoperative vitreous hemorrhage at 1 month also was less in the IVB group compared with the control group (p > 0.05. The rate of bleeding immediately after surgery was higher in IVT group with 4 (44.4% cases. The overall mean visual acuity was 1.72 ± 0.37 logMAR preoperatively and 1.32 ± 0.73 logMAR in 6 months after surgery. Accessing visual acuity by group evidenced that the IVB group had initial mean logMAR VA of 1.87 and 1.57 logMAR VA at the six months (p = 0.84. In IVT group, initial mean VA was 1.75 logMAR and 0.96 logMAR VA at six months (p OBJETIVO: Avaliar o efeito no pré-operatório da injecao intravítrea de bevacizumab (IVB ou triancinolona (IVT sobre a taxa de hemorragia precoce pos-vitrectomia na retinopatia diabética proliferativa. MÉTODOS: Os olhos foram distribuídos em três grupos: IVB - 1,25 mg bevacizumab, IVT - 4,0 mg de triancinolona e o grupo controle - simulação da injeção. O objetivo primário foi a avaliação da incidência da hemorragia precoce pós-vitrectomia. Os objetivos secundários incluíram mudanças na acuidade visual corrigida e eventos adversos relacionados à injeção. RESULTADOS: Dos Vinte e sete olhos, 9 foram randomizados em cada grupo. A incidência de hemorragia vítrea foi menor no grupo IVB (P=0

  5. Effects of Intravitreal Ranibizumab in the Treatment of Retinopathy of Prematurity in Chinese Infants.

    Science.gov (United States)

    Yi, Zuohuizi; Su, Yu; Zhou, Yunyun; Zheng, Hongmei; Ye, Meihong; Xu, Yonghong; Chen, Changzheng

    2016-08-01

    To evaluate the efficacy associated with intravitreal ranibizumab in the treatment of retinopathy of prematurity (ROP). A retrospective case series study. Infants diagnosed with Type 1 ROP, or aggressive posterior ROP (AP-ROP) were enrolled in the study. All infants in the study received intravitreal ranibizumab (0.25 mg/0.025 ml) as the initial treatment. Follow-up examinations were performed the day after treatment, then weekly for 1 month, bi-monthly for two additional months, then monthly until vascularization of zone III occurred. Additional treatments were initiated in cases of disease recurrence. Thirty-three premature infants (a total of 66 eyes) receiving intravitreal ranibizumab were included. The mean birth weight was 1291 ± 211 g (range: 650-1650 g) and the mean gestational age was 29.8 ± 1.6 weeks (range: 27.0-33.6 weeks). The mean gestational age at the time of the first injection was 35.8 ± 1.6 weeks (range: 32.7-38.4 weeks). The mean follow-up time was 12.9 ± 4.9 months (range: 6-22 months). Single injections were administered to 58 eyes (87.9%), whereas eight eyes (12.1%) received additional treatments. Recurrence was observed in eight eyes (12.1%), with a mean time to recurrence of 6.9 ± 1.8 weeks (range: 4-8 weeks). Intravitreal ranibizumab is effective for the treatment of retinopathy of prematurity, although a small amount of patients recurred. Compared with intravitreal bevacizumab, a higher incidence and shorter time to recurrence were observed after intravitreal ranibizumab treatment, thus longer and more frequent follow-ups are needed.

  6. Intravitreal injection analysis at the Bascom Palmer Eye Institute: evaluation of clinical indications for the treatment and incidence rates of endophthalmitis

    Directory of Open Access Journals (Sweden)

    Ludimila L Cavalcante

    2010-05-01

    Full Text Available Ludimila L Cavalcante, Milena L Cavalcante, Timothy G Murray, Michael M Vigoda, Yolanda Piña, Christina L Decatur, R Prince Davis, Lisa C Olmos, Amy C Schefler, Michael B Parrott, Kyle J Alliman, Harry W Flynn, Andrew A MoshfeghiBascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL, USAObjective: To report the incidence of endophthalmitis, in addition to its clinical and microbiological aspects, after intravitreal injection of vascular-targeting agents.Methods: A retrospective review of a consecutive series of 10,142 intravitreal injections of vascular targeting agents (bevacizumab, ranibizumab, triamcinolone acetonide, and preservative-free triamcinolone acetonide between June 1, 2007 and January 31, 2010, performed by a single service (TGM at the Bascom Palmer Eye Institute.Results: One case of clinically-suspected endophthalmitis was identified out of a total of 10,142 injections (0.009%, presenting within three days of injection of bevacizumab. The case was culture-positive for Staphylococcus epidermidis. Final visual acuity was 20/40 after pars plana vitrectomy surgery.Conclusions: In this series, the incidence of culture-positive endophthalmitis after intravitreal injection of vascular agents in an outpatient setting was very low. We believe that following a standardized injection protocol, adherence to sterile techniques and proper patient follow-up are determining factors for low incidence rates.Keywords: endophthalmitis, intravitreal injections, vascular targeting agents 

  7. Bevacizumab plus chemotherapy in elderly patients with previously untreated metastatic colorectal cancer: single center experience

    International Nuclear Information System (INIS)

    Ocvirk, Janja; Moltara, Maja Ebert; Mesti, Tanja; Boc, Marko; Rebersek, Martina; Volk, Neva; Benedik, Jernej; Hlebanja, Zvezdana

    2016-01-01

    Metastatic colorectal cancer (mCRC) is mainly a disease of elderly, however, geriatric population is underrepresented in clinical trials. Patient registries represent a tool to assess and follow treatment outcomes in this patient population. The aim of the study was with the help of the patients’ register to determine the safety and efficacy of bevacizumab plus chemotherapy in elderly patients who had previously untreated metastatic colorectal cancer. The registry of patients with mCRC was designed to prospectively evaluate the safety and efficacy of bevacizumab-containing chemotherapy as well as selection of patients in routine clinical practice. Patient baseline clinical characteristics, pre-specified bevacizumab-related adverse events, and efficacy data were collected, evaluated and compared according to the age categories. Between January 2008 and December 2010, 210 patients with mCRC (median age 63, male 61.4%) started bevacizumab-containing therapy in the 1 st line setting. Majority of the 210 patients received irinotecan-based chemotherapy (68%) as 1 st line treatment and 105 patients (50%) received bevacizumab maintenance therapy. Elderly (≥ 70 years) patients presented 22.9% of all patients and they had worse performance status (PS 1/2, 62.4%) than patients in < 70 years group (PS 1/2, 35.8%). Difference in disease control rate was mainly due to inability to assess response in elderly group (64.6% in elderly and 77.8% in < 70 years group, p = 0.066). The median progression free survival was 10.2 (95% CI, 6.7–16.2) and 11.3 (95% CI, 10.2–12.6) months in elderly and < 70 years group, respectively (p = 0.58). The median overall survival was 18.5 (95% CI, 12.4–28.9) and 27.4 (95% CI, 22.7–31.9) months for elderly and < 70 years group, respectively (p = 0.03). Three-year survival rate was 26% and 37.6% in elderly vs. < 70 years group (p = 0.03). Overall rates of bevacizumab-related adverse events were similar in both groups: proteinuria 21

  8. Systemic safety of bevacizumab versus ranibizumab for neovascular age-related macular degeneration

    Science.gov (United States)

    Moja, Lorenzo; Lucenteforte, Ersilia; Kwag, Koren H; Bertele, Vittorio; Campomori, Annalisa; Chakravarthy, Usha; D’Amico, Roberto; Dickersin, Kay; Kodjikian, Laurent; Lindsley, Kristina; Loke, Yoon; Maguire, Maureen; Martin, Daniel F; Mugelli, Alessandro; Mühlbauer, Bernd; Püntmann, Isabel; Reeves, Barnaby; Rogers, Chris; Schmucker, Christine; Subramanian, Manju L; Virgili, Gianni

    2014-01-01

    substantially alter the findings of our review. Fixed-effect analysis for deaths did not substantially alter the findings of our review, but fixed-effect analysis of All SSAEs showed an increased risk for bevacizumab (RR 1.12; 95% CI 1.00 to 1.26, P value = 0.04; nine studies, 3665 participants): the meta-analysis was dominated by a single study (weight = 46.9%). The available evidence was sensitive to the exclusion of CATT or unpublished results. For All SSAEs, the exclusion of CATT moved the overall estimate towards no difference (RR 1.01; 95% CI 0.82 to 1.25, P value = 0.92), while the exclusion of LUCAS yielded a larger RR, with more SSAEs in the bevacizumab group, largely driven by CATT (RR 1.19; 95% CI 1.06 to 1.34, P value = 0.004). The exclusion of all unpublished studies produced a RR of 1.12 for death (95% CI 0.78 to 1.62, P value = 0.53) and a RR of 1.21 for SSAEs (95% CI 1.06 to 1.37, P value = 0.004), indicating a higher risk of SSAEs in those assigned to bevacizumab than ranibizumab. Authors’ conclusions This systematic review of non-industry sponsored RCTs could not determine a difference between intravitreal bevacizumab and ranibizumab for deaths, All SSAEs, or specific subsets of SSAEs in the first two years of treatment, with the exception of gastrointestinal disorders. The current evidence is imprecise and might vary across levels of patient risks, but overall suggests that if a difference exists, it is likely to be small. Health policies for the utilisation of ranibizumab instead of bevacizumab as a routine intervention for neovascular AMD for reasons of systemic safety are not sustained by evidence. The main results and quality of evidence should be verified once all trials are fully published. PMID:25220133

  9. Bevacizumab plus chemotherapy in elderly patients with previously untreated metastatic colorectal cancer: single center experience

    Directory of Open Access Journals (Sweden)

    Ocvirk Janja

    2016-06-01

    Full Text Available Metastatic colorectal cancer (mCRC is mainly a disease of elderly, however, geriatric population is underrepresented in clinical trials. Patient registries represent a tool to assess and follow treatment outcomes in this patient population. The aim of the study was with the help of the patients’ register to determine the safety and efficacy of bevacizumab plus chemotherapy in elderly patients who had previously untreated metastatic colorectal cancer.

  10. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial) : a randomised controlled phase 2 trial

    NARCIS (Netherlands)

    Taal, Walter; Oosterkamp, Hendrika M.; Walenkamp, Annemiek M. E.; Dubbink, Hendrikus J.; Beerepoot, Laurens V.; Hanse, Monique C. J.; Buter, Jan; Honkoop, Aafke H.; Boerman, Dolf; de Vos, Filip Y. F.; Dinjens, Winand N. M.; Enting, Roeline; Taphoorn, Martin J. B.; van den Berkmortel, Franchette W. P. J.; Jansen, Rob L. H.; Brandsma, Dieta; Bromberg, Jacoline E. C.; van Heuvel, Irene; Vernhout, Rene M.; van der Holt, Bronno; van den Bent, Martin J.

    BACKGROUND: Treatment options for recurrent glioblastoma are scarce, with second-line chemotherapy showing only modest activity against the tumour. Despite the absence of well controlled trials, bevacizumab is widely used in the treatment of recurrent glioblastoma. Nonetheless, whether the high

  11. Optical imaging for monitoring tumor oxygenation response after initiation of single-agent bevacizumab followed by cytotoxic chemotherapy in breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Shigeto Ueda

    Full Text Available PURPOSE: Optical imaging techniques for measuring tissue hemoglobin concentration have been recently accepted as a way to assess tumor vascularity and oxygenation. We investigated the correlation between early optical response to single-agent bevacizumab and treatment outcome. METHODS: Seven patients with advanced or metastatic breast cancer were treated with single-agent bevacizumab followed by addition of weekly paclitaxel. Optical imaging of patient's breasts was performed to measure tumor total hemoglobin concentration (tHb and oxygen saturation (stO2 at baseline and on days 1, 3, 6, 8, and 13 after the first infusion of bevacizumab. To assess early metabolic response, 2-deoxy-2-(18F-fluoro-D-glucose (FDG positron emission tomography/computed tomography (PET/CT, 18F-fluoromisonidazole (FMISO-PET/CT, and magnetic resonance imaging were performed at baseline and after two cycles of the regimen. RESULTS: Seven patients were grouped as responders (n = 4 and nonresponders (n = 3 on the basis of metabolic response measured by FDG-PET/CT. The responders showed remarkable tumor shrinkage and low accumulations of FMISO tracer relative to those of the nonresponders at the completion of two cycles of chemotherapy. Tumors of both groups showed remarkable attenuation of mean tHb as early as day 1 after therapy initiation. The nonresponders had lower baseline stO2 levels compared with adjacent breast tissue stO2 levels along with a pattern of steadily low stO2 levels during the observation window. On the other hand, the responders appeared to sustain high stO2 levels with temporal fluctuation. CONCLUSIONS: Low tumor stO2 level after single-agent bevacizumab treatment was characteristic of the nonresponders. Tumor stO2 level could be a predictor of an additional benefit of bevacizumab over that provided by paclitaxel.

  12. The effect of prophylactic topical antibiotics on bacterial resistance patterns in endophthalmitis following intravitreal injection.

    Science.gov (United States)

    Storey, Philip; Dollin, Michael; Rayess, Nadim; Pitcher, John; Reddy, Sahitya; Vander, James; Hsu, Jason; Garg, Sunir

    2016-02-01

    The purpose of this study was to evaluate the effect of prophylactic topical antibiotics on bacterial resistance patterns in endophthalmitis following intravitreal injection of anti-vascular endothelial growth factor (VEGF) medications. In this retrospective case-control study, billing records and an infection log were used to identify all cases of endophthalmitis following intravitreal injection of ranibizumab, bevacizumab, or aflibercept between January 1, 2009 and September 30, 2013 at a single retina practice. A 28-month period when topical antibiotic drops were prescribed for use four times a day for 4 days following intravitreal injection was compared to a 21-month period when topical antibiotics were not prescribed. Patients treated during an 8-month transition period were excluded as prescription practices were changed. During the study period, a total of 172,096 anti-VEGF injections were performed. During the period when antibiotics were prescribed, 28 cases of suspected infectious endophthalmitis occurred from a total of 57,654 injections, ten of which were culture-positive. During the period when antibiotics were not used, 24 cases of suspected endophthalmitis occurred from a total of 89,825 injections, six of which were culture-positive. During the antibiotic period, four of the ten (40 %) culture-positive cases grew bacteria resistant to the prescribed prophylactic antibiotics. In contrast, none of the six culture-positive cases grew bacteria resistant to those antibiotics during the period when antibiotics were not used (odds ratio = 9.0; 95 % confidence interval = 0.40-203.3; p = 0.17). The use of prophylactic topical antibiotics following intravitreal injection may lead to higher rates of antibiotic-resistant bacteria in culture-positive endophthalmitis cases.

  13. The predictive value of single nucleotide polymorphisms in the VEGF system to the efficacy of first-line treatment with bevacizumab plus chemotherapy in patients with metastatic colorectal cancer : Results from the Nordic ACT trial

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Christensen, René Depont; Andersen, Rikke Fredslund

    2012-01-01

    PURPOSE: Bevacizumab and chemotherapy is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). So far, no predictive markers have been identified. The aim was to investigate the possible predictive value of single nucleotide polymorphisms (SNPs) in the vascular endothel......PURPOSE: Bevacizumab and chemotherapy is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). So far, no predictive markers have been identified. The aim was to investigate the possible predictive value of single nucleotide polymorphisms (SNPs) in the vascular...... endothelial growth factor (VEGF) system in this setting. METHODS: Pre-treatment blood samples and response evaluations were available from 218 of the 249 included patients. All patients received bevacizumab and chemotherapy comprising fluorouracil and leucovorin or capecitabine combined with either...... marker for bevacizumab plus chemotherapy in patients with mCRC. Patients with the A allele appeared to have increased response rates. The results call for validation....

  14. The relation between bevacizumab injection and the formation of subretinal fibrosis in diabetic patients with panretinal photocoagulation.

    Science.gov (United States)

    Batman, Cosar; Ozdamar, Yasemin

    2010-01-01

    To report the development of subretinal fibrosis after the injection of intravitreal bevacizumab in eyes with proliferative diabetic retinopathy (PDR) refractory to panretinal laser photocoagulation (PRP). Twenty-one eyes of 15 patients treated with PRP and intravitreal injection of bevacizumab were included in this study. The clinical outcomes of 21 eyes having subretinal fibrosis after intravitreal bevacizumab injection were reviewed. There were 9 men and 6 women with a mean age of 51.3 +/- 8.9 years. All eyes had PDR refractory to panretinal photocoagulation and were treated with at least one intravitreal injection of 1.25 mg of bevacizumab (mean number of injections: 1.8). Before injection, there was subretinal fibrosis in 5 eyes and vitreoretinal traction in 19 eyes. After a mean follow-up period of 7 months, the development or progression of subretinal fibrosis was detected in all eyes. Intravitreal injection of bevacizumab may cause formation or progression of subretinal fibrosis in patients with PDR refractory to PRP. Copyright 2010, SLACK Incorporated.

  15. Comparison of Ranibizumab and Bevacizumab for Macular Edema Associated with Branch Retinal Vein Occlusion.

    Science.gov (United States)

    Son, Bo Kwon; Kwak, Hyung Woo; Kim, Eung Suk; Yu, Seung Young

    2017-06-01

    To assess the effectiveness and safety of intravitreal ranibizumab compared with bevacizumab for the treatment of macular edema associated with branch retinal vein occlusion (BRVO). This was a retrospective study of 80 eyes with macular edema associated with BRVO. Patients received either 0.5 mg of ranibizumab (n = 24) or 1.25 mg of bevacizumab (n = 56) intravitreally. Both groups received three initial monthly injections followed by as-needed injections. The best-corrected visual acuity, central subfield thickness, mean number of injections, and retreatment rate were evaluated monthly for 6 months after the initial injection. The best-corrected visual acuity significantly improved from logarithm of the minimal angle of resolution (logMAR) 0.55 ± 0.26 at baseline to 0.24 ± 0.26 at 6 months in the ranibizumab group (p bevacizumab group (p bevacizumab group (p bevacizumab injections were 3.25 ± 0.53 and 3.30 ± 0.53, respectively (p = 0.602). In addition, after the three initial monthly injections, the retreatment rates for ranibizumab and bevacizumab injections were 20.8% and 26.7%, respectively (p = 0.573). Both ranibizumab and bevacizumab were effective for the treatment of BRVO and produced similar visual and anatomic outcomes. In addition, the mean number of injections and the retreatment rates were not significantly different between the groups. © 2017 The Korean Ophthalmological Society

  16. Bevacizumab compared with Diode Laser in stage 3 posterior retinopathy of prematurity: a 5 year follow-up

    LENUS (Irish Health Repository)

    O’Keeffe, N

    2016-02-01

    We conducted a prospective randomized study to compare outcomes of intravitreal Bevacizumab versus diode laser in thirty eyes of fifteen premature babies with zone 1 or posterior zone 2 retinopathy of prematurity (ROP). We recorded complications, regression\\/reactivation of ROP, visual outcome, refractive error and systemic complications. The Bevacizumab-treated eyes showed rapid regression of the ROP with resolution of plus disease and flattening of the ridge at 48 hours post injection. In 3 Bevacizumab-treated eyes, reactivation occurred and were treated with laser (3 eyes) or a further Bevacizumab injection (1 eye). Of the diode laser treated eyes, one showed progression and was treated with Bevacizumab. At 5-year follow-up, good outcomes were observed in both treatment groups. However, less myopia was found in the Bevacizumab compared with the diode laser treated eyes.

  17. A randomized, single-blind, Phase I trial (INVICTAN-1) assessing the bioequivalence and safety of BI 695502, a bevacizumab biosimilar candidate, in healthy subjects.

    Science.gov (United States)

    Hettema, Willem; Wynne, Christopher; Lang, Benjamin; Altendorfer, Mario; Czeloth, Niklas; Lohmann, Ragna; Athalye, Sandeep; Schliephake, Dorothee

    2017-08-01

    This Phase I trial (INVICTAN®-1) evaluated three-way bioequivalence and safety of BI 695502 a bevacizumab biosimilar candidate, and reference product bevacizumab from two sources (US-approved Avastin®, Genentech; EU-approved Avastin, Roche). Healthy male subjects (N = 91) were randomized 1:1:1 to receive a single intravenous infusion of 1 mg/kg of BI 695502 or US- or EU-approved Avastin. An interim analysis was planned when ~50% of subjects were evaluable for the primary end point to determine if the prespecified criteria for bioequivalence were achieved; if demonstrated, the study could be stopped early. The primary end point was area under the concentration-time curve (AUC) of the analyte in plasma from time zero extrapolated to infinity (AUC 0-∞ ). Other pharmacokinetic (PK) parameters, safety, and in vitro binding affinity were also evaluated. The interim analysis demonstrated three-way bioequivalence for all comparisons. The confidence intervals around the geometric mean ratios of the primary and secondary PK parameters were within the predefined acceptance ranges. Study drugs were well tolerated with no clinically relevant differences in safety. BI 695502 and US- and EU-approved Avastin showed three-way bioequivalence with similar safety profile. NCT01608087.

  18. Safety and efficacy of single-agent bevacizumab-containing therapy in elderly patients with platinum-resistant recurrent ovarian cancer : Subgroup analysis of the randomised phase III AURELIA trial

    NARCIS (Netherlands)

    Sorio, Roberto; Roemer-Becuwe, Célia; Hilpert, Felix; Gibbs, Emma; García, Yolanda; Kaern, Janne; Huizing, Manon; Witteveen, Petronella|info:eu-repo/dai/nl/17530808X; Zagouri, Flora; Coeffic, David; Lück, Hans-Joachim; González-Martín, Antonio; Kristensen, Gunnar; Levaché, Charles-Briac; Lee, Chee Khoon; Gebski, Val; Pujade-Lauraine, Eric

    BACKGROUND: The AURELIA trial demonstrated significantly improved progression-free survival (PFS) with bevacizumab added to chemotherapy for platinum-resistant ovarian cancer (PROC). METHODS: Patients with PROC were randomised to receive investigator-selected single-agent chemotherapy alone or with

  19. Bevacizumab (Avastin and Thermal Laser Combination Therapy for Peripapillary Choroidal Neovascular Membranes

    Directory of Open Access Journals (Sweden)

    Sean D. Adrean

    2017-01-01

    Full Text Available Objective. This is a retrospective interventional case series describing the results of 5 eyes from 5 patients with symptomatic peripapillary choroidal neovascularization (CNVM receiving initial bevacizumab treatment followed by thermal laser and bevacizumab combination therapy. Methods. Patients received intravitreal bevacizumab injections until the lesions were well-defined. Thermal laser ablation was then administered and followed by an additional bevacizumab injection after one week. Visual outcomes, OCT changes, and rates of recurrence were recorded and analyzed. Results. Median visual outcomes improved from 20/50 to 20/30 (p=0.0232. Median central macular thickness decreased from 347 μm to 152 μm (p=0.0253. The mean visual improvement was 3 lines. An average of 3.8 bevacizumab injections per patient were given overall. Patients were followed for an average of 24 months, during which all eyes were absent for recurrence. Conclusion. Symptomatic peripapillary CNVM may be successfully managed with bevacizumab followed by a combination of thermal laser and bevacizumab without the need for frequent retreatment. The area requiring treatment may be better defined using bevacizumab, limiting the ablation of the healthy retina and improving treatment margins. With this treatment regimen, the patients experience improved visual outcomes and have a low rate of recurrence.

  20. Contralateral eye-to-eye comparison of intravitreal ranibizumab and a sustained-release dexamethasone intravitreal implant in recalcitrant diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Thomas BJ

    2016-08-01

    Full Text Available Benjamin J Thomas, Yoshihiro Yonekawa, Jeremy D Wolfe, Tarek S Hassan Department of Vitreoretinal Surgery, William Beaumont Hospital, Royal Oak, MI, USA Objective: To compare the effects of intravitreal ranibizumab (RZB or dexamethasone (DEX intravitreal implant in cases of recalcitrant diabetic macular edema (DME.Methods: Retrospective, interventional study examining patients with symmetric bilateral, center-involved DME recalcitrant to treatment with RZB, who received DEX in one eye while the contralateral eye continued to receive RZB every 4–5 weeks for a study period of 3 months.Results: Eleven patients (22 eyes were included: mean logarithm of the minimal angle of resolution (logMAR visual acuity (VA for the DEX arm improved from 0.415 (standard deviation [SD] ±0.16 to 0.261 (SD ±0.18 at final evaluation, and mean central macular thickness (CMT improved from 461 µm (SD ±156 to 356 µm (SD ±110; net decrease: 105 µm, P=0.01. Mean logMAR VA for the RZB arm improved from 0.394 (SD ±0.31 to 0.269 (SD ±0.19 at final evaluation. Mean CMT improved from 421 µm (SD ±147 to 373 µm (SD ±129; net decrease: 48 µm, P=0.26.Conclusion: A subset of recalcitrant DME patients demonstrated significant CMT reduction and VA improvement after a single DEX injection. Keywords: aflibercept, bevacizumab, central macular thickness, macular edema, dexamethasone implant, diabetic macular edema, diabetic retinopathy, ranibizumab

  1. Safety of cupping during bevacizumab therapy.

    Science.gov (United States)

    Klempner, Samuel J; Costa, Daniel B; Wu, Peggy A; Ariyabuddhiphongs, Kim D

    2013-08-01

    This study reports on the safety of the complementary and alternative medicine (CAM) practice of cupping in a patient undergoing concomitant therapy with bevacizumab for advanced non-small-cell lung cancer (NSCLC), and raises awareness of the need for improved communication between CAM practitioners and oncologists during the care of patients with cancer. The practice of cupping generates local hyperemia, disrupts superficial vasculature in the dermis, and leads to cutaneous lesions including circular erythema, edema, and subsequently ecchymosis. There are no data on the safety of cupping in patients being treated with bevacizumab. This is a single-institution case report. The setting for this study was a tertiary-care academic medical center. A patient with advanced NSCLC received four cycles of carboplatin AUC 6, paclitaxel 200 mg/m(2), and bevacizumab 15 mg/kg, and was continued on every-3-week maintenance bevacizumab 15 mg/kg. The patient underwent glass dry cupping during cycle six of maintenance bevacizumab treatment without overt cutaneous adverse events or bleeding. The patient did not realize he should have communicated his cupping plans or recent bevacizumab treatment with his providers.

  2. OUTCOMES AFTER LASER VERSUS COMBINED LASER AND BEVACIZUMAB TREATMENT FOR TYPE 1 RETINOPATHY OF PREMATURITY IN ZONE I.

    Science.gov (United States)

    Yoon, Je Moon; Shin, Dong Hoon; Kim, Sang Jin; Ham, Don-Il; Kang, Se Woong; Chang, Yun Sil; Park, Won Soon

    2017-01-01

    To investigate the anatomical and refractive outcomes in patients with Type 1 retinopathy of prematurity in Zone I. The medical records of 101 eyes of 51 consecutive infants with Type 1 retinopathy of prematurity in Zone I were analyzed. Infants were treated by conventional laser photocoagulation (Group I), combined intravitreal bevacizumab injection and Zone I sparing laser (Group II), or intravitreal bevacizumab with deferred laser treatment (Group III). The proportion of unfavorable anatomical outcomes including retinal fold, disc dragging, retrolental tissue obscuring the view of the posterior pole, retinal detachment, and early refractive errors were compared among the three groups. The mean gestational age at birth and the birth weight of all 51 infants were 24.3 ± 1.1 weeks and 646 ± 143 g, respectively. In Group I, an unfavorable anatomical outcome was observed in 10 of 44 eyes (22.7%). In contrast, in Groups II and III, all eyes showed favorable anatomical outcomes without reactivation or retreatment. The refractive error was less myopic in Group III than in Groups I and II (spherical equivalent of -4.62 ± 4.00 D in Group I, -5.53 ± 2.21 D in Group II, and -1.40 ± 2.19 D in Group III; P prematurity in Zone I, intravitreal bevacizumab with concomitant or deferred laser therapy yielded a better anatomical outcome than conventional laser therapy alone. Moreover, intravitreal bevacizumab with deferred laser treatment resulted in less myopic refractive error.

  3. Bevacizumab vs ranibizumab for neovascular age-related macular degeneration in Chinese patients

    Directory of Open Access Journals (Sweden)

    Zhe-Li Liu

    2013-04-01

    Full Text Available AIM:To compare the clinical efficacy of intravitreal injections of bevacizumab and ranibizumab for treating Chinese patients with neovascular age-related macular degeneration (AMD. METHODS: Among 60 Chinese patients with exudative AMD (60 eyes, 28 received intravitreal bevacizumab injections (1.25mg and 32 received intravitreal ranibizumab injections (0.5mg, once a month for 3 months and were followed for a total of 6 months. Monthly optical coherence tomography (OCT was used to determine whether the patients received additional treatments during the follow-up. We compared the baseline and 6-month follow-up values of mean best-corrected visual acuity (BCVA and central retinal thickness (CRT in both groups of patients. We also compared the occurrence of adverse events. RESULTS:At the 6-month follow-up, the mean BCVA (logMAR of the bevacizumab and ranibizumab treatment groups improved from the baseline measurements of 0.72±0.23 and 0.73±0.22 to 0.47±0.14 and 0.45±0.20, respectively (P<0.05 for both groups. However, the change was not significantly different between the two groups. As evaluated by OCT, CRT decreased from 366.71±34.72μm and 352±36.9μm at baseline to 250.86±41.51μm and 243.22±41.38μm in the bevacizumab and ranibizumab groups, respectively (P<0.05 for both groups. However, the change was not significantly different between the two groups. There were no severe local adverse reactions or systemic adverse events. CONCLUSION:Intravitreal bevacizumab and ranibizumab have equivalent effects on BCVA and CRT and appeare safe over the short-term.

  4. NONINFECTIOUS VITRITIS AFTER INTRAVITREAL INJECTION OF ANTI-VEGF AGENTS: Variations in Rates and Presentation by Medication.

    Science.gov (United States)

    Williams, Patrick D; Chong, Deborah; Fuller, Timothy; Callanan, David

    2016-05-01

    The purpose of this study was to describe and compare the rates and characteristics of noninfectious vitritis after intravitreal injection of bevacizumab (Avastin, Genentech, South San Francisco, CA), ranibizumab (Lucentis, Genentech), and aflibercept (Eylea, Regeneron, Tarrytown, NY). A retrospective case series evaluated intravitreal injections from 2006 to 2013. Cases of inflammatory response were separated into culture-positive endophthalmitis, noninfectious vitritis (not treated with intravitreal antibiotics), and indeterminate. Noninfectious cases were analyzed for rate, presentation, and clinical course. A total of 66,356 bevacizumab, 26,161 ranibizumab, and 8071 aflibercept injections were screened. The rates of noninfectious vitritis were 0.10% (67 cases) for bevacizumab, 0.02% (6 cases) for ranibizumab, and 0.16% (13 cases) for aflibercept. The differences were statistically significant based on Chi-square analysis (P medication according to Fisher exact test (P medication based on Fisher exact testing (P = 0.2, P = 0.18, P = 0.16, respectively). Bevacizumab and aflibercept cases tended to present in separate chronological clusters. The results suggest a difference in rates of noninfectious vitritis for antivascular endothelial growth factor medications. Many cases tended to cluster instead of occurring at a consistent rate each year.

  5. Radiation Retinopathy Is Treatable With Anti-Vascular Endothelial Growth Factor Bevacizumab (Avastin)

    International Nuclear Information System (INIS)

    Finger, Paul T.

    2008-01-01

    Purpose: To report on bevacizumab treatment for radiation retinopathy affecting the macula. Patients and Methods: Twenty-one patients with radiation retinopathy (edema, hemorrhages, capillary dropout, and neovascularization) and a subjective or objective loss of vision were treated. Treatment involved intravitreal injection of bevacizumab (1.25 mg in 0.05 mL) every 6-12 weeks. Treatment was discontinued at patient request or if there was no measurable response to therapy. Main outcome measures included best corrected visual acuity, ophthalmic examination, retinal photography, and angiography. Results: Bevacizumab treatment was followed by reductions in retinal hemorrhage, exudation, and edema. Visual acuities were stable or improved in 86% (n = 18). Three patients discontinued therapy. Each was legally blind before treatment (n = 1), experienced little to no subjective improvement (n = 2), or was poorly compliant (n = 2). Three patients (14%) regained 2 or more lines of visual acuity. No ocular or systemic bevacizumab-related side effects were observed. Conclusions: Intravitreal bevacizumab can be used to treat radiation retinopathy. In most cases treatment was associated with decreased vascular leakage, stabilization, or improved vision. An anti-vascular endothelial growth factor strategy may reduce tissue damage associated with radiation vasculopathy and neuropathy

  6. Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer and activating EGFR mutations (BELIEF): an international, multicentre, single-arm, phase 2 trial.

    Science.gov (United States)

    Rosell, Rafael; Dafni, Urania; Felip, Enriqueta; Curioni-Fontecedro, Alessandra; Gautschi, Oliver; Peters, Solange; Massutí, Bartomeu; Palmero, Ramon; Aix, Santiago Ponce; Carcereny, Enric; Früh, Martin; Pless, Miklos; Popat, Sanjay; Kotsakis, Athanasios; Cuffe, Sinead; Bidoli, Paolo; Favaretto, Adolfo; Froesch, Patrizia; Reguart, Noemí; Puente, Javier; Coate, Linda; Barlesi, Fabrice; Rauch, Daniel; Thomas, Michael; Camps, Carlos; Gómez-Codina, Jose; Majem, Margarita; Porta, Rut; Shah, Riyaz; Hanrahan, Emer; Kammler, Roswitha; Ruepp, Barbara; Rabaglio, Manuela; Kassapian, Marie; Karachaliou, Niki; Tam, Rachel; Shames, David S; Molina-Vila, Miguel A; Stahel, Rolf A

    2017-05-01

    The tyrosine kinase inhibitor erlotinib improves the outcomes of patients with advanced non-small-cell lung carcinoma (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations. The coexistence of the T790M resistance mutation with another EGFR mutation in treatment-naive patients has been associated with a shorter progression-free survival to EGFR inhibition than in the absence of the T790M mutation. To test this hypothesis clinically, we developed a proof-of-concept study, in which patients with EGFR-mutant NSCLC were treated with the combination of erlotinib and bevacizumab, stratified by the presence of the pretreatment T790M mutation. BELIEF was an international, multicentre, single-arm, phase 2 trial done at 29 centres in eight European countries. Eligible patients were aged 18 years or older and had treatment-naive, pathologically confirmed stage IIIB or stage IV lung adenocarcinoma with a confirmed, activating EGFR mutation (exon 19 deletion or L858R mutation). Patients received oral erlotinib 150 mg per day and intravenous bevacizumab 15 mg/kg every 21 days and were tested centrally for the pretreatment T790M resistance mutation with a peptide nucleic acid probe-based real-time PCR. The primary endpoint was progression-free survival. The primary efficacy analysis was done in the intention-to-treat population and was stratified into two parallel substudies according to the centrally confirmed pretreatment T790M mutation status of enrolled patients (T790M positive or negative). The safety analysis was done in all patients that have received at least one dose of trial treatment. This trial was registered with ClinicalTrials.gov, number NCT01562028. Between June 11, 2012, and Oct 28, 2014, 109 patients were enrolled and included in the efficacy analysis. 37 patients were T790M mutation positive and 72 negative. The overall median progression-free survival was 13·2 months (95% CI 10·3-15·5), with a 12 month progression-free survival of 55% (95% CI

  7. Population pharmacokinetics of bevacizumab in cancer patients with external validation.

    Science.gov (United States)

    Han, Kelong; Peyret, Thomas; Marchand, Mathilde; Quartino, Angelica; Gosselin, Nathalie H; Girish, Sandhya; Allison, David E; Jin, Jin

    2016-08-01

    Bevacizumab is approved for various cancers. This analysis aimed to comprehensively evaluate bevacizumab pharmacokinetics and the influence of patient variables on bevacizumab pharmacokinetics. Rich and sparse bevacizumab serum concentrations were collected from Phase I through IV studies in early and metastatic cancers. Bevacizumab was given intravenously as single agent or in combination with chemotherapy for single- and multiple-dose schedules. Model-building used 8943 bevacizumab concentrations from 1792 patients with colon/colorectal, non-small cell lung, kidney, pancreatic, breast, prostate and brain cancer. Bevacizumab doses ranged from 1 to 20 mg/kg given once every 1, 2 or 3 weeks. A two-compartment model best described the data. The population estimates of clearance (CL), central volume of distribution (V1) and half-life for a typical 70-kg patient were 9.01 mL/h, 2.88 L and 19.6 days. CL and V1 increased with body weight and were higher in males than females by 14 and 18 %, respectively. CL decreased with increasing albumin and decreasing alkaline phosphatase. The final model was externally validated using 1670 concentrations from 146 Japanese patients that were not used for model-building. Mean prediction errors were -2.1, 3.1 and 1.0 % for concentrations, CL and V1, respectively, confirming adequate predictive performance. A robust bevacizumab pharmacokinetic model was developed and externally validated, which may be used to simulate bevacizumab exposure to optimize dosing strategies. Asian and non-Asian patients exhibited similar bevacizumab pharmacokinetics. Given the similarity in pharmacokinetics among monoclonal antibodies, this may inform pharmacokinetic studies in different ethnic groups for other therapeutic antibodies.

  8. Bevacizumab Injection in Patients with Age-Related Macular Degeneration Associated with Poor Initial Visual Acuity

    Directory of Open Access Journals (Sweden)

    Leila El Matri

    2012-01-01

    Full Text Available Purpose. To evaluate functional and anatomic effects of intravitreal bevacizumab in patients with neovascular AMD and initial low visual acuity. Methods. Retrospective case series of 38 eyes with neovascular AMD and initial visual acuity of 20/200 or less, treated with intravitreal bevacizumab injection. Results. Mean followup was 14.1 months ±7.1 (range: 5 to 24 months. Mean logMAR vision at baseline was 1.38 logMAR ±0.33, at 6 months was 1.14 logMAR ±0.37 (=0.001 and at 12 months was 1.22 logMar ±0.33 (=0.004. Mean baseline central retinal thickness was 431 μm ±159.7 at 6 months was 293.43 μm  ±122.79 (=10−4 and at 12 months was 293.1 μm  ±130 (=0.004. Visual acuity improved in both patients with or without prior PDT treatment. Conclusions. Intravitreal bevacizumab injection may increase the chance of visual acuity gain in neovascular AMD even in cases with initial low visual acuity.

  9. Optical Coherence Tomographic and Visual Results at Six Months after Transitioning to Aflibercept for Patients on Prior Ranibizumab or Bevacizumab Treatment for Exudative Age-Related Macular Degeneration (An American Ophthalmological Society Thesis)

    Science.gov (United States)

    Chan, Clement K.; Jain, Atul; Sadda, Srinivas; Varshney, Neeta

    2014-01-01

    Purpose: To study optical coherence tomographic (OCT) results and vision at 6 months after transition (post-Tx) from intravitreal bevacizumab and/or ranibizumab to aflibercept for treatment of neovascular age-related macular degeneration (nAMD). The null hypothesis was the lack of improvements in OCT metrics and vision outcome in study eyes at 6 months after transitioning from bevacizumab or ranibizumab to aflibercept. Methods: This retrospective study assessed 6 monthly OCT (Cirrus) data after transitioning to aflibercept for eyes on prior Legacy-ranibizumab, Legacy-bevacizumab, or mixed treatment for nAMD. Outcome measures were subretinal fluid (SRF), cystoid macular edema (CME), pigment epithelial detachment (PED) heights and volumes, central 1- and 3-mm subfield, Macular Volume, and best spectacle and pinhole visual acuity (VA). A single masked investigator performed all OCT measurements. Results: One hundred eighty-nine eyes in 172 patients in Legacy-bevacizumab (95 eyes), Legacy-ranibizumab (84 eyes), or Mixed Group(10 eyes) were switched to aflibercept and followed for 6 months. Significant post-Tx reductions were noted in SRF/CME heights and volumes (all P<.001). Similar findings were noted for PED heights (122.8 μm vs 79.4 μm) and PED volumes (all P<.001). Post-Tx VA was better (20/43 vs 20/51, P<.001). There were no differences between Legacy-bevacizumab and Legacy-ranibizumab groups in OCT and VA changes. Post-Tx VA, SRF/CME, and PED heights and volumes were improved for Nonresponders (suboptimal response to bevacizumab/ranibizumab) (P=.001 to <.001), but not Responders (good responses to same). The only adverse event was a retinal pigment epithelial tear in one eye. Conclusions: Significant improvements in vision and OCT metrics developed in Nonresponders but not in Responders. Post-Tx VA and OCT measures were similar for eyes on prior bevacizumab or ranibizumab. Post-Tx adverse events were uncommon. PMID:25646034

  10. Nanoparticles in Porous Microparticles Prepared by Supercritical Infusion and Pressure Quench Technology for Sustained Delivery of Bevacizumab

    Science.gov (United States)

    K.Yandrapu, Sarath; Upadhyay, Arun K.; Petrash, J. Mark; Kompella, Uday B.

    2014-01-01

    Nanoparticles in porous microparticles (NPinPMP), a novel delivery system for sustained delivery of protein drugs, was developed using supercritical infusion and pressure quench technology, which does not expose proteins to organic solvents or sonication. The delivery system design is based on the ability of supercritical carbon dioxide (SC CO2) to expand poly(lactic-co-glycolic) acid (PLGA) matrix but not polylactic acid (PLA) matrix. The technology was applied to bevacizumab, a protein drug administered once a month intravitreally to treat wet age related macular degeneration. Bevacizumab coated PLA nanoparticles were encapsulated into porosifying PLGA microparticles by exposing the mixture to SC CO2. After SC CO2 exposure, the size of PLGA microparticles increased by 6.9 fold. Confocal and scanning electron microscopy studies demonstrated the expansion and porosification of PLGA microparticles and infusion of PLA nanoparticles inside PLGA microparticles. In vitro release of bevacizumab from NPinPMP was sustained for 4 months. Size exclusion chromatography, fluorescence spectroscopy, circular dichroism spectroscopy, SDS-PAGE, and ELISA studies indicated that the released bevacizumab maintained its monomeric form, conformation, and activity. Further, in vivo delivery of bevacizumab from NPinPMP was evaluated using noninvasive fluorophotometry after intravitreal administration of Alexa Flour 488 conjugated bevacizumab in either solution or NPinPMP in a rat model. Unlike the vitreal signal from Alexa-bevacizumab solution, which reached baseline at 2 weeks, release of Alexa-bevacizumab from NPinPMP could be detected for 2 months. Thus, NPinPMP is a novel sustained release system for protein drugs to reduce frequency of protein injections in the therapy of back of the eye diseases. PMID:24131101

  11. Intravitreal injection of perfluoropropane for the treatment of vitreomacular traction

    Directory of Open Access Journals (Sweden)

    Xiao-Ping Wan

    2013-07-01

    Full Text Available AIM: To study the efficacy of a single intravitreal injection of perfluoropropane(C3F8in releasing vitreomacular traction. METHODS: Twelve eyes of 12 consecutive patients with vitreomacular traction received a single intravitreal injection of 0.3mL 100%(C3F8were retrospectively analyzed. The best corrected vision acuity and the neural epithelium thickness of central macular were observed. RESULTS: One month following treatment, vitreomacular traction was released in 5 eyes(42%, mean final visual acuity(VAimproved 0.04 and mean central foveal thickness decreased by 69μm. The vision acuity before and after treatment were 0.20±0.07, 0.25±0.04 respectively.CONCLUSION: Intravitreal C3F8 injection could offer a minimally invasive alternative to pars plana vitrectomy in patients with vitreomacular traction.

  12. Clinical study on Bevacizumab for macular edema induced by retinal vein occlusion

    Directory of Open Access Journals (Sweden)

    Zhi-Guang Duan

    2014-09-01

    Full Text Available AIM: To evaluate the safety and efficacy of intravitreal bevacizumab injection in patients with macular edema(MEinduced by retinal vein occlusion(RVO.METHODS: The records of patients treated with intravitreal injection of 1.75mg bevacizumab for ME induced by RVO were retrospectively reviewed. All patients were evaluated by complete ophthalmic examination, optical coherence tomography(OCTand fundus fluorescein angiography(FFA, etc. Best corrected visual acuity(BCVA, intraocular pressure, the change of lens and vitreous, central foveal thickness(CFTwere observed at 1, 2, 3, 6mo after treatment and compared with before treatment. Repeated treatment with intravitreous bevacizumab occurred if there were signs of persistent or recurrent exudation. All the cases were followed up at least 6mo. An intravitreal injection of bevacizumab(1.75mgwas given at 6wk intervals.RESULTS: Fifty patients(56 eyeswith the average of(57±18.56years old were included. The mean baseline of BCVA, CFT were(logMAR0.82±0.63,(626.5±178.0μm respectively. Although there was no significant decrease in mean CFT at 1wk after injection, the mean BCVA had significant improvement. Followed up at mean 10.26±5.87mo, BCVA, CFT showed significant improvements over baseline values. The statistics of CFT at 1, 2, 3mo after injection were significant differences compared with before injection in each of the three groups. CFT at 1, 3, 12mo after injection were(365.11±23.212μm,(333.42±35.526μm,(267.6±116.8μm, which had a significant difference(PP>0.05. OCT image showed that after injection macular retinal thickness was becoming thinner. FFA showed that after injection macular fluorescein leakage decreased. BCVA was improved by at least two lines in 48 eyes(86%,remained stable in 8 eyes(14%at the last visit. A total of 112 injections were performed and the average number of injections was 1.96 in the group. About 50% of reinjections gained at least two lines of vision improvement at 1

  13. Irradiation and Bevacizumab in High-Grade Glioma Retreatment Settings

    Energy Technology Data Exchange (ETDEWEB)

    Niyazi, Maximilian; Ganswindt, Ute; Schwarz, Silke Birgit [Department of Radiation Oncology, Ludwig-Maximilians-University Munich, Munich (Germany); Kreth, Friedrich-Wilhelm; Tonn, Joerg-Christian [Department of Neurosurgery, Ludwig-Maximilians-University Munich, Munich (Germany); Geisler, Julia; Fougere, Christian la [Department of Nuclear Medicine, Ludwig-Maximilians-University Munich, Munich (Germany); Ertl, Lorenz; Linn, Jennifer [Department of Neuroradiology, Ludwig-Maximilians-University Munich, Munich (Germany); Siefert, Axel [Department of Radiation Oncology, Ludwig-Maximilians-University Munich, Munich (Germany); Belka, Claus, E-mail: claus.belka@med.uni-muenchen.de [Department of Radiation Oncology, Ludwig-Maximilians-University Munich, Munich (Germany)

    2012-01-01

    Purpose: Reirradiation is a treatment option for recurrent high-grade glioma with proven but limited effectiveness. Therapies directed against vascular endothelial growth factor have been shown to exert certain efficacy in combination with chemotherapy and have been safely tested in combination with radiotherapy in a small cohort of patients. To study the feasibility of reirradiation combined with bevacizumab treatment, the toxicity and treatment outcomes of this approach were analyzed retrospectively. Patients and Methods: After previous treatment with standard radiotherapy (with or without temozolomide) patients with recurrent malignant glioma received bevacizumab (10 mg/kg intravenous) on Day 1 and Day 15 during radiotherapy. Maintenance therapy was selected based on individual considerations, and mainly bevacizumab-containing regimens were chosen. Patients received 36 Gy in 18 fractions. Results: The data of the medical charts of the 30 patients were analyzed retrospectively. All were irradiated in a single institution and received either bevacizumab (n = 20), no additional substance (n = 7), or temozolomide (n = 3). Reirradiation was tolerated well, regardless of the added drug. In 1 patient treated with bevacizumab, a wound dehiscence occurred. Overall survival was significantly better in patients receiving bevacizumab (p = 0.03, log-rank test). In a multivariate proportional hazards Cox model, bevacizumab, Karnovsky performance status, and World Health Organization grade at relapse turned out to be the most important predictors for overall survival. Conclusion: Reirradiation with bevacizumab is a feasible and effective treatment for patients with recurrent high-grade gliomas. A randomized trial is warranted to finally answer the question whether bevacizumab adds substantial benefit to a radiotherapeutic retreatment setting.

  14. A case report of long term bevacizumab treatment in multiresistant ovarian cancer

    DEFF Research Database (Denmark)

    Kargo, Anette Stolberg; Adimi, Parvin; Dahl-Steffensen, Karina

    2016-01-01

    Treatment of multiresistant ovarian cancer is palliative and patients have needs for less toxic treatment. Anti-angiogenic treatments have a less toxic profile, and bevacizumab has shown improvement of progression free survival (PFS) in front-line trials. Bevacizumab is generally introduced in co...... in combination with chemotherapy; however this case report will describe the use of single-agent bevacizumab for more than five years (102 cycles) in a patient with relapse of advanced ovarian cancer...

  15. A systematic analysis of the off-label use of bevacizumab for severe retinopathy of prematurity.

    Science.gov (United States)

    Micieli, Jonathan A; Surkont, Michael; Smith, Andrew F

    2009-10-01

    To examine the quality of evidence and the variability in the off-label use of bevacizumab (Avastin; Genentech Inc, South San Francisco, California, USA) in the treatment of retinopathy of prematurity (ROP) and to discuss the implications for the design of future randomized controlled trials. Systematic literature review. A systematic review of the literature indexed by Ovid MEDLINE, EMBASE, and the Cochrane database was performed with a broad and inclusive search strategy. All case reports and retrospective and prospective trials in peer-reviewed journals reporting the use of bevacizumab in ROP were included. Nine articles, including 6 case reports, 2 retrospective studies, and 1 prospective case series representing 77 eyes of 48 infants, were selected for the review. The doses used ranged from 0.4 to 1.25 mg, with 0.75 mg being the most common, used in 3 of the 9 studies. A total of 8 of the 11 eyes in the case received bevacizumab as a first-line therapy and two articles noted worsening of an already present retinal detachment. One retrospective study and the prospective case series used bevacizumab alone, whereas the other retrospective study used bevacizumab before and with retinal surgery. Considerable variability exists in how bevacizumab is used for the treatment of ROP in the literature to date. Further randomized control trials are warranted and should aim to assess statistically the optimal timing, frequency, and dose of the drug. Careful attention should be given to the potential for systemic complications and long-term effects of intravitreal bevacizumab in infants.

  16. The effect of intravitreal anti-VEGF agents on peripheral wound healing in a rabbit model

    Directory of Open Access Journals (Sweden)

    Christoforidis J

    2012-01-01

    Full Text Available John Christoforidis1, Robert Ricketts1, Cedric Pratt1, Jordan Pierce1, Scott Bean1, Michael Wells1, Xiaoli Zhang2, Krista La Perle31College of Medicine, 2Center for Biostatistics, 3College of Veterinary Medicine, The Ohio State University, Columbus, OH, USAPurpose: To investigate the effect of intravitreal pegaptanib, bevacizumab, and ranibizumab on blood-vessel formation during cutaneous wound healing in a rabbit model and to compare this effect to placebo controls.Methods: Forty New Zealand albino rabbits underwent full thickness cutaneous wounds using 6-mm dermatologic punch biopsies. The rabbits were assigned to four groups of ten, each receiving intravitreal injections of pegaptanib, bevacizumab, ranibizumab, or no injection (untreated controls. Five rabbits from each group underwent wound harvesting on day 7 and five from each group on day 14. The skin samples were stained with hematoxylin and eosin (HE, Masson's trichrome (MT, and CD34 for vascular endothelial cells. Semiquantitative evaluation of HE- and MT-stained slides was performed by one pathologist. Quantitative assessment of mean neovascularization (MNV scores was obtained from five contiguous biopsy margin 400× fields of CD34-stained sections by four independent observers.Results: Week 1 MNV scores in CD-34 stained sections were: untreated controls: 11.51 ± 4.36; bevacizumab: 7.41 ± 2.82 (P = 0.013; ranibizumab: 8.71 ± 4.08 (P = 0.071; and pegaptanib: 10.15 ± 5.59 (P = 0.378. Week 2 MNV data were: untreated controls: 6.14 ± 2.25; bevacizumab: 7.25 ± 2.75 (P = 0.471; ranibizumab: 4.53 ± 3.12 (P = 0.297; and, pegaptanib: 6.35 ± 3.09 (P = 0.892. Interobserver variability using intraclass correlation coefficient was 0.961.Conclusions: At week 1, all three anti-VEGF agents had suppressed MNV scores compared to controls. Although not statistically significant, there was an inhibitory trend, particularly with bevacizumab and ranibizumab. These effects were diminished at 2 weeks

  17. Bevacizumab combined with capecitabine and oxaliplatin in patients with advanced adenocarcinoma of the small bowel or ampulla of vater: A single-center, open-label, phase 2 study.

    Science.gov (United States)

    Gulhati, Pat; Raghav, Kanwal; Shroff, Rachna T; Varadhachary, Gauri R; Kopetz, Scott; Javle, Milind; Qiao, Wei; Wang, Huamin; Morris, Jeffrey; Wolff, Robert A; Overman, Michael J

    2017-05-15

    Capecitabine with oxaliplatin (CAPOX) has previously demonstrated clinical activity in patients with small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). Herein, the authors conducted a phase 2 trial to evaluate the benefit of adding bevacizumab to CAPOX. In this phase 2, single-arm, single-center, open-label study, patients aged ≥18 years with untreated, advanced SBA or AAC were recruited. Patients received capecitabine at a dose of 750 mg/m 2 orally twice daily on days 1 to 14, oxaliplatin at a dose of 130 mg/m 2 intravenously on day 1, and bevacizumab at a dose of 7.5 mg/kg intravenously on day 1 of a 21-day cycle. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary objectives included response rate, overall PFS, overall survival, and toxicity. Between August 2011 and November 2014, a total of 30 patients were enrolled into the study (male/female ratio of 13/17; median age of 63 years [range, 33-78 years]; and 7 patients with an Eastern Cooperative Oncology Group performance status [ECOG PS] of 0, 20 patients with an ECOG PS of 1, and 3 patients with an ECOG PS of 2). Of the 30 patients, 23 (77%) had SBA (18 of duodenal origin and 5 of jejunal/ileal origin) and 7 patients (23%) had AAC (5 of pancreaticobiliary subtype, 1 of mixed subtype, and 1 of intestinal subtype). The most common grade 3 toxicities observed were fatigue and hypertension (7 patients each [23%]), neutropenia (6 patients [20%]), and diarrhea (3 patients [10%]) (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). The probability of PFS at 6 months was 68% (95% confidence interval [95% CI], 52% to 88%). The response rate was 48.3%, with 1 complete response and 13 partial responses; 10 patients achieved stable disease. At a median follow-up of 25.9 months, the median PFS was 8.7 months (95% CI, 4.9-10.5 months) and the median overall survival was 12.9 months (95% CI, 9

  18. Antivascular Endothelial Growth Factor Bevacizumab for Radiation Optic Neuropathy: Secondary to Plaque Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Finger, Paul T., E-mail: pfinger@eyecancer.com [New York Eye Cancer Center, New York, NY (United States); Chin, Kimberly J. [New York Eye Cancer Center, New York, NY (United States)

    2012-02-01

    Purpose: To evaluate the intravitreal antivascular endothelial growth factor, bevacizumab, for treatment of radiation optic neuropathy (RON). Methods and Materials: A prospective interventional clinical case series was performed of 14 patients with RON related to plaque radiotherapy for choroidal melanoma. The RON was characterized by optic disc edema, hemorrhages, microangiopathy, and neovascularization. The entry criteria included a subjective or objective loss of vision, coupled with findings of RON. The study subjects received a minimum of two initial injections of intravitreal bevacizumab (1.25 mg in 0.05 mL) every 6-8 weeks. The primary objectives included safety and tolerability. The secondary objectives included the efficacy as measured using the Early Treatment Diabetic Retinopathy Study chart for visual acuity, fundus photography, angiography, and optical coherence tomography/scanning laser ophthalmoscopy. Results: Reductions in optic disc hemorrhage and edema were noted in all patients. The visual acuity was stable or improved in 9 (64%) of the 14 patients. Of the 5 patients who had lost vision, 2 had relatively large posterior tumors, 1 had had the vision decrease because of intraocular hemorrhage, and 1 had developed optic atrophy. The fifth patient who lost vision was noncompliant. No treatment-related ocular or systemic side effects were observed. Conclusions: Intravitreal antivascular endothelial growth factor bevacizumab was tolerated and generally associated with improved vision, reduced papillary hemorrhage, and resolution of optic disc edema. Persistent optic disc neovascularization and fluorescein angiographic leakage were invariably noted. The results of the present study support additional evaluation of antivascular endothelial growth factor medications as treatment of RON.

  19. Subconjunctival Bevacizumab Injection in Treatment of Pterygium

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Besharati

    2011-03-01

    Full Text Available This study determined the clinical effect of subconjunctival administration of bevacizumab in patients with primary and recurrent pterygium. The study was an off-label, single-dosing, interventional case series involving 22 patients with primary and recurrent pterygium. They received subconjunctival bevacizumab (0.2cc. Pterygium vascularity and thickness was graded. The size of the pterygium (measured by surface area in cm2 was recorded from baseline to 12 weeks, after injection. Treatment-related complications and adverse events were reported. The main outcome of measurements was the change in size, vascularity, thickness, color intensity. There were 15 males (68.2% and 7 females (31.8% of 22 patients with a mean age of 45.5 years (SD 11.68 years. One cases didn't cooperate, and excluded. There was a significant difference in the mean surface area of pterygium at different intervals (P 0.05. There was a significant reduction in the mean pterygium size of patients younger than 45 years in comparison to those older than 45 years after three month (P =0.037, but after 6 months, this difference was not significant (P = 0.338. Average changes in pterygium size for both eyes were not different. The reduction of color intensity in both eyes was significant (P =0.031. Subconjuctival bevacizumab injection is useful in management of patients with primary and recurrent pterygium without significant local or systemic adverse effects

  20. Genetic predisposition to bevacizumab-induced hypertension.

    Science.gov (United States)

    Frey, Melissa K; Dao, Fanny; Olvera, Narciso; Konner, Jason A; Dickler, Maura N; Levine, Douglas A

    2017-12-01

    Bevacizumab, a monoclonal antibody to VEGF, has shown efficacy in ovarian, cervical and endometrial cancer in addition to several other solid tumors. Serious side effects include hypertension, proteinuria, bowel perforation, and thrombosis. We tested the hypothesis that genetic variation in hypertension-associated genes is associated with bevacizumab-induced hypertension (BIH). Patients with solid tumors treated with bevacizumab in combination with other therapy were identified from six clinical trials. Haplotype-tagging (ht) SNPs for 10 candidate genes associated with hypertension were identified through the International Hapmap Project. Germline DNA was genotyped for 103 htSNPs using mass spectrometry. Bevacizumab toxicities were identified from clinical trial reports. Haplotypes were reconstructed from diploid genotyping data and frequencies were compared using standard two-sided statistical tests. The study included 114 patients with breast, lung, ovarian, or other cancers, of whom 38 developed BIH. WNK1, KLKB1, and GRK4 were found to contain single loci associated with BIH. Haplotype analysis of WNK1, KLKB1, and GRK4 identified risk haplotypes in each gene associated with grade 3/4 BIH. A composite risk model was created based on these haplotypes. Patients with the highest risk score were the most likely to develop grade 3/4 BIH (OR=6.45; P=0.005; 95%CI, 1.86-22.39). We concluded that genetic variation in WNK1, KLKB1, and GRK4 may be associated with BIH. These genes are biologically plausible mediators due to their role in blood pressure control, regulating sodium homeostasis and vascular tone. This preliminary risk model performed better than population-based risk models and when further validated may help risk-stratify patients for BIH prior to initiating therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Intrastromal Delivery of Bevacizumab Using Microneedles to Treat Corneal Neovascularization

    Science.gov (United States)

    Kim, Yoo C.; Grossniklaus, Hans E.; Edelhauser, Henry F.; Prausnitz, Mark R.

    2014-01-01

    Purpose. This study tested the hypothesis that highly targeted intrastromal delivery of bevacizumab using coated microneedles allows dramatic dose sparing compared with subconjunctival and topical delivery for treatment of corneal neovascularization. Methods. Stainless steel microneedles 400 μm in length were coated with bevacizumab. A silk suture was placed in the cornea approximately 1 mm from the limbus to induce corneal neovascularization in the eyes of New Zealand white rabbits that were divided into different groups: untreated, microneedle delivery, topical eye drop, and subconjunctival injection of bevacizumab. All drug treatments were initiated 4 days after suture placement and area of neovascularization was measured daily by digital photography for 18 days. Results. Eyes treated once with 4.4 μg bevacizumab using microneedles reduced neovascularization compared with untreated eyes by 44% (day 18). Eyes treated once with 2500 μg bevacizumab using subconjunctival injection gave similar results to microneedle-treated eyes. Eyes treated once with 4.4 μg subconjunctival bevacizumab showed no significant effect compared with untreated eyes. Eyes treated with 52,500 μg bevacizumab by eye drops three times per day for 14 days reduced the neovascularization area compared with untreated eyes by 6% (day 18), which was significantly less effective than the single microneedle treatment. Visual exam and histological analysis showed no observable effect of microneedle treatment on corneal transparency or microanatomical structure. Conclusions. This study shows that microneedles can target drug delivery to corneal stroma in a minimally invasive way and demonstrates effective suppression of corneal neovascularization after suture-induced injury using a much lower dose compared with conventional methods. PMID:25212779

  2. Switch to aflibercept or ranibizumab after initial treatment with bevacizumab in eyes with neovascular AMD.

    Science.gov (United States)

    Waizel, Maria; Todorova, Margarita G; Masyk, Michael; Wolf, Katharina; Rickmann, Annekatrin; Helaiwa, Khaled; Blanke, Björn R; Szurman, Peter

    2017-05-23

    To evaluate changes in central macular thickness (CMT) and visual outcome in patients with neovascular age-related macular degeneration (AMD) treated initially with bevacizumab and subsequently switched to either aflibercept or ranibizumab. Observational clinical study was performed. We measured the structural outcome (CMT on SD-OCT; μm) and the visual outcome (best corrected visual acuity (BCVA); logMAR), as follows: before treatment (at baseline), following bevacizumab treatment (switch follow-up) and after switching from bevacizumab to aflibercept- or ranibizumab treatment (final follow-up, AG/, RG). From a total of 96 eyes treated with intravitreal injections of bevacizumab (10.5 ± 7.6 (mean ± SD)), 58 eyes switched to aflibercept (6.5 ± 3.9; AG) and 38 eyes switched to ranibizumab (7.1 ± 5.3; RG) (≥ 3 injections, each). In addition, these eyes were compared to 37 eyes under bevacizumab monotherapy. In the AG, the CMT decreased slightly from 430 ± 220 μm at baseline to 419 ± 212 μm at switch follow-up (p = 0.86), but decreased significantly to 318 ± 159 μm at final follow-up, AG (p bevacizumab to either aflibercept, or ranibizumab, has a strong anatomical effect in eyes with neovascular AMD. Nevertheless, even if the switch to aflibercept shows a minimal functional benefit over that to ranibizumab, visual prognosis remains limited.

  3. Bevacizumab versus ranibizumab for neovascular age-related macular degeneration:a Meta-analysis

    Directory of Open Access Journals (Sweden)

    Wen-Jie Wang

    2015-02-01

    Full Text Available AIM: To systematically compare the efficacy and safety of off-label bevacizumab versus licensed ranibizumab intravitreal injections as well as monthly regimen versus pro re nata [PRN (as needed] regimen in the treatment of neovascular age-related macular degeneration (nAMD. METHODS: Relevant publications were identified through automatically retrieve of database and manually retrieving. The methodological quality of studies included was assessed using the Jadad score and the risk-of-bias assessment. The efficacy estimates were measured by the weight mean difference (WMD for the improvement of best-corrected visual acuity (BCVA and central retinal thickness (CRT reduction. The safety estimates were measured by odds ratios (OR for adverse events rates. Statistical analysis was conducted by Revman 5.2.7. RESULTS: Seven studies were included in the Meta-analysis. There were no statistically significant differences between bevacizumab and ranibizumab in BCVA at 1 and 2y (P=0.37, P=0.18, respectively, However, both drugs has better BCVA given monthly than given as needed at 1 and 2y (PCONCLUSION: Bevacizumab was equivalent to ranibizumab for BCVA, however bevacizumab tended to gain less decrease in CRT and had higher rates of serious adverse events. Compared with treatment as needed, treatment monthly showed superior efficacy in BCVA improvement and CRT reduction, while the rates of adverse events were similar in the two dosing regimens.

  4. Neurodevelopmental Outcomes in Infants with Retinopathy of Prematurity and Bevacizumab Treatment.

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    Reyin Lien

    Full Text Available The current study aims to investigate the neurodevelopment of premature infants after intravitreal injections of bevacizumab (IVB for the treatment of retinopathy of prematurity (ROP up to the age of 2 years.The study design was retrospective observational case series conducted at an institutional referral center. Infants with type 1 ROP were classified into 3 groups: laser only, IVB only, and a combination of IVB and laser treatment. Main Outcome Measures were neurodevelopmental outcomes of the patients after treatment were assessed by Bayley Scales for Infant Development.Sixty-one patients who finished the neurodevelopmental survey were included. No detrimental effects on neurodevelopment were found in IVB group compared with the patients who received laser treatment only. The patients in the IVB + laser group had a higher incidence of significant mental (p = 0.028 and psychomotor (p = 0.002 impairment at 24 months than the patients in the laser group. The odds ratio of having severe psychomotor defects in the IVB + laser group was 5.3 compared with the laser group (p = 0.041. The causal source for the differences that were detected remained unknown due to lack of randomization in the study and accompanying bias in patient selection.Two years after laser and/or intravitreal injections of bevacizumab for infants with retinopathy of prematurity, no difference on neurodevelopment for those who received only bevacizumab versus only laser treatment were found. Those infants who required rescue therapy with laser or bevacizumab injection after initial, unsuccessful treatment showed some detrimental, neurodevelopmental effects.

  5. Clinical and histological findings after intravitreal injection of bevacizumsb (Avastin®) in a porcine model of choroidal neovascularisation

    DEFF Research Database (Denmark)

    Lassota, Nathan; Prause, Jan Ulrik; Scherfig, Erik

    2010-01-01

    PURPOSE: To examine the effect of intravitreally injected bevacizumab (Avastin) on the histological and angiographic morphology of choroidal neovascularization (CNV) in a masked and placebo-controlled animal study. METHODS: Choroidal neovascularization was induced surgically in 11 porcine eyes...... by perforating Bruch's membrane with a retinal perforator. After closure of the ports used for the vitrectomy, which was performed to facilitate the Bruch's membrane rupture, 0.05 ml of either bevacizumab or Ringer-Lactat (placebo) was injected into the vitreous cavity. Eyes were enucleated after 14 days. Fundus...... photographs and fluorescein angiograms (FAs) were obtained immediately prior to enucleation. Sections of formalin- and paraffin-embedded eyes were examined by light microscopy and by immunohistochemical staining. RESULTS: Placebo-injected eyes exhibited the highest propensity to leak, with five of six eyes...

  6. Aflibercept, bevacizumab or ranibizumab for diabetic macular oedema: recent clinically relevant findings from DRCR.net Protocol T.

    Science.gov (United States)

    Cai, Sophie; Bressler, Neil M

    2017-11-01

    The aim of this study was to provide clinically relevant findings from the DRCR.net Protocol T, a multicentre randomized clinical trial comparing intravitreous aflibercept, repackaged (compounded) bevacizumab and ranibizumab for vision-impairing centre-involved diabetic macular oedema (DME). At 1 year, all three antivascular endothelial growth factor (anti-VEGF) drugs, on average, improved visual acuity. There was no difference among drugs in mean change in visual acuity from baseline among eyes with baseline Snellen equivalent visual acuity of 20/32 to 20/40, whereas aflibercept yielded superior vision outcomes among eyes with baseline visual acuity of 20/50 to 20/320. At 2 years, aflibercept remained superior, on average, to bevacizumab, but not ranibizumab, among eyes with baseline visual acuity of 20/50 to 20/320. Over 2 years, in post-hoc area-under-the-curve analysis, aflibercept vision outcomes were superior to bevacizumab or ranibizumab among these eyes. All three drugs had comparable ocular and systemic safety profiles. The substantial cost differential between aflibercept and bevacizumab raises challenges when safety and efficacy are at odds with cost-effectiveness results. When initial visual acuity loss is mild, there are no apparent differences, on average, among aflibercept, bevacizumab and ranibizumab for treating DME. When visual acuity loss is moderate or worse, aflibercept is more likely to improve visual acuity.

  7. Intravitreal anti-VEGF injections for treating wet age-related macular degeneration: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Ba J

    2015-09-01

    Full Text Available Jun Ba,1,2,* Run-Sheng Peng,2,* Ding Xu,1 Yan-Hong Li,1 Hui Shi,1,3 Qianyi Wang,1 Jing Yu11Department of Ophthalmology, Shanghai Tenth People’s Hospital Affiliated with Tongji University, 2Department of Cardiac Surgery, Institute of Cardiovascular Diseases of Fudan University, Affiliated Zhongshan Hospital of Fudan University, Shanghai, People’s Republic of China; 3Department of First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China*Co-first authors of this workAims: Age-related macular degeneration (AMD is the main cause of blindness. Anti-vascular endothelial growth factor is used to prevent further neovascularization due to wet AMD. The purpose of this systematic review was to investigate the effect and protocol of anti-vascular endothelial growth factor treatment on wet AMD.Methods: A comprehensive literature search was performed in PubMed, Embase, the Cochrane Library, CNKI, and reference lists. Meta-analysis was performed using Stata12.0 software, best corrected visual acuity (BCVA, retinal thickness, and lesion size were evaluated.Results: Twelve randomized controlled trials spanning from 2010 to 2014 and involving 5,225 patients were included. A significant difference was observed between the intravitreal ranibizumab (IVR group and the intravitreal bevacizumab group (standard mean difference =-0.14, 95% confidence interval [CI] =-0.23 to -0.05. No significant differences were observed in best corrected VA, retinal thickness, or lesion size between IVR and the intravitreal aflibercept group. Compared to monthly injection, IVR as-needed injections (PRN can raise VA by 1.97 letters (weighted mean difference =1.97, 95% CI =0.14–3.794. Combination therapy of IVR and photodynamic therapy can significantly raise VA by 2.74 letters when combined with IVR monotherapy (weighted mean difference =2.74, 95% CI =0.26–5.21.Conclusion: The superiority remains unclear between IVR and

  8. Use of S-100B to Evaluate Therapy Effects during Bevacizumab Induction Treatment in AJCC Stage III Melanoma

    NARCIS (Netherlands)

    Kruijff, S.; Bastiaannet, E.; Brouwers, A. H.; Nagengast, W. B.; Speijers, M. J.; Suurmeijer, A. J. H.; Hospers, G. A.; Hoekstra, H. J.

    To investigate the feasibility of using bevacizumab to improve the survival of American Joint Committee on Cancer (AJCC) stage III melanoma patients, we investigated how a single bevacizumab treatment affected nodal disease and a panel of biomarkers in clinically fluorodeoxyglucose positron emission

  9. Incidence of endophthalmitis and use of antibiotic prophylaxis after intravitreal injections.

    Science.gov (United States)

    Cheung, Crystal S Y; Wong, Amanda W T; Lui, Alex; Kertes, Peter J; Devenyi, Robert G; Lam, Wai-Ching

    2012-08-01

    To report the incidence of endophthalmitis in association with different antibiotic prophylaxis strategies after intravitreal injections of anti-vascular endothelial growth factors and triamcinolone acetonide. Retrospective, comparative case series. Fifteen thousand eight hundred ninety-five intravitreal injections (9453 ranibizumab, 5386 bevacizumab, 935 triamcinolone acetonide, 121 pegaptanib sodium) were reviewed for 2465 patients between January 5, 2005, and August 31, 2010. The number of injections was determined from billing code and patient records. The indications for injection included age-related macular degeneration, diabetic macular edema, central and branch retinal vein occlusion, and miscellaneous causes. Three strategies of topical antibiotic prophylaxis were used by the respective surgeons: (1) antibiotics given for 5 days after each injection, (2) antibiotics given immediately after each injection, and (3) no antibiotics given. The primary outcome measures were the incidence of culture-positive endophthalmitis and culture-negative cases of suspected endophthalmitis. Nine eyes of 9 patients with suspected endophthalmitis after injection were identified. Three of the 9 cases had culture-positive results. The overall incidence of endophthalmitis was 9 in 15 895. The incidence of culture-negative cases of suspected endophthalmitis and culture-proven endophthalmitis after injection was 6 in 15 895 and 3 in 15 895, respectively. Taking into account both culture-positive endophthalmitis and culture-negative cases of suspected endophthalmitis, the incidence per injection was 5 in 8259 for patients who were given antibiotics for 5 days after injection, 2 in 2370 for those who received antibiotics immediately after each injection, and 2 in 5266 who received no antibiotics. However, if considering culture-proven endophthalmitis alone, the use of topical antibiotics, given immediately or for 5 days after injection, showed lower rates of endophthalmitis

  10. Prognostic importance of cell-free DNA in chemotherapy resistant ovarian cancer treated with bevacizumab

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Madsen, Christine Vestergaard; Andersen, Rikke Fredslund

    2014-01-01

    of EOC in combination with chemotherapy. However, only a minor subgroup will benefit from the treatment and there is an obvious need for new markers to select such patients. The purpose of this study was to investigate the effect of single-agent bevacizumab in multiresistant EOC and the importance...... of circulating cell-free DNA (cfDNA) in predicting treatment response. METHODS: One hundred and forty-four patients with multi-resistant EOC were treated with single-agent bevacizumab 10mg/kg every three weeks. Baseline plasma samples were analysed for levels of cfDNA by real-time polymerase chain reaction (PCR......-agent bevacizumab treatment in multiresistant EOC appears to be a valuable treatment option with acceptable side-effects. Cell-free DNA showed independent prognostic importance in patients treated with bevacizumab and could be applied as an adjunct for treatment selection....

  11. Bevacizumab reduces the growth rate constants of renal carcinomas: a novel algorithm suggests early discontinuation of bevacizumab resulted in a lack of survival advantage.

    Science.gov (United States)

    Stein, Wilfred D; Yang, James; Bates, Susan E; Fojo, Tito

    2008-10-01

    To hasten cancer drug development, new paradigms are needed to assess therapeutic efficacy. In a randomized phase II study in patients with renal cell carcinoma, 10 microg/kg bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) administered every 2 weeks resulted in a longer time to progression but a statistically significant difference in overall survival could not be demonstrated. We developed a novel two-phase equation to estimate concomitant rates of tumor regression (regression rate constant) and tumor growth (growth rate constant). This method allows us to assess therapeutic efficacy using tumor measurements gathered while a patient receives therapy in a clinical trial. The growth rate constants of renal cell carcinomas were significantly lower during therapy with 10 microg/kg bevacizumab than those of tumors in patients receiving placebo. In all cohorts the tumor growth rate constants were correlated with survival. That a survival advantage was not demonstrated with bevacizumab appears to have been a result of early discontinuation of bevacizumab. Single-agent bevacizumab significantly affects the growth rate constants of renal cell carcinoma. Extrapolating from the growth rate constants, we conclude that the failure to demonstrate a survival advantage in the original study was a result of premature discontinuation of bevacizumab. The mathematical model described herein has applications to many tumor types and should aid in evaluating the relative efficacies of different therapies. Quantitating tumor growth rate constants using data gathered while patients are enrolled in a clinical trial, as in the present study, may streamline and assist in drug development.

  12. Electrophysiological assessment of retinal function during 6 months of bevacizumab treatment in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Pedersen, Karen Bjerg; Møller, Flemming; Sjølie, Anne Katrin

    2010-01-01

    PURPOSE: The purpose of this study was to assess the alteration of retinal function by multifocal electroretinography and full-field electroretinography in patients with age-related macular degeneration treated with bevacizumab. METHODS: We performed a prospective pilot study of 26 eyes of 26...... previously treatment-naïve patients with neovascular age-related macular degeneration receiving intravitreal injections with 1.25 mg bevacizumab. Patients were examined with multifocal electroretinography, full-field electroretinography, optical coherence tomography, and visual acuity. Follow......-field electroretinography results indicated a decrease in cone photoreceptor function at 3 months, which was normalized at 6 months compared with baseline. Furthermore, 2 of 3 of the combined rod-cone responses showed signs of decreased retinal function at 6 months. CONCLUSION: Our results indicate passing signs...

  13. Successful Treatment of Retinal Angiomatous Proliferation with Intravitreal Triamcinolone and Ranibizumab Injections in a 67-Year-Old Male

    Directory of Open Access Journals (Sweden)

    Adnaan Haq

    2014-11-01

    Full Text Available A 67-year-old male who presented to the eye casualty department with deterioration in his vision was diagnosed with retinal angiomatous proliferation. After initial deterioration with ranibizumab intravitreal injections, we have demonstrated successful treatment and stabilised vision with ranibizumab and a single intravitreal triamcinolone injection. Stringent follow-up and top-up ranibizumab injections have stabilised his vision and have shown foveal improvement on optical coherence tomography imaging.

  14. Treatment of Corneal Neovascularization Using Anti-VEGF Bevacizumab

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    Deli Krizova

    2014-01-01

    Full Text Available Purpose. To evaluate antiangiogenic effect of local use of bevacizumab (anti-VEGF antibody in patients with corneal neovascularization. Methods. Patients were divided into two groups. All patients suffered from some form of corneal neovascularization (NV. Patients in group A received 0.2–0.5 mL of bevacizumab solution subconjunctivally (concentration 25 mg/mL in a single dose. Group A included 28 eyes from 27. Patients in group B applied bevacizumab eye drops twice daily (concentration 2.5 mg/mL for two weeks. Group B included 38 eyes from 35 patients. We evaluated the number of corneal segments affected by NV, CDVA, and the incidence of complications and subjective complaints related to the treatment. The minimum follow-up period was six months. Results. By the 6-month follow-up, in group A the percentage reduction of the affected peripheral segments was 21.6% and of the central segments was 9.6%; in group B the percentage reduction of the central segments was 22.7% and of the central segments was 38.04%. In both groups we noticed a statistically significant reduction in the extent of NV. Conclusion. The use of bevacizumab seems to be an effective and safe method in the treatment of corneal neovascularization, either in the subconjunctival or topical application form.

  15. The effect of bevacizumab for anterior segment neovascularization after silicone oil removal in eyes with previous vitreoretinal surgery.

    Science.gov (United States)

    Batman, C; Ozdamar, Y

    2010-07-01

    To report the outcomes of the use of intracameral bevacizumab for iris neovascularization occurring after silicone oil (SO) removal in eyes undergoing vitreoretinal surgery (VRS). This study included 12 eyes that had iris neovascularization after SO removal. The clinical outcomes of 12 eyes after intravitreal bevacizumab injection were reviewed. There were eight men and four women with an average age of 41.58+/-12.68 years. All eyes had VRS for various vitreoretinal diseases. After the mean follow-up period of 9.7+/-5.3 months, SO removal was performed. Then, the patients were followed for more than 2 months and detailed retinal examinations and intraocular pressure (IOP) were normal during this period, but rubeosis iridis (RI) developed. RI was treated with 1 dose of 1.25 mg bevacizumab into the anterior chamber. After a mean follow-up period of 4.8+/-2.2 months, the regression of iris neovacularization was detected and IOP was below 21 mmHg in all eyes. Anterior segment neovascularization (ASNV) may develop through various mechanisms in patients with VRS after SO removal, and anterior chamber injection of bevacizumab may lead to regression of ASNV.

  16. Topical bevacizumab treatment in aniridia

    NARCIS (Netherlands)

    Lapid-Gortzak, Ruth; Santana, Nathalie T. Y.; Nieuwendaal, Carla P.; Mourits, Maarten P.; van der Meulen, Ivanka J. E.

    2017-01-01

    To report the results of long-term topical treatment with bevacizumab (Avastin) 5 mg/mL eyedrops in a case of aniridia-related neovacularization of the cornea. Interventional case report. A female patient with aniridia had a decrease in the best corrected visual acuity from 0.32 to 0.02 in the OS

  17. Fusarium Endophthalmitis following Cataract Surgery: Successful Treatment with Intravitreal and Systemic Voriconazole

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    Paulo A. Alves da Costa Pertuiset

    2016-01-01

    Full Text Available Purpose. To report a case of postoperative endophthalmitis caused by Fusarium species successfully treated with intravitreal and systemic voriconazole after treatment failure with amphotericin B. Methods. Clinical case report of a 60-year-old immunocompetent woman who presents with endophthalmitis of unknown origin 4 weeks after uneventful cataract extraction and IOL implantation surgery. IOL explantation, vitrectomy with capsular bag removal, vitreous aspiration for culture, and intravitreal injection of amphotericin B (5 μg/0.1 mL were performed. Diagnosis was established by culturing the vitreous aspirate on a Sabouraud agar medium and staining with lactophenol blue solution. Five days later, there was no clinical response. The decision was made to administer a single dose of intravitreal voriconazole (2.5 μg/0.1 mL and oral voriconazole (200 mg BID for 30 days. Results. Fusarium sp. grew on culture. Treatment with local and systemic voriconazole was started after no improvement with vitrectomy, IOL explantation, and intravitreal amphotericin B. After 1 month of treatment, the infection resolved and best-corrected visual acuity was 20/25. Conclusion. In patients with endophthalmitis caused by Fusarium sp., topical and systemic voriconazole treatment should be considered in cases resistant to intravitreal amphotericin B.

  18. Combination of Intravitreal Ranibizumab and Laser Photocoagulation for Aggressive Posterior Retinopathy of Prematurity

    Directory of Open Access Journals (Sweden)

    Ágata Mota

    2012-04-01

    Full Text Available Purpose: To report on 2 cases of aggressive posterior retinopathy of prematurity (ROP treated with intravitreal ranibizumab (Lucentis® and laser photocoagulation. Methods: Two premature females, born at 25 and 26 weeks’ gestation with a birth weight of 530 and 550 g, respectively, with aggressive posterior ROP received combined treatment with laser photocoagulation and intravitreal ranibizumab (0.3 mg [30 µl] to each eye. Structural outcomes were evaluated by indirect ophthalmoscopy and documented by retinography. Results: An intravitreal injection was made at 34 weeks of postmenstrual age in the first case, followed by laser photocoagulation 1 week later. There was a partial regression of ROP with treatment. Five weeks later, neovascularization regrowth with bleeding in both eyes (intraretinal and subhyaloid occurred and retreatment with combined therapy was performed. In the second case, single therapy with laser photocoagulation was made at 34 weeks of postmenstrual age. In spite of the confluent photocoagulation in the avascular area, progression to 4A ROP stage occurred 1 week later. Both eyes were retreated 1 week later with intravitreal ranibizumab and laser photocoagulation. Treatment resulted in ROP regression in both cases. There were no signs of systemic or ocular adverse side effects. Conclusion: The cases presented show that combination therapy of indirect laser photocoagulation and intravitreal ranibizumab can be effective in the management of aggressive posterior ROP. Further investigation on anti-VEGF safety in premature infants is necessary . Additional studies are needed to define the role of anti-VEGF in ROP treatment.

  19. [Strategies of Intravitreal Injections with Anti-VEGF: "Pro re Nata versus Treat and Extend"].

    Science.gov (United States)

    Hufendiek, K; Pielen, A; Framme, C

    2017-01-23

    The goal of this report is to provide a review on different strategies for the use of pro re nata (PRN) and treat and extend (T&E) regimens with intravitreal anti-VEGF agents (bevacizumab, ranibizumab or aflibercept) in patients with retinal diseases such as neovascular AMD, diabetic macular oedema and macular oedema due to retinal vein occlusion. The main focus is to present the effectiveness and visual outcomes of both PRN and T&E regimens in the main pivotal trials and studies based on currently available evidence. We also discuss the advantages and disadvantages of both regimens, as well as monitoring and treatment of the disease, including treatment intervals and injection frequency. Currently there is increasing interest in establishing a regimen which offers the best visual outcome with lower injection frequency, and with reduced treatment burden by individualising treatment intervals and minimising the number of clinic visits and costs. Studies have shown that the PRN regimens in a clinical setting are insufficient in assuring the best visual outcome. The PRN regime requires frequent clinic visits to monitor disease status and intravitreal treatment if needed in a reactive approach. Individualised T&E regimens can improve visual outcome and require fewer injections than those administered in a monthly regimen and fewer monitoring visits than those in a PRN regimen. Georg Thieme Verlag KG Stuttgart · New York.

  20. Nasal septal perforation secondary to systemic bevacizumab.

    Science.gov (United States)

    Geltzeiler, Mathew; Steele, Toby O

    A case of nasal septal perforation secondary to systemic bevacizumab therapy for ovarian cancer is reported. Bevacizumab is a vascular endothelial growth factor A (VEGF-A) inhibitor that is becoming more widely utilized in the oncologic community. There is only one prior report of septal perforation secondary to bevacizumab in the Otolaryngology specific literature. The purpose of this report is: 1) to raise awareness and discuss the literature surrounding the sinonasal complications of bevacizumab and 2) provide workup and treatment recommendations based on the sum of the available literature. We review the clinical record of a 59year old patient who presented with an anterior septal perforation while taking bevacizumab therapy for ovarian cancer. She had mild symptoms. Her oncologist held bevacizumab and topical moisture therapy was started. After several weeks, the perforation remained stable and bevacizumab was restarted for her ovarian cancer. Bevacizumab is associated with both septal perforation and more widespread sinonasal toxicity. These lesions tend to produce only mild symptoms and can usually be managed conservatively. The decision to hold bevacizumab therapy should be made in conjunction with the patient and medical oncologist. Otolaryngologists should be aware of the toxicity from this increasingly common oncologic therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Efficacy of Bevacizumab combined with EX-PRESS in the treatment of refractory glaucoma

    Directory of Open Access Journals (Sweden)

    Qian Wang

    2018-03-01

    Full Text Available AIM:To investigate the efficacy of Bevacizumab intravitreal injection combined with EX-PRESS in the treatment of refractory glaucoma. METHODS: The research objects were 150 cases(150 eyesof patients with refractory glaucoma from June 2014 to December 2016 in our hospital. All patients were treated with EX-PRESS glaucoma drainage device implantation, and their medicine data were analyzed retrospectively. Totally 70 cases(70 eyeswere treated with EX-PRESS only were set as the control group; 80 cases(80 eyesreceived bevacizumab intravitreal injection on the basis of the treatment of the control group were set as the observation group. The successful rate of operation was evaluated, the intraocular pressure was measured before operation and at 7d, 1, 3, 6mo after treatment by non-contact conometer, followed by record of the visual acuity and complications before and after 6mo of treatment. RESULTS: The observation group's total surgical success rate was 72.5%, which was sharply higher than that of the control group(58.6%; while the partial success rate was 17.5%, which was significantly lower than that of the control group(30.0%, with statistical significance(χ2=5.453, P=0.028; χ2=4.213, P=0.047. Two groups' surgical failure rate had no distinct difference(χ2=0.000, P=1.000. There was no significant difference in visual acuity of the two groups before and after operation(P>0.05. There was no significant difference in intraocular pressure between the two groups(Fgroups=982.27, PFtime=941.88, PPP>0.05. The observation group's low intraocular pressure, anterior chamber bleeding and shallow anterior chamber incidence were significantly lower than those of the control group, there was statistical meaning(PCONCLUSION: Intravitreal injection of bevacizumab combined with EX-PRESS in the treatment of refractory glaucoma can improve the complete success rate, as well as perform effective control on complications such as short-term intraocular pressure

  2. A Phase II single-arm trial of palonosetron for the prevention of acute and delayed chemotherapy-induced nausea and vomiting in malignant glioma patients receiving multidose irinotecan in combination with bevacizumab

    Directory of Open Access Journals (Sweden)

    Affronti ML

    2016-12-01

    Full Text Available Mary Lou Affronti,1–3 Sarah Woodring,1,2 Katherine B Peters,1,4 James E Herndon II,5 Frances McSherry,5 Patrick N Healy,5 Annick Desjardins,1,4 James J Vredenburgh,6 Henry S Friedman1,2 1The Preston Robert Tisch Brain Tumor Center at Duke, South Hospital, Duke University Medical Center, 2Department of Neurosurgery, Duke University Health System, 3Duke University School of Nursing, 4Department of Neurology, 5Department of Biostatistics and Bioinformatics, Duke University Health System, Durham, NC, 6Saint Francis Cancer Center, Hartford, CT, USA Purpose: Given that the prognosis of recurrent malignant glioma (MG remains poor, improving quality of life (QoL through symptom management is important. Meta-analyses establishing antiemetic guidelines have demonstrated the superiority of palonosetron (PAL over older 5-hydroxytryptamine 3-receptor antagonists in chemotherapy-induced nausea and vomiting (CINV prevention, but excluded patients with gliomas. Irinotecan plus bevacizumab is a treatment frequently used in MG, but is associated with low (55% CINV complete response (CR; no emesis or use of rescue antiemetic with commonly prescribed ondansetron. A single-arm Phase II trial was conducted in MG patients to determine the efficacy of intravenous PAL (0.25 mg and dexamethasone (DEX; 10 mg received in conjunction with biweekly irinotecan–bevacizumab treatment. The primary end point was the proportion of subjects achieving acute CINV CR (no emesis or antiemetic ≤24 hours postchemotherapy. Secondary end points included delayed CINV CR (days 2–5, overall CINV CR (days 1–5, and QoL, fatigue, and toxicity.Materials and methods: A two-stage design of 160 patients was planned to differentiate between CINV CR of 55% and 65% after each dose of PAL–DEX. Validated surveys assessed fatigue and QoL.Results: A total of 63 patients were enrolled, after which enrollment was terminated due to slow accrual; 52 patients were evaluable for the primary outcome

  3. The Prognostic Value of Plasma YKL-40 in Patients With Chemotherapy-Resistant Ovarian Cancer Treated With Bevacizumab

    DEFF Research Database (Denmark)

    Boisen, Mogens K; Madsen, Christine V; Dehlendorff, Christian

    2016-01-01

    with ovarian cancer treated with bevacizumab. METHODS: One hundred forty patients with chemotherapy-refractory epithelian ovarian cancer were treated with single-agent bevacizumab 10 mg/kg every 3 weeks in a prospective trial. Plasma YKL-40 was determined by enzyme-linked immunosorbent assay before and during...... = 0.003). Increase in plasma YKL-40 during bevacizumab treatment, with correction for baseline plasma YKL-40, was a predictor of shorter PFS. Using normal versus elevated plasma YKL-40 as a cutoff did not provide the same discriminative value. CONCLUSIONS: Low plasma YKL-40 at baseline and during...... treatment is associated with improved outcomes in patients with chemotherapy-refractory advanced ovarian cancer treated with single-agent bevacizumab....

  4. P08.43 Bevacizumab discontinuation and bevacizumab re-challenge in glioblastoma patients

    Science.gov (United States)

    Bonnet, C.; Cartalat-Carel, S.; Thomas, L.; Joubert, B.; Meyronet, D.; D’Hombres, A.; Jouanneau, E.; Guyotat, J.; Honnorat, J.; Ducray, F.

    2016-01-01

    Abstract Background and objective . In glioblastoma (GBM) patients who benefit from bevacizumab, it is unknown how long this treatment should be continued and whether it may be safely stopped. The aim of the present study was to describe the outcome of 36 responding GBM patients in whom bevacizumab was discontinued in the absence of tumour progression. Material and methods: We retrospectively reviewed the characteristics of GBM patients who received bevacizumab (10mg/kg every 2 weeks) either as first-line treatment in association with temozolomide radiochemotherapy (n=13) or at recurrence (n=23) in association with temozolomide, CCNU or irinotecan. In all of the patients, bevacizumab was discontinued while they had achieved a partial (63%) or a complete response (37%) according to RANO criteria. Reasons for bevacizumab discontinuation were physician’s decision in 80% of cases and toxicity in 20% of cases. Results: In patients treated with first-line bevacizumab (median number of infusions = 4, range 1 to 44), median time to progression and median survival after bevacizumab discontinuation, were 11.8 months and 29 months, respectively. In patients treated with bevacizumab at recurrence (median number of infusions = 10, range 2 to 36), median time to progression and median survival after bevacizumab discontinuation were 6.9 months and 16 months, respectively. In none of the patients rebound tumor recurrence upon bevacizumab discontinuation was observed. At the time of tumor progression, 22 patients were re-treated with bevacizumab with a 53% response rate and a median progression-free survival of 6 months. Conclusion: In responding patients, bevacizumab may be discontinued without rebound recurrence and a prolonged response may be observed in the absence of prolonged treatment. At the time of tumor progression, previously responding patients may benefit from bevacizumab re-challenge.

  5. Posterior capsule opacification and neovascularization treated with intravitreal bevacizumab and Nd:YAG capsulotomy

    OpenAIRE

    Velez-Montoya, Raul

    2008-01-01

    Grimelda Yuriana Sánchez-Castro1, Alejandra Hitos-Fájer1, Erick Mendoza-Schuster1, Raul Velez-Montoya2, Cecilio Francisco Velasco-Barona11Asociación para Evitar la Ceguera en México. Hospital “Dr. Luis Sánchez Bulnes”, México, D.F. Ophthalmology Department – Anterior Segment; 2Asociación para Evitar la Ceguera en México. Hospital “Dr. Luis Sánchez Bulnes&a...

  6. Combination systemic and intravitreal antiviral therapy in the management of acute retinal necrosis syndrome.

    Science.gov (United States)

    Yeh, Steven; Suhler, Eric B; Smith, Justine R; Bruce, Beau; Fahle, Gary; Bailey, Steven T; Hwang, Thomas S; Stout, J Timothy; Lauer, Andreas K; Wilson, David J; Rosenbaum, James T; Flaxel, Christina J

    2014-01-01

    Acute retinal necrosis (ARN) may lead to severe visual loss because of its rapid progression and high likelihood of retinal detachment (RD). This study investigates whether combination systemic and intravitreal antiviral therapy is superior to systemic antiviral therapy alone. Single-center, interventional, comparative case series of patients with ARN treated with combination systemic antiviral and intravitreal foscarnet injection therapy or systemic antiviral therapy alone. Survival analysis and incidence rates of visual acuity (VA) gain of two lines or greater, severe visual loss of 20/200 or worse, and RD were assessed. Twelve patients received combination therapy and 12 received systemic therapy alone. Patients receiving combination therapy were more likely to gain two or more lines of VA and showed decreased incidences of severe visual loss and RD. Combination oral and intravitreal antiviral therapy may improve the likelihood for VA gain and decrease the risk of RD in patients with ARN. Clinicians should consider administering combination systemic and intravitreal antiviral therapy for patients with the ARN syndrome.

  7. Bevacizumab: Off-label use in ophthalmology

    Directory of Open Access Journals (Sweden)

    Grisanti Salvatore

    2007-01-01

    Full Text Available Bevacizumab is a full-length, humanized monoclonal antibody directed against all the biologically active isoforms of vascular endothelial growth factor (VEGF-A. The antibody was initially designed and studied as an anti-angiogenic strategy to treat a variety of solid tumors. After approval by the US Food and Drug Administration, bevacizumab gained access into ophthalmology to treat various types of neovascular diseases. Since the first report in 2005 more than 100 publications share the experience with bevacizumab in ophthalmology. Two authors independently assessed the research results from Pubmed to April 2007. The reference list is a selection of key publications related to the issue. Currently, there is no well-designed randomized controlled trial yet to establish the efficacy and safety of intraocular bevacizumab for any ocular disease in spite of its assumed characteristics representing the most cost-effective VEGF inhibitor.

  8. Anti vascular endothelial growth factor (bevacizumab) in central retinal vein occlusion: an interventional case series

    International Nuclear Information System (INIS)

    Jan, S.; Khan, M.N.; Karim, S.; Khan, M.T.; Hussain, Z.; Khan, S.; Nazim, M.

    2010-01-01

    Vascular endothelial growth factor plays major role in ocular angio genesis and retinal edema production and is a step forward in the management of ocular neovascularization and retinal edematous pathologies. To determine the efficacy and safety of intra-vitreal Avastin (Bevacizumab) in cases having central retinal vein occlusion. All patients with central retinal occlusion occurring in the past 3 months and seen between the study period were included in the study. Diagnosis of central retinal vein occlusion was made clinically by slit lamp biomicroscopy with 78D examination Patients who had received any treatment for and eyes which already had developed Anterior Segment Neovascularization, Neovascularization elsewhere or Neovascularization on disc at presentation were excluded. Dose of 0.05 ml (1.25mg) of Avastin (Bevacizumab) was used as intra vitreal injection every month for 3 months in cases that presented within a month of occlusion and less injections were given in dose presenting later. Follow-up was done at 30th, 60th, 90th and 120th day after the onset of disease. Visual outcome was defined as Snellen's or LogMar Best Corrected Visual Acuity at final follow up, of 120th day, compared to the visual acuity at presentation. Data were analyzed by SPSS version 17. Total of 17 eyes of 17 patients were included in this study. Eleven (64.7%) patients were males while 6(35.3%) were females. Total of 40 intra-vitreal injections of Avastin were given to patients with a mean of 2.35 injections per eye. Good visual outcome was achieved in 10(58.8%) eyes, while 7(41.2%) had stable visual outcome. Mean initial Best Corrected Visual Acuity (LogMar) in all 17 eyes was 1.79(SD+0.87) which significantly improved to a mean of 1.18 (SD+0.77) at final follow up. Mean improvement in Best Corrected Visual Acuity (LogMar) after paired sample test in all patients at final follow up on day 120 was 0.61(SD+0.84). Retinal hemorrhages and macular edema decreased clinically on

  9. The efficacy of intravitreal antivascular endothelial growth factor as primary treatment of retinopathy of prematurity: Experience from a tertiary hospital

    Directory of Open Access Journals (Sweden)

    H Kana

    2017-03-01

    Full Text Available Background. Retinopathy of prematurity (ROP is a vasoproliferative disease affecting premature babies and a major cause of blindness in childhood. Appropriate screening and treatment can prevent blindness. Objective. To report on the efficacy of using antivascular endothelial growth factor (bevacizumab as first-line therapy in ROP. Methods. This was a retrospective analysis of patients with ROP treated at St John Eye Hospital, Johannesburg, South Africa, over a 3-year period. Outcome measures were the clinical response to intravitreal bevacizumab (IVB as well as the economic impact of IVB therapy. Results. Twenty-three patients were treated for active ROP or type 1 disease, in 44 eyes. Two patients required treatment in one eye only. The mean birth weight of these patients was 1 074 g (range 810 - 1 480. Response to treatment outcome was available for 22 patients (43 eyes. The mean follow-up period was 9 months (range 1 - 18. Forty-one eyes (95.3% showed complete regression or non-progression of the disease. Two eyes (one eye each in two patients progressed to advanced disease. There were no short-term adverse events. A cost-effective model showed that IVB treatment was much more economical than laser therapy. Conclusion. IVB is a safe and effective first-line treatment for ROP and should be considered in resource-limited centres.

  10. Randomized Double-Blind Placebo-Controlled Trial of Bevacizumab Therapy for Radiation Necrosis of the Central Nervous System

    International Nuclear Information System (INIS)

    Levin, Victor A.; Bidaut, Luc; Hou, Ping; Kumar, Ashok J.; Wefel, Jeffrey S.; Bekele, B. Nebiyou; Prabhu, Sujit; Loghin, Monica; Gilbert, Mark R.; Jackson, Edward F.

    2011-01-01

    Purpose: To conduct a controlled trial of bevacizumab for the treatment of symptomatic radiation necrosis of the brain. Methods and Materials: A total of 14 patients were entered into a placebo-controlled randomized double-blind study of bevacizumab for the treatment of central nervous system radiation necrosis. All patients were required to have radiographic or biopsy proof of central nervous system radiation necrosis and progressive neurologic symptoms or signs. Eligible patients had undergone irradiation for head-and-neck carcinoma, meningioma, or low- to mid-grade glioma. Patients were randomized to receive intravenous saline or bevacizumab at 3-week intervals. The magnetic resonance imaging findings 3 weeks after the second treatment and clinical signs and symptoms defined the response or progression. Results: The volumes of necrosis estimated on T 2 -weighted fluid-attenuated inversion recovery and T 1 -weighted gadolinium-enhanced magnetic resonance imaging scans demonstrated that although no patient receiving placebo responded (0 of 7), all bevacizumab-treated patients did so (5 of 5 randomized and 7 of 7 crossover) with decreases in T 2 -weighted fluid-attenuated inversion recovery and T 1 -weighted gadolinium-enhanced volumes and a decrease in endothelial transfer constant. All bevacizumab-treated patients-and none of the placebo-treated patients-showed improvement in neurologic symptoms or signs. At a median of 10 months after the last dose of bevacizumab in patients receiving all four study doses, only 2 patients had experienced a recurrence of magnetic resonance imaging changes consistent with progressive radiation necrosis; one patient received a single additional dose of bevacizumab and the other patient received two doses. Conclusion: The Class I evidence of bevacizumab efficacy from the present study in the treatment of central nervous system radiation necrosis justifies consideration of this treatment option for people with radiation necrosis

  11. Short-term Results of Trabeculectomy Using Adjunctive Intracameral Bevacizumab Versus Mitomycin C: A Randomized Controlled Trial.

    Science.gov (United States)

    Vahedian, Zakieh; Mafi, Mostafa; Fakhraie, Ghasem; Zarei, Reza; Eslami, Yadollah; Ghadimi, Hadi; Mohebbi, Masomeh

    2017-09-01

    To compare the outcome of trabeculectomy using adjunctive intracameral bevacizumab versus intraoperative mitomycin C (MMC). In this double-blind, randomized clinical trial 87 eyes of 87 patients with primary open-angle or pseudoexfoliation glaucoma were assigned to each treatment group (44 cases received 1.25 mg intracameral bevacizumab at the end of operation and in 43 cases MMC was applied during surgery). Success was defined as intraocular pressure (IOP) between 6 and 21 mm Hg and at least 30% IOP drop with (qualified) or without (complete) glaucoma medications without additional glaucoma surgery. The follow-up time was 17.12±2.58 months in the bevacizumab group and 17.23±2.42 months in the MMC group (P=0.845). The preoperative IOP was 29.17±3.94 and 28.8±4.08 mm Hg in the bevacizumab and MMC groups, respectively (P=0.689). Last visit IOP was 17.41±3.11 mm Hg in the bevacizumab group and 15.34±3.62 mm Hg in the MMC group (Pbevacizumab and MMC groups, respectively (P=0.207). At last visit, complete success was achieved in 25 cases (61%) of bevacizumab group and 23 cases (66%) of MMC group (P=0.669). Early filtering bleb leak was more prevalent in bevacizumab group (29% vs. 11%). A single 1.25 mg dose of intracameral bevacizumab improves the success of trabeculectomy comparable with MMC; however, it increases the risk of early filtering bleb leakage.

  12. Retrospective study of carmustine or lomustine with bevacizumab in recurrent glioblastoma patients who have failed prior bevacizumab

    Science.gov (United States)

    Rahman, Rifaquat; Hempfling, Kelly; Norden, Andrew D.; Reardon, David A.; Nayak, Lakshmi; Rinne, Mikael L.; Beroukhim, Rameen; Doherty, Lisa; Ruland, Sandra; Rai, Arun; Rifenburg, Jennifer; LaFrankie, Debra; Alexander, Brian M.; Huang, Raymond Y.; Wen, Patrick Y.; Lee, Eudocia Q.

    2014-01-01

    Background Currently, there are no known effective treatments for recurrent glioblastoma once patients have progressed on a bevacizumab-containing regimen. We examined the efficacy of adding nitrosoureas to bevacizumab in patients who progressed while on an initial bevacizumab-containing regimen. Methods In this retrospective study, we identified adult patients with histologically confirmed glioblastoma (WHO grade IV) who were treated with lomustine or carmustine in combination with bevacizumab as a second or third regimen after failing an alternative initial bevacizumab-containing regimen. Response rate (RR), 6-month progression free survival (PFS6), and progression-free survival (PFS) were assessed for each treatment. Results Forty-two patients were identified (28 males) with a median age of 49 years (range, 24–78 y). Of 42 patients, 28 received lomustine (n = 22) or carmustine (n = 6) with bevacizumab as their second bevacizumab-containing regimen, and 14 received lomustine (n = 11) or carmustine (n = 3) as their third bevacizumab-containing regimen. While the median PFS for the initial bevacizumab-containing regimen was 16.3 weeks, the median PFS for the nitrosourea-containing bevacizumab regimen was 6.3 weeks. Patients had an RR of 44% and a PFS6 rate of 26% during the initial bevacizumab regimen and an RR of 0% and a PFS6 rate of 3% during the nitrosourea-containing bevacizumab regimen. There was increased grade 3–4 toxicity (45% vs 19%, P = .010) during the nitrosourea-containing bevacizumab regimen relative to the initial bevacizumab regimen. Median overall survival was 18.7 weeks from initiation of the nitrosourea-containing bevacizumab regimen. Conclusion The addition of lomustine or carmustine to bevacizumab after a patient has already progressed on a bevacizumab-containing regimen does not appear to provide benefit for most patients and is associated with additional toxicity with the doses used in this cohort. PMID:24958095

  13. Acquired-resistance of bevacizumab treatment for radiation brain necrosis: a case report

    OpenAIRE

    Zhuang, Hongqing; Yuan, Xiangkun; Sun, Dayong; Bian, Jianliang; Chang, Joe Y.; Yuan, Zhiyong; Wang, Ping

    2016-01-01

    The case study reported on acquired bevacizumab resistance in one patient receiving re-treatment with bevacizumab following radiation brain necrosis progression after bevacizumab was discontinued. This case offers novel and additional insight for bevacizumab treatment. Low-dose bevacizumab is effective for radiation brain necrosis, and radiation brain necrosis may progress after bevacizumab discontinuation, whereas too many cycles of bevacizumab treatment may induce drug-resistance and re-tre...

  14. A Mathematical Analysis of Intravitreal Drug Transport | Avtar ...

    African Journals Online (AJOL)

    Purpose: The aim of our present work is the development of a quasi steady-state model for the distribution of intravitreally injected drugs and investigation of the effects of various model parameters on the drug distribution in normal and diseased eyes. Method: A simple mathematical model for the intravitreal transport of ...

  15. Combination systemic and intravitreal antiviral therapy in the management of acute retinal necrosis syndrome (an American Ophthalmological Society thesis).

    Science.gov (United States)

    Flaxel, Christina J; Yeh, Steven; Lauer, Andreas K

    2013-09-01

    To compare the outcomes of combination systemic and intravitreal antiviral therapy vs systemic antiviral therapy alone for treating acute retinal necrosis syndrome (ARN). We hypothesize that combination therapy might result in superior visual acuity (VA) and retinal detachment (RD) outcomes vs traditional systemic antiviral therapy alone. A retrospective, interventional, comparative single-center study of patients with ARN. We reviewed demographic data, herpesvirus diagnoses, polymerase chain reaction (PCR) results, VA, RD, and the use of systemic and intravitreal antiviral therapy. Outcome measures included VA improvement by 2 or more lines, severe visual loss, VA ≤20/200, and RD. We studied 29 eyes of 24 patients, treated from 1987 through 2009. Mean age was 42.6 years and mean follow-up was 44.0 months. Twelve patients (14 eyes) were treated with combined systemic and intravitreal antiviral therapy and 12 patients (15 eyes) with systemic therapy alone. Kaplan-Meier survival analysis revealed that patients receiving combination intravitreal and systemic antiviral therapy were more likely to have VA improved by 2 lines or greater (P=.006). Patients receiving combination therapy also showed a decreased incidence of progression to severe visual loss (0.13/patient-years [PY]) compared to patients receiving systemic therapy alone (0.54/PY, P=.02) and had decreased incidence of RD (0.29/PY vs 0.74/PY, P=.03). Combination oral and intravitreal antiviral therapy may improve visual and functional outcomes in patients with ARN. Clinicians should consider prompt administration of combination systemic and intravitreal antiviral therapy as first-line treatment for patients with clinical features of ARN.

  16. Use of bevacizumab in recurrent glioblastoma.

    Science.gov (United States)

    Ghiaseddin, Ashley; Peters, Katherine B

    2015-01-01

    Glioblastoma (GBM) is the most common adult primary brain neoplasm. Despite advances in treatment, GBM continues to be associated with considerable morbidity and mortality as compared with other malignancies. Standard treatment for GBM results in survival of 12.9 months (95% CI: 12.3-13.7 months) with a median progression-free survival of 7.2 months (95% CI: 6.4-8.2 months) in a modern GBM cohort. These aggressive tumors recur and treatment for recurrent GBM continues to have very poor outcomes. Prior to the use of bevacizumab, monoclonal antibody to VEGF, 6-month progression-free survival in clinical trials for recurrent GBM ranged from 9 to 15%. Trials utilizing bevacizumab and its subsequent US FDA approval have given more hope to recurrent GBM and this concise review discusses bevacizumab in recurrent GBM. This review focuses on time-to-event outcomes (overall survival, progression-free survival and 6-month progression-free survival) in clinical trials utilizing bevacizumab for the treatment of recurrent GBM. For this review, we have chosen to focus primarily on Phase II clinical trials that have been published and available in the literature (PubMed). While we focused primarily on time-to-event variables, toxicity and safety of bevacizumab is very important and this agent can be associated with serious life-threatening toxicities. We have included a general section of toxicities but for a more lengthy review please see the excellent study by Odia and colleagues.

  17. The role of intravitreal chemotherapy for retinoblastoma

    Directory of Open Access Journals (Sweden)

    Fairooz P Manjandavida

    2015-01-01

    Full Text Available Targeted therapy in retinoblastoma (RB is widely accepted as the current management tool with an aim of increasing drug availability at the tumor location. Inevitably the effect is several times higher compared to systemic delivery of chemotherapeutic drugs and carries less systemic toxicity. Despite tremendous advancement in saving life, eye salvage in advanced RB especially with active vitreous seeds remains a challenge. The hypoxic environment of the vitreous and reduced vitreous concentration of the drugs delivered makes these tumor seeds resistant to chemotherapy. Direct delivery of chemotherapeutic drugs into the vitreous cavity aids to overcome these challenges and is progressively being accepted worldwide. However, intraocular procedure in RB was abandoned due to high risk of extraocular tumor dissemination. Recently, the forbidden therapeutic technique was re-explored and modified for safe use. Although eye salvage rate has tremendously improved after intravitreal chemotherapy (IVitC, retinal toxicity, and vision salvage are yet to be validated. In our preliminary report of intravitreal melphalan in 11 eyes, we reported 100% eye salvage and 0% recurrence with an extended 15 months mean follow-up. In this review, we analyzed published reports on IVitC in RB via PubMed, Medline, and conference proceedings citation index, electronic database search, without language restriction that included case series and reports of humans and experimental animal eyes with RB receiving IVitC.

  18. Intravitreal triamcinolone for diffuse diabetic macular oedema.

    LENUS (Irish Health Repository)

    Gibran, S K

    2012-02-03

    AIM: To evaluate the efficacy of intravitreal triamcinolone (IVTA) for the treatment of diffuse diabetic macular oedema (DME) refractory to conventional argon macular laser therapy. METHODS: A prospective, consecutive, and noncomparative case series was undertaken involving 38 eyes of 38 patients with refractory DME. Triamcinolone acetonide (4 mg) in 0.1 ml was injected intravitreally. LogMar visual acuity (VA) and macular thickness measured by ocular coherence tomography (OCT) were assessed preoperatively and postoperatively at 1, 3, and 6 months. RESULTS: All patients completed 6 months of follow up. VA (mean+\\/-SD) improved from 0.905+\\/-0.23 to 0.605+\\/-0.28, 0.555+\\/-0.29, and 0.730+\\/-0.30 at 1, 3, and 6 months, respectively. Macular thickness baseline (mean+\\/-SD) on OCT was 418.7+\\/-104.2 microm and this decreased to 276.9+\\/-72.6 microm, 250.6+\\/-53.1 microm, and 308.8+\\/-87.3 microm at 1, 3, and 6 months, respectively. CONCLUSIONS: IVTA may be a potential temporary treatment for refractory DME. It is effective in decreasing macular thickness and improving VA but the effect lasts approximately for 6 months in the majority of patients. Further investigations are required to establish the safety of IVTA for the treatment of DME.

  19. Bevacizumab for the treatment of glioblastoma.

    Science.gov (United States)

    Gil-Gil, Miguel J; Mesia, Carlos; Rey, Montserrat; Bruna, Jordi

    2013-01-01

    Glioblastoma (GBM) or grade IV glioma is the most common primary brain tumor in adults. Standard treatment median overall survival (OS) is only 14-15 months and less than 10% of patients will survive 5 years after diagnosis. There is no standard treatment in recurrent GBM and OS ranges from 3 to 9 months. GBM is 1 of the most vascularized human tumors and GBM cells produce vascular endothelial growth factor (VEGF). Bevacizumab, a humanized monoclonal antibody against VEGF, has demonstrated activity in vitro and in phase II trials in relapse, as well as in 1 phase III trial as first line therapy. Bevacizumab also improves quality of life for patients suffering GBM. This paper reviews the mechanism of action of bevacizumab, its metabolism and pharmacokinetic profile. It summarizes the clinical studies in recurrent and newly diagnosed GBM, its potential side effects and complications and its place in therapy.

  20. Regression Rates Following the Treatment of Aggressive Posterior Retinopathy of Prematurity with Bevacizumab Versus Laser: 8-Year Retrospective Analysis

    Science.gov (United States)

    Nicoară, Simona D.; Ştefănuţ, Anne C.; Nascutzy, Constanta; Zaharie, Gabriela C.; Toader, Laura E.; Drugan, Tudor C.

    2016-01-01

    Background Retinopathy is a serious complication related to prematurity and a leading cause of childhood blindness. The aggressive posterior form of retinopathy of prematurity (APROP) has a worse anatomical and functional outcome following laser therapy, as compared with the classic form of the disease. The main outcome measures are the APROP regression rate, structural outcomes, and complications associated with intravitreal bevacizumab (IVB) versus laser photocoagulation in APROP. Material/Methods This is a retrospective case series that includes infants with APROP who received either IVB or laser photocoagulation and had a follow-up of at least 60 weeks (for the laser photocoagulation group) and 80 weeks (for the IVB group). In the first group, laser photocoagulation of the retina was carried out and in the second group, 1 bevacizumab injection was administered intravitreally. The following parameters were analyzed in each group: sex, gestational age, birth weight, postnatal age and postmenstrual age at treatment, APROP regression, sequelae, and complications. Statistical analysis was performed using Microsoft Excel and IBM SPSS (version 23.0). Results The laser photocoagulation group consisted of 6 premature infants (12 eyes) and the IVB group consisted of 17 premature infants (34 eyes). Within the laser photocoagulation group, the evolution was favorable in 9 eyes (75%) and unfavorable in 3 eyes (25%). Within the IVB group, APROP regressed in 29 eyes (85.29%) and failed to regress in 5 eyes (14.71%). These differences are statistically significant, as proved by the McNemar test (P<0.001). Conclusions The IVB group had a statistically significant better outcome compared with the laser photocoagulation group, in APROP in our series. PMID:27062023

  1. Storage stability of bevacizumab in polycarbonate and polypropylene syringes

    Science.gov (United States)

    Khalili, H; Sharma, G; Froome, A; Khaw, P T; Brocchini, S

    2015-01-01

    Purpose To compare and examine the storage stability of compounded bevacizumab in polycarbonate (PC) and polypropylene (PP) syringes over a 6-month period. PC syringes have been used in a recent clinical study and bevacizumab stability has not been reported for this type of syringe. Methods Repackaged bevacizumab was obtained from Moorfields Pharmaceuticals in PC and PP syringes. Bevacizumab from the stored syringes was analysed at monthly time points for a 6-month period and compared with bevacizumab from a freshly opened vial at each time point. SDS-PAGE electrophoresis and size-exclusion chromatography (SEC) was used to observe aggregation and degradation. Dynamic light scattering (DLS) provided information about the hydrodynamic size and particle size distribution of bevacizumab in solution. VEGF binding and the active concentration of bevacizumab was determined by surface plasmon resonance (SPR) using Biacore. Results SDS-PAGE and SEC analysis did not show any changes in the presence of higher molecular weight species (HMWS) or degradation products in PC and PP syringes from T0 to T6 compared with bevacizumab sampled from a freshly opened vial. The hydrodynamic diameter of bevacizumab in the PC syringe after 6 months of storage was not significantly different to bevacizumab taken from a freshly opened vial. Using SPR, the VEGF binding activity of bevacizumab in the PC syringe was comparable to bevacizumab taken from a freshly opened vial. Conclusion No significant difference over a 6-month period was observed in the quality of bevacizumab repackaged into prefilled polycarbonate and polypropylene syringes when compared with bevacizumab that is supplied from the vial. PMID:25853399

  2. Real-time measurement of needle forces and acute pressure changes during intravitreal injections.

    Science.gov (United States)

    Christensen, Logan; Cerda, Ashlee; Olson, Jeffrey L

    2017-11-01

    The purpose of this study was to use a physiological pressure transducer to measure real-time, continuous pressure changes in an ex vivo study model of porcine eyes to record the amount of force needed for scleral penetration and to measure acute intraocular pressure rise during intravitreal injections. A pressure transducer was inserted into the anterior chamber of 30 fresh porcine eyes, and intraocular pressure was measured 2 s prior to intravitreal injection until 2 s after. A force transducer plate was used to insert various gauge needles into the vitreous cavity and the amount of force in Newtons (N) required for scleral penetration was recorded. For scleral perforation, 32- and 30-gauge needles required 0.44 N and 0.45 N, significantly less than larger gauge needles (P time continuous recordings of pressure reveal that an instantaneous intraocular pressure spike occurs during intravitreal injection and appears to be separate from the intraocular pressure spike that occurs during needle insertion. This pressure spike is transient and has not been captured by previous methods of intraocular pressure measurement, which rely on single time point measurements. The clinical significance of this brief intraocular pressure spike is unclear and warrants further investigation. © 2017 Royal Australian and New Zealand College of Ophthalmologists.

  3. Oral Doxycycline Reduces the Total Number of Intraocular Bevacizumab Injections Needed to Control Neovascular Age-related Macular Degeneration.

    Science.gov (United States)

    Mirshahi, Ahmad; Azimi, Pourya; Abdolahi, Ali; Mirshahi, Romina; Abdollahian, Mahnaz

    2017-01-01

    Tetracyclines, especially doxycycline, play a role in the regulation of inflammation, immunomodulation, cell proliferation, and angiogenesis. Treatment of corneal angiogenesis or choroidal neovascularization with tetracyclines has been shown to be effective in animal models. The aim of this study was to evaluate the efficacy of oral doxycycline in reducing the total number of intraocular injections needed for controlling neovascular age-related macular degeneration in human patients. In this interventional case series, 28 random consecutive patients with neovascular age-related macular degeneration from Farabi Eye Hospital, Tehran, Iran were treated for 4 months with 200 mg doxycycline once a day after the first intravitreal bevacizumab injection in addition to standard therapy in agreement with as-needed regimen. After 12 months of follow-up, total number of injections, foveal thickness and visual acuity were compared to those at baseline and of similar studies. Similar to standard treatment, co-treatment with doxycycline was able to control active disease (intraretinal or subretinal fluid or leakage, new-onset of macular hemorrhage, and reduction of visual acuity more than 5 letters based on Early Treatment Diabetic Retinopathy Study [ETDRS] charts) yet with fewer injections (for current study and standard treatment, respectively 3.14 vs. 5.92, P 0.05). If confirmed in larger studies, the findings of this interventional case series could provide a strategy to control neovascular age-related macular degeneration with fewer intraocular bevacizumab injections by co-administering a well-known oral agent-doxycycline.

  4. Fulminant toxoplasmic retinochoroiditis following intravitreal triamcinolone administration

    Directory of Open Access Journals (Sweden)

    Ryan Rush

    2012-01-01

    Full Text Available We report two cases of fulminant toxoplasmic retinochoroiditis following intravitreal triamcinolone acetonide (IVTA administration. Case 1: A 42-year-old female received IVTA for presumed non-infectious panuveitis. Within 2 months, she developed diffuse macular retinochoroiditis with optic disc edema. Upon starting anti-toxoplasmic therapy (ATT, her intraocular inflammation resolved with catastrophic damage to the disc and macula. Case 2: A 30-year-old male received IVTA for presumed reactivation of previously scarred toxoplasmic retinochoroiditis. Despite simultaneous ATT, within 6 weeks, he developed extensive, multifocal macular retinochoroiditis. He continued to require ATT for 18 months and later underwent vitrectomy with silicone oil placement for severe epiretinal proliferation. Aqueous tap polymerase chain reactions were found positive for Toxoplasma gondii in both cases. In conclusion, IVTA administration can lead to fulminant toxoplasmic retinochoroiditis even when used with appropriate ATT. Extreme caution should be exercised while administering depot corticosteroids in eyes with panuveitis of unknown origin.

  5. Scleral melt following Retisert intravitreal fluocinolone implant

    Directory of Open Access Journals (Sweden)

    Georgalas I

    2014-11-01

    Full Text Available Ilias Georgalas,1 Chrysanthi Koutsandrea,1 Dimitrios Papaconstantinou,1 Dimitrios Mpouritis,1 Petros Petrou1,2 1Ophthalmology Department, University of Athens, Athens, Greece; 2Moorfields Eye Hospital, London, UKAbstract: Intravitreal fluocinolone acetonide implant (Retisert has a high potency, a low solubility, and a very short duration of action in the systemic circulation, enabling the steroid pellet to be small and reducing the risk of systemic side effects. Scleral melt has not been reported as a possible complication of Retisert implant. The authors describe the occurrence of scleral melt 18 months after the implantation of fluocinolone acetonide implant in a 42-year-old Caucasian woman. To the authors’ knowledge, this is the first report of this possible complication.Keywords: Retisert, scleral melt, complication, surgical management

  6. Dexamethasone intravitreal implant in the treatment of diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Dugel PU

    2015-07-01

    Full Text Available Pravin U Dugel,1,2 Francesco Bandello,3 Anat Loewenstein4 1Retinal Consultants of Arizona, Phoenix, AZ, 2Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 3Department of Ophthalmology, University Vita-Salute Scientific Institute San Raffaele, Milan, Italy; 4Department of Ophthalmology, Tel Aviv Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Abstract: Diabetic macular edema (DME resembles a chronic, low-grade inflammatory reaction, and is characterized by blood–retinal barrier (BRB breakdown and retinal capillary leakage. Corticosteroids are of therapeutic benefit because of their anti-inflammatory, antiangiogenic, and BRB-stabilizing properties. Delivery modes include periocular and intravitreal (via pars plana injection. To offset the short intravitreal half-life of corticosteroid solutions (~3 hours and the need for frequent intravitreal injections, sustained-release intravitreal corticosteroid implants have been developed. Dexamethasone intravitreal implant provides retinal drug delivery for ≤6 months and recently has been approved for use in the treatment of DME. Pooled findings (n=1,048 from two large-scale, randomized Phase III trials indicated that dexamethasone intravitreal implant (0.35 mg and 0.7 mg administered at ≥6-month intervals produced sustained improvements in best-corrected visual acuity (BCVA and macular edema. Significantly more patients showed a ≥15-letter gain in BCVA at 3 years with dexamethasone intravitreal implant 0.35 mg and 0.7 mg than with sham injection (18.4% and 22.2% vs 12.0%. Anatomical assessments showed rapid and sustained reductions in macular edema and slowing of retinopathy progression. Phase II study findings suggest that dexamethasone intravitreal implant is effective in focal, cystoid, and diffuse DME, in vitrectomized eyes, and in combination with laser therapy. Ocular complications of

  7. Irinotecan and bevacizumab in recurrent glioblastoma multiforme

    DEFF Research Database (Denmark)

    Jakobsen, Jan Nyrop; Hasselbalch, Benedikte; Stockhausen, Marie-Thérése

    2011-01-01

    INTRODUCTION: Glioblastoma multiforme (GBM) is the most common high grade primary brain tumor in adults. Despite significant advances in treatment, the prognosis remains poor. Bevacizumab (BVZ) and irinotecan (CPT-11) are currently being investigated in the treatment of GBM patients. Although...

  8. Comparison of Bevacizumab, Ranibizumab, and Laser Photocoagulation in the Treatment of Retinopathy of Prematurity in Turkey.

    Science.gov (United States)

    Gunay, Murat; Sukgen, Emine Alyamac; Celik, Gokhan; Kocluk, Yusuf

    2017-03-01

    To evaluate the efficacies and treatment outcomes following intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR), and laser photocoagulation (LPC) in retinopathy of prematurity (ROP). This was a retrospective interventional case series study including the data of 134 infants (264 eyes) who were treated with IVB, IVR, or LPC for ROP. The data were collected from two major ROP treatment centers in Turkey without any randomization or masking. Regression of ROP, recurrence profile, complications after each treatment modality, and indications for retreatment were evaluated. The main outcome measures included the total inactivation of ROP with anatomic and refractive outcomes at 1.5 years of adjusted age. There were 55 infants (41.1%) in the IVB group, 22 infants (16.4%) in the IVR group, and 57 infants (42.5%) in the LPC group. All but 3 infants (5.5%) in the IVB group and 11 infants (50%) in the IVR group showed recurrence to stage 1 and 2 ROP following IVB and IVR (p < 0.001). Retreatment was performed in three infants in both IVB and IVR groups (p = 0.098). At 1.5 years of adjusted age, all infants showed favorable anatomic outcome except one infant in the LPC group. No significant difference of the mean spherical equivalent (SE) was observed between the groups (p = 0.131). In Zone I ROP, laser treated infants had significantly higher rates of myopia and high myopia than IVB and IVR treated infants (p = 0.040 and p = 0.019, respectively). Both IVB and IVR treated infants had significantly better refractive outcomes in Zone I ROP as compared to LPC treated infants at 1.5 years of adjusted age. The higher rate of disease recurrence was associated with IVR. Gestational age (GA) and the zone of ROP were also predictive factors for recurrence of ROP in the study.

  9. Bevacizumab-Related Microvascular Angina and Its Management with Nicorandil.

    Science.gov (United States)

    Katoh, Manami; Takeda, Norihiko; Arimoto, Takahide; Abe, Hajime; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki; Komuro, Issei

    2017-10-21

    Bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF)-A, is currently used to treat patients with ovarian or colon cancer. While several cardiovascular toxicities related to bevacizumab-containing regimens have been reported, the effect of bevacizumab on the coronary microcirculation has not been fully elucidated. Here we report a case of 54-year-old female patient who developed microvascular angina after a series of bevacizumab-containing chemotherapeutic regimen. The discontinuation of bevacizumab and nicorandil administration was effective in alleviating her chest discomfort and the ischemic changes on her ECG. This highlights the possibility that coronary microvascular angina can be induced in patients treated with bevacizumab-containing chemotherapy. It should also be noted that nicorandil can be effective in managing microvascular angina.

  10. Reversible posterior leukoencephalopathy syndrome in a child treated with bevacizumab.

    Science.gov (United States)

    Levy, Carolyn Fein; Oo, Khine Zin; Fireman, Fernando; Pierre, Louisdon; Bania, Marita A; Sadanandan, Swayamprabha; Yamashiro, Darrell J; Glade Bender, Julia L

    2009-05-01

    Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF). Hypertension is a well-recognized, common side effect of VEGF blocking agents. The reversible posterior leukoencephalopathy syndrome (RPLS) has been described as a rare but serious consequence of bevacizumab administration. We present a case of a 6-year-old child with refractory hepatoblastoma who developed hypertensive crisis, seizures and MRI changes consistent with RPLS while receiving bevacizumab with gemcitabine and oxaliplatin. Findings completely resolved without neurologic sequelae with stringent blood-pressure control. Better understanding of risk for RPLS, prompt recognition and aggressive management will be required as bevacizumab gains wider use in pediatrics. (c) 2008 Wiley-Liss, Inc.

  11. Intravitreal NGF administration counteracts retina degeneration after permanent carotid artery occlusion in rat

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    De Sordi Nadia

    2009-05-01

    Full Text Available Abstract Background The neurotrophin nerve growth factor (NGF is produced by different cell types in the anterior and posterior eye, exerting a neuroprotective role in the adult life. The visual system is highly sensitive to NGF and the retina and optic nerve provides suitable subjects for the study of central nervous system degeneration. The model of bilateral carotid occlusion (two-vessel occlusion, 2VO is a well-established model for chronic brain hypoperfusion leading to brain capillary pathology, to retina and optic nerve degeneration. In order to study if a single intravitreal injection of NGF protects the retina and the optic nerve from degeneration during systemic circulatory diseases, we investigated morphological and molecular changes occurring in the retina and optic nerve of adult rats at different time-points (8, 30 and 75 days after bilateral carotid occlusion. Results We demonstrated that a single intravitreal injection of NGF (5 μg/3 μl performed 24 hours after 2VO ligation has a long-lasting protective effect on retina and optic nerve degeneration. NGF counteracts retinal ganglion cells degeneration by early affecting Bax/Bcl-2 balance- and c-jun- expression (at 8 days after 2VO. A single intravitreal NGF injection regulates the demyelination/remyelination balance after ischemic injury in the optic nerve toward remyelination (at 75 days after 2VO, as indicated by the MBP expression regulation, thus preventing optic nerve atrophy and ganglion cells degeneration. At 8 days, NGF does not modify 2VO-induced alteration in VEFG and related receptors mRNA expression. Conclusion The protective effect of exogenous NGF during this systemic circulatory disease seems to occur also by strengthening the effect of endogenous NGF, the synthesis of which is increased by vascular defect and also by the mechanical lesion associated with NGF or even vehicle intraocular delivery.

  12. Grid laser with modified pro re nata injection of bevacizumab and ranibizumab in macular edema due to branch retinal vein occlusion: MARVEL report no 2.

    Science.gov (United States)

    Narayanan, Raja; Panchal, Bhavik; Stewart, Michael W; Das, Taraprasad; Chhablani, Jay; Jalali, Subhadra; Hasnat Ali, Mohd

    2016-01-01

    The purpose of this study was to prospectively study the efficacy of grid laser combined with intravitreal bevacizumab or ranibizumab in eyes with macular edema due to branch retinal vein occlusion. Treatment-naïve eyes were enrolled to receive injections of ranibizumab or bevacizumab. During the first 6 months, patients were evaluated monthly and injected if the best-corrected visual acuity changed by five or more letters or fluid was noted on spectral domain optical coherence tomography (OCT); during the next 6 months, patients were evaluated bimonthly and injected only if the best-corrected visual acuity decreased by five or more letters with the associated fluid. Grid laser photocoagulation was performed if there was fluid on OCT and was repeated if patients were eligible after a minimum interval of 3 months. The mean numbers of ranibizumab and bevacizumab injections were, respectively, 3.2±1.5 and 3.0±1.4 in the first 6 months and 0.3±0.6 and 0.3±0.6 in the last 6 months. Moreover, 55/75 (73.33%) participants did not receive any injections in the last 6 months. The mean reductions in central retinal thickness at 12 months were 165.67 μm (P<0.001; 95% confidence interval -221.50 to -135.0) in the ranibizumab group and 184.78 μm (P<0.001; 95% confidence interval -246.49 to -140.0) in the bevacizumab group (P=0.079). More patients in the bevacizumab group compared to those in the ranibizumab group required rescue laser at 12 months (20 vs eleven; P=0.06). Bimonthly evaluations after month 6 with very few pro re nata injections were effective in maintaining visual gains achieved during the first 6 months. Grid laser photocoagulation is effective in maintaining the vision even in the presence of fluid on OCT, although it's required more often in patients treated with bevacizumab.

  13. Bevacizumab-Induced Reversible Thrombocytopenia in a Patient with Adenocarcinoma of Colon: Rare Adverse Effect of Bevacizumab

    Directory of Open Access Journals (Sweden)

    Jeevan Kumar

    2012-01-01

    Full Text Available We report a case of bevacizumab- (BEV- induced thrombocytopenia in a 59-year-old man with adenocarcinoma of colon. After colectomy, the patient was treated with twelve cycles of FOLFOX-4 (folinic acid, 5-fluorouracil, and oxaliplatin regimen. On relapse, he was treated with FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan regimen along with BEV 10 mg/kg for 6 cycles. After that, BEV was continued for maintenance as a single agent at an interval of three weeks. After the13th cycle of BEV, the patient developed melena with epistaxis and thrombocytopenia, from which he recovered on withdrawal of BEV. On rechallenge with half the initial dose, there was once again a reversible drop in platelet count. The proposed mechanism of thrombocytopenia may be immune-mediated peripheral destruction of platelets.

  14. Evaluation of toxicity after periocular and intravitreal administration of carboplatin in rabbit eyes

    Directory of Open Access Journals (Sweden)

    Denisa Darsová

    2011-01-01

    Full Text Available The aim of this study was to characterize the extent of toxicity of focal carboplatin administration and to identify the dose limiting toxicity in rabbit eyes depending on administered concentrations. New Zealand white male rabbits (n = 18 were treated with 1 of 3 regimens: a single periocular injection of 15 mg of carboplatin (group I, a single periocular injection of 30 mg of carboplatin (group II and a single transcorneal intravitreal injection of 0.05 mg of carboplatin (group III. Ophthalmologic examinations and vitreous samplings were performed under dissociative anaesthesia at regular intervals during next 2 (groups I and III or 3 (group II weeks. Carboplatin concentrations in vitreous samples were assessed by atomic absorption spectroscopy. At the end of experiments, all rabbit eyes were obtained for histopathologic examination. Clinical and histological evidence of toxicity was graded into four grades according to anatomical structures of the rabbit eye. The dose limiting toxicity was reached in group II after periocular injection of 30 mg of carboplatin and in group III after intravitreal injection of 0.05 mg of carboplatin. No systemic toxicity was observed in any group. Focal carboplatin administration may decrease systemic exposure to this cytotoxic drug in the retinoblastoma treatment. This moreover suggests that focal carboplatin administration is a promising approach and challenge for advanced retinoblastoma chemotherapy.

  15. A phase 3 trial of bevacizumab in ovarian cancer

    DEFF Research Database (Denmark)

    Perren, Timothy J; Swart, Ann Marie; Pfisterer, Jacobus

    2011-01-01

    Angiogenesis plays a role in the biology of ovarian cancer. We examined the effect of bevacizumab, the vascular endothelial growth factor inhibitor, on survival in women with this disease.......Angiogenesis plays a role in the biology of ovarian cancer. We examined the effect of bevacizumab, the vascular endothelial growth factor inhibitor, on survival in women with this disease....

  16. Prefilled syringes for intravitreal injection reduce preparation time

    DEFF Research Database (Denmark)

    Subhi, Yousif; Kjer, Birgit; Munch, Inger Christine

    2016-01-01

    INTRODUCTION: The demand for intravitreal therapy has increased dramatically with the introduction of vascular endo-thelial growth factor inhibitors. Improved utilisation of existing resources is crucial to meeting the increased future demand. We investigated time spent preparing intravitreal...... injection treatment using either prefilled syringes or vials in routine clinical practice. METHODS: We video-recorded preparations of intravitreal injections (n = 172) for each preparation type (ranibizumab prefilled syringe (n = 56), ranibizumab vial (n = 56) and aflibercept vial (n = 60)) in a multi......-centre time and motion study. The preparation times for each step were extracted from videos and the three preparation types were compared. RESULTS: Prefilled syringes eliminated several steps in the preparation process. Total preparation time was 40.3-45.1 sec. using vials, and the use of prefilled syringes...

  17. [Corneal neovascularisation treatments compared: Subconjunctival bevacizumab injections and/or photodynamic therapy].

    Science.gov (United States)

    Hamdan, J; Boulze, M; Aziz, A; Alessi, G; Hoffart, L

    2015-12-01

    To evaluate and compare the efficacy of subconjunctival bevacizumab injections alone, photodynamic therapy alone and combined treatments for reduction of corneal neovascularization. This study was conducted as a prospective case series. A total of seven eyes of 7 patients with corneal neovascularization caused by ocular surface disorders including fungal infectious keratitis and penetrating keratoplasty were included in the study. Patients were randomized into the three following groups: patients in group A received a single subconjunctival injection of 10mg (0.4mL) of bevacizumab, patients in group B were treated with photodynamic therapy with verteporfin (6mg/m(2)) to the neovascularized area and those in group C received a subconjunctival injection of bevacizumab and photodynamic therapy 7 days later. Morphological changes in neovascularization were evaluated over 6 months using slit-lamp biomicroscopy and digital corneal photography. A computer-assisted semi-automatic analysis of the area of corneal neovascularization was performed with Image J software. Recession of corneal vessels was observed in all eyes at 1 month post-treatment. The neovascularized surface area in all groups combined showed a decrease in the first month after treatment and this decrease continued up to the 6th month. The surface area of corneal neovascularization decreased by 34.05±8.28% in group A (subconjunctival injection of bevacizumab), by 42.06±28.36% in group B (photodynamic therapy with verteporfin) and by 51.67±18.93% in group C (combined subconjunctival injection of bevacizumab and photodynamic therapy). A combined treatment consisting of a subconjunctival injection followed by a PDT session 7 days later might be more effective for the treatment of corneal neovascularisation. No serious local or systemic adverse events were observed. Our medium-term results suggest that combined subconjunctival injection of bevacizumab and photodynamic therapy with verteporfin might be used

  18. Reirradiation with concurrent bevacizumab for recurrent high-grade gliomas in adult patients.

    Science.gov (United States)

    Schernberg, A; Dhermain, F; Ammari, S; Dumont, S N; Domont, J; Patrikidou, A; Pallud, J; Dezamis, É; Deutsch, É; Louvel, G

    2018-02-01

    To analyse feasibility, prognostic factors and patterns of recurrence after concurrent reirradiation and bevacizumab for recurrent high-grade gliomas. Between 2009 and 2015, 35 patients (median 57-year-old; 21 men, 14 women) with WHO grade III (n=11) or grade IV (n=24) gliomas were included in this retrospective and consecutive single-centre study. All patients received bevacizumab (median number of treatments: 12) concomitant with reirradiation (median dose: 45Gy, median number of fractions: 18) for recurrence with median 22 months (range: 5.6-123.7 months) from first irradiation (median dose: 60Gy). The median follow-up was 9.2 months from reirradiation. The median overall survival from reirradiation was 10.5 months (95% confidence interval [95% CI]: 4.9-16.1) and the progression-free survival from reirradiation was 6.7 months (95% CI: 2.9-10.5). The median overall survival from initial diagnosis was 44.6 months (95% CI: 32-57.1). No grade 3 toxicity or above was reported. Prognostic factors significantly correlated with better overall survival in univariate analysis were: age at least 55 (P=0.024), initial surgery (P=0.003), and 2Gy equivalent dose (EQD2) at least 50Gy at reirradiation (P=0.046). Twenty-two patients bevacizumab-naïve at time of reirradiation had a significantly increased overall survival from reirradiation compared to patients treated with reirradiation after bevacizumab failure (17.7 vs. 5.4 months, P0.05). Concomitant reirradiation with bevacizumab in high-grade recurrent gliomas shows encouraging results in terms of survival and toxicities. Our data suggest that reirradiation should be favoured at initiation of bevacizumab, with EQD2 at least 50Gy. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  19. Periodontal disease in a patient receiving Bevacizumab: a case report

    Directory of Open Access Journals (Sweden)

    Gujral Dorothy M

    2008-02-01

    Full Text Available Abstract Introduction Bevacizumab is a monoclonal antibody that inhibits the action of vascular endothelial growth factor (VEGF thereby acting as an angiogenesis inhibitor. As a result, supply of oxygen and nutrients to tissues is impaired and tumour cell growth is reduced. Reported side effects due to bevacizumab are hypertension and increased risk of bleeding. Bowel perforation has also been reported. Periodontal disease in patients on bevacizumab therapy has not been reported before. Case Presentation We report a case of a forty-three year old woman who developed periodontitis whilst receiving bevacizumab for lung cancer. The periodontal disease remained stable on discontinuation of the drug. Conclusion Further investigations are needed to determine the mechanism for bevacizumab-induced periodontal disease.

  20. Management of noninfectious posterior uveitis with intravitreal drug therapy

    Directory of Open Access Journals (Sweden)

    Tan HY

    2016-10-01

    Full Text Available Hui Yi Tan,1 Aniruddha Agarwal,2 Cecilia S Lee,3 Jay Chhablani,4 Vishali Gupta,5 Manoj Khatri,6 Jayabalan Nirmal,7 Carlos Pavesio,8 Rupesh Agrawal1,7–9 1Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Department of Vitreoretina, Stanley M Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, 3Department of Ophthalmology, University of Washington, Seattle, WA, USA; 4Department of Vitreoretina, L V Prasad Eye Institute, Hyderabad, Telangana, 5Department of Retina and Uvea, Post Graduate Institute of Medical Education and Research, Chandigarh, 6Department of Retina, Rajan Eye Care Hospital, Chennai, Tamil Nadu, India; 7School of Material Science and Engineering, Nanyang Technological University, Singapore; 8Department of Medical Retina, Moorfields Eye Hospital, NHS Foundation Trust, London, UK; 9Department of Ophthalmology, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore Abstract: Uveitis is an important cause of vision loss worldwide due to its sight-threatening complications, especially cystoid macular edema, as well as choroidal neovascularization, macular ischemia, cataract, and glaucoma. Systemic corticosteroids are the mainstay of therapy for noninfectious posterior uveitis; however, various systemic side effects can occur. Intravitreal medication achieves a therapeutic level in the vitreous while minimizing systemic complications and is thus used as an exciting alternative. Corticosteroids, antivascular endothelial growth factors, immunomodulators such as methotrexate and sirolimus, and nonsteroidal anti-inflammatory drugs are currently available for intravitreal therapy. This article reviews the existing literature for efficacy and safety of these various options for intravitreal drug therapy for the management of noninfectious uveitis (mainly intermediate, posterior, and panuveitis. Keywords: intravitreal therapy, noninfectious uveitis, posterior uveitis

  1. Bevacizumab targeting diffuse intrinsic pontine glioma : Results of 89Zr-bevacizumab PET imaging in brain tumor models

    NARCIS (Netherlands)

    Jansen, Marc H A; Lagerweij, Tonny; Sewing, A. Charlotte P; Vugts, Danielle J.; Van Vuurden, Dannis G.; Molthoff, Carla F M; Caretti, Viola; Veringa, Susanna J E; Petersen, Naomi; Carcaboso, Angel M.; Noske, David P.; Vandertop, W. Peter; Wesseling, Pieter; Van Dongen, Guus A M S; Kaspers, Gertjan J L; Hulleman, Esther

    2016-01-01

    The role of the VEGF inhibitor bevacizumab in the treatment of diffuse intrinsic pontine glioma (DIPG) is unclear. We aim to study the biodistribution and uptake of zirconium-89 (89Zr)-labeled bevacizumab in DIPG mouse models. Human E98-FM, U251-FM glioma cells, and HSJD-DIPG-007-FLUC primary DIPG

  2. Bevacizumab Targeting Diffuse Intrinsic Pontine Glioma: Results of 89Zr-Bevacizumab PET Imaging in Brain Tumor Models

    NARCIS (Netherlands)

    Jansen, Marc H. A.; Lagerweij, Tonny; Sewing, A. Charlotte P.; Vugts, Danielle J.; van Vuurden, Dannis G.; Molthoff, Carla F. M.; Caretti, Viola; Veringa, Susanna J. E.; Petersen, Naomi; Carcaboso, Angel M.; Noske, David P.; Vandertop, W. Peter; Wesseling, Pieter; van Dongen, Guus A. M. S.; Kaspers, Gertjan J. L.; Hulleman, Esther

    2016-01-01

    The role of the VEGF inhibitor bevacizumab in the treatment of diffuse intrinsic pontine glioma (DIPG) is unclear. We aim to study the biodistribution and uptake of zirconium-89 ((89)Zr)-labeled bevacizumab in DIPG mouse models. Human E98-FM, U251-FM glioma cells, and HSJD-DIPG-007-FLUC primary DIPG

  3. Platinum-based doublet chemotherapy plus bevacizumab without bevacizumab maintenance in advanced non-small cell lung cancer (NSCLC)

    DEFF Research Database (Denmark)

    Nørøxe, Dorte Schou; Wallerek, Sandra; Sørensen, Jens Benn

    2013-01-01

    We report on a retrospective, consecutive non-randomized group of patients who received bevacizumab plus chemotherapy without bevazicumab maintenance.......We report on a retrospective, consecutive non-randomized group of patients who received bevacizumab plus chemotherapy without bevazicumab maintenance....

  4. Safety study of 38 503 intravitreal ranibizumab injections performed mainly by physicians in training and nurses in a hospital setting

    DEFF Research Database (Denmark)

    Hasler, Pascal W; Bloch, Sara Brandi; Villumsen, Jørgen

    2015-01-01

    PURPOSE: To evaluate and to compare the safety of intravitreal ranibizumab injections performed by physicians and nurses at a single large hospital clinic in Denmark during 5 years. DESIGN: Retrospective, interventional, non-comparative study. METHODS: SETTING: All eyes that underwent...... a protocolized ranibizumab injection procedure performed in an operating room mainly by nurses and physicians in their first year of ophthalmology training. STUDY POPULATION: A total of 4623 eyes in 3679 patients with subretinal neovascularization secondary to a variety of retinal diseases, mainly neovascular...... detachment from 2007 to 2012. RESULTS: Overall, 38,503 intravitreal ranibizumab injections were performed in 4623 eyes. Injections were performed by nurses (32.5%), ophthalmology residents (61.3%) and vitreoretinal surgeons (6.2%). Severe complications to treatment were observed in 17 eyes: Endophthalmitis...

  5. Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Nyflot, Matthew J., E-mail: nyflot@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Kruser, Tim J. [Department of Radiation Oncology, Cadence Cancer Center at Delnor Hospital, Geneva, Illinois (United States); Traynor, Anne M. [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Khuntia, Deepak [Varian Medical Systems, Palo Alto, California (United States); Yang, David T. [Departments of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hartig, Gregory K.; McCulloch, Timothy M. [Department of Surgery-Otolaryngology, H& N Surgery Division, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Wiederholt, Peggy A. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Gentry, Lindell R. [Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hoang, Tien [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Jeraj, Robert [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Medical Physics, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); and others

    2015-04-01

    Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m{sup 2} and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [{sup 18}F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [{sup 61}Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging

  6. Neoadjuvant bevacizumab and irinotecan versus bevacizumab and temozolomide followed by concomitant chemoradiotherapy in newly diagnosed glioblastoma multiforme

    DEFF Research Database (Denmark)

    Hofland, Kenneth F; Hansen, Steinbjørn; Sorensen, Morten

    2014-01-01

    BACKGROUND: Surgery followed by radiotherapy and concomitant and adjuvant temozolomide is standard therapy in newly diagnosed glioblastoma multiforme (GBM). Bevacizumab combined with irinotecan produces impressive response rates in recurrent GBM. In a randomized phase II study, we investigated...... the efficacy of neoadjuvant bevacizumab combined with irinotecan (Bev-Iri) versus bevacizumab combined with temozolomide (Bev-Tem) before, during and after radiotherapy in newly diagnosed GBM. MATERIAL AND METHODS: After surgery, patients were randomized to Bev-Iri or Bev-Tem for eight weeks, followed...... by standard radiotherapy (60 Gy/30 fractions) and concomitant Bev-Iri or Bev-Tem followed by adjuvant Bev-Iri or Bev-Tem for another eight weeks. Bev-Iri: Bevacizumab and irinotecan were given every 14 days before, during and after radiotherapy. Bev-Tem: Bevacizumab was given as in Bev-Iri and temozolomide...

  7. Bevacizumab and osteonecrosis of the jaw: incidence and association with bisphosphonate therapy in three large prospective trials in advanced breast cancer.

    Science.gov (United States)

    Guarneri, Valentina; Miles, David; Robert, Nicholas; Diéras, Véronique; Glaspy, John; Smith, Ian; Thomssen, Christoph; Biganzoli, Laura; Taran, Tanya; Conte, PierFranco

    2010-07-01

    Long-term bisphosphonate therapy is associated with increased risk of osteonecrosis of the jaw (ONJ). In a retrospective analysis, a 16% ONJ incidence was reported in patients receiving bisphosphonates with anti-angiogenic therapy (bevacizumab or sunitinib) for bone metastases from breast, colon, or renal cell cancers. To assess ONJ incidence with bevacizumab, we analysed data from 3,560 patients receiving bevacizumab-containing therapy for locally recurrent or metastatic breast cancer (LR/MBC) in two double-blind, randomised trials (AVADO and RIBBON-1) and a large, non-randomised safety study (ATHENA). The overall incidence of ONJ with bevacizumab was 0.3% in the blinded phase of the two randomised trials and 0.4% in the single-arm study. There was a trend towards increased ONJ incidence in patients who received bisphosphonate therapy versus those with no bisphosphonate exposure (0.9 vs. 0.2%, respectively, in the pooled analysis of the randomised trials; 2.4 vs. 0%, respectively, in ATHENA). In conclusion, this is the largest analysis of ONJ in patients receiving bevacizumab for LR/MBC. The 0.3-0.4% incidence is considerably lower than previously suggested with anti-angiogenic therapy in a small retrospective analysis. The risk of ONJ appeared to be increased in patients exposed to bisphosphonates, a pattern consistent with observations before the introduction of anti-angiogenic therapy to breast cancer management. The 0.9-2.4% incidence seen in bisphosphonate-exposed patients receiving bevacizumab is within the 1-6% range reported for bisphosphonates alone. Good oral hygiene, dental examination, and avoidance of invasive dental procedures remain important in patients receiving bisphosphonates, irrespective of bevacizumab administration.

  8. Bevacizumab for glioblastoma: current indications, surgical implications, and future directions

    Science.gov (United States)

    Castro, Brandyn A.; Aghi, Manish K.

    2016-01-01

    Initial enthusiasm after promising Phase II trials for treating recurrent glioblastomas with the antiangiogenic drug bevacizumab—a neutralizing antibody targeting vascular endothelial growth factor—was tempered by recent Phase III trials showing no efficacy for treating newly diagnosed glioblastomas. As a result, there is uncertainty about the appropriate indications for the use of bevacizumab in glioblastoma treatment. There are also concerns about the effects of bevacizumab on wound healing that neurosurgeons must be aware of. In addition, biochemical evidence suggests a percentage of tumors treated with bevacizumab for an extended period of time will undergo transformation into a more biologically aggressive and invasive phenotype with a particularly poor prognosis. Despite these concerns, there remain numerous examples of radiological and clinical improvement after bevacizumab treatment, particularly in patients with recurrent glioblastoma with limited therapeutic options. In this paper, the authors review clinical results with bevacizumab for glioblastoma treatment to date, ongoing trials designed to address unanswered questions, current clinical indications based on existing data, neurosurgical implications of bevacizumab use in patients with glioblastoma, the current scientific understanding of the tumor response to short- and long-term bevacizumab treatment, and future studies that will need to be undertaken to enable this treatment to fulfill its therapeutic promise for glioblastoma. PMID:25581938

  9. Rothia dentocariosa endophthalmitis following intravitreal injection-a case report.

    Science.gov (United States)

    Hayes, R A; Bennett, H Y; O'Hagan, S

    2017-12-16

    This report describes the first recognised case of Rothia dentocariosa endophthalmitis following intravitreal injection. A 57-year-old indigenous Australian diabetic female developed pain, redness and decreased vision 3 days after intravitreal aflibercept injection to the right eye-administered for diabetic vitreous haemorrhage with suspected macular oedema and proliferative diabetic retinopathy. Examination revealed best corrected visual acuity (BCVA) of hand movements, ocular hypertension and marked anterior chamber inflammation. The left eye was unaffected but had a BCVA of 6/24 due to pre-existing diabetic retinopathy. Vitreous culture isolated Rothia dentocariosa as the organism responsible for the endophthalmitis. The following treatment with intraocular cephazolin, vancomycin and ceftazidime, topical ciprofloxacin and gentamicin and systemic ciprofloxacin, the patient underwent vitrectomy. Nine weeks after onset, the patient's BCVA had improved to 6/36, and fundal examination revealed extensive retinal necrosis. Rothia dentocariosa is presented as a rare cause of endophthalmitis following intravitreal injection and reports the appearance of 'pink hypopyon' previously observed with other organisms. Its identification also demonstrates the risk of oral bacterial contamination during intraocular injections. Vigilance with strategies to minimise bacterial contamination in the peri-injection period are important. Further research to identify additional techniques to prevent contamination with oral bacteria would be beneficial, including whether a role exists for patients wearing surgical masks during intravitreal injections.

  10. Intravitreal Triamcinolone in Posterior Segment Diseases – Method ...

    African Journals Online (AJOL)

    DR OLULEYE

    Intravitreal Triamcinolone in Posterior Segment Diseases – Method of administration. TS Oluleye, O Ajayi. 1. 2. Retina Unit, Department of Ophthalmology, University College Hospital, Ibadan. 1. Department of Ophthalmology, Obafemi Awolowo University Teaching Hospital, Ile-Ife. 2. Triamcinolone is an intermediate-acting ...

  11. A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Johnsson, Anders; Hagman, H; Frödin, J-E

    2013-01-01

    The main objective was to study the effect on progression-free survival (PFS) of adding erlotinib to bevacizumab as maintenance treatment following chemotherapy and bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC).......The main objective was to study the effect on progression-free survival (PFS) of adding erlotinib to bevacizumab as maintenance treatment following chemotherapy and bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC)....

  12. Clinical outcomes with bevacizumab-containing and non-bevacizumab?containing regimens in patients with recurrent glioblastoma from US community practices

    OpenAIRE

    Chen, Clara; Ravelo, Arliene; Yu, Elaine; Dhanda, Rahul; Schnadig, Ian

    2015-01-01

    This analysis evaluated the efficacy and safety of bevacizumab as monotherapy and with irinotecan for recurrent glioblastoma in community-based practices. Adult patients with bevacizumab-naive, recurrent glioblastoma initiating second-line treatment (July 2006?June 2010) were identified using McKesson Specialty Health/US Oncology Network health records. Overall (OS) and progression-free survival (PFS) estimates were analyzed through July 2011 and compared for bevacizumab and non-bevacizumab r...

  13. Lomustine and Bevacizumab in Progressive Glioblastoma.

    Science.gov (United States)

    Wick, Wolfgang; Gorlia, Thierry; Bendszus, Martin; Taphoorn, Martin; Sahm, Felix; Harting, Inga; Brandes, Alba A; Taal, Walter; Domont, Julien; Idbaih, Ahmed; Campone, Mario; Clement, Paul M; Stupp, Roger; Fabbro, Michel; Le Rhun, Emilie; Dubois, Francois; Weller, Michael; von Deimling, Andreas; Golfinopoulos, Vassilis; Bromberg, Jacoline C; Platten, Michael; Klein, Martin; van den Bent, Martin J

    2017-11-16

    Bevacizumab is approved for the treatment of patients with progressive glioblastoma on the basis of uncontrolled data. Data from a phase 2 trial suggested that the addition of bevacizumab to lomustine might improve overall survival as compared with monotherapies. We sought to determine whether the combination would result in longer overall survival than lomustine alone among patients at first progression of glioblastoma. We randomly assigned patients with progression after chemoradiation in a 2:1 ratio to receive lomustine plus bevacizumab (combination group, 288 patients) or lomustine alone (monotherapy group, 149 patients). The methylation status of the promoter of O 6 -methylguanine-DNA methyltransferase (MGMT) was assessed. Health-related quality of life and neurocognitive function were evaluated at baseline and every 12 weeks. The primary end point of the trial was overall survival. A total of 437 patients underwent randomization. The median number of 6-week treatment cycles was three in the combination group and one in the monotherapy group. With 329 overall survival events (75.3%), the combination therapy did not provide a survival advantage; the median overall survival was 9.1 months (95% confidence interval [CI], 8.1 to 10.1) in the combination group and 8.6 months (95% CI, 7.6 to 10.4) in the monotherapy group (hazard ratio for death, 0.95; 95% CI, 0.74 to 1.21; P=0.65). Locally assessed progression-free survival was 2.7 months longer in the combination group than in the monotherapy group: 4.2 months versus 1.5 months (hazard ratio for disease progression or death, 0.49; 95% CI, 0.39 to 0.61; Pbevacizumab to lomustine affected neither health-related quality of life nor neurocognitive function. The MGMT status was prognostic. Despite somewhat prolonged progression-free survival, treatment with lomustine plus bevacizumab did not confer a survival advantage over treatment with lomustine alone in patients with progressive glioblastoma. (Funded by an

  14. The efficacy of intravitreal antivascular endothelial growth factor as ...

    African Journals Online (AJOL)

    such as retinal vein occlusion[6] and diabetic retinopathy[7] have led to a paradigm shift in the management of these conditions. As an extension of this, anti-VEGF (bevacizumab) therapy has been used in treating ROP, initially as an adjunct to laser therapy and subsequently as primary treatment. Several case studies have ...

  15. Survey of intravitreal injection techniques among retina specialists in Israel

    Directory of Open Access Journals (Sweden)

    Segal O

    2016-06-01

    Full Text Available Ori Segal,1,2 Yael Segal-Trivitz,1,3 Arie Y Nemet,1,2 Noa Geffen,1,2 Ronit Nesher,1,2 Michael Mimouni4 1Department of Ophthalmology, Meir Medical Center, Kfar Saba, 2The Sackler School of Medicine, Tel Aviv University, Tel Aviv, 3Department of Psychiatry, Geha Psychiatric Hospital, Petah Tikva, 4Department of Ophthalmology, Rambam Health Care Campus, Haifa, Israel Purpose: The purpose of this study was to describe antivascular endothelial growth factor intravitreal injection techniques of retinal specialists in order to establish a cornerstone for future practice guidelines. Methods: All members of the Israeli Retina Society were contacted by email to complete an anonymous, 19-question, Internet-based survey regarding their intravitreal injection techniques. Results: Overall, 66% (52/79 completed the survey. Most (98% do not instruct patients to discontinue anticoagulant therapy and 92% prescribe treatment for patients in the waiting room. Three quarters wear sterile gloves and prepare the patient in the supine position. A majority (71% use sterile surgical draping. All respondents apply topical analgesics and a majority (69% measure the distance from the limbus to the injection site. A minority (21% displace the conjunctiva prior to injection. A majority of the survey participants use a 30-gauge needle and the most common quadrant for injection is superotemporal (33%. Less than half routinely assess postinjection optic nerve perfusion (44%. A majority (92% apply prophylactic antibiotics immediately after the injection. Conclusion: The majority of retina specialists perform intravitreal injections similarly. However, a relatively large minority performs this procedure differently. Due to the extremely low percentage of complications, it seems as though such differences do not increase the risk. However, more evidence-based medicine, a cornerstone for practice guidelines, is required in order to identify the intravitreal injection techniques

  16. Which dose of bevacizumab is more effective for the treatment of aggressive posterior retinopathy of prematurity: lower or higher dose?

    Directory of Open Access Journals (Sweden)

    Seyhan Dikci

    Full Text Available ABSTRACT Purpose: To compare 0.5 mg and 0.625 mg of bevacizumab for treating aggressive posterior retinopathy of prematurity (AP-ROP. Methods: The medical records of patients with AP-ROP who were administered intravitreal bevacizumab (IVB as a primary treatment at a university clinic were evaluated retrospectively. Five eyes of three patients (Group 1 who received 0.625 mg/0.025 ml IVB and 10 eyes of another five patients (Group 2 who received 0.5 mg/0.02 ml IVB were evaluated. Laser photocoagulation was used as additional treatment after relapses. Anatomic results and complications were evaluated in both groups. Results: We evaluated 15 eyes of eight patients (four girls and four boys with a flat demarcation line at posterior zone 2 and plus disease or stage-3 disease in this study. The mean gestational age of the three babies in Group 1 was 26 ± 1 weeks and the mean birth weight was 835.33 ± 48.01 g. The corresponding values were 25.2 ± 1.6 weeks and 724 ± 139.03 g, respectively, for the five babies in Group 2. Retinal vascularization was completed at a mean postmenstrual duration of 53.6 ± 1.5 weeks without additional treatment in the five eyes in Group 1. Laser photocoagulation for relapse was administered to five of the 10 eyes in Group 2. Retinal vascularization was completed at a mean postmenstrual duration of 47.6 ± 1.5 weeks in the remaining five eyes. None of the patients developed complications such as cataract, glaucoma, retinal tear, retinal or vitreous hemorrhage, or retinal detachment. Conclusion: Although lower IVB doses in the treatment of AP-ROP are expected to be safer in terms of local and systemic side effects in premature infants, these patients may require additional treatment with IVB or laser photocoagulation.

  17. Combining Chemotherapy with Bevacizumab Improves Outcomes for Ovarian Cancer Patients

    Science.gov (United States)

    Results from two phase III randomized clinical trials suggest that, at least for some patients with ovarian cancer, adding the antiangiogenesis agent bevacizumab to chemotherapy increases the time to disease progression and may improve survival.

  18. Bevacizumab improves survival for patients with advanced cervical cancer

    Science.gov (United States)

    Patients with advanced, recurrent, or persistent cervical cancer that was not curable with standard treatment who received the drug bevacizumab (Avastin) lived 3.7 months longer than patients who did not receive the drug, according to an interim analysis

  19. Practical Management of Bevacizumab-Related Toxicities in Glioblastoma

    Science.gov (United States)

    Bartolotti, Marco; Tosoni, Alicia; Poggi, Rosalba; Franceschi, Enrico

    2015-01-01

    Bevacizumab, currently an option for treatment of different types of tumors including glioblastoma, has a peculiar toxicity profile related to its antiangiogenic effect. Because some bevacizumab-related adverse events can be life threatening, it is important to identify risk factors and to establish treatment protocols to minimize treatment-related morbidity and mortality. In glioblastoma patients, the risk of developing certain side effects, such as gastrointestinal perforation, venous thromboembolism, and intracranial hemorrhages, is slightly higher than in patients treated with bevacizumab for other tumor types. We performed a systematic review of the side effects of bevacizumab and their incidence, causal mechanisms, and available treatments. Finally, we identified risk factors and proposed preventive and therapeutic measures for these adverse events. PMID:25568148

  20. A systematic review of bevacizumab efficacy in breast cancer

    DEFF Research Database (Denmark)

    Kümler, Iben; Christiansen, Ole Grummedal; Nielsen, Dorte Lisbet

    2014-01-01

    UNLABELLED: Angiogenesis is a key component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for the treatment of cancer. We systematically describe phase II and III clinical trials of bevacizumab for the treatment of breast cancer. METHODS......: A computer-based literature search was carried out using PUBMED and conference databases. Original phase II and III studies reporting ≥15 patients who received bevacizumab were included. RESULTS: 41 phase II trials were identified in the metastatic setting. Most trials found bevacizumab treatment feasible...... increased response rates in both the metastatic and neoadjuvant setting, bevacizumab has failed to show any OS benefit. Future trials should include identification of robust predictive biomarkers in order to improve our understanding of molecular biomarkers and mechanisms....

  1. Trials of bevacizumab in breast cancer - a safety review

    DEFF Research Database (Denmark)

    Kümler, Iben; Nielsen, Dorte Lisbet

    2012-01-01

    enables the reader to overview current knowledge on the efficacy and safety of bevacizumab in breast cancer. Expert opinion: Insight into complex risk-benefit calculations for bevacizumab is missing. In unselected patients with HER2-negative metastatic breast cancer, the risk of serious side effects......Introduction: Despite the significant gains in the treatment of breast cancer over the last decade, further improvements in survival using traditional chemotherapeutic agents have begun to plateau. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, has provided promise...... for continued gains in therapy efficacy. Areas covered: The authors review Phase III data concerning the safety of bevacizumab in breast cancer, summarize data on efficacy and discuss the risk:benefit ratio of the drug. The data for this review were obtained by searching in the PubMed database. This review...

  2. Tumor Microvessel Density as a Potential Predictive Marker for Bevacizumab Benefit: GOG-0218 Biomarker Analyses.

    Science.gov (United States)

    Bais, Carlos; Mueller, Barbara; Brady, Mark F; Mannel, Robert S; Burger, Robert A; Wei, Wei; Marien, Koen M; Kockx, Mark M; Husain, Amreen; Birrer, Michael J

    2017-11-01

    Combining bevacizumab with frontline chemotherapy statistically significantly improved progression-free survival (PFS) but not overall survival (OS) in the phase III GOG-0218 trial. Evaluation of candidate biomarkers was an exploratory objective. Patients with stage III (incompletely resected) or IV ovarian cancer were randomly assigned to receive six chemotherapy cycles with placebo or bevacizumab followed by single-agent placebo or bevacizumab. Five candidate tumor biomarkers were assessed by immunohistochemistry. The biomarker-evaluable population was categorized into high or low biomarker-expressing subgroups using median and quartile cutoffs. Associations between biomarker expression and efficacy were analyzed. All statistical tests were two-sided. The biomarker-evaluable population (n = 980) comprising 78.5% of the intent-to-treat population had representative baseline characteristics and efficacy outcomes. Neither prognostic nor predictive associations were seen for vascular endothelial growth factor (VEGF) receptor-2, neuropilin-1, or MET. Higher microvessel density (MVD; measured by CD31) showed predictive value for PFS (hazard ratio [HR] for bevacizumab vs placebo = 0.40, 95% confidence interval [CI] = 0.29 to 0.54, vs 0.80, 95% CI = 0.59 to 1.07, for high vs low MVD, respectively, P interaction = .003) and OS (HR = 0.67, 95% CI = 0.51 to 0.88, vs 1.10, 95% CI = 0.84 to 1.44, P interaction = .02). Tumor VEGF-A was not predictive for PFS but showed potential predictive value for OS using a third-quartile cutoff for high VEGF-A expression. These retrospective tumor biomarker analyses suggest a positive association between density of vascular endothelial cells (the predominant cell type expressing VEGF receptors) and tumor VEGF-A levels and magnitude of bevacizumab effect in ovarian cancer. The potential predictive value of MVD (CD31) and tumor VEGF-A is consistent with a mechanism of action driven by VEGF-A signaling blockade. © The

  3. Systemic bevacizumab for recurrent respiratory papillomatosis: A national survey.

    Science.gov (United States)

    Best, Simon R; Mohr, Michael; Zur, Karen B

    2017-10-01

    Aggressive laryngeal, tracheal, and pulmonary papilloma is an extremely challenging clinical problem without proven treatment options. A recent German report documented promising results with systemic bevacizumab. The objective of this study is to report the initial experience of this novel treatment in the United States for recurrent respiratory papillomatosis (RRP). Cases series. Electronic survey of the RRP Task Force of the American Society of Pediatric Otolaryngology, American Broncho-Esophagological Association, and physicians known to the authors to have used systemic bevacizumab for RRP. Eleven completed surveys were obtained. In three cases, systemic bevacizumab was considered clinically but not administered. Eight patients were treated with systemic bevacizumab, all for aggressive papillomatosis uncontrolled by surgical and adjuvant therapy, including seven of eight with pulmonary disease. Treatment dosing ranged from 5 to 10 mg/kg every 2 to 4 weeks, with all patients responding (7/8 partial response, 1/8 complete response). In four patients who had postbevacizumab chest imaging, three demonstrated improvement of disease and one stabilization. Treatment interval could be lengthened in seven patients and clinical response maintained. One patient with long-standing pulmonary disease (>10 years) was diagnosed with malignant transformation while on treatment, and bevacizumab was discontinued in lieu of other chemotherapeutic agents. All other patients continue on systemic bevacizumab with minimal complications (hemoptysis n = 1, proteinuria n = 1). Systemic bevacizumab appears to have significant promise in the most treatment-resistant and aggressive forms of papillomatosis with a low complication profile. These results suggest bevacizumab should be studied in a formal clinical trial for RRP. 4. Laryngoscope, 127:2225-2229, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  4. Bevacizumab safety in Japanese patients with colorectal cancer.

    Science.gov (United States)

    Hatake, Kiyohiko; Doi, Toshihiko; Uetake, Hiroyuki; Takahashi, Yoichiro; Ishihara, Yumi; Shirao, Kuniaki

    2016-03-01

    Bevacizumab (Avastin(®)) was approved in Japan in April 2007 for patients with advanced or metastatic colorectal cancer. To address the limited clinical experience in Japanese patients, a post-approval surveillance study was undertaken in bevacizumab-treated patients in Japan. Bevacizumab (5 or 10 mg/kg every 2 weeks) was administered with chemotherapy; patients were observed for 26 weeks from initiation of treatment. The primary objective was to investigate the incidence of adverse drug reactions, particularly those of interest for bevacizumab. Univariate and multivariate analyses were performed to identify potential risk factors for adverse drug reactions. In total, 2712 patients were registered and 2696 patients were included in the safety analysis. Hypertension (13.1%), hemorrhage (10.5%) and proteinuria (4.5%) were the most common adverse drug reaction. The incidences of serious adverse drug reactions were low: gastrointestinal perforation occurred in 0.9% of patients, hemorrhage in 1.3%, arterial thromboembolic events in 0.3%, venous thromboembolic events in 1.3% and wound-healing complications in 0.4%. The incidence of bevacizumab-specific adverse drug reactions was not influenced by the bevacizumab dose. Multivariate analyses identified risk factors for the following adverse drug reactions: hypertension (prior/concurrent hypertension); tumor-associated bleeding (performance status, prior/concomitant anticoagulant or nonsteroidal anti-inflammatory drug use); proteinuria (sex, performance status, prior/concurrent diabetes and proteinuria); gastrointestinal perforation (primary tumor in situ, concurrent nonsteroidal anti-inflammatory drug use); venous thromboembolic event (treatment stage, port insertion). The safety profile of bevacizumab-containing regimens in this Japanese population was comparable with studies performed in Western countries. Bevacizumab is generally well tolerated in Japanese patients with advanced or metastatic colorectal cancer. © The

  5. Dexamethasone Intravitreal Implant for Diabetic Macular Edema During Pregnancy

    DEFF Research Database (Denmark)

    Concillado, Michael; Lund-Andersen, Henrik; Mathiesen, Elisabeth R

    2016-01-01

    PURPOSE: To describe the management of diabetic macular edema during pregnancy with the use of a dexamethasone slow-release intravitreal implant. DESIGN: Retrospective, observational, consecutive case series. METHODS: The study included 5 pregnant women who presented with diabetic macular edema...... during pregnancy in the period from 2011 to 2014. Review of charts and photographs comprised best-corrected visual acuity (BCVA), foveal center field thickness assessed by optical coherence tomography, blood pressure, glycated hemoglobin, medications, and changes in such parameters after implant...... injection. RESULTS: Diabetic macular edema involving the foveal center was observed between gestational weeks 9 and 23 in 10 eyes of 5 patients. Dexamethasone intravitreal implant injection was given 10 times in 9 eyes with a mean preinjection center field retinal thickness of 535 μm (range, 239-727 μm...

  6. Repeat Intravitreal Dexamethasone Implant for Refractory Cystoid Macular Edema in Syphilitic Uveitis

    Directory of Open Access Journals (Sweden)

    Cassandra C. Lautredou

    2018-01-01

    Full Text Available Purpose. To report the successful utilization of adjunctive repeat intravitreal corticosteroid therapy for the treatment of cystoid macular edema in syphilis-related uveitis. Methods/Patients. An HIV-positive patient with treated ocular syphilis who developed refractory cystoid macular edema (CME was treated with repeat intravitreal corticosteroid therapy including dexamethasone intravitreal implants. Results. Treatment led to the resolution of CME and improvement in visual acuity. Conclusions. Intravitreal corticosteroid therapy may be a viable adjunctive treatment for refractory CME in patients with treated syphilitic uveitis. Corticosteroid-induced exacerbation of infection is unlikely in patients with an adequate serologic treatment response.

  7. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer

    Science.gov (United States)

    Willett, Christopher G; Boucher, Yves; di Tomaso, Emmanuelle; Duda, Dan G; Munn, Lance L; Tong, Ricky T; Chung, Daniel C; Sahani, Dushyant V; Kalva, Sanjeeva P; Kozin, Sergey V; Mino, Mari; Cohen, Kenneth S; Scadden, David T; Hartford, Alan C; Fischman, Alan J; Clark, Jeffrey W; Ryan, David P; Zhu, Andrew X; Blaszkowsky, Lawrence S; Chen, Helen X; Shellito, Paul C; Lauwers, Gregory Y; Jain, Rakesh K

    2009-01-01

    The effects of vascular endothelial growth factor (VEGF) blockade on the vascular biology of human tumors are not known. Here we show here that a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion, vascular volume, microvascular density, interstitial fluid pressure and the number of viable, circulating endothelial and progenitor cells, and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients. These data indicate that VEGF blockade has a direct and rapid antivascular effect in human tumors. PMID:14745444

  8. Safety of intravitreal quinupristin/dalfopristin in an animal model

    Directory of Open Access Journals (Sweden)

    Veronica E. Giordano

    2016-03-01

    Full Text Available AIM: To determine whether different intravitreal doses of quinupristin/dalfopristin lead to electroretinographic or histological changes in the rabbit retina over one month period after injection. METHODS: Eighteen New Zealand white rabbits were divided into three treatment groups (groups 1 to 3 and different intravitreal doses of quinupristin/dalfopristin were tested in each group. The right eye was injected with the drug and the left eye received intravitreal injection of 5% dextrose water and served as control eye. The doses delivered to each group were 0.1 mg/0.1 mL, 1 mg/0.1 mL and 10 mg/0.1 mL. Simultaneous, bilateral, dark-adapted electroretinography and clinical images of both eyes were obtained in all groups before injection (baseline and after 7, 14, 21 and 28d, followed by enucleation for histological examination. RESULTS: Subjects in the group 1 showed no signs of toxicity in the electroretinogram when compared with groups 2 and 3 (Kruskall-Wallis test, P=0.000. By day 7, no electrical response to light stimuli was recorded in the treated eyes in groups 2 and 3, consistent with severe damage due to retinal toxicity. Light microscopy revealed no significant histopathological changes in the group 1, while rabbits in groups 2 and 3 had signs of granulomatous inflammation in most cases. CONCLUSION: Intravitreal 0.1 mg/0.1 mL doses of quinupristin/dalfopristin do not lead to electroretinographic or histological signs of retinal toxicity compared with 1 mg/0.1 mL and 10 mg/0.1 mL in this rabbit model.

  9. Isolated sixth nerve palsy after intravitreal ranibizumab injection.

    Science.gov (United States)

    Caglar, Cagatay; Kocamis, Sücattin Ilker; Durmus, Mustafa

    2016-09-01

    After intravitreal ranibizumab injection for diabetic macular edema (DME) in a 55-year-old man, the patient was admitted to our ophthalmology clinic with the complaint of diplopia. Given the results of the patient's history, physical exam, and negative magnetic resonance imaging (MRI), we believed that the patient had a sixth nerve palsy related to ranibizumab injection. To the best of our knowledge, this is the first case with isolated abducens palsy after ranibizumab injection.

  10. Intravitreal ranibizumab injections in patients with retinopathy of prematurity (ROP

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    Zuluaga Gómez, Liliana María

    2018-01-01

    Full Text Available Purpose: To describe ocular outcomes after intravitreal ranibizumab injections in patients with retinopathy of prematurity (ROP, who had transpupillary laser thermotherapy without regression of the disease. Methods: Historical cohort in Clínica Universitaria Bolivariana (CUB during 2008-2015. Evaluation of patients with aggressive posterior ROP, threshold disease, who received intravitreal ranibizumab secondary to treatment with transpupillary thermotherapy. The primary outcome was treatment success defined as the resolution of neovascularization (NV and no recurrence. The secondary endpoints were visual acuity and ocular and systemic complications. Results: Eight eyes of four patients were included in the study. Six eyes had resolution of retinopathy, Incidence density 48 x 100 person years, 95 % CI = 17.6 - 100 with a median follow-up of 23.5 months, range 13-90 months. No ocular or systemic complications associated with the procedure was found. Conclusion: This cohort suggests that intravitreal injection of ranibizumab for ROP in refractory laser photocoagulation cases, results in apparent ocular preservation a long-term the outcome.

  11. Experiment study of retinal ultrastructure after intravitreal FK506.

    Science.gov (United States)

    Li, Shuangnong; Tang, Shibo; Li, Wei; Li, Dongping

    2004-03-01

    To investigate the retinal toxicity of FK506 by intravitreal administration. Twenty-two eyes of 14 New Zealand rabbits were investigated. FK506 at concentrations of 5,25 and 50 micrograms/eye was injected into the vitreous cavities respectively. The control eyes were received mixed solution of balanced salt and ethanol. All eyes were examined by tonometry, slit lamp and indirect ophthalmoscopy preoperatively and postoperatively at the 1st, 3rd, 7th, and 14th day respectively. In the final examination, all eyes were enucleated and processed for light and electron microscopy. No evidence of toxic reaction was seen in the eyes received 25 micrograms FK506 or less of FK506. Several eyes received 50 micrograms FK506 and control eyes developed conjunctival congestion and slightly bloody exudates in anterior chamber which may be related to irritation of ethanol. Two of five eyes received 50 micrograms developed transient vitreous opacities. Electron microscopically, the mitochondria of the photoreceptor cells were swelled in the eyes treated with 50 micrograms FK 506. It is safety with intravitreal FK506. There are no irritation and toxicity to the rabbits eyes with the intravitreal doses of 25 micrograms FK506 or less. The doses of 50 micrograms FK506 are proved to be toxic to the retina.

  12. Selective Gene Transfer to the Retina Using Intravitreal Ultrasound Irradiation

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    Shozo Sonoda

    2012-01-01

    Full Text Available This paper aims to evaluate the efficacy of intravitreal ultrasound (US irradiation for green fluorescent protein (GFP plasmid transfer into the rabbit retina using a miniature US transducer. Intravitreal US irradiation was performed by a slight modification of the transconjunctival sutureless vitrectomy system utilizing a small probe. After vitrectomy, the US probe was inserted through a scleral incision. A mixture of GFP plasmid (50 μL and bubble liposomes (BLs; 50 μL was injected into the vitreous cavity, and US was generated to the retina using a SonoPore 4000. The control group was not exposed to US. After 72 h, the gene-transfer efficiency was quantified by counting the number of GFP-positive cells. The retinas that received plasmid, BL, and US showed a significant increase in the number (average ± SEM of GFP-positive cells (32±4.9; n=7; P<0.01 . No GFP-positive cells were observed in the control eyes (n=7. Intravitreal retinal US irradiation can transfer the GFP plasmid into the retina without causing any apparent damage. This procedure could be used to transfer genes and drugs directly to the retina and therefore has potential therapeutic value.

  13. Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats.

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    Jeong Hun Bae

    Full Text Available Choroidal neovascularization (CNV is a major cause of severe visual loss in patients with age-related macular degeneration (AMD. Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS as controls. On day 14 after laser induction, fluorescein angiography (FA was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2 mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA. Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p<0.001 for CNV area and volume. Quantitative RT-PCR showed significantly lower expression of VEGFR2 mRNA in the RPE-choroid complexes of itraconazole-injected eyes than those of BSS-injected eyes on days 7 and 14 (p = 0.003 and p = 0.006. Western blots indicated that VEGFR2 was downregulated after itraconazole treatment. ELISA showed a significant difference in VEGF level between itraconazole-injected and BSS-injected eyes on days 7 and 14 (p = 0.04 and p = 0.001. Our study demonstrated that intravitreal itraconazole significantly inhibited the development of laser-induced CNV in rats. Itraconazole had anti-angiogenic activity along with the reduction of VEGFR2 and VEGF levels. Itraconazole may prove beneficial for treating CNV as an alternative or

  14. Monitoring monoclonal antibody delivery in oncology: the example of bevacizumab.

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    Guillaume Nugue

    Full Text Available Developing therapeutic monoclonal antibodies paves the way for new strategies in oncology using targeted therapy which should improve specificity. However, due to a lack of biomarkers, a personalized therapy scheme cannot always be applied with monoclonal antibodies. As a consequence, the efficacy or side effects associated with this type of treatment often appear to be sporadic. Bevacizumab is a therapeutic monoclonal antibody targeting Vascular Endothelial Growth Factor (VEGF. It is used to limit tumor vascularization. No prognosis or response biomarker is associated with this antibody, we therefore assessed whether the administration protocol could be a possible cause of heterogeneous responses (or variable efficacy. To do this, we developed a bevacizumab assay with a broad sensitivity range to measure blood bevacizumab concentrations. We then analyzed bevacizumab concentrations in 17 patients throughout the first quarter of treatment. In line with previously published data, average blood concentrations were 88+/-27 mg/L following the first dose administered, and 213+/-105 mg/L after the last (6(th dose administered. However, the individual values were scattered, with a mean 4-fold difference between the lowest and the highest concentration for each dose administered. We demonstrated that the bevacizumab administration schedule results in a high inter-individual variability in terms of blood concentrations. Comparison of assay data with clinical data indicates that blood concentrations above the median are associated with side effects, whereas values below the median favor inefficacy. In conclusion, bevacizumab-based therapy could benefit from a personalized administration schedule including follow-up and adjustment of circulating bevacizumab concentrations.

  15. One-year outcome of bevacizumab therapy for chronic macular edema in central and branch retinal vein occlusions in real-world clinical practice in the UK.

    Science.gov (United States)

    Lip, Peck Lin; Malick, Huzaifa; Damer, Kenan; Elsherbiny, Samer; Darrad, Kanupriya M; Mushtaq, Bushra; Mitra, Arijit; Stavrou, Panagiota; Yang, Yit

    2015-01-01

    The purpose of this study was to investigate the 12-month outcome of macular edema secondary to both chronic and new central and branch retinal vein occlusions treated with intravitreal bevacizumab in the real-life clinical setting in the UK. Retrospective case notes analysis of consecutive patients with retinal vein occlusions treated with bevacizumab in 2010 to 2012. Outcome measures were visual acuity (measured with Snellen, converted into logMAR [logarithm of the minimum angle of resolution] for statistical calculation) and central retinal thickness at baseline, 4 weeks post-loading phase, and at 1 year. There were 56 and 100 patients with central and branch retinal vein occlusions, respectively, of whom 62% had chronic edema and received prior therapies and another 32% required additional laser treatments post-baseline bevacizumab. Baseline median visual acuity was 0.78 (interquartile range [IQR] 0.48-1.22) in the central group and 0.6 (IQR 0.3-0.78) in the branch group. In both groups, visual improvement was statistically significant from baseline compared to post-loading (P<0.001 and P=0.03, respectively), but was not significant by month 12 (P=0.058 and P=0.166, respectively); 30% improved by at least three lines and 44% improved by at least one line by month 12. Baseline median central retinal thickness was 449 μm (IQR 388-553) in the central group and 441 μm (IQR 357-501) in the branch group. However, the mean reduction in thickness was statistically significant at post-loading (P<0.001) and at the 12-month time point (P<0.001) for both groups. The average number of injections in 1 year was 4.2 in the central group and 3.3 in the branch group. Our large real-world cohort results indicate that bevacizumab introduced to patients with either new or chronic edema due to retinal vein occlusion can result in resolution of edema and stabilization of vision in the first year.

  16. One-year outcome of bevacizumab therapy for chronic macular edema in central and branch retinal vein occlusions in real-world clinical practice in the UK

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    Lip PL

    2015-09-01

    Full Text Available Peck Lin Lip,1 Huzaifa Malick,1 Kenan Damer,1 Samer Elsherbiny,1 Kanupriya M Darrad,1 Bushra Mushtaq,1 Arijit Mitra,1 Panagiota Stavrou,1 Yit Yang1,2 1Birmingham and Midland Eye Centre, City Hospital, 2School of Health and Life Sciences, Aston University, Birmingham, UK Background: The purpose of this study was to investigate the 12-month outcome of macular edema secondary to both chronic and new central and branch retinal vein occlusions treated with intravitreal bevacizumab in the real-life clinical setting in the UK.Methods: Retrospective case notes analysis of consecutive patients with retinal vein occlusions treated with bevacizumab in 2010 to 2012. Outcome measures were visual acuity (measured with Snellen, converted into logMAR [logarithm of the minimum angle of resolution] for statistical calculation and central retinal thickness at baseline, 4 weeks post-loading phase, and at 1 year.Results: There were 56 and 100 patients with central and branch retinal vein occlusions, respectively, of whom 62% had chronic edema and received prior therapies and another 32% required additional laser treatments post-baseline bevacizumab. Baseline median visual acuity was 0.78 (interquartile range [IQR] 0.48–1.22 in the central group and 0.6 (IQR 0.3–0.78 in the branch group. In both groups, visual improvement was statistically significant from baseline compared to post-loading (P<0.001 and P=0.03, respectively, but was not significant by month 12 (P=0.058 and P=0.166, respectively; 30% improved by at least three lines and 44% improved by at least one line by month 12. Baseline median central retinal thickness was 449 µm (IQR 388–553 in the central group and 441 µm (IQR 357–501 in the branch group. However, the mean reduction in thickness was statistically significant at post-loading (P<0.001 and at the 12-month time point (P<0.001 for both groups. The average number of injections in 1 year was 4.2 in the central group and 3.3 in the branch

  17. Electrospun formulations of bevacizumab for sustained release in the eye.

    Science.gov (United States)

    Angkawinitwong, Ukrit; Awwad, Sahar; Khaw, Peng T; Brocchini, Steve; Williams, Gareth R

    2017-12-01

    Medicines based on vascular endothelial growth factor (VEGF) neutralising antibodies such as bevacizumab have revolutionized the treatment of age related macular degeneration (AMD), a common blinding disease, and have great potential in preventing scarring after surgery or accelerating the healing of corneal injuries. However, at present frequent invasive injections are required to deliver these antibodies. Such administration is uncomfortable for patients and expensive for health service providers. Much effort is thus focused on developing dosage forms that can be administered less frequently. Here we use electrospinning to prepare a solid form of bevacizumab designed for prolonged release while maintaining antibody stability. Electrospun fibers were prepared with bevacizumab encapsulated in the core, surrounded by a poly-ε-caprolactone sheath. The fibers were generated using aqueous bevacizumab solutions buffered at two different pH values: 6.2 (the pH of the commercial product; F beva ) and 8.3 (the isoelectric point of bevacizumab; F bevaP ). The fibers had smooth and cylindrical morphologies, with diameters of ca. 500nm. Both sets of bevacizumab loaded fibers gave sustained release profiles in an in vitro model of the subconjunctival space of the eye. F beva displayed first order kinetics with t 1/2 of 11.4±4.4 days, while F bevaP comprises a zero-order reservoir type release system with t 1/2 of 52.9±14.8 days. Both SDS-PAGE and surface plasmon resonance demonstrate that the bevacizumab in F bevaP did not undergo degradation during fiber fabrication or release. In contrast, the antibody released from F beva had degraded, and failed to bind to VEGF. Our results demonstrate that pH control is crucial to maintain antibody stability during the fabrication of core/shell fibers and ensure release of functional protein. Bevacizumab is a potent protein drug which is highly effective in the treatment of degenerative conditions in the eye. To be effective, frequent

  18. Effect of bevacizumab on radiation necrosis of the brain

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    Gonzalez, Javier; Kumar, Ashok J.; Conrad, Charles A.; Levin, Victor A.

    2007-01-01

    Purpose: Because blocking vascular endothelial growth factor (VEGF) from reaching leaky capillaries is a logical strategy for the treatment of radiation necrosis, we reasoned that bevacizumab might be an effective treatment of radiation necrosis. Patients and Methods: Fifteen patients with malignant brain tumors were treated with bevacizumab or bevacizumab combination for their tumor on either a 5 mg/kg/2-week or 7.5 mg/kg/3-week schedule. Radiation necrosis was diagnosed in 8 of these patients on the basis of magnetic resonance imaging (MRI) and biopsy. MRI studies were obtained before treatment and at 6-week to 8-week intervals. Results: Of the 8 patients with radiation necrosis, posttreatment MRI performed an average of 8.1 weeks after the start of bevacizumab therapy showed a reduction in all 8 patients in both the MRI fluid-attenuated inversion-recovery (FLAIR) abnormalities and T1-weighted post-Gd-contrast abnormalities. The average area change in the T1-weighted post-Gd-contrast abnormalities was 48% (±22 SD), and the average change in the FLAIR images was 60% (±18 SD). The average reduction in daily dexamethasone requirements was 8.6 mg (±3.6). Conclusion: Bevacizumab, alone and in combination with other agents, can reduce radiation necrosis by decreasing capillary leakage and the associated brain edema. Our findings will need to be confirmed in a randomized trial to determine the optimal duration of treatment

  19. Role of bevacizumab therapy in the management of glioblastoma

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    Scott J Peak

    2010-04-01

    Full Text Available Scott J Peak, Victor A LevinNeuro-Oncology Program, Department of Neurosurgery and Neuroscience, Kaiser Permanente, Redwood City, CA, USAAbstract: Glioblastoma is one of the most common primary brain tumors and one of the most difficult to treat. In population-based studies only 30% of patients will survive 1 year and in the most efficacious surgery, irradiation, and chemotherapy clinical trials approximately 20% will live 2 years. Bevacizumab is a recombinant, antivascular epidermal growth factor receptor (VEGF monoclonal antibody with 6 VEGF-binding residues that binds to VEGF, preventing VEGF from binding to its target, VEGFR-1 and VEGFR-2, on endothelial cells. Through its binding to VEGF ligands bevacizumab reduces tumor angiogenesis and vasogenic brain edema; the consequences are that bevacizumab reduces the rate of glioblastoma tumor growth and its associated tumoral edema, thereby improving quality of life and survival for patients suffering from cerebral glioblastoma. In this review, we will summarize the studies that led to the use of bevacizumab in glioblastoma and the potential side-effects and complications that can be associated with its use and, finally, new opportunities for drug combinations with bevacizumab.Keywords: chemotherapy, VEGF, edema, central nervous system

  20. Bevacizumab alleviates radiation-induced brain necrosis: A report of four cases

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    Li Xiang-Pan

    2015-01-01

    Full Text Available To analyze the therapeutic effect of bevacizumab on radiation-induced brain necrosis. Four radiation-induced brain necrosis patients, administered with bevacizumab at a dose of 7.5 mg/kg every 3 weeks, 2 times. One case of brain metastasis of lung cancer and one case of nasopharyngeal carcinoma with brain necrosis after radiotherapy. However, their physical signs disappeared after the treatment with bevacizumab. One case of brainstem lesion and one case of brain glioma patient showed a transient improvement in signs and symptoms after treatment with bevacizumab. Bevacizumab can significantly alleviate the radiation-induced brain edema, and can improve the symptoms successively.

  1. Early dissemination of bevacizumab for advanced colorectal cancer: a prospective cohort study

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    Fouad Mona N

    2011-08-01

    Full Text Available Abstract Background We describe early dissemination patterns for first-line bevacizumab given for metastatic colorectal cancer treatment. Methods We analyzed patient surveys and medical records for a population-based cohort with metastatic colorectal cancer treated in multiple regions and health systems in the United States (US. Eligible patients were diagnosed with metastatic colorectal cancer and initiated first-line chemotherapy after US Food & Drug Administration (FDA bevacizumab approval in February 2004. First-line bevacizumab therapy was defined as receiving bevacizumab within 8 weeks of starting chemotherapy for metastatic colorectal cancer. We evaluated factors associated with first-line bevacizumab treatment using logistic regression. Results Among 355 patients, 31% received first-line bevacizumab in the two years after FDA approval, including 26% of men, 41% of women, and 16% of those ≥ 75 years. Use rose sharply within 6 months after FDA approval, then plateaued. 20% of patients received bevacizumab in combination with irinotecan; 53% received it with oxaliplatin. Men were less likely than women to receive bevacizumab (adjusted OR 0.55; 95% CI 0.32-0.93; p = 0.026. Patients ≥ 75 years were less likely to receive bevacizumab than patients Conclusions One-third of eligible metastatic colorectal cancer patients received first-line bevacizumab shortly after FDA approval. Most patients did not receive bevacizumab as part of the regimen used in the pivotal study leading to FDA approval.

  2. Interferon-regulatory factor-1 (IRF1) regulates bevacizumab induced autophagy

    Science.gov (United States)

    Henry, Verlene; Tiao, Ningyi; de Groot, John F.

    2015-01-01

    Purpose Antiangiogenic therapy is commonly being used for the treatment of glioblastoma. However, the benefits of angiogenesis inhibitors are typically transient and resistance often develops. Determining the mechanism of treatment failure of the VEGF monoclonal antibody bevacizumab for malignant glioma would provide insight into approaches to overcome therapeutic resistance. Experimental Design In this study, we evaluated the effects of bevacizumab on the autophagy of glioma cells and determined target genes involving in the regulation of bevacizumab-induced autophagy. Results We demonstrated that bevacizumab treatment increased expression of autophagy markers and autophagosome formation in cell culture experiments as well as in in vivo studies. Gene expression profile analysis performed on murine xenograft models of glioblastoma showed increased transcriptional levels of STAT1/IRF1 signaling in bevacizumab resistant tumors compared to control tumors. In vitro experiments showed that bevacizumab treatment increased IRF1 expression in a dose and time dependent manner, which was coincident with bevacizumab-mediated autophagy. Down regulation of IRF1 by shRNA blocked autophagy and increased AIF-dependent apoptosis in bevacizumab-treated glioma cells. Consistently, IRF1 depletion increased the efficacy of anti-VEGF therapy in a glioma xenograft model, which was due to less bevacizumab-promoted autophagy and increased apoptosis in tumors with down-regulated IRF1. Conclusions These data suggest that IRF1 may regulate bevacizumab-induced autophagy, and may be one important mediator of glioblastoma resistant to bevacizumab. PMID:26362401

  3. Efficacy and safety of bevacizumab treatment for refractory brain edema: Case report.

    Science.gov (United States)

    Meng, Xiangying; Zhao, Rugang; Shen, Ge; Dong, Dapeng; Ding, Lijuan; Wu, Shikai

    2017-11-01

    This retrospective study investigated the efficacy and safety of bevacizumab treatment for refractory brain edema. Between March 2009 and December 2015, bevacizumab was used to treat 59 cases of brain metastatic patients with refractory brain edema. The median dose of bevacizumab was 4.68 mg/kg (range 2.8-6.52 mg/kg). The clinical-pathological data, the efficacy, and the side effects of bevacizumab were recorded. Magnetic resonance imaging (MRI) was performed before and after bevacizumab treatment. Tumor and edema volumes were measured separately. The clinical symptoms of 50 out of 59 cases (84.74%) improved the day after the bevacizumab treatment, and the edema volumes of 55 (93.22%) cases were reduced after the bevacizumab treatment. The average edema volume was significantly reduced after bevacizumab treatment from 125,583.43 ± 14,093.27 to 71,613.42 ± 9473.42 mm (Mann-Whitney rank test, P bevacizumab for refractory brain edema is 84.74%. Hypertension was the main side effect of the bevacizumab treatment. Bevacizumab is an effective and relatively safe treatment for brain edema.

  4. Neoadjuvant Bevacizumab, Oxaliplatin, 5-Fluorouracil, and Radiation for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dipetrillo, Tom; Pricolo, Victor; Lagares-Garcia, Jorge; Vrees, Matt; Klipfel, Adam; Cataldo, Tom; Sikov, William; McNulty, Brendan; Shipley, Joshua; Anderson, Elliot; Khurshid, Humera; Oconnor, Brigid; Oldenburg, Nicklas B.E.; Radie-Keane, Kathy; Husain, Syed [Brown University Oncology Group, Providence, RI (United States); Safran, Howard, E-mail: hsafran@lifespan.org [Brown University Oncology Group, Providence, RI (United States)

    2012-01-01

    Purpose: To evaluate the feasibility and pathologic complete response rate of induction bevacizumab + modified infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) 6 regimen followed by concurrent bevacizumab, oxaliplatin, continuous infusion 5-fluorouracil (5-FU), and radiation for patients with rectal cancer. Methods and Materials: Eligible patients received 1 month of induction bevacizumab and mFOLFOX6. Patients then received 50.4 Gy of radiation and concurrent bevacizumab (5 mg/kg on Days 1, 15, and 29), oxaliplatin (50 mg/m{sup 2}/week for 6 weeks), and continuous infusion 5-FU (200 mg/m{sup 2}/day). Because of gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m{sup 2}/week. Resection was performed 4-8 weeks after the completion of chemoradiation. Results: The trial was terminated early because of toxicity after 26 eligible patients were treated. Only 1 patient had significant toxicity (arrhythmia) during induction treatment and was removed from the study. During chemoradiation, Grade 3/4 toxicity was experienced by 19 of 25 patients (76%). The most common Grade 3/4 toxicities were diarrhea, neutropenia, and pain. Five of 25 patients (20%) had a complete pathologic response. Nine of 25 patients (36%) developed postoperative complications including infection (n = 4), delayed healing (n = 3), leak/abscess (n = 2), sterile fluid collection (n = 2), ischemic colonic reservoir (n = 1), and fistula (n = 1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU, and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen was similar to other fluorouracil chemoradiation regimens. The high incidence of postoperative wound complications is concerning and consistent with other reports utilizing bevacizumab with chemoradiation before major surgical resections.

  5. Diffusion of Bevacizumab Across Oncology Practices: An Observational Study.

    Science.gov (United States)

    Keating, Nancy L; Huskamp, Haiden A; Schrag, Deborah; McWilliams, John M; McNeil, Barbara J; Landon, Bruce E; Chernew, Michael E; Normand, Sharon-Lise T

    2018-01-01

    Technological advances can improve care and outcomes but are a primary driver of health care spending growth. Understanding diffusion and use of new oncology therapies is important, given substantial increases in prices and spending on such treatments. Examine diffusion of bevacizumab, a novel (in 2004) and high-priced biologic cancer therapy, among US oncology practices during 2005-2012 and assess variation in use across practices. Population-based observational study. A total of 2329 US practices providing cancer chemotherapy. Random 20% sample of 236,304 Medicare fee-for-service beneficiaries aged above 65 years in 2004-2012 undergoing infused chemotherapy for cancer. Diffusion of bevacizumab (cumulative time to first use and 10% use) in practices, variation in use across practices overall and by higher versus lower-value use. We used hierarchical models with practice random effects to estimate the between-practice variation in the probability of receiving bevacizumab and to identify factors associated with use. We observed relatively rapid diffusion of bevacizumab, particularly in independent practices and larger versus smaller practices. We observed substantial variation in use; the adjusted odds ratio (95% confidence interval) of bevacizumab use was 2.90 higher (2.73-3.08) for practices 1 SD above versus one standard deviation below the mean. Variation was less for higher-value [odds ratio=2.72 (2.56-2.89)] than lower-value uses [odds ratio=3.61 (3.21-4.06)]. Use of bevacizumab varied widely across oncology practices, particularly for lower-value indications. These findings suggest that interventions targeted to practices have potential for decreasing low-value use of high-cost cancer therapies.

  6. Treatment Patterns and Clinical Outcomes in Patients With Metastatic Colorectal Cancer Initially Treated with FOLFOX–Bevacizumab or FOLFIRI–Bevacizumab: Results From ARIES, a Bevacizumab Observational Cohort Study

    Science.gov (United States)

    Bekaii-Saab, Tanios S.; Cohn, Allen L.; Hurwitz, Herbert I.; Kozloff, Mark; Tezcan, Haluk; Roach, Nancy; Mun, Yong; Fish, Susan; Flick, E. Dawn; Dalal, Darshan; Grothey, Axel

    2012-01-01

    Background. The Avastin® Registry: Investigation of Effectiveness and Safety (ARIES) study is a prospective, community-based observational cohort study that evaluated the effectiveness and safety of first-line treatment patterns, assessing the impact of chemotherapy choice and treatment duration. Methods. The ARIES study enrolled patients with metastatic colorectal cancer (mCRC) receiving first-line chemotherapy with bevacizumab and followed them longitudinally. The protocol did not specify treatment regimens or assessments. Analyses included all patients who initiated bevacizumab in combination with either first-line oxaliplatin with infusional 5-fluorouracil and leucovorin (FOLFOX) or irinotecan with infusional 5-fluorouracil and leucovorin (FOLFIRI). Progression-free survival (PFS) and overall survival (OS) times were estimated using Kaplan–Meier methods. Hazard ratios (HRs) were estimated with multivariate Cox regression analysis, adjusting for potential confounding factors. Results. In total, 1,550 patients with first-line mCRC were enrolled (median follow-up, 21 months) and most received FOLFOX–bevacizumab (n = 968) or FOLFIRI–bevacizumab (n = 243) as first-line therapy. The baseline characteristics and median treatment duration were generally similar between subgroups. There were no significant differences in the median PFS (10.3 months vs. 10.2 months) or OS (23.7 months vs. 25.5 months) time between the FOLFOX–bevacizumab and FOLFIRI–bevacizumab subgroups, respectively, by unadjusted analyses. Multivariate analyses showed FOLFIRI–bevacizumab resulted in a similar PFS (HR, 1.03; 95% confidence interval [CI], 0.88–1.21) and OS (HR, 0.95; 95% CI, 0.78–1.16) outcome as with FOLFOX–bevacizumab. The incidence proportions of bevacizumab-associated adverse events were similar for FOLFOX- and FOLFIRI-based therapies. Conclusions. In first-line mCRC patients, the FOLFOX–bevacizumab and FOLFIRI–bevacizumab regimens were associated with similar

  7. Influence of intravitreal triamcinolone acetonide injection in scleral buckling surgery for macula-off retinal detachment.

    Science.gov (United States)

    Mirshahi, Ahmad; Karkhaneh, Reza; Zamani Amir, Javad; Movassat, Morteza; Azadi, Pejvak

    2014-01-01

    in group 1 was significantly higher (p = 0.03). The incidence of cystoid macular edema did not differ in a statistically significant way between the groups (p = 0.19). IOP in 4 (15%) patients in group 1 rose above 21 mm Hg but responded quickly to 2 weeks of topical antiglaucoma medication. There was no cataract progression in either group. There was no correlation between the incidence of persistent SRF and the extent of detachment in both groups (p = 0.83). There was no surgical failure or redetachment in either group during the study period. Single-dose intravitreal triamcinolone may increase the final BCVA in macula-off RRD patients despite persistent SRF, suggesting the anti-inflammatory role of this drug. © 2014 S. Karger AG, Basel.

  8. Bevacizumab Plus Pemetrexed Versus Pemetrexed Alone as Maintenance Therapy for Patients With Advanced Nonsquamous Non-Small-cell Lung Cancer: Update From the Swiss Group for Clinical Cancer Research (SAKK) 19/09 Trial.

    Science.gov (United States)

    Gautschi, Oliver; Rothschild, Sacha I; Li, Qiyu; Matter-Walstra, Klazien; Zippelius, Alfred; Betticher, Daniel C; Früh, Martin; Stahel, Rolf A; Cathomas, Richard; Rauch, Daniel; Pless, Miklos; Peters, Solange; Froesch, Patrizia; Zander, Thilo; Schneider, Martina; Biaggi, Christine; Mach, Nicolas; Ochsenbein, Adrian F

    2017-05-01

    Pemetrexed and bevacizumab as single agents have been approved for maintenance therapy after platinum-based induction in patients with advanced nonsquamous non-small-cell lung cancer. It is currently unknown whether bevacizumab plus pemetrexed is superior to pemetrexed alone. We conducted a nonrandomized phase II trial with 2 sequential cohorts. In the first cohort, 77 patients were treated with 4 cycles of cisplatin, bevacizumab, and pemetrexed every 3 weeks, followed by bevacizumab plus pemetrexed maintenance until progression. In the second cohort, we treated 52 patients without bevacizumab, using maintenance with pemetrexed alone. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), adverse events, and the treatment costs of the 2 cohorts were compared. The median PFS from the time of registration was 6.9 months in cohort 1 and 5.6 months in cohort 2. The ORR was 62.3% in cohort 1% and 44.2% in cohort 2. The PFS (hazard ratio, 0.7; 95% confidence interval [CI], 0.5-1.0; P = .041) and ORR (odds ratio, 2.1; 95% CI, 1.0-4.3; P = .049) were better in cohort 1 than in cohort 2. No OS difference was found (hazard ratio, 1.0; 95% CI, 0.7-1.6; P = .890) after a median follow-up period of 47 months for cohort 1 and 27 months for cohort 2. The rate of grade ≥ 3 adverse events was greater in cohort 1. The treatment costs per patient were on average 1.4 times greater for cohort 1. The addition of bevacizumab increased the ORR and PFS, but not OS, in our nonrandomized trial. Furthermore, the addition of bevacizumab was associated with greater toxicity and higher costs. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Evaluation of Efficacy and Safety of Bevacizumab Combined with Chemotherapy 
for Chinese Patients with Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiao ZHAO

    2012-01-01

    Full Text Available Background and objective The current study reported the result of bevacizumab treatment administered to 25 Chinese patients with advanced non-small cell lung cancer (NSCLC who were treated at the Peking Union Medical College Hospital as a part of the SAiL (MO19390 trial. This trial is an open, international multicenter, single-arm clinical study that assesses the safety and efficacy of first-line bevacizumab-based therapy in advanced NSCLC. Methods Twenty-five Chinese patients with advanced non-squamous NSCLC received bevacizumab (15 mg/kg combined with chemotherapy (carboplatin plus paclitaxel treatment from August 2007 to February 2008. Adverse effects (AEs, objective response rate (ORR, median time to progression (TTP, and overall survival (OS were measured. Results AEs were generally mild and reversible. The most frequent AEs were alopecia, peripheral neuropathy, rash, proteinuria, nausea/vomitting, fatigue, myalgia, bleeding, and hypertension. The partial remission and stable disease rates were 68% and 28%, respectively. The median TTP and OS of all patients were 11.2 and 19.3 months, respectively. Conclusion Bevacizumab combined with carboplatin-based chemotherapy may be well tolerated and beneficial for Chinese patients with non-squamous NSCLC.

  10. Post-bevacizumab Clinical Outcomes and the Impact of Early Discontinuation of Bevacizumab in Patients with Recurrent Malignant Glioma.

    Science.gov (United States)

    Cha, Yongjun; Kim, Yu Jung; Lee, Se-Hoon; Kim, Tae-Min; Choi, Seung Hong; Kim, Dong-Wan; Park, Chul-Kee; Kim, Il Han; Kim, Jee Hyun; Kim, Eunhee; Choi, Byungse; Kim, Chae-Yong; Kim, In Ah; Heo, Dae Seog

    2017-01-01

    Bevacizumab±irinotecan is effective for treatment of recurrent malignant gliomas. However, the optimal duration of treatment has not been established. Ninety-four consecutive patients with recurrent malignant glioma who were treated with bevacizumab at our institutions were identified. Patients who continued bevacizumab until tumor progression were enrolled in a late discontinuation (LD) group, while those who stopped bevacizumab before tumor progression were enrolled in an early discontinuation (ED) group. Landmark analyses were performed at weeks 9, 18, and 26 for comparison of patient survival between the two groups. Among 89 assessable patients, 62 (69.7%) and 27 (30.3%) patients were categorized as the LD and ED groups, respectively. According to landmark analysis, survival times from weeks 9, 18, and 26 were not significantly different between the two groups in the overall population. However, the LD group showed a trend toward increased survival compared to the ED group among responders. In the ED group, the median time from discontinuation to disease progression was 11.4 weeks, and none of the patients showed a definite rebound phenomenon. Similar median survival times after disease progression were observed between groups (14.4 weeks vs. 15.7 weeks, p=0.251). Of 83 patients, 38 (45.8%) received further therapy at progression, and those who received further therapy showed longer survival in both the LD and ED groups. In recurrent malignant glioma, duration of bevacizumab was not associated with survival time in the overall population. However, ED of bevacizumab in responding patients might be associated with decreased survival.

  11. Triplet therapy with afatinib, cetuximab, and bevacizumab induces deep remission in lung cancer cells harboring EGFR T790M in vivo.

    Science.gov (United States)

    Kudo, Kenichiro; Ohashi, Kadoaki; Makimoto, Go; Higo, Hisao; Kato, Yuka; Kayatani, Hiroe; Kurata, Yasuko; Takami, Yoichiro; Minami, Daisuke; Ninomiya, Takashi; Kubo, Toshio; Ichihara, Eiki; Sato, Akiko; Hotta, Katsuyuki; Yoshino, Tadashi; Tanimoto, Mitsune; Kiura, Katsuyuki

    2017-06-01

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment strategy for EGFR-mutant lung cancers; however, resistance usually occurs due to a secondary mutation, T790M, in EGFR. Combination therapy using afatinib and cetuximab has had good results in lung tumors harboring EGFR T790M mutations in clinical trials. The effect of bevacizumab, an antivascular endothelial growth factor (VEGF) antibody, combined with EGFR-TKIs has also been investigated. We hypothesized that the dose of afatinib and cetuximab could be reduced by combination with bevacizumab and that the triplet therapy may result in better tumor inhibition with tolerable toxicity. Using a xenograft mouse model with H1975-harboring EGFR L 858R+T790M and RPC-9-harboring EGFR 19DEL+T790M , we tested the efficacy of the triplet therapy with a modified dose of afatinib, cetuximab, and bevacizumab, and compared this therapy to single and double therapies. Triplet therapy with afatinib, cetuximab, and bevacizumab induced pathological complete remission in xenograft tumors with H1975 and RPC-9 cells versus tumors treated with single or double therapies. We saw no body weight loss in the mice. The triple therapy induced a significant reduction in CD31-positive vascular endothelial cells and increased cleaved caspase-3-positive cells in the tumors. This suggests that one mechanism underlying the deep remission could be suppression of neovascularization and induction of apoptosis by intensive inhibition of driver oncoproteins and VEGF. These results highlight the potential of afatinib, cetuximab, and bevacizumab to induce deep remission in tumors harboring EGFR T 790M mutations. Therefore, clinical trials of this combination therapy are warranted. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  12. Grid laser with modified pro re nata injection of bevacizumab and ranibizumab in macular edema due to branch retinal vein occlusion: MARVEL report no 2

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    Narayanan R

    2016-06-01

    Full Text Available Raja Narayanan,1 Bhavik Panchal,1 Michael W Stewart,2 Taraprasad Das,1 Jay Chhablani,1 Subhadra Jalali,1 Mohd Hasnat Ali3 On behalf of MARVEL study group 1Smt. Kanuri Santhamma Centre for Vitreo Retinal Diseases, L V Prasad Eye Institute, Hyderabad, India; 2Department of Ophthalmology, Mayo Clinic, Jacksonville, FL, USA; 3Department of Biostatistics, L V Prasad Eye Institute, Hyderabad, India Purpose: The purpose of this study was to prospectively study the efficacy of grid laser combined with intravitreal bevacizumab or ranibizumab in eyes with macular edema due to branch retinal vein occlusion.Patients and methods: Treatment-naïve eyes were enrolled to receive injections of ranibizumab or bevacizumab. During the first 6 months, patients were evaluated monthly and injected if the best-corrected visual acuity changed by five or more letters or fluid was noted on spectral domain optical coherence tomography (OCT; during the next 6 months, patients were evaluated bimonthly and injected only if the best-corrected visual acuity decreased by five or more letters with the associated fluid. Grid laser photocoagulation was performed if there was fluid on OCT and was repeated if patients were eligible after a minimum interval of 3 months.Results: The mean numbers of ranibizumab and bevacizumab injections were, respectively, 3.2±1.5 and 3.0±1.4 in the first 6 months and 0.3±0.6 and 0.3±0.6 in the last 6 months. ­Moreover, 55/75 (73.33% participants did not receive any injections in the last 6 months. The mean reductions in central retinal thickness at 12 months were 165.67 µm (P<0.001; 95% ­confidence interval -221.50 to -135.0 in the ranibizumab group and 184.78 µm (P<0.001; 95% confidence interval -246.49 to -140.0 in the bevacizumab group (P=0.079. More patients in the bevacizumab group compared to those in the ranibizumab group required rescue laser at 12 months (20 vs eleven; P=0.06.Conclusion: Bimonthly evaluations after month 6

  13. Intravitreal gas injection for the treatment of diabetic macular edema

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    McHugh D

    2011-10-01

    Full Text Available Dominic McHugh, Bhaskar Gupta, Manzar Saeed King's College Hospital, Denmark Hill, London, England, UK Purpose: This study investigates the efficacy of an intravitreal gas injection in inducing a posterior vitreous detachment (PVD in patients with clinically significant diabetic macular edema refractory to laser therapy. Methods: A local ethics committee-approved technique of an intravitreal injection of pure perfluoropropane gas (C3F8 was performed for all participants. After a period of prone positioning, the patients underwent regular and detailed clinical review. Main outcome measures: The induction of a PVD, change in macular thickness, change in visual acuity. Results: A PVD was induced in all five eyes with subsequent signs of reduction in macular thickness and resolution of exudates. Mean visual improvement was 11 ETDRS (Early Treatment Diabetic Retinopathy Study letters (range 4–21. Apart from a transient vitreous hemorrhage in one eye, there were no significant treatment-related complications. Conclusion: The induction of a PVD by pneumatic retinopexy appears to have a significant influence on diabetic macular edema in eyes which have not successfully responded to macular laser therapy. A randomized clinical trial is justified on the basis of the initial promising data. Keywords: optical coherence tomography, OCT, posterior vitreous detachment, perfluoropropane

  14. Therapeutical evaluation of bevacizumab application in relapsed pterygium

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    Mayara Martins Abrahão

    Full Text Available Abstract Objective: Therapeutic evaluation of Bevacizumab application in relapsed pterygium concerning visual acuity, keratometry, refraction, symptomatology. Methods: Group 1 (4 patients received 0.1 ml of Bevacizumab (avastin, being evaluated posteriorly on the tenth and thirtieth days after the application, seeking to compare with the exam previously made, being it realized with the other two groups, in which Group 2 (4 patients received 0.2 ml of Bevacizumab and the Group 3 (3 patients received 1 ml of the placebo injection. Results: In this study, eleven eyes of eleven patients were evaluated. Among these patients, 7 were women (63.6% and 4 men (36.4%. There was a variation in the cylindrical diopter after the treatment with a dose of 0.1 ml of bevaciumab during the evaluation on the thirtieth day. Whereas the cylindrical shaft had a significantly larger modification after the application of 0.2 ml. Regarding the spherical diopter variation, there were modifications in the 3 groups. The keratometry varied in the 3 groups, mostly after the thirtieth day of evaluation. In relation to symptomatology, it was observed a reduction in the subjective evaluation of the eye burning sensation, the prurience mentioned by the patient and a reduction of the hyperemia biomicroscopy evaluation. Conclusion: In bevacizumab application in the recurrent pterygium treatment, there is modification of the spherical and cylindrical parameters of refraction, besides the changes in keratometry and the reduction of the symptomatology.

  15. Erlotinib and bevacizumab in newly diagnosed performance status 2 or elderly patients with nonsquamous non-small-cell lung cancer, a phase II study of the Hoosier Oncology Group: LUN04-77.

    Science.gov (United States)

    Riggs, Heather; Jalal, Shadia I; Baghdadi, Tareq Al; Bhatia, Sumeet; McClean, John; Johnson, Cynthia; Yu, Menggang; Taber, David; Harb, Wael; Hanna, Nasser

    2013-05-01

    Poor PS is a negative prognostic factor for survival and a risk factor for treatment-related toxicity with standard platinum-doublet chemotherapy for advanced NSCLC. A phase II study combining erlotinib and bevacizumab for treatment of recurrent NSCLC showed encouraging efficacy and acceptable toxicity. This single-arm phase II study evaluated erlotinib and bevacizumab as first-line therapy for newly diagnosed nonsquamous advanced NSCLC patients with Eastern Cooperative Oncology Group PS ≥ 2 or age 70 or older. Only patients eligible for bevacizumab per label were enrolled. Patients received erlotinib 150 mg orally daily and bevacizumab 15 mg/kg intravenously on day 1 every 21 days for up to 6 cycles. The primary end point was the rate of nonprogressive disease at 4 months (alternative hypothesis > 60%). Twenty-five patients were enrolled, with median age 77 years (range, 52-90 years), 44% female, 20% never- or remote-smokers. Ninety-two percent of patients enrolled had PS of 2 per investigator assessment. The rate of nonprogressive disease at 4 months was 28%. There were no complete responses, 1 patient achieved a partial response, and 11 patients (44%) experienced stable disease as best response. Rash, fatigue, and diarrhea were the most common toxicities. The combination of erlotinib and bevacizumab had insufficient activity in the absence of known activating epidermal growth factor receptor gene mutations to warrant study in newly diagnosed elderly or poor PS patients with nonsquamous NSCLC. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Germline Genetic Variants in TEK, ANGPT1, ANGPT2, MMP9, FGF2 and VEGFA Are Associated with Pathologic Complete Response to Bevacizumab in Breast Cancer Patients.

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    Issam Makhoul

    Full Text Available We previously reported improved pathologic complete response (pCR in a prospective phase II study using neoadjuvant bevacizumab in combination with chemotherapy compared to chemotherapy alone in breast cancer patients (41% vs. 25%, p = 0.0291. In this study, we queried germline single-nucleotide polymorphisms (SNPs in angiogenesis-related genes for their impact on pCR and overall survival (OS.DNA for genotyping was available from 34 subjects who received bevacizumab in addition to chemotherapy and 29 subjects who did not. Using Illumina® technology, we queried 504 SNPs with a minor allele frequency (MAF of at least 5%, located in 10 angiogenesis-related genes, for their effect on pCR via logistic regression with an additive-inheritance model while adjusting for race and bevacizumab treatment. SNPs that showed significant associations with pCR were selected for additional characterization.After adjusting for race and tumor type, patients who had bevacizumab added to their neoadjuvant therapy were found to experience a significantly improved rate of pCR compared to patients who did not (adjusted OR 8.40, 95% CI 1.90-37.1. When patients were analyzed for SNP effects via logistic regression with race and bevacizumab treatment included as covariates, two SNPs in angiopoietin 1 (ANGPT1, six in ANGPT2, three in fibroblast growth factor 2 (FGF2, four in matrix metalloproteinase 9 (MMP9, three in tyrosine kinase, endothelial (TEK and two in vascular endothelial growth factor A (VEGFA were associated with pCR (P<0.05. However, when overall survival was considered, there was no difference between treatment groups or between genotypes.Genetic variability in TEK, ANGPT1, ANGPT2, FGF2, MMP9 and VEGFA is associated with pCR in bevacizumab-treated patients. Consistent with other studies, adding bevacizumab to standard chemotherapy did not impact OS, likely due to other factors and thus, while SNPs in TEK, ANGPT1, ANGPT2, FGF2, MMP9 and VEGFA were associated

  17. Utilización del bevacizumab en la neovascularización corneal Use of Bevacizumab in corneal neovascularization

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    Taimi Cárdenas Díaz

    2012-12-01

    Full Text Available La neovascularización corneal es causa de pérdida de su transparencia y también es un factor de riesgo para el rechazo secundario de trasplantes en esa estructura. El bevacizumab es un anticuerpo monoclonal humanizado que bloquea selectivamente la cascada de formación del VEGF y con esto disminuye la formación de vasos sanguíneos. Se presentan tres casos con neovascularización corneal por diferentes causas, a los cuales se le administró tres dosis subconjuntival de 2,5 mg de bevacizumab, con una frecuencia mensual. En los ojos tratados se observó una regresión parcial de la neovascularización corneal y fue más visible en el paciente con antecedente de quemadura corneal.Neovascularization of the cornea is a cause of loss of transparency of the same and is also a risk factor for secondary rejection corneal transplants. Bevacizumab is a humanized monoclonal antibody that selectively blocks the formation of the VEGF cascade and, with this, decreases the formation of blood vessels. Three cases with corneal neovascularization from different causes were presented, which were given three doses of 2.5 mg subconjunctival bevacizumab once a month. A partial regression of corneal neovascularization was observed in the treated eyes, being more visible in the patient with a history of corneal burn.

  18. Cotargeting VEGF and Neuropilins With Bevacizumab and Secreted Wnt Inhibitors in Prostate Cancer

    Science.gov (United States)

    2013-09-01

    Bevacizumab and Secreted Wnt Inhibitors in Prostate Cancer PRINCIPAL INVESTIGATOR: Xiaolin Zi CONTRACTING ORGANIZATION: University of...With Bevacizumab and Secreted Wnt Inhibitors in Prostate Cancer” 5b. GRANT NUMBER W81XWH-11-1-0312 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...cleavage. In addition, our results showed that Bevacizumab increased Wnt signaling and expression of c-Met and NRP2 protein, leading to increased migration

  19. Efficacy of first Ranibizumab intravitreal injection on macular edema caused by retinal vein occlusion

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    Hong Cao

    2015-09-01

    Full Text Available AIM: To observe the efficacy of first Ranibizumab intravitreal injection on macular edema caused by retinal vein occlusion(RVO. METHODS: Thirty-nine eyes of 39 patients with macular edema due to RVO were treated in our hospital during June 2014 to December 2014. Patients received intravitreal injection of 0.05mL ranibizumab. Best corrected visual acuity(BCVA, central macular thickness(CMTand cube average thickness(CATwere analyzed at 2d, 2, and 4wk after injection, respectively. RESULTS: The baseline BCVA(LogMAR, CMT and CAT were 0.82±0. 45, 541±136μm and 382±107μm before treatment. After first ranibizumab intravitreal injection, mean BVCA significantly improved at 2d(0. 56±0.35,PPPPPPPPPCONCLUSION: First intravitreal injection of ranibizumab can improve macular edema caused by RVO in short-term, but long-term effects is needed further observed.

  20. Impact of treatment with bevacizumab beyond disease progression: a randomized phase II study of docetaxel with or without bevacizumab after platinum-based chemotherapy plus bevacizumab in patients with advanced nonsquamous non–small cell lung cancer (WJOG 5910L)

    International Nuclear Information System (INIS)

    Takeda, Masayuki; Okamoto, Isamu; Yamanaka, Takeharu; Nakagawa, Kazuhiko; Nakanishi, Yoichi

    2012-01-01

    Bevacizumab, a humanized antibody to vascular endothelial growth factor (VEGF), shows clinical activity against human cancer, with its addition to standard chemotherapy having been found to improve outcome in patients with advanced nonsquamous non–small cell lung cancer (NSCLC). However, there have been no evidence-based studies to support the continued use of bevacizumab beyond disease progression in such patients treated with the drug in first-line therapy. We have now designed a randomized phase II trial to examine the clinical benefit and safety of continued bevacizumab treatment in patients with advanced nonsquamous NSCLC whose disease has progressed after first-line treatment with bevacizumab plus a platinum-based doublet. WJOG 5910L was designed as a multicenter, open-label, randomized, phase II trial by the West Japan Oncology Group of docetaxel (arm A) versus docetaxel plus bevacizumab (arm B) in patients with recurrent or metatstatic nonsquamous NSCLC whose disease has progressed after first-line treatment with bevacizumab plus a platinum-based doublet. Patients in arm A will receive docetaxel at 60 mg/m 2 and those in arm B will receive docetaxel at 60 mg/m 2 plus bevacizumab at 15 mg/kg, with each drug administered on day 1 every 21 days until progression or unacceptable toxicity. The primary endpoint of the study is progression-free survival, with secondary endpoints including response rate, overall survival, and safety, for patients treated in either arm. UMIN (University Hospital Medical Information Network in Japan) 000004715

  1. Intravitreal triamcinolone for intraocular inflammation and associated macular edema

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    Steven M Couch

    2008-11-01

    Full Text Available Steven M Couch, Sophie J BakriMayo Clinic Department of Ophthalmology, Mayo Clinic, Rochester, MN, USAAbstract: Triamcinolone acetonide (TA is a corticosteroid that has many uses in the treatment of ocular diseases because of its potent anti-inflammatory and anti-permeability actions. Intraocular inflammation broadly referred to as uveitis can result from several causes, including the immune system and after ophthalmic surgery. One of the most common reasons for vision loss with uveitis is macular edema. TA has been used for many years as an intravitreal injection for the treatment of ocular diseases. Several case control studies have been reported showing the efficacy of TA in the treatment of intraocular inflammation and associated macular edema caused by Behcet’s disease, Vogt-Koyanagi-Harada syndrome, sympathetic ophthalmia and white dot syndromes. It has also been shown efficacious in cases of pars planitis and idiopathic posterior uveitis. Some authors have reported its use in postoperative cystoid macular edema. Many of the studies on the use of TA in controlling intraocular inflammation and concomitant macular edema showed its effect to be transient in many patients requiring reinjection. Complications can arise from intravitreal injection of TA including elevated intraocular pressure and cataract. Rarely, it can be associated with infectious and non-infectious endophthalmitis. TA may be useful as an adjuvant in the treatment of uveitis and its associated macular edema, especially in patients resistant or intolerant to standard treatment.Keywords: triamcinolone acetonide, Behcet’s disease, sympathetic ophthalmia, Vogt-Koyanagi-Harada syndrome, white dot syndromes, uveitis, cataract surgery, macular edema, endophthalmitis

  2. Ocular hypertension after intravitreal triamcinolone with vitrectomy and phacoemulsification

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    Parke III DW

    2012-06-01

    Full Text Available D Wilkin Parke III, Robert A Sisk, Samuel K Houston, Timothy G MurrayDepartment of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL, USAObjective: To evaluate the effect of adjunctive intravitreal triamcinolone (IVTA on intraocular pressure (IOP in the setting of combined vitrectomy with phacoemulsification.Design: Retrospective case series.Participants: One hundred thirty-one consecutive eyes undergoing nonemergent vitrectomy with phacoemulsification and IVTA were reviewed and included in the analysis. All 131 eyes received 4 mg IVTA at the end of surgery.Methods: Pre- and postoperative IOP, use of pressure-lowering medications, and rate of glaucoma surgery were analyzed. Pre-operative risk factors were analyzed.Main outcome measures: IOP, glaucoma medications, or glaucoma surgery.Results: Secondary ocular hypertension (defined as IOP ≥25 mmHg was found in 28 eyes (21%, the majority during postoperative day 1 only. Twelve eyes (9% had an elevated IOP measurement noted at a visit after the first postoperative day. Five (4% had an IOP rise of ≥10 mmHg over baseline at any time after postoperative day 1. Six (5% required glaucoma medications. One eye required a glaucoma drainage implant for diabetic neovascular angle closure glaucoma, and one eye required enucleation for intractable neovascular glaucoma due to radiation retinopathy. Elevated postoperative IOP was statistically associated with higher baseline IOP and presence of preoperative glaucoma.Conclusions: Therapeutic intravitreal triamcinolone with combined vitrectomy and phacoemulsification causes infrequent and usually mild secondary ocular hypertension. Secondary ocular hypertension is associated with preoperative glaucoma and high IOP.Keywords: glaucoma, cataract, inflammation

  3. Efficacy of reduced dose of intravitreal triamcinolone acetonide in a case of active serpiginous choroiditis

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    Avirupa Ghose

    2016-01-01

    Full Text Available Active serpiginous choroiditis (SC is a vision-threatening condition which requires intensive treatment using corticosteroids and/or immunosuppressives, especially if the lesions are involving or encroaching on the macula. Use of oral and intravenous high-dose steroids are contraindicated in uncontrolled diabetics. Intravitreal steroid delivers a localized dose in such situations. This case report highlights the efficacy of reduced dose of intravitreal triamcinolone acetonide (2 mg in the treatment of active SC.

  4. Bevacizumab-induced transient sixth nerve palsy in ovarian cancer: A case report.

    Science.gov (United States)

    Momeni, Mazdak; Veras, Laura; Zakashansky, Konstantin

    2016-03-01

    We report a case of transient sixth nerve palsy after systemic administration of bevacizumab. Two days after systemic administration of bevacizumab in conjunction with gemcitabine and carboplatin in a 67-year-old woman with recurrent primary ovarian cancer, the patient developed sixth nerve palsy. After bevacizumab was stopped, the complete left sixth nerve palsy resolved spontaneously over the course of 3 months. This is the first reported case of bevacizumab-induced cranial sixth nerve palsy in the treatment of gynecologic malignancy. © 2013 Wiley Publishing Asia Pty Ltd.

  5. Bevacizumab treatment in malignant meningioma with additional radiation necrosis. An MRI diffusion and perfusion case study

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    Bostroem, J.P. [University of Bonn Medical Center, Department of Neurosurgery, Bonn (Germany); MediClin Robert Janker Clinic and MVZ MediClin, Department of Radiosurgery and Stereotactic Radiotherapy, Bonn (Germany); Seifert, M.; Greschus, S. [University of Bonn Medical Center, Department of Radiology, Bonn (Germany); Schaefer, N.; Herrlinger, U. [University of Bonn Medical Center, Division of Clinical Neurooncology, Department of Neurology, Bonn (Germany); Glas, M. [University of Bonn Medical Center, Division of Clinical Neurooncology, Department of Neurology, Bonn (Germany); University of Bonn Medical Center, Stem Cell Pathologies, Institute of Reconstructive Neurobiology, Bonn (Germany); MediClin Robert Janker Clinic, Clinical Cooperation Unit Neurooncology, Bonn (Germany); Lammering, G. [MediClin Robert Janker Clinic and MVZ MediClin, Department of Radiosurgery and Stereotactic Radiotherapy, Bonn (Germany); MediClin Robert Janker Clinic, Clinical Cooperation Unit Neurooncology, Bonn (Germany); Heinrich-Heine-University of Duesseldorf, Department of Radiotherapy and Radiation Oncology, Duesseldorf (Germany)

    2014-04-15

    Recently two retrospective cohort studies report efficacy of bevacizumab in patients with recurrent atypical and anaplastic meningioma. Another successful therapeutic option of bevacizumab seems to be treatment of cerebral radiation necrosis. However, the antiangiogenic effects in MRI diffusion and perfusion in meningiomas have not been previously described in detail. The objective of this research was to evaluate the clinical and MR imaging effects of bevacizumab in a malignant meningioma patient harboring additional cerebral radiation necrosis. We report the case of an 80-year-old woman who underwent bevacizumab therapy (5 mg/kg every 2 weeks for 2 months) for treatment of a symptomatic radiation necrosis in malignant meningiomatosis of World Health Organization (WHO) grade III. The patient was closely monitored with MRI including diffusion and perfusion studies. Upon bevacizumab therapy, the clinical situation was well stabilized over a period of 4 months until the patient unfortunately died due to pneumonia/septicemia probably unrelated to bevacizumab therapy. Consecutive MRI demonstrated 4 important aspects: (1) considerable decrease of the contrast medium (CM)-enhanced radiation necrosis, (2) mixed response with respect to the meningiomatosis with stable and predominantly growing tumor lesions, (3) a new diffusion-weighted imaging (DWI) lesion in a CM-enhanced tumor as described in gliomas, which we did not interpret as a response to bevacizumab therapy, and (4) new thrombembolic infarcts, which are a known side-effect of bevacizumab treatment. Bevacizumab is effective in the treatment of radiation necrosis. We could not confirm the potential antitumor effect of bevacizumab in this patient. However, we could describe several new radiographic effects of bevacizumab therapy in malignant meningioma. (orig.) [German] In zwei aktuellen retrospektiven Kohortenstudien konnte eine Wirksamkeit von Bevacizumab bei Patienten mit rezidivierenden atypischen und

  6. Comparison of dexamethasone intravitreal implant and intravitreal triamcinolone acetonide for the treatment of pseudophakic cystoid macular edema in diabetic patients

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    Dang Y

    2014-09-01

    Full Text Available Yalong Dang,1,* Yalin Mu,2,* Lin Li,3,* Yahui Mu,2 Shujing Liu,2 Chun Zhang,4 Yu Zhu,1 Yimin Xu4 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 2Department of Ophthalmology, Yellow River Hospital, Henan University of Science and Technology, Sanmenxia, Henan Province, 3Department of Ophthalmology, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan Province, 4Department of Ophthalmology, Peking University Third Hospital, Haidian District, Beijing, People's Republic of China *These authors contributed equally to this work. Background and objective: Our objective was to investigate the efficacy and safety of dexamethasone (DEX implant for the treatment of pseudophakic cystoid macular edema (PCME in diabetic patients. Study design: This was a prospective, non-randomized, interventional case series of 43 participants. Eighteen patients were enrolled in the DEX implant group and 25 were enrolled in an intravitreal triamcinolone acetonide (IVTA group. Main outcome measures: The primary efficacy measurement was the percentage of patients who gained improvements of more than ten letters in best corrected visual acuity (BCVA during 6 months of follow-up. Other efficacy measurements included change in BCVA, change in central macular thickness (CMT, and number of retreatments. The primary safety evaluation was the percentage of patients with intraocular hypertension and variation in intraocular pressure (IOP during 6 months of follow-up. Other adverse events, such as conjunctival hemorrhage, eye pain, secondary infection, endophthalmitis, noninfectious inflammation, retinal detachment, and implant migration, were also recorded during follow-up. Results: At month 1, we observed that the percentage of patients gaining improvement of more than ten letters was similar in both groups (P=0.625. As patients in the IVTA group were retreated several times, this

  7. Surface Engineering of Porous Silicon Microparticles for Intravitreal Sustained Delivery of Rapamycin

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    Nieto, Alejandra; Hou, Huiyuan; Moon, Sang Woong; Sailor, Michael J.; Freeman, William R.; Cheng, Lingyun

    2015-01-01

    Purpose. To understand the relationship between rapamycin loading/release and surface chemistries of porous silicon (pSi) to optimize pSi-based intravitreal delivery system. Methods. Three types of surface chemical modifications were studied: (1) pSi-COOH, containing 10-carbon aliphatic chains with terminal carboxyl groups grafted via hydrosilylation of undecylenic acid; (2) pSi-C12, containing 12-carbon aliphatic chains grafted via hydrosilylation of 1-dodecene; and (3) pSiO2-C8, prepared by mild oxidation of the pSi particles followed by grafting of 8-hydrocarbon chains to the resulting porous silica surface via a silanization. Results. The efficiency of rapamycin loading follows the order (micrograms of drug/milligrams of carrier): pSiO2-C8 (105 ± 18) > pSi-COOH (68 ± 8) > pSi-C12 (36 ± 6). Powder X-ray diffraction data showed that loaded rapamycin was amorphous and dynamic drug-release study showed that the availability of the free drug was increased by 6-fold (compared with crystalline rapamycin) by using pSiO2-C8 formulation (P = 0.0039). Of the three formulations in this study, pSiO2-C8-RAP showed optimal performance in terms of simultaneous release of the active drug and carrier degradation, and drug-loading capacity. Released rapamycin was confirmed with the fingerprints of the mass spectrometry and biologically functional as the control of commercial crystalline rapamycin. Single intravitreal injections of 2.9 ± 0.37 mg pSiO2-C8-RAP into rabbit eyes resulted in more than 8 weeks of residence in the vitreous while maintaining clear optical media and normal histology of the retina in comparison to the controls. Conclusions. Porous silicon–based rapamycin delivery system using the pSiO2-C8 formulation demonstrated good ocular compatibility and may provide sustained drug release for retina. PMID:25613937

  8. Macropinocytosis of Bevacizumab by Glioblastoma Cells in the Perivascular Niche Affects their Survival.

    Science.gov (United States)

    Müller-Greven, Gaëlle; Carlin, Cathleen R; Burgett, Monica E; Ahluwalia, Manmeet S; Lauko, Adam; Nowacki, Amy S; Herting, Cameron J; Qadan, Maha A; Bredel, Markus; Toms, Steven A; Lathia, Justin D; Hambardzumyan, Dolores; Sarkaria, Jann N; Hamerlik, Petra; Gladson, Candece L

    2017-11-15

    Purpose: Bevacizumab, a humanized monoclonal antibody to VEGF, is used routinely in the treatment of patients with recurrent glioblastoma (GBM). However, very little is known regarding the effects of bevacizumab on the cells in the perivascular space in tumors. Experimental Design: Established orthotopic xenograft and syngeneic models of GBM were used to determine entry of monoclonal anti-VEGF-A into, and uptake by cells in, the perivascular space. Based on the results, we examined CD133 + cells derived from GBM tumors in vitro Bevacizumab internalization, trafficking, and effects on cell survival were analyzed using multilabel confocal microscopy, immunoblotting, and cytotoxicity assays in the presence/absence of inhibitors. Results: In the GBM mouse models, administered anti-mouse-VEGF-A entered the perivascular tumor niche and was internalized by Sox2 + /CD44 + tumor cells. In the perivascular tumor cells, bevacizumab was detected in the recycling compartment or the lysosomes, and increased autophagy was found. Bevacizumab was internalized rapidly by CD133 + /Sox2 + -GBM cells in vitro through macropinocytosis with a fraction being trafficked to a recycling compartment, independent of FcRn, and a fraction to lysosomes. Bevacizumab treatment of CD133 + GBM cells depleted VEGF-A and induced autophagy thereby improving cell survival. An inhibitor of lysosomal acidification decreased bevacizumab-induced autophagy and increased cell death. Inhibition of macropinocytosis increased cell death, suggesting macropinocytosis of bevacizumab promotes CD133 + cell survival. Conclusions: We demonstrate that bevacizumab is internalized by Sox2 + /CD44 + -GBM tumor cells residing in the perivascular tumor niche. Macropinocytosis of bevacizumab and trafficking to the lysosomes promotes CD133 + cell survival, as does the autophagy induced by bevacizumab depletion of VEGF-A. Clin Cancer Res; 23(22); 7059-71. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. Growth of Scytalidium sp. in a counterfeit bevacizumab bottle

    Directory of Open Access Journals (Sweden)

    Gerardo Garcia-Aguirre

    2013-01-01

    Full Text Available After drawing a dose from an closed bevacizumab (Avastin bottle, a fungus-like foreign body was observed inside. Samples from the vial were cultured in Sabouraud Emmons media. Growth of multiple light brown colonies with dark pigment was observed after 10 days. The species was identified as Scytalidium sp.Vial, analysis reported that the seal was lacking proper identification measures and that the label, batch number and expiry date did not correspond to a genuine product. Chemical analysis showed no protein, but 3% of polyethylene glycol, citrate and ethanol. Counterfeit bevacizumab is a real situation that poses a significant risk for ophthalmology and oncology patients. The medical community should be aware of this situation in order to enforce adequate preventive measures.

  10. Heparan Sulfate Binding Promotes Accumulation of Intravitreally Delivered Adeno-associated Viral Vectors at the Retina for Enhanced Transduction but Weakly Influences Tropism.

    Science.gov (United States)

    Woodard, Kenton T; Liang, Katharine J; Bennett, William C; Samulski, R Jude

    2016-11-01

    Many adeno-associated virus (AAV) serotypes efficiently transduce the retina when delivered to the subretinal space but show limited success when delivered to the vitreous due to the inner limiting membrane (ILM). Subretinal delivery of AAV serotype 2 (AAV2) and its heparan sulfate (HS)-binding-deficient capsid led to similar expression, indicating transduction of the outer retina occurred by HS-independent mechanisms. However, intravitreal delivery of HS-ablated recombinant AAV2 (rAAV2) led to a 300-fold decrease in transduction compared to AAV2. Fluorescence in situ hybridization of AAV transgenes was used to identify differences in retinal trafficking and revealed that HS binding was responsible for AAV2 accumulation at the ILM. This mechanism was tested on human ex vivo retinas and showed similar accumulation with HS-binding AAV2 capsid only. To evaluate if HS binding could be applied to other AAV serotypes to enhance their transduction, AAV1 and AAV8 were modified to bind HS with a single-amino-acid mutation and tested in mice. Both HS-binding mutants of AAV1 and AAV8 had higher intravitreal transduction than their non-HS-binding parent capsid due to increased retinal accumulation. To understand the influence that HS binding has on tropism, chimeric AAV2 capsids with dual-glycan usage were tested intravitreally in mice. Compared to HS binding alone, these chimeric capsids displayed enhanced transduction that was correlated with a change in tropism. Taken together, these data indicate that HS binding serves to sequester AAV capsids from the vitreous to the ILM but does not influence retinal tropism. The enhanced retinal transduction of HS-binding capsids provides a rational design strategy for engineering capsids for intravitreal delivery. Adeno-associated virus (AAV) has become the vector of choice for viral gene transfer and has shown great promise in clinical trials. The need for development of an easy, less invasive injection route for ocular gene therapy

  11. CCR 20th Anniversary Commentary: Bevacizumab in the Treatment of Glioblastoma--The Progress and the Limitations.

    Science.gov (United States)

    Mar, Nataliya; Desjardins, Annick; Vredenburgh, James J

    2015-10-01

    Vredenburgh and colleagues conducted the first phase II study of bevacizumab plus irinotecan in recurrent malignant glioma, confirming the safety and efficacy of bevacizumab. This study, which was published in the February 15, 2007, issue of Clinical Cancer Research, was a stepping stone for subsequent research, leading to regulatory approval of bevacizumab for recurrent glioblastoma. ©2015 American Association for Cancer Research.

  12. Intravitreal Triamcinolone for Acute Branch Retinal Vein Occlusion: a Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Alireza Ramezani

    2011-01-01

    Full Text Available Purpose: To evaluate the therapeutic effect of intravitreal triamcinolone (IVT injection for recent branch retinal vein occlusion (BRVO. Methods: In a randomized controlled clinical trial, 30 phakic eyes with recent (less than 10 weeks′ duration BRVO were assigned to two groups. The treatment group (16 eyes received 4 mg IVT and the control group (14 eyes received subconjunctival sham injections. Changes in visual acuity (VA were the main outcome measure. Results: VA and central macular thickness (CMT changes were not significantly different between the study groups at any time point. Within group analysis showed significant VA improvement from baseline in the IVT group up to three months (P 0.05. Significant reduction in CMT was noticed only in the treatment group (‑172 ± 202 μm, P = 0.029 and at 4 months. Ocular hypertension occurred in 4 (25% and 2 (14.3% eyes in the IVT and control groups, respectively. Conclusion: A single IVT injection had a non-significant beneficial effect on VA and CMT in acute BRVO as compared to the natural history of the condition. The 3-month deferred treatment protocol advocated by the Branch Vein Occlusion Study Group may be a safer option than IVT injection considering its potential side effects.

  13. A prospective randomized evaluation of topical gatifloxacin on conjunctival flora in patients undergoing intravitreal injections.

    Science.gov (United States)

    Moss, Jason M; Sanislo, Steven R; Ta, Christopher N

    2009-08-01

    We sought to assess the efficacy of 3-day topical gatifloxacin use in combination with povidone-iodine (PVI) versus PVI alone in eliminating conjunctival bacterial flora in patients scheduled to undergo intravitreal (IVT) injection. Prospective, randomized single-blind clinical trial. We included 129 patients scheduled to undergo 273 IVT injections at California Vitreoretinal Center at Stanford University. Study patients were randomized to self-administration of gatifloxacin drops for 3 days before injection, or no pretreatment antibiotics. Cultures were collected from the bulbar conjunctiva at the injection site and at the corresponding location in the fellow eye before PVI preparation. After topical PVI treatment and immediately before injection, a third culture was obtained at the injection site. Additionally, the injection needle was also cultured after the procedure. Incidence of positive bacterial samples collected from injection site conjunctiva and injection needles. Three-day gatifloxacin use resulted in a significantly lower rate of SeptiChek (Becton Dickinson, Franklin Lakes, NJ) positive cultures compared with untreated controls (21% vs 48% respectively, P = 0.005). After topical PVI, the rate of positive bacterial cultures in gatifloxacin-treated and control eyes were similar (8% and 4%, respectively; P = 0.324). Although 3-day topical gatifloxacin use is effective in reducing the frequency of conjunctival bacterial growth relative to untreated eyes, antibiotic use confers no additional benefit in combination with PVI than eyes receiving PVI alone. This supports that topical PVI is an effective preinjection monotherapy for infection prophylaxis in the setting of IVT injections.

  14. Nurse-led ranibizumab intravitreal injections in wet age-related macular degeneration: a literature review.

    Science.gov (United States)

    Gregg, Emma

    2017-04-12

    Aim The aim of this literature review was to explore the development of the role of specialist ophthalmic nurses in delivering ranibizumab intravitreal injections to patients with wet age-related macular degeneration (AMD), and to evaluate their contribution to reducing capacity pressures in medical retina services, while maintaining safe and effective standards of care. Method A systematic literature search was undertaken to identify relevant articles published between January 2000 and June 2015. A search of electronic databases was undertaken, and selected relevant journals were searched manually. A free text and subject heading search strategy was conducted, in which the abstracts of publications identified for review were assessed for relevance. Inclusion criteria were: nurses delivering ranibizumab intravitreal treatment; studies performed in the UK and other countries; and patients with AMD, diabetic macular oedema or central retinal vein occlusion receiving nurse-led ranibizumab (Lucentis) intravitreal treatment. Findings Five studies were identified from the literature search, which audited a total of 31,303 injections delivered by nurse practitioners between January 2007 and November 2013. The visual outcomes and the rate of complications from intravitreal injections delivered by trained ophthalmic nurse practitioners were comparable to intravitreal injections delivered by ophthalmologists. Four of the five studies reported increased patient satisfaction, patients consenting to nurse-delivered intravitreal injections, favourable pain experience, and absence of complaints. Conclusion Practice innovation is an example of a quality, innovation, productivity and prevention process. Role expansion, in which specialist ophthalmic nurses deliver intravitreal injections, has been shown to be economical, safe and effective. It enables timely delivery of the service, thereby preventing irreversible blindness for individuals with wet AMD.

  15. Panretinal photocoagulation versus intravitreal injection retreatment pain in high-risk proliferative diabetic retinopathy

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    Célia Regina Farias de Araújo Lucena

    2013-02-01

    Full Text Available PURPOSE: To compare pain related to intravitreal injection and panretinal photocoagulation in the management of patients with high-risk proliferative diabetic retinopathy. METHODS: Prospective study including patients with high-risk proliferative diabetic retinopathy and no prior laser treatment randomly assigned to receive panretinal photocoagulation (PRP group or panretinal photocoagulation plus intravitreal ranibizumab (PRPplus group. In all patients, panretinal photocoagulation was administered in two sessions (weeks 0 and 2, and intravitreal ranibizumab was administered at the end of the first laser session in the PRPplus group. Retreatment was performed at weeks 16 and 32 if active new vessels were detected at fluorescein angiography. Patients in the PRPplus group received intravitreal ranibizumab and patients in the PRP group received 500-µm additional spots per quadrant of active new vessels. After the end of retreatment, a 100-degree Visual Analog Scale was used for pain score estimation. The patient was asked about the intensity of pain during the whole procedure (retinal photocoagulation session or intravitreal ranibizumab injection. Statistics for pain score comparison were performed using a non-parametric test (Wilcoxon rank sums. RESULTS: Seventeen patients from PRPplus and 14 from PRP group were evaluated for pain scores. There were no significant differences between both groups regarding gender, glycosylated hemoglobin and disease duration. Mean intravitreal injection pain (±SEM was 4.7 ± 2.1 and was significantly lower (p<0.0001 than mean panretinal photocoagulation pain (60.8 ± 7.8. Twelve out of 17 patients from the PRPplus group referred intensity pain score of zero, while the minimal score found in PRP group was found in one patient with 10.5. CONCLUSION: In patients with high-risk proliferative diabetic retinopathy who needed retreatment for persistent new vessels, there was more comfort for the patient when retreatment

  16. Bevacizumab Demonstrates Prolonged Disease Stabilization in Patients with Heavily Pretreated Metastatic Renal Cell Carcinoma: A Case Series and Review of the Literature

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    Nicole M. Agostino

    2010-01-01

    Full Text Available There are now a variety of therapies approved for the treatment of metastatic renal cell carcinoma (RCC. These include the immunotherapeutics, alfa-interferon, and interleukin-2, and agents that target the vascular endothelial growth factor receptor (VEGFR via its tyrosine kinase, such as sorafenib, sunitinib, and pazopanib, or the mammalian target of rapamycin (mTOR, such as temsirolimus and everolimus. Bevacizumab, a monoclonal antibody directed against the ligand, VEGF, has shown activity against RCC as a single agent in patients who had failed prior cytokine therapy and as first line therapy in combination with interferon. The activity of bevacizumab in patients who had received and failed prior therapy has not been described. We report our experience in 4 patients with metastatic RCC who had failed prior cytokine, TKI, and mTOR inhibitors who were treated with bevacizumab as single agent therapy. These heavily pretreated patients sustained very prolonged periods of stable disease (median of 12 months with very little toxicity and excellent quality of life. The activity of this agent in patients who had failed prior therapies directed against the VEGFR and mTOR suggests that therapy targeting the ligand, VEGF, is still a viable approach in these patients and deserves further study.

  17. In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft

    NARCIS (Netherlands)

    Nagengast, Wouter B.; Hospers, Geke A.; Mulder, Nanno H.; de Jong, Johan R.; Hollema, Harry; Brouwers, Adrienne H.; van Dongen, Guns A.; Perk, Lars R.; Lub-de Hooge, Marjolijn N.

    Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor angiogenesis. The humanized monoclonal antibody bevacizumab blocks VEGF-induced tumor angiogenesis by binding, thereby neutralizing VEGF. Our aim was to develop radiolabeled bevacizumab for

  18. An updated meta-analysis of fatal adverse events caused by bevacizumab therapy in cancer patients.

    Directory of Open Access Journals (Sweden)

    Hongxin Huang

    Full Text Available BACKGROUND: The risk of fatal adverse events (FAEs due to bevacizumab-based chemotherapy has not been well described; we carried out an updated meta-analysis regarding this issue. METHODS: An electronic search of Medline, Embase and The Cochrane Central Register of Controlled Trials was conducted to investigate the effects of randomized controlled trials on bevacizumab treatment on cancer patients. Random or fixed-effect meta-analytical models were used to evaluate the risk ratio (RR of FAEs due to the use of bevacizumab. RESULTS: Thirty-four trials were included. Allocation to bevacizumab therapy significantly increased the risk of FAEs; the RR was 1.29 (95% CI:1.05-1.57. This association varied significantly with tumor types (P=0.002 and chemotherapeutic agents (P=0.005 but not with bevacizumab dose (P=0.90. Increased risk was seen in patients with non-small cell lung cancer, pancreatic cancer, prostate cancer, and ovarian cancer. However, FAEs were lower in breast cancer patients treated with bevacizumab. In addition, bevacizumab was associated with an increased risk of FAEs in patients who received concomitant agents of taxanes and/or platinum. CONCLUSION: Compared with chemotherapy alone, the addition of bevacizumab was associated with an increased risk of FAEs among patients with special tumor types, particularly when combined with chemotherapeutic agents such as platinum.

  19. Primary tumor location and bevacizumab effectiveness in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Boisen, M K; Johansen, J S; Dehlendorff, Christian

    2013-01-01

    There is an unmet need for predictive markers for the antiangiogenic agent bevacizumab in metastatic colorectal cancer (mCRC). We aimed to assess whether the location of the primary tumor is associated with bevacizumab effectiveness when combined with capecitabine and oxaliplatin (CAPEOX...

  20. Influence of the American ODAC Statement on Austrian Bevacizumab Prescribing Practice for Metastatic Breast Cancer

    OpenAIRE

    Preusser, Matthias; Fülöp, Gerhard; Berghoff, Anna Sophie; Heinzl, Harald; Steger, Guenther G.; Greil, Richard; Zielinski, Christoph C.; Bartsch, Rupert

    2012-01-01

    The influence of the discrepancy between the Oncologic Drugs Advisory Committee (ODAC) and European Medicines Agency positions on bevacizumab prescribing practice for metastatic breast cancer in Austria during January 2006 to June 2011 was investigated. The Austrian bevacizumab prescribing practice was found to be significantly influenced by the ODAC statement issued in July 2010.

  1. Discontinuous Schedule of Bevacizumab in Colorectal Cancer Induces Accelerated Tumor Growth and Phenotypic Changes

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    Selma Becherirat

    2018-04-01

    Full Text Available Antiangiogenics administration in colorectal cancer patients seemed promising therapeutic approach. Inspite of early encouraging results, it however gave only modest clinical benefits. When AAG was administered with discontinuous schedule, the disease showed acceleration in certain cases. Though resistance to AAG has been extensively studied, it is not documented for discontinuous schedules. To simulate clinical situations, we subjected a patient-derived CRC subcutaneous xenograft in mice to three different protocols: 1 AAG (bevacizumab treatment for 30 days (group A (group B was the control, 2 bevacizumab treatment for 50 days (group C and bevacizumab for 30 days and 20 without treatment (group D, and 3 bevacizumab treatment for 70 days (group E and 70 days treatment with a drug-break period between day 30 and 50 (group F. The tumor growth was monitored, and at sacrifice, the vascularity of tumors was measured and the proangiogenic factors quantified. Tumor phenotype was studied by quantifying cancer stem cells. Interrupting bevacizumab during treatment accelerated tumor growth and revascularization. A significant increase of proangiogenic factors was observed when therapy was stopped. On withdrawal of bevacizumab, as also after the drug-break period, the plasmatic VEGF increased significantly. Similarly, a notable increase of CSCs after the withdrawal and drug-break period of bevacizumab was observed (P<.01. The present study indicates that bevacizumab treatment needs to be maintained because discontinuous schedules tend to trigger tumor regrowth, and increase tumor resistance and CSC heterogeneity.

  2. Cetuximab Reduces the Accumulation of Radiolabeled Bevacizumab in Cancer Xenografts without Decreasing VEGF Expression

    NARCIS (Netherlands)

    Heskamp, Sandra; Boerman, Otto C.; Molkenboer-Kuenen, Janneke D. M.; Sweep, Fred C. G. J.; Geurts-Moespot, Anneke; Engelhardt, Mallory S.; van der Graaf, Winette T. A.; Oyen, Wim J. G.; van Laarhoven, Hanneke W. M.

    2014-01-01

    Bevacizumab and cetuximab are approved for the treatment of cancer. However, in advanced colorectal cancer, addition of cetuximab to chemotherapy with bevacizumab did not improve survival. The reason for the lack of activity remains unclear. The aim of this study was to determine the effect of

  3. The predictive value of serum VEGF in multiresistant ovarian cancer patients treated with bevacizumab

    DEFF Research Database (Denmark)

    Smerdel, M P; Steffensen, K D; Waldstrøm, M

    2010-01-01

    Bevacizumab, a humanized monoclonal antibody against VEGF (vascular endothelial growth factor), has shown antitumor activity, but so far no biomarkers have been identified to predict outcome. The purpose of the present study was to investigate the efficacy of bevacizumab in patients...

  4. Gastrointestinal ulceration as a possible side effect of bevacizumab which may herald perforation

    NARCIS (Netherlands)

    Tol, J.; Cats, A.; Mol, L.; Koopman, M.; Bos, M. M. E. M.; van der Hoeven, J. J. M.; Antonini, N. F.; van Krieken, J. H. J. M.; Punt, C. J. A.

    2008-01-01

    Chemotherapy plus bevacizumab is currently considered as the standard 1st line treatment of advanced colorectal cancer (ACC). Whereas GI perforation is a known side effect of bevacizumab, the development of GI ulcers has not been reported. We identified 18 patients with ACC who participated in a

  5. Monitoring hypoxia and vasculature during bevacizumab treatment in a murine colorectal cancer model

    NARCIS (Netherlands)

    Heijmen, L.; ter Voert, E. G. W.; Punt, C. J. A.; Heerschap, A.; Oyen, W. J. G.; Bussink, J.; Sweep, C. G. J.; Laverman, P.; Span, P. N.; de Geus-Oei, L. F.; Boerman, O. C.; van Laarhoven, H. W. M.

    2014-01-01

    The purpose of this study was to assess the effect of bevacizumab on vasculature and hypoxia in a colorectal tumor model. Nude mice with subcutaneous LS174T tumors were treated with bevacizumab or saline. To assess tumor properties, separate groups of mice were imaged using (18) F-Fluoromisonidazole

  6. 77 FR 11554 - Final Decision on Withdrawal of Breast Cancer Indication for AVASTIN (Bevacizumab) Following...

    Science.gov (United States)

    2012-02-27

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0621] Final Decision on Withdrawal of Breast Cancer Indication for AVASTIN (Bevacizumab) Following Public... the breast cancer indication for AVASTIN (Bevacizumab). The Commissioner of Food and Drugs (the...

  7. Preclinical aspects of anti-VEGF agents for the treatment of wet AMD: ranibizumab and bevacizumab

    Science.gov (United States)

    Meyer, C H; Holz, F G

    2011-01-01

    Three anti-vascular endothelial growth factor (VEGF) therapies are currently used for the treatment of patients with wet age-related macular degeneration (AMD): pegaptanib, ranibizumab, and bevacizumab. Ranibizumab is an antibody fragment approved for the treatment of wet AMD. Bevacizumab is a full-length antibody registered for use in oncology but unlicensed for wet AMD. However, it is used off-label worldwide not only for wet AMD but also for various other ocular diseases associated with macular edema and abnormal vessel growth. We consider aspects of ranibizumab and bevacizumab in relation to their molecular characteristics, in vitro and in vivo properties, and preclinical safety data. Before 2009, most studies described the short-term toxicity of bevacizumab in multiple cell types of the eye. Since 2009, an increasing number of studies have compared the properties of ranibizumab and bevacizumab and investigated their impact on retinal cell functioning. Compared with bevacizumab, ranibizumab neutralizes VEGF better at low concentrations, maintains efficacy for longer, and has a higher retinal penetration and potency. Studies in animals demonstrate ranibizumab to be better localized to the injected eye, whereas bevacizumab appears to have a greater effect in the fellow eye. In humans, a localized and systemic effect has been reported for both molecules. In conclusion, overlapping yet distinct pharmacological properties of ranibizumab and bevacizumab indicate that safety or efficacy data from one cannot be extrapolated to the other. PMID:21455242

  8. 76 FR 27332 - Proposal To Withdraw Approval for the Breast Cancer Indication for Bevacizumab; Hearing

    Science.gov (United States)

    2011-05-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0621] Proposal To Withdraw Approval for the Breast Cancer Indication for Bevacizumab; Hearing AGENCY: Food and...) proposal to withdraw approval of the breast cancer indication for bevacizumab (Avastin). Genentech is the...

  9. Gene expression profile and angiogenic marker correlates with response to neoadjuvant bevacizumab followed by bevacizumab plus chemotherapy in breast cancer.

    Science.gov (United States)

    Yang, Sherry X; Steinberg, Seth M; Nguyen, Dat; Wu, Thomas D; Modrusan, Zora; Swain, Sandra M

    2008-09-15

    To identify biomarkers and gene expression profile signatures to distinguish patients with partial response (PR) from those with stable disease (SD) and progressive disease (PD). Twenty patients with inflammatory breast cancer and one patient with locally advanced breast cancer received one cycle of bevacizumab followed by six cycles of bevacizumab plus docetaxel-doxorubicin before surgery. Baseline angiogenic/tumor markers were examined by immunohistochemistry and gene expression profiles were measured by Agilent Whole Human Genome arrays. All were assessed for clinical response. Fourteen patients (67%, 95% confidence interval, 43-85.4%) had PR, five had SD, and two had PD. Expression of CD31 and platelet-derived growth factor receptor-beta (PDGFR-beta) in the tumor vasculature by immunohistochemistry was significantly associated with response (PR versus SD/PD; CD31 median, 33.5 versus 13.2; P = 0.0004; PDGFR-beta median, 5.9 versus 0.6; P = 0.01). Tumor VEGF-A showed a trend towards association with response (2.65 versus 0.25; P = 0.04). pVEGFR2(Y996), pVEGFR2(Y951), MVD, Ki67, apoptosis, grade, ER, HER-2/neu, and p53 were not associated with response. Twenty-six of 1,339 Gene Ontology (GO) classes at the gene transcriptional level were differentially expressed between patients with PR and SD/PD (P < 0.005). Representative significant GO classes include spindle (11 genes; P = 0.001), vascular endothelial growth factor receptor activity including PDGFR-beta (5 genes; P = 0.002), and cell motility including CD31 (80 genes; P = 0.005). Baseline CD31, PDGFR-beta, and GO classes for vascular endothelial growth factor receptor activity and mitosis were significantly associated with response to bevacizumab followed by bevacizumab plus chemotherapy.

  10. [Surgery in posterior luxated lens fragments through intravitreal phacofragmentation].

    Science.gov (United States)

    Branisteanu, D; Moraru, Andreea

    2013-01-01

    To assess the intra and postoperative difficulties, the anatomical and functional results after intravitreal phacoemulsification during pars plana vitrectomy for retained intraocular lens fragments. Retrospective, non-comparative case series of 48 eyes who underwent vitrectomy for posterior dislocated lens fragments during phacoemulsification between January 2000 and January 2010. In 11 cases the vitrectomy was performed immediately, within 24 hours, and in 37 cases it was delayed 2 to 10 days after cataract surgery. During pars plana vitrectomy the lens fragments were separated of vitreous strings and then phacoemulsification was performed into the center of vitreous cavity. All cases were performed under local anesthesia by the same surgeon. During vitrectomy PFCL was used in 5 cases to protect central retina. Cases were followed-up at least 6 months. Statistical analysis was performed using Wilcoxon and chi square tests. Mean age in the study group was 65.38% 9.49 years (ranging 52-82 years). The mean visual acuity improved from 0.12% 0.07 (0.04-0.3) preoperatively to 0.3% 0.2 (0.05-0.6) postoperatively (p < 0.01). Mean intraocular pressure decreased postoperatively from 26.24% 9.3 mmHg (16-48 mmHg) to 15.95% 3.69 mmHg(12-24 mmHg) (p < 0.01). In all cases corneal edema and intraocular inflammation ceased after vitrectomy. In those 11 cases operated immediately the intravitreal phacoemulsification time was longer, as well as greater number of intraoperative complication (corneal edema, corneal leakage). In 4 out of these 11 cases (36.36%) severe postoperative retinal complications were noticed (2 cases of retinal detachment, 1 case of choroidal detachment and 1 case of choroidal hematoma). In the delayed group the only postoperative complication was cystoid macular edema in 9 out of 37 cases (24.32%). Removal of retained intraocular lens fragments suspended the intraocular inflammation and normalized intraocular pressure in all cases. Our results are in favor of

  11. Efficacy of intravitreal dexamethasone implant for prostaglandin-induced refractory pseudophakic cystoid macular edema: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Sacchi M

    2014-07-01

    Full Text Available Matteo Sacchi, Edoardo Villani, Francesca Gilardoni, Paolo Nucci University Eye Clinic, San Giuseppe Hospital, University of Milan, Milan, Italy Background: Macular edema is a known complication even after uneventful cataract surgery. The chronic use of prostaglandin analogs is a risk factor for the development of pseudophakic cystoid macular edema (CME. Nonsteroidal anti-inflammatory drugs (NSAIDs are considered first-line therapy but refractory postsurgical CME represents a therapeutic challenge, as there is not an evidence-based treatment.Objective: To report the use of a single implant of intravitreal dexamethasone for tafluprost-associated pseudophakic CME refractory to NSAIDs and to sub-Tenon’s corticosteroid injections.Case report: A 64-year-old female with ocular hypertension treated with tafluprost experienced decreased vision (visual acuity 20/60 and metamorphopsia 2 months after uneventful cataract extraction. Spectral domain optical coherence tomography (SD-OCT revealed CME. After 1 month of topical and oral NSAIDs, CME was still evident on SD-OCT (visual acuity 20/50. Two sub-Tenon’s betamethasone injections were performed at a 2-week interval. As CME was still present, 2 months after the diagnosis of CME (visual acuity 20/40, the patient underwent a single dexamethasone intravitreal implant. One month later, macular appearance was normal, and visual acuity increased to 20/30. This result was maintained throughout the 6 months of follow-up.Conclusion: In this report, a single implant of intravitreal dexamethasone successfully treated pseudophakic CME associated with the use of prostaglandin analogs unresponsive to NSAIDs and sub-Tenon’s betamethasone. The results of this report need to be corroborated by powered, prospective, randomized trials. The need for repeated treatments as well as the retreatment interval in patients requiring more than a single injection are issues still needing further investigations. Keywords

  12. Prophylactic plastic surgery closure of neurosurgical scalp incisions reduces the incidence of wound complications in previously-operated patients treated with bevacizumab (Avastin®) and radiation.

    Science.gov (United States)

    Golas, Alyssa Reiffel; Boyko, Tatiana; Schwartz, Theodore H; Stieg, Philip E; Boockvar, John A; Spector, Jason A

    2014-09-01

    Neurosurgical craniotomy, craniectomy, or other trans-galeal interventions are performed for a variety of indications, including the resection of benign or malignant tumors, hematoma evacuation, and for the management of intractable seizure disorders. Despite an overall low complication rate of intervention, wound healing complications such as dehiscence, surgical site infection, and cerebrospinal fluid leak are not uncommon. A retrospective review was performed of all patients who underwent scalp incision closure at a single institution by a single plastic surgeon between 2006 and 2013. Sixty patients (83 procedures) were included in the study. Fifty-seven patients (95.0 %) underwent previous craniotomy, craniectomy, or other trans-galeal procedure. Of the total 60 patients, 35 patients received preoperative radiation. Sixteen patients received bevacizumab prior to their index case, while 12 received bevacizumab postoperatively. Ten patients (16.7 %) required additional plastic surgical intervention for wound complications after their index plastic surgery procedure. Plastic surgery was consulted prophylactically in 34 patients (38 procedures). When plastic surgery was consulted prophylactically, 4 patients (11.8 %) required further wound revision. None of the 14 patients who underwent prophylactic plastic surgery closure for previous scalp incision, preoperative bevacizumab, and XRT administration required re-intervention. Plastic surgery closure of complex scalp incisions reduces the incidence of wound complications among patients who underwent previous neurosurgical intervention, XRT administration, and preoperative bevacizumab administration. This is particularly true when plastic surgery closure is performed "prophylactically." Further collaboration between the neurosurgical and plastic surgery teams is therefore warranted, particularly in the setting of these high-risk cases.

  13. Bevacizumab in the Treatment of Metastatic Breast Cancer: Friend or Foe?

    Science.gov (United States)

    Montero, Alberto J.; Escobar, Mauricio; Lopes, Gilberto; Glück, Stefan; Vogel, Charles

    2011-01-01

    Metastatic breast cancer (MBC) is a major cause of death among women worldwide. Progress has been made in treating MBC with the advent of anti-estrogen therapies, potent cytotoxic agents, and monoclonal antibodies. Bevacizumab is a monoclonal antibody against circulating vascular endothelial growth factor (VEGF), which was approved in 2008 by the US Food and Drug Administration (FDA), for first-line treatment of HER-2 negative MBC in combination with paclitaxel. The FDA then reversed this decision in December 2010 by recommending removal of the MBC indication from bevacizumab, citing primarily safety concerns, and that these risks did not outweigh the ability of bevacizumab to significantly prolong progression-free survival. This decision was unexpected in the oncology community and remains controversial. This review looks at all available phase 3 data with bevacizumab in the MBC setting to determine whether the data support this decision by the FDA, and discusses the future of bevacizumab in breast cancer. PMID:22012632

  14. Bevacizumab (Avastin) conjugated microbubbles for anti-VEGF treatment of neovascular age-related macular degeneration

    Science.gov (United States)

    Zhang, Leilei; Xu, Jeff; Huang, Jiwei; Roberts, Cynthia; Xu, Ronald

    2010-02-01

    Bevacizumab (Avastin) has been used as one of the anti-VEGF therapies to manage neovascular age-related macular degeneration (AMD). The drug delivery system for bevacizumab needs to be improved in order to decrease the frequency of injection and reduce the adverse effects. In our study, bevacizumab was conjugated with poly (lactic-co-glycolic acid) (PLGA) microbubbles by activating carboxyl functional groups. The averaged size of microbubbles was estimated 1.055+/-0.258μm, allowing for ultrasound guided drug delivery. The binding efficiency between bevacizumab and microbubbles was evaluated in an enzyme-linked immunosorbent assay plate. The test results demonstrated the potential of using PLGA microbubbles to deliver bevacizumab with imaging guidance.

  15. Severe Cardiotoxicity in a Patient with Colorectal Cancer Treated with Bevacizumab.

    Science.gov (United States)

    Chen, Jian; Du, Fengcai; Hu, Baohong; Chi, Cheng; Chu, Hongjin; Jiang, Lixin; Li, Peng; Gong, Zhaohua

    2017-08-01

    Bevacizumab combined with standard chemotherapeutics has become a choice of treatment for several kinds of cancers. Hypertension, third-degree albuminuria, thrombosis and cardiotoxicity are the reported side-effects of bevacizumab. Among them, cardiotoxicity is a most severe, but rare outcome. We report a case of a 62-year-old female with colorectal carcinoma who was given bevacizumab-containing chemotherapy for more than 20 months and achieved a stable disease during the entire course of treatment. Thereafter, she developed cardiotoxicity including grade 3 hypertension, tricuspid regurgitation, pulmonary hypertension, left ventricular diastolic dysfunction and pericardial effusion, and was discontinued from the regimen with bevacizumab. Although clinically-effective, the severe cardiotoxicity of bevacizumab developed after over 20 courses of treatment prompted us to look for optimal chemotherapy prescription in order to achieve a better clinical outcome. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  16. Angiotensinogen and HLA class II predict bevacizumab response in recurrent glioblastoma patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Michaelsen, Signe Regner; Olsen, Lars Rønn

    2016-01-01

    Background: Bevacizumab combination therapy is among the most frequently used treatments in recurrent glioblastoma and patients who achieve response to bevacizumab have improved survival as well as quality of life. Accordingly, the aim of this study was to identify predictive biomarkers...... for bevacizumab response in recurrent glioblastoma patients. Methods: The study included a total of 82 recurrent glioblastoma patients treated with bevacizumab combination therapy whom were both response and biomarker evaluable. Gene expression of tumor tissue was analyzed by using a customized Nano.......0009) and high expression of a HLA class II gene (2-fold increase in HLA-DQA1; OR = 1.22; 95% CI: 1.01-1.47; P = 0.04). These two genes were included in a model that is able predict response to bevacizumab combination therapy in clinical practice. When stratified for a validated prognostic index, the predictive...

  17. Developing a Noninvasive Procedure Using Labeled Monoclonal Antibody Anti-VEGF (Bevacizumab) for Detection of Endometriosis

    Science.gov (United States)

    Machado, Daniel Escorsim; Perini, Jamila Alessandra; Orlando, Margarida Maria Camoes

    2015-01-01

    The off-label use of bevacizumab labeled with 99mTc as a new radiopharmaceutical for imaging of endometriosis is a promising noninvasive, new clinical procedure. The bevacizumab in monoclonal antibodies targeted at vascular endothelial growth factor (VEGF) is superexpressed in cases of endometriosis. In this study we evaluate the imaging of endometriosis lesion in rats (induced to endometriosis) using bevacizumab-99mTc. The results showed that bevacizumab-99mTc imaged the lesion and support his use for Nuclear Medicine applied to gynecology. Also the results appointed that this radiopharmaceutical has a hepatobiliary excretion. It is important to notice that the dose used was almost 0,01% of the usual dose for the bevacizumab. PMID:26240826

  18. Bevacizumab in high-grade gliomas: a review of its uses, toxicity assessment, and future treatment challenges

    Directory of Open Access Journals (Sweden)

    Rahmathulla G

    2013-04-01

    Full Text Available Gazanfar Rahmathulla,1 Elizabeth J Hovey,2,3 Neda Hashemi-Sadraei,4 Manmeet S Ahluwalia4 1Department of Neurological Surgery, Cleveland Clinic, Cleveland, OH, 2Department of Medical Oncology, Prince of Wales Hospital, Sydney, NSW, Australia; 3School of Medicine, University of New South Wales, Sydney, NSW, Australia; 4Department of Medical Oncology, Neurological and Taussig Cancer Institutes, Cleveland Clinic, Cleveland, OH, USA Abstract: High-grade gliomas continue to have dismal prognosis despite advances made in understanding the molecular genetics, signaling pathways, cytoskeletal dynamics, and the role of stem cells in gliomagenesis. Conventional treatment approaches, including surgery, radiotherapy, and cytotoxic chemotherapy, have been used with limited success. Therapeutic advances using molecular targeted therapy, immunotherapy, and others such as dietary treatments have not been able to halt tumor progression and disease-related death. High-grade gliomas (World Health Organization grades III/IV are histologically characterized by cellular and nuclear atypia, neoangiogenesis, and necrosis. The expression of vascular endothelial growth factor, a molecular mediator, plays a key role in vascular proliferation and tumor survival. Targeting vascular endothelial growth factor has demonstrated promising results, with improved quality of life and progression-free survival. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor, is approved by the Food and Drug Administration as a single agent in recurrent glioblastoma and is associated with manageable toxicity. This review discusses the efficacy, practical aspects, and response assessment challenges with the use of bevacizumab in the treatment of high-grade gliomas. Keywords: bevacizumab, antiangiogenesis, glioma, glioblastoma, vascular endothelial growth factor

  19. Bevacizumab toxicity in heavily pretreated recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancers

    Science.gov (United States)

    Goff, Barbara A.

    2016-01-01

    Objective Bevacizumab was recently approved by the US Food and Drug Administration for use in recurrent platinum resistant epithelial ovarian cancer (EOC), fallopian tube cancer (FTC), or primary peritoneal cancer (PPC) when no more than two prior cytotoxic regimens have been used; due to concerns for gastrointestinal perforation. We sought to determine bevacizumab-related toxicities in heavily pretreated recurrent EOC. Methods We performed a retrospective chart review of patients with recurrent EOC, FTC, and PPC from 2001 to 2011. Patients who received at least two prior chemotherapy regimens before bevacizumab were included. Medical records were reviewed for bevacizumab associated toxicities. The Wilcoxon-Mann-Whitney test was used to compare quantitative variables. Survival was estimated with the Kaplan-Meier method. Results Sixty patients met inclusion criteria. At the start of bevacizumab treatment, the median age was 60 years and the median body mass index was 26.5 kg/m2. More than 50% of patients received bevacizumab after three prior cytotoxic regimens. Grade 3 or higher bevacizumab associated toxicity events occurred in four patients, including one patient who developed a rectovaginal fistula. The median overall survival from the start of bevacizumab treatment was 21.05 months (95% CI, 18.23 to 32.67; range, 1.9 to 110 months). The number of cytotoxic regimens prior to bevacizumab treatment did not differ in those that experienced a toxicity versus those that did not (p=0.66). Conclusion The use of bevacizumab in heavily pretreated EOC, FTC, or PPC is worth consideration. PMID:27329195

  20. Rational design of therapeutic mAbs against aggregation through protein engineering and incorporation of glycosylation motifs applied to bevacizumab

    Science.gov (United States)

    Courtois, Fabienne; Agrawal, Neeraj J; Lauer, Timothy M; Trout, Bernhardt L

    2016-01-01

    The aggregation of biotherapeutics is a major hindrance to the development of successful drug candidates; however, the propensity to aggregate is often identified too late in the development phase to permit modification to the protein's sequence. Incorporating rational design for the stability of proteins in early discovery has numerous benefits. We engineered out aggregation-prone regions on the Fab domain of a therapeutic monoclonal antibody, bevacizumab, to rationally design a biobetter drug candidate. With the purpose of stabilizing bevacizumab with respect to aggregation, 2 strategies were undertaken: single point mutations of aggregation-prone residues and engineering a glycosylation site near aggregation-prone residues to mask these residues with a carbohydrate moiety. Both of these approaches lead to comparable decreases in aggregation, with an up to 4-fold reduction in monomer loss. These single mutations and the new glycosylation pattern of the Fab domain do not modify binding to the target. Biobetters with increased stability against aggregation can therefore be generated in a rational manner, by either removing or masking the aggregation-prone region or crowding out protein-protein interactions. PMID:26514585

  1. Intravitreal ranibizumab for diabetic macular oedema in previously vitrectomized eyes

    DEFF Research Database (Denmark)

    Laugesen, Caroline Schmidt; Ostri, Christoffer; Brynskov, Troels

    2017-01-01

    PURPOSE: There is little information about the efficacy of intravitreal vascular endothelial growth factor (VEGF) inhibition in vitrectomized eyes. This study aimed to evaluate the efficacy of anti-VEGF (ranibizumab) on diabetic macular oedema in previously vitrectomized eyes. METHODS: A nationwide...... retrospective review of medical records from 2010 to 2013. RESULTS: We identified 33 previously vitrectomized eyes in 28 patients treated with ranibizumab injections for diabetic macular oedema. Median follow-up was 323 days (interquartile range 72-1404 days). Baseline mean visual acuity was 0.57 logMAR (95% CI...... 0.13-1.01) before injections. After an average of 4.7 injections (range 1-15), mean visual acuity remained stable at 0.54 logMAR (95% CI 0.13-0.95) with a mean improvement of 0.03 (p = 0. 45, 95% CI -0.12 to 0.06). In 12 eyes (36%), visual acuity improved 0.1 logMAR or more, in 12 eyes (36%), vision...

  2. Intravitreal low molecular weight heparin in PVR surgery.

    Directory of Open Access Journals (Sweden)

    Kumar Atul

    2003-01-01

    Full Text Available Purpose: To evaluate the efficacy of low molecular weight heparin (LMWH in prevention of postoperative fibrin formation following vitreoretinal surgery with proliferative vitreoretinopathy (PVR. Material and Methods: Thirty consecutive patients of retinal detachment with advanced PVR were enrolled in the study. They were randomised to study and control groups (n = 15 each. Study group patients received vitreoretinal surgery with 5 IU/cc of LMWH in vitrectomy infusion fluid. The control group patients received vitroretinal surgery without heparin in the infusion fluid. Patients were followed up at 1 week, 1 month and 3 months after surgery. Postoperative bleeding, media clarity, best-corrected visual acuity and success of the surgery at the end of 3 months were compared between the two groups. Results: At each follow-up visit, the study group showed a better media clarity, which was statistically significant ( P = 0.0042. The study group had a 50% better chance of retinal reattachment compared to the control group. Five patients had intraoperative bleeding in the study group (33% compared to 3 patients in the control group (20%. Conclusion: Use of intravitreal LMWH prevents postoperative fibrin formation and is beneficial in repair of retinal detachments with PVR.

  3. Aqueous Chlorhexidine for Intravitreal Injection Antisepsis: A Case Series and Review of the Literature.

    Science.gov (United States)

    Merani, Rohan; McPherson, Zachary E; Luckie, Alan P; Gilhotra, Jagjit S; Runciman, Jim; Durkin, Shane; Muecke, James; Donaldson, Mark; Aralar, Albert; Rao, Anupam; Davies, Peter E

    2016-12-01

    To determine the incidence of endophthalmitis in a large clinical series using aqueous chlorhexidine for antisepsis before intravitreal injection and to review the ophthalmic literature regarding chlorhexidine efficacy and safety. Multicenter retrospective case series. All patients receiving intravitreal injections from 7 retinal specialists. An audit of intravitreal injections performed by retinal specialists who exclusively used aqueous chlorhexidine 0.05% or 0.1% for prophylaxis of infective endophthalmitis was undertaken. The incidence of endophthalmitis was determined from August 1, 2011, to February 28, 2015. A literature review was performed to critically appraise the ocular safety and efficacy of aqueous chlorhexidine. Incidence of endophthalmitis after intravitreal injections. A total of 40 535 intravitreal injections were performed by 7 retinal specialists across 3 centers. Chlorhexidine was well tolerated, and only 1 patient with a suspected allergic reaction was noted. Three cases of endophthalmitis were identified with 1 culture-positive case. The 0.0074% (1 in 13 512) per-injection rate of endophthalmitis in this series compares favorably with previous series in which povidone-iodine has been used. Aqueous chlorhexidine was associated with a low rate of postinjection endophthalmitis and was well tolerated by patients. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  4. Intravenous Bevacizumab Therapy in a Patient with Hereditary Hemorrhagic Telangiectasia, ENG E137K, Alcoholic Cirrhosis, and Portal Hypertension

    Directory of Open Access Journals (Sweden)

    Luigi F. Bertoli

    2017-05-01

    Full Text Available Intravenous bevacizumab decreased mucosal bleeding in some patients with hereditary hemorrhagic telangiectasia (HHT. We treated a 47-year-old male who had HHT, severe epistaxis, and gastrointestinal bleeding, alcoholic cirrhosis, and portal hypertension with intravenous bevacizumab 2.5 mg/kg every 2 weeks. We tabulated these measures weekly during weeks 1–33 (no bevacizumab; 34–57 (bevacizumab; and 58–97 (no bevacizumab: hemoglobin (Hb levels; platelet counts; units of transfused packed erythrocytes (PRBC units; and quantities of iron infused as iron dextran to support erythropoiesis. We performed univariate and multivariable analyses. We sequenced his ENG and ACVRL1 genes. Epistaxis and melena decreased markedly during bevacizumab treatment. He reported no adverse effects due to bevacizumab. Mean weekly Hb levels were significantly higher and mean weekly PRBC units and quantities of intravenous iron were significantly lower during bevacizumab treatment. We performed a multiple regression on weekly Hb levels using these independent variables: bevacizumab treatment (dichotomous; weekly platelet counts; weekly PRBC units; and weekly quantities of intravenous iron. There was 1 positive association: (bevacizumab treatment; p = 0.0046 and 1 negative association (PRBC units; p = 0.0004. This patient had the novel ENG mutation E137K (exon 4; c.409G→A. Intravenous bevacizumab treatment 2.5 mg/kg every 2 weeks for 24 weeks was well-tolerated by a patient with HHT due to ENG E137K and was associated with higher weekly Hb levels and fewer weekly PRBC units.

  5. Intravitreal injection of bone marrow mesenchymal stem cells in patients with advanced retinitis pigmentosa; a safety study

    Directory of Open Access Journals (Sweden)

    Leila Satarian

    2017-01-01

    Conclusion: Intravitreal injection of autologous bone marrow MSCs into patients' eyes with advanced RP does not meet safety standards. Major side effects of this therapy can include fibrosis and TRD. We propose thorough evaluation of MSCs prior to transplantation by intravitreal injection in the laboratory animals.\\

  6. Comparison of efficiency of intravitreal ceftazidime and intravitreal cefepime in the treatment of experimental Pseudomonas aeruginosa endophthalmitis

    Directory of Open Access Journals (Sweden)

    Nurettin Deniz

    2013-01-01

    Full Text Available In this study, we evaluated the efficiency of cefepime in the treatment of experimental Pseudomonas aeruginosa endophthalmitis. We compared the findings with the standard dose of ceftazidime (1 mg/0.1 ml. Thirty-six New-Zealand White rabbits were divided into 6 equal groups and were treated with different methods (Group 1 = sham, Group 2 = 0.5 mg/0.1 ml cefepime, Group 3 = 1 mg/0.1 ml cefepime, Group 4 = 2 mg/0.1 ml cefepime, Group 5 = 1 mg/0.1 ml ceftazidime, Group 6 = control. The eyes of rabbits in each group were examined clinically on 1 st , 3 rd , and 6 th day of the experiment. At 6 th day, 0.1 ml vitreous humor aspirates were obtained and plated for quantification on the blood agar and the results were expressed as colony-forming unit/ml. Subsequently, the eyeballs were enucleated and the histopathological evaluation was performed. Our findings denoted beneficial effects of cefepime in treatment groups (especially, in Groups 3 and 4. Intravitreal cefepime may be an alternative drug in the treatment of P. aeruginosa endophthalmitis.

  7. INTRAVITREAL AFLIBERCEPT IN THE TREATMENT OF POLYPOIDAL CHOROIDAL VASCULOPATHY ASSOCIATED WITH MORNING GLORY SYNDROME.

    Science.gov (United States)

    Iovino, Claudio; Fossarello, Maurizio; Peiretti, Enrico

    2018-01-10

    To describe an unusual case of polypoidal choroidal vasculopathy secondary to morning glory syndrome successfully treated with three aflibercept intravitreal injections. Case report. A 68-year-old white man presented with a 2-month history of diminished vision of his left eye. Fundus examination showed a morning glory syndrome disk anomaly with some perimacular subretinal hemorrhages and lipid depositions. Fundus autofluorescence, fluorescein and green indocyanine angiography, spectral domain optical coherence tomography, and optical coherence tomography angiography were performed and confirmed the presence of a juxtapapillary polypoidal choroidal vasculopathy with intraretinal and subretinal fluid. Patient underwent 3 monthly intravitreal injections of aflibercept and at 4-month follow-up visit, multimodal imaging findings did not show any kind of neovascular lesion activity. Polypoidal choroidal vasculopathy can occur in morning glory syndrome and it can be successfully treated with anti-vascular endothelial growth factor intravitreal injections of aflibercept.

  8. Role of Kras status in patients with metastatic colorectal cancer receiving first-line chemotherapy plus bevacizumab: a TTD group cooperative study.

    Directory of Open Access Journals (Sweden)

    Eduardo Díaz-Rubio

    Full Text Available In the MACRO study, patients with metastatic colorectal cancer (mCRC were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS, overall survival (OS and response rates.KRAS data (tumour KRAS status and type of mutation were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1% in the MACRO study. Wild-type (WT KRAS tumours were found in 219 patients (56% and mutant (MT KRAS in 175 patients (44%. Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p=0.0038; HR: 1.40; 95% CI:1.12-1.77. The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p=0.0002; HR: 1.55; 95% CI: 1.23-1.96. Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5% with WT KRAS tumours and 76 patients (43.4% with MT KRAS tumours (p=0.0054; OR: 1.77; 95% CI: 1.18-2.64.This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.

  9. [A Case of Abdominal Wall Hernia Rupture during Bevacizumab Treatment].

    Science.gov (United States)

    Sugimoto, Satoshi; Miyazaki, Yasuaki; Hirose, Sou; Michiura, Toshiya; Fujita, Shigeo; Yamabe, Kazuo; Miyazaki, Satoru; Nagaoka, Makio

    2015-11-01

    A 78 -year-old man with rectal cancer underwent abdominoperineal resection of the rectum. In the postoperative period, the patient experienced wound infection, leading to an abdominal wall hernia. Two years following surgery, a rise in the serum CEA level was seen. A metastatic tumor was detected in the right lung on chest CT. VATS right lung inferior lobe segmental resection was performed. After lobectomy, the serum CEA level continued to increase. Another metastatic tumor was detected in the right lung on chest CT. Chemotherapy with capecitabine, oxaliplatin, and bevacizumab was commenced. The erosive part of the abdominal wall scar hernia extended during the nine weeks of chemotherapy. The chemotherapy was then discontinued. In the follow-up CT scan, a right pleural recurrence, local recurrence in the pelvis, and a liver metastasis were detected. Chemotherapy was re-introduced 3 years after surgery. The erosive part of the abdominal wall hernia again began to spread with chemotherapy recommencement. Four months after restarting chemotherapy, the hernia ruptured, with a loop of the small intestine protruding out of it. The patient covered this with a sheet of vinyl and was taken by the ambulance to our hospital. The erosive part of the abdominal wall hernia had split by 10 cm, and a loop of the small intestine was protruding. As ischemia of the small intestine was not observed, we replaced it into the abdominal cavity, and performed a temporary suture repair of the hernia sac. Following this, bevacizumab was discontinued, and the erosive part reduced. We performed a radical operation for abdominal wall scar hernia repair 11 weeks after the discontinuation of bevacizumab.

  10. Re-188 Enhances the Inhibitory Effect of Bevacizumab in Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jie Xiao

    2016-09-01

    Full Text Available The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC, we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that, after 188ReO4− or 188Re-bevacizumab at different concentration for 4 and 24 h, a time- and radioactivity does-dependent reduction in cell viability occurred. Also, an apoptosis assay conformed great apoptosis in the 188Re-bevacizumab group compared with controls and other treatment groups. In vivo, tumor volumes in the 188Re-bevacizumab (11.1 MBq/mice group were not reduced but growth was delayed compared with other groups. Thus, 188Re-bevacizumab enhanced the therapeutic effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC treatment.

  11. Bevacizumab as Therapy for Radiation Necrosis in Four Children With Pontine Gliomas

    International Nuclear Information System (INIS)

    Liu, Arthur K.; Macy, Margaret E.; Foreman, Nicholas K.

    2009-01-01

    Purpose: Diffuse pontine gliomas are a pediatric brain tumor that is fatal in nearly all patients. Given the poor prognosis for patients with this tumor, their quality of life is very important. Radiation therapy provides some palliation, but can result in radiation necrosis and associated neurologic decline. The typical treatment for this necrosis is steroid therapy. Although the steroids are effective, they have numerous side effects that can often significantly compromise quality of life. Bevacizumab, an antibody against vascular endothelial growth factor, has been suggested as a treatment for radiation necrosis. We report on our initial experience with bevacizumab therapy for radiation necrosis in pediatric pontine gliomas. Materials and Methods: Four children with pontine gliomas treated at the Children's Hospital in Denver and the University of Colorado Denver developed evidence of radiation necrosis both clinically and on imaging. Those 4 children then received bevacizumab as a treatment for the radiation necrosis. We reviewed the clinical outcome and imaging findings. Results: After bevacizumab therapy, 3 children had significant clinical improvement and were able to discontinue steroid use. One child continued to decline, and, in retrospect, had disease progression, not radiation necrosis. In all cases, bevacizumab was well tolerated. Conclusions: In children with pontine gliomas, bevacizumab may provide both therapeutic benefit and diagnostic information. More formal evaluation of bevacizumab in these children is needed.

  12. Non-physician delivered intravitreal injection service is feasible and safe

    DEFF Research Database (Denmark)

    Rasul, Asrin; Subhi, Yousif; Sørensen, Torben Lykke

    2016-01-01

    INTRODUCTION: Non-physicians such as nurses are trained to give injections into the vitreous body of the eye to meet the increasing demand for intravitreal therapy with vascular endothelial growth factor inhibitors against common eye diseases, e.g. age-related macular degeneration and diabetic...... by 16 nurses. The studies found that having nurses perform the intravitreal injections produced to a short-term capacity improvement and liberated physicians for other clinical work. Training was provided through courses and direct supervision. The rates of endophthalmitis were 0-0.40‰, which...

  13. Aqueous Humor Levels of Vascular Endothelial Growth Factor Before and After Intravitreal Bevacizumab in Type 3 Versus Type 1 and 2 Neovascularization. A Prospective, Case-Control Study

    NARCIS (Netherlands)

    Dell'Omo, Roberto; Cassetta, Marilluccia; Dell'Omo, Ermanno; di Salvatore, Angela; Hughes, John M.; Aceto, Fabiana; Porcellini, Antonio; Costagliola, Ciro

    2012-01-01

    PURPOSE: To determine the aqueous levels of vascular endothelial growth factor (VEGF) in patients with type 3 neovascularization (NV) secondary to age-related macular degeneration (AMD) and to compare the levels of those with type 1 and 2 NV secondary to AMD before and after administration of

  14. Choroidal thickness after intravitreal ranibizumab injections for choroidal neovascularization

    Directory of Open Access Journals (Sweden)

    Ellabban AA

    2012-05-01

    Full Text Available Abdallah A Ellabban, Akitaka Tsujikawa, Ken Ogino, Sotaro Ooto, Kenji Yamashiro, Akio Oishi, Nagahisa YoshimuraDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, JapanPurpose: To study changes in choroidal thickness with ranibizumab treatment for choroidal neovascularization (CNV.Design: Prospective case series.Methods: This prospective study consisted of 60 CNV-affected eyes of 60 patients treated with intravitreal injections of ranibizumab using an on-demand protocol after an initial loading phase. The eyes studied included 20 with age-related macular degeneration (AMD, 20 with polypoidal choroidal vasculopathy (PCV, and 20 with myopic CNV. In the eyes with AMD and PCV, choroidal thickness at the fovea was measured with optical coherence tomography using enhanced depth imaging. In eyes with myopic CNV, the choroidal thickness was measured using standard optical coherence tomography without the enhanced depth imaging technique.Results: With ranibizumab treatment, central retinal thickness decreased significantly (P < 0.001 and visual acuity improved significantly (P < 0.001. However, central choroidal thickness (167.2 ± 108.3 µm showed no significant change at 1 month after the loading phase (165.2 ± 107.8 µm, P = 0.120 or at final examination (164.8 ± 107.7 µm, P = 0.115. At baseline, central retinal thickness in eyes with AMD was significantly greater that those with PCV (P = 0.005 or high myopia (P = 0.029. However, central choroidal thickness in eyes with myopic CNV was significantly thinner than in eyes with AMD (P < 0.001 or PCV (P < 0.001. In each type of disease, there was no significant change in central choroidal thickness with ranibizumab treatment.Conclusion: The effect of ranibizumab on the choroidal thickness is minimal, if any.Keywords: choroidal thickness, ranibizumab, optical coherence tomography

  15. Bevacizumab-related toxicities in the National Cancer Institute malignant glioma trial cohort.

    Science.gov (United States)

    Odia, Yazmin; Shih, Joanna H; Kreisl, Teri N; Fine, Howard A

    2014-11-01

    Bevacizumab is an antiangiogenic agent approved for recurrent glioblastoma due to high response rates. Prior reviews focused on severe or cardiovascular bevacizumab toxicities. We performed a comprehensive review of toxicities experienced among 210 patients enrolled in 3 phase II bevacizumab trials for recurrent malignant gliomas at the National Cancer Institute. No bevacizumab toxicities were experienced by 20 % patients, 40.2 % on monotherapy versus ≤9.5 % on combination therapy. Hypertension and proteinuria occurred in ~25 %. Fatigue, hypophosphatemia, aspartate aminotransferase elevation, rashes were common. Low grade headache, hoarseness, myalgias/arthralgias, liver enzyme elevation, azotemia and electrolyte abnormalities were noted. Rare severe toxicities, including thrombosis, hemorrhage, wound complications and colonic perforations, occurred at rates seen in other diseases. Leukopenia and neutropenia occurred solely with combination therapy, while thrombocytopenia occurred in 12.5 % on bevacizumab monotherapy. Thrombocytopenia was generally mild, but severe in (1.4 %) and increased in frequency with prolonged or combination therapy. Bevacizumab-related deaths occurred in 4 (1.9 %) patients, including brain ischemia (n = 1) and sudden unexplained deaths (n = 2). Prior hypertension increased the odds of hypertension by ≥3.4-fold (p < 0.001) and grade 3+ hypertension by ≥11.2 (p < 0.001). Prior hypertension increased the odds of hypophosphatemia by 2.4-fold (p = 0.011), but failed to predict proteinuria or azotemia. Age did not greatly impact toxicity. Hypertension, proteinuria and hypophosphatemia often occurred concurrently, more frequently and severely with prolonged use. Our study shows bevacizumab monotherapy is well tolerated, but toxicity increases with combination therapy. Balancing the risks and benefits of bevacizumab requires understanding the spectrum of bevacizumab toxicities and predisposing factors.

  16. Bevacizumab in high-grade gliomas: a review of its uses, toxicity assessment, and future treatment challenges.

    Science.gov (United States)

    Rahmathulla, Gazanfar; Hovey, Elizabeth J; Hashemi-Sadraei, Neda; Ahluwalia, Manmeet S

    2013-01-01

    High-grade gliomas continue to have dismal prognosis despite advances made in understanding the molecular genetics, signaling pathways, cytoskeletal dynamics, and the role of stem cells in gliomagenesis. Conventional treatment approaches, including surgery, radiotherapy, and cytotoxic chemotherapy, have been used with limited success. Therapeutic advances using molecular targeted therapy, immunotherapy, and others such as dietary treatments have not been able to halt tumor progression and disease-related death. High-grade gliomas (World Health Organization grades III/IV) are histologically characterized by cellular and nuclear atypia, neoangiogenesis, and necrosis. The expression of vascular endothelial growth factor, a molecular mediator, plays a key role in vascular proliferation and tumor survival. Targeting vascular endothelial growth factor has demonstrated promising results, with improved quality of life and progression-free survival. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor, is approved by the Food and Drug Administration as a single agent in recurrent glioblastoma and is associated with manageable toxicity. This review discusses the efficacy, practical aspects, and response assessment challenges with the use of bevacizumab in the treatment of high-grade gliomas.

  17. Anterior uveitis after treatment of age-related macular degeneration with ranibizumab and bevacizumab: uncommon complication

    Directory of Open Access Journals (Sweden)

    Damasceno N

    2012-07-01

    Full Text Available Nadyr Damasceno,1 Soraya Horowitz,2 Eduardo Damasceno31,2Ophthalmology Department, Hospital Naval Marcilio Dias, Rio de Janeiro, Brazil; 3Department of Ophthalmology, Universidade Federal Fluminense, Niteroi, BrazilAbstract: The authors describe one case of anterior uveitis after treatment of age-related macular degeneration with both antiangiogenic drugs: ranibizumab and bevacizumab. The case is described as a complication of ranibizumab and bevacizumab due to an inflammatory process. Several reasons are suggested to explain this possibility, and the authors conclude that the main cause remains unknown.Keywords: antiangiogenic agent, complications, ocular inflammatory process, ranibizumab, bevacizumab, anterior uveitis

  18. Bevacizumab plus irinotecan in the treatment patients with progressive recurrent malignant brain tumours

    DEFF Research Database (Denmark)

    Poulsen, H.S.; Grunnet, K.; Sorensen, M.

    2009-01-01

    MATERIAL AND METHODS: We retrospectively determined the efficacy and safety of a combination of bevacizumab and irinotecan in a consecutive series of 52 heavily pre-treated patients with recurrent high-grade brain tumours. Patients received bevacizumab (10 mg/kg) and irinotecan [340 mg/m(2...... glioma and 32 weeks for grade III glioma. Four patients discontinued treatment because of unmanageable toxicity: cerebral haemorrhage, cardiac arrhythmia, intestinal perforation and diarrhoea, the latter resulting in death. DISCUSSION: We conclude that the combination of bevacizumab and irinotecan shows...

  19. Predictive Biomarkers for Bevacizumab in Anti-tumor Therapy

    Directory of Open Access Journals (Sweden)

    Qingqing PAN

    2011-07-01

    Full Text Available Bevacizumab, the monoclonal antibody of vascular endothelial growth factor (VEGF has been applied to the therapy of several neoplasms, but an appropriate biomarker to predict the efficacy has not been found. Those markers can originate from peripheral circulation, tumor tissue and genes. Some researches have found that low level of vascular cell adhesion molecule-1 (VCAM-1, E-selectin, angiopoietin 2 (Ang-2 in circulation or carbonic anhydrase 9 (CA9, CD31-microvessel density (CD31-MVD in tumor tissue can predict better activity of bevacizumab. Moreover, high level of soluble VEGFR2 (sVEGFR2 in circulation or the ratio of phosphorylated-VEGFR2 (p-VEGFR2 and VEGFR2 in tumor tissue increasing has the same predictive function. As to the gene, VEGF-634 CC, VEGF-1498 TT and VEGFR2 H472Q are only related to the side effct. Thus more clinical tirals and basic researches should be performed to find out effective biomarkers in bevacizumab’s therapy.

  20. Bevacizumab Improves Achilles Tendon Repair in a Rat Model

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    Herbert Tempfer

    2018-04-01

    Full Text Available Background/Aims: Effective wound-healing generally requires efficient re-vascularization after injury, ensuring sufficient supply with oxygen, nutrients, and various cell populations. While this applies to most tissues, tendons are mostly avascular in nature and harbor relatively few cells, probably contributing to their poor regenerative capacity. Considering the minimal vascularization of healthy tendons, we hypothesize that controlling angiogenesis in early tendon healing is beneficial for repair tissue quality and function. Methods: To address this hypothesis, Bevacizumab, a monoclonal antibody blocking VEGF-A signaling, was locally injected into the defect area of a complete tenotomy in rat Achilles tendon. At 28 days post-surgery, the defect region was investigated using immunohistochemistry against vascular and lymphatic epitopes. Polarization microscopy and biomechanical testing was used to determine tendon integrity and gait analysis for functional testing in treated vs non-treated animals. Results: Angiogenesis was found to be significantly reduced in the Bevacizumab treated repair tissue, accompanied by significantly reduced cross sectional area, improved matrix organization, increased stiffness and Young’s modulus, maximum load and stress. Further, we observed an improved gait pattern when compared to the vehicle injected control group. Conclusion: Based on the results of this study we propose that reducing angiogenesis after tendon injury can improve tendon repair, potentially representing a novel treatment-option.

  1. Bevacizumab: an option for refractory epistaxis in hereditary haemorrhagic telangiectasia.

    Science.gov (United States)

    Amann, Arno; Steiner, Normann; Gunsilius, Eberhard

    2015-08-01

    Recurrent epistaxis in hereditary haemorrhagic telangiectasia (HHT) patients significantly decreases their quality of life. Treatment in therapy refractory patients is limited although various options have been tested so far. Herein, one patient is described that was treated for HHT for over 20 years with only intermediate benefits. As epistaxis duration and frequency increased continuously, bevacizumab 5 mg/kg was administered every 2 weeks. During the time of treatment (six doses) and up to 3 month afterwards clinical symptoms, blood pressure, cardiac output, pulmonary arterial hypertension (PAH), bleeding duration and frequency were assessed as criteria for treatment benefit. Duration and frequency of epistaxis decreased immediately after the first application resulting in reduced need of blood transfusions. After completion of six cycles, a further decrease in frequency and duration of bleeding was noted. Cardiac output and PAH decreased or remained stable, respectively, during time and after treatment. No increase in blood pressure could be found but a significant increase in heart rate was experienced after completion of all six applications. Unfortunately, the patient died due to a cerebral abscess. Bevacizumab led to an improvement of HHT related epistaxis, refractory to other treatments.

  2. Intravitreal Ampicillin Sodium for Antibiotic-Resistant Endophthalmitis: Streptococcus uberis First Human Intraocular Infection Report

    Directory of Open Access Journals (Sweden)

    Raul Velez-Montoya

    2010-01-01

    Full Text Available Purpose. To describe the clinical characteristics, diagnosis, and treatment with intravitreal ampicillin sodium of a postoperative endophthalmitis case due to Streptococcus uberis; an environmental pathogen commonly seen in mastitis cases of lactating cows. Methods. Case Report. A 52-year-old, Hispanic diabetic patient who suddenly developed severe pain and severe loss of vision, following vitrectomy. Results. The patient was diagnosed with postoperative endophthalmitis secondary to a highly resistant strain of Streptococcus uberis that did not respond to intravitreal antibiotics. He was treated with an air-fluid interchange, anterior chamber washout, intravitreal ampicillin sodium (5 mg/0.1 mL, and silicon oil tamponade (5000 ck. The eye was anatomically stabilized, though there was no functional recovery. Conclusion. Streptococcus uberis is an uncommon pathogen to the human eye, which has unique features that help the strain in developing resistance to antibiotics. While treatment with intravitreal ampicillin is feasible, there are still concerns about its possible toxicity.

  3. Subconjunctival hemorrhage after intravitreal injection of anti-vascular endothelial growth factor.

    Science.gov (United States)

    Yun, Cheolmin; Oh, Jaeryung; Hwang, Soon-Young; Kim, Seong-Woo; Huh, Kuhl

    2015-09-01

    To investigate the risk factors for subconjunctival hemorrhage (SCH) after intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) and evaluate the relationship between hemodynamic status at the time of injection and SCH. We retrospectively reviewed the medical records of 598 cases of 173 patients who underwent intravitreal injection of ranibizumab whose hemodynamic status was monitored at the time of the injection. Cases with SCH after the injection were included in the SCH group. We compared systemic factors, including the hemodynamic status between the SCH group and the control group. The SCH group included 67 cases and the control group included 531 cases without SCH. Baseline hemodynamic status was not significantly related to development of SCH. However, systolic blood pressure (BP) at injection was a significant risk factors for SCH (P = 0.034). Elevated systolic BP, mean arterial pressure (MAP), and pulse rate from baseline to time of injection were significantly related to the development of SCH (P = 0.011, P = 0.014, P = 0.036, respectively). In multivariate analysis, hypertension, a large change in MAP, and a fewer previous injections were significant risk factors for SCH after intravitreal injection (P = 0.030, P = 0.032, P = 0.028, respectively). Hemodynamic risk factors exist for SCH after intravitreal injection of anti-VEGF. To reduce the risk of SCH, strategies should seek to decrease patient anxiety, especially in those with hypertension.

  4. NO CASES OF ENDOPHTHALMITIS AFTER 20,293 INTRAVITREAL INJECTIONS IN AN OPERATING ROOM SETTING

    DEFF Research Database (Denmark)

    Brynskov, Troels; Kemp, Henrik; Sørensen, Torben Lykke

    2013-01-01

    Intravitreal injection has become a common procedure worldwide. A rare, but sight threatening, complication is bacterial endophthalmitis that has a poor visual prognosis. To identify practices that minimize the risk of endophthalmitis, the setting of a Danish University hospital is described....

  5. LOW ENDOPHTHALMITIS RATES AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS IN AN OPERATION ROOM

    DEFF Research Database (Denmark)

    Freiberg, Florentina J; Brynskov, Troels; Munk, Marion R

    2017-01-01

    PURPOSE: To evaluate the rate of presumed endophthalmitis (EO) after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in three European hospitals performed in an operation room (OR) under sterile conditions. METHODS: A retrospective multicenter study between 2003 and 20...

  6. Use of Intravitreal Dexamethasone in a Case of Anterior Ischemic Optic Neuropathy

    Directory of Open Access Journals (Sweden)

    Raffaele Nuzzi

    2017-08-01

    Full Text Available Nowadays there is no unique and well-established treatment for nonarteritic anterior ischemic optic neuropathy, despite being the main acute pathology that affects the optic nerve in the elderly population and often resulting in a significant loss of visual acuity. The effectiveness of oral steroids is still under debate in the international literature, although many studies show that patients treated with high doses of systemic corticosteroids have a significantly higher chance of improved visual acuity and visual fields. The authors propose an intravitreal dexamethasone injection/implant as initial and acute therapy. Compared to systemic corticosteroids, intravitreal dexamethasone has the advantage of avoiding any systemic side effects of steroids. On the other hand, a rise in intraocular pressure might occur, manageable with local antiglaucoma drugs, especially in patients at risk, and there is a risk of induced cataract. The pharmacodynamics of the intravitreal dexamethasone slow-release implant is characterized by a first step with high release concentrations and a second following phase with decreasing concentrations. Therefore, the use of emergency dexamethasone (high concentration intravitreal injection is justified as a treatment after the first detection of an ischemic optic anterior neuropathy.

  7. Role of implants in the treatment of diabetic macular edema: focus on the dexamethasone intravitreal implant

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    Cebeci Z

    2015-11-01

    Full Text Available Zafer Cebeci, Nur KirDepartment of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, TurkeyAbstract: Diabetic macular edema (DME is the leading cause of sight-threatening complication in diabetic patients, and several treatment modalities have been developed and evaluated to treat this pathology. Intravitreal agents, such as anti-vascular endothelial growth factors (anti-VEGF or corticosteroids, have become more popular in recent years and are widely used for treating DME. Sustained release drugs appear to be mentioned more often nowadays for extending the period of intravitreal activity, and corticosteroids play a key role in inhibiting the inflammatory process in DME. A potent corticosteroid, dexamethasone (Ozurdex®, in the form of an intravitreal implant, has been approved for various ocular etiologies among which DME is also one. This review evaluates the role of implants in the treatment of DME, mainly focusing on the dexamethasone intravitreal implant.Keywords: diabetes mellitus, diabetic macular edema, vascular endothelial growth factor, dexamethasone, Iluvien, corticosteroid

  8. [Clinical observation on treating diabetic macular edema with intravitreal triamcinolone acetonide and laser].

    Science.gov (United States)

    Wang, Yongbo; Shi, Anna; Shi, Xun; Liu, Weifeng

    2010-08-01

    To evaluate the effect of intravitreal injection of triamcinolone acetonide(IVTA) combining with retinal laser treating for diabetic macular edema(DME). Twenty five patients(32 eyes) with DME who has microangioma in macula lutea were randomly divided into group A, B,C and D(8 eyes each group). Eyes in group A were treated with laser photocoagulation. Eyes in group B were treated with multiplier-532 laser photocoagulation and transpupillary thermotherapy. Eyes in group C were treated with multiplier-532 laser photocoagulation and intravitreal triamcinolone acetonide. Eyes in group D were treated with multiplier-532 laser, transpupillary thermotherapy plus triamcinolone acetonide injection. Intravitreal injection of 4 mg triamcinolone acetonide was done 1 week after laser photocoagulation in group C and D. The visual acuity, intraocular pressure, macular thickness (foveal thickness) of the eyes in 4 groups were observed before and 1, 3 and 6 months after treatment. The visual acuity, intraocular pressure and foveal thickness of the 4 groups before treatment showed no significant difference(p> ). The visual acuity, intraocular pressure, macular thickness of eyes in group A, B were better than those of group C, D at 1, 3 and 6 months after treatment, and they had significant difference(p0.05). The effect of laser photocoagulation and intravitreal triamcinolone acetonide, laser photocoagulation combining with transpupillary thermotherapy plus triamcinolone acetonide injectionvisual treating for DME was better than laser photocoagulation alone, laser photocoagulation combining with transpupillary thermotherapy.

  9. Microplasmin intravitreal administration in patients with vitreomacular traction scheduled for vitrectomy: the MIVI I trial

    NARCIS (Netherlands)

    de Smet, Marc D.; Gandorfer, Arnd; Stalmans, Peter; Veckeneer, Marc; Feron, Eric; Pakola, Steve; Kampik, Anselm

    2009-01-01

    PURPOSE: To evaluate the safety and preliminary efficacy of 4 doses and several exposure times of intravitreal microplasmin given before pars plana vitrectomy for vitreomacular traction maculopathy. DESIGN: A multicenter, prospective, uncontrolled, dose-escalation, phase I/II clinical trial.

  10. Oxaliplatin/Irinotecan/Bevacizumab Followed by Docetaxel/Bevacizumab in Inoperable Locally Advanced or Metastatic Gastric Cancer Patients - AGMT_GASTRIC-3.

    Science.gov (United States)

    Wöll, Ewald; Thaler, Josef; Keil, Felix; Gruenberger, Birgit; Hejna, Michael; Eisterer, Wolfgang; Fridrik, Michael A; Ulmer, Hanno; Trommet, Vera; Huemer, Florian; Weiss, Lukas; Greil, Richard

    2017-10-01

    Although high response rates using the doublet-chemotherapy of oxaliplatin and irinotecan as well as its combination with cetuximab in advanced gastric cancer were shown in previous trials, time to progression was short, suggesting acquired chemotherapy resistance. Sequential chemotherapy (oxaliplatin and irinotecan followed by docetaxel) combined with bevacizumab was investigated in the GASTRIC-3 trial. Patients achieving at least stable disease were continued on maintenance bevacizumab. Objective response rate was available in 33 patients: Complete response (CR) 12.1%, partial response (PR) 39.4%, stable disease (SD) 27.3%. Median time to progression was 7.0 months (95%CI=5.0-11.0) and median overall survival was 11 months (95%CI=9.0-15.0). Of note, two patients continue to receive bevacizumab maintenance therapy for more than 5 years with ongoing CR. Combining sequential chemotherapy with oxaliplatin/irinotecan and docetaxel with bevacizumab followed by bevacizumab maintenance is feasible and clinically active in advanced gastric cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Influence of dosage form on the intravitreal pharmacokinetics of diclofenac.

    Science.gov (United States)

    Durairaj, Chandrasekar; Kim, Stephen J; Edelhauser, Henry F; Shah, Jaymin C; Kompella, Uday B

    2009-10-01

    To prepare a suspension form of diclofenac and compare the influence of the injected form (suspension versus solution) on the intravitreal pharmacokinetics of diclofenac in Dutch belted pigmented rabbits. Diclofenac acid was prepared and characterized in a suspension formulation. Rabbit eyes were injected with either diclofenac sodium solution (0.3 mg) or diclofenac acid suspension (10 mg) prepared in 0.1 mL balanced salt solution. Rabbits were killed at regular time intervals, the eyes enucleated, and drug content quantified in the vitreous humor and retina-choroid tissue by high-performance liquid chromatography. Pharmacokinetic models were developed for both the dosage forms, and simulations were performed for different doses. Diclofenac acid with an approximate 5-mum particle size exhibited 3.5-fold lower solubility in vitreous humor, when compared with its sodium salt. The estimated settling velocity of the suspension in the vitreous humor was 3 cm/h. After diclofenac sodium salt solution injection, drug levels declined rapidly with no drug levels detectable after 24 hours in the vitreous humor and 4 hours in the RC. Throughout the assessed time course, drug levels were higher in the vitreous. However, sustained, high drug levels were observed in both the vitreous humor and the retina-choroid even on day 21 after diclofenac acid suspension injection, with retina-choroid drug levels being higher beginning at 0.25 hour. The elimination half-life of diclofenac suspension was 24 and 18 days in vitreous and retina-choroid, respectively, compared to 2.9 and 0.9 hours observed with diclofenac sodium. The pharmacokinetic models developed indicated a slow-release distribution or depot compartment for the diclofenac acid suspension in the posterior segment. Simulations indicated the inability of a 10-mg dose of diclofenac sodium solution to sustain drug levels in the vitreous beyond 11 days. By choosing a less soluble form of a drug such as diclofenac acid, vitreous

  12. Bevacizumab increases the incidence of cardiovascular events in patients with metastatic breast or colorectal cancer

    Directory of Open Access Journals (Sweden)

    Ioannis Kapelakis

    2017-05-01

    Conclusions: The addition of bevacizumab to conventional chemotherapy for metastatic breast or colorectal cancer increases the incidence of cardiovascular events, which is mainly due to the increased prevalence of myocardial infarction and thromboembolic events.

  13. Evaluation of the effects of resveratrol and bevacizumab on experimental corneal alkali burn.

    Science.gov (United States)

    Doganay, Selim; Firat, Penpe Gul; Cankaya, Cem; Kirimlioglu, Hale

    2013-03-01

    To evaluate the effects of resveratrol and bevacizumab on experimental corneal neovascularization. A corneal alkali burn was performed in 62 eyes of 31 male white Vienna rabbits. Resveratrol (group 1), dimethyl sulfoxide (group 2), bevacizumab (group 3) and 0.9% NaCl (group 4) were administered to both eyes of the rabbits by subconjunctival injection for 7 days. Corneal photos were taken at 15 days after alkali injury. Inflammatory index scores and neovascularization areas were calculated. In bevacizumab group both inflammatory index scores and the calculation of the corneal neovascularization area was significantly less than the groups. The subconjunctival administration of bevacizumab inhibits corneal neovascularization effectively in the rabbit corneal alkali burn model. No effect of resveratrol to the corneal neovascularization on experimental model of the corneal alkali burn was seen at the doses of usage. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  14. Diverticular Bleeding of the Colon during Combination Chemotherapy with Bevacizumab and Paclitaxel for Recurrent Breast Cancer

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    Yoshie Nakayama

    2013-01-01

    Full Text Available Background: Bevacizumab has been increasingly used in combination chemotherapy with paclitaxel for treatment of metastatic or recurrent breast cancer. The aim of this report is to underline possible risks associated with the new combination chemotherapy. Case Presentation: A 39-year-old woman with recurrent breast cancer was treated with bevacizumab and paclitaxel. Positron emission tomography revealed breast cancer metastasis to the left supraclavicular lymph nodes and right axillary lymph nodes, with no distant metastasis. Results: After the third cycle of bevacizumab and paclitaxel, the patient developed a bloody bowel discharge. Emergent colonoscopy demonstrated diverticular bleeding on one of the multiple diverticula in the ascending colon. The bleeding point was successfully clipped colonoscopically. Conclusion: The factors for diverticular bleeding are believed to be non-steroidal anti-inflammatory drugs, constipation, and bevacizumab. We recommend reviewing anamneses for diverticulitis, multiple prior abdominal surgeries, peritoneal carcinomatosis, and regular use of certain drugs.

  15. Bevacizumab-Based Therapies in the First-Line Treatment of Metastatic Colorectal Cancer

    Science.gov (United States)

    Hurwitz, Herbert I.

    2012-01-01

    Since its approval for the first-line treatment of metastatic colorectal cancer (mCRC), bevacizumab has become a standard treatment option in combination with chemotherapy for patients with mCRC. Bevacizumab has demonstrated efficacy in combination with a number of different backbone chemotherapy regimens, and its widespread use has introduced several important questions regarding the selection and optimization of bevacizumab-based treatment regimens, its use in various patient populations, and the identification of associated adverse events. This review discusses the results of several phase II and phase III clinical trials, as well as large observational studies, to address the use of bevacizumab in the treatment of patients with mCRC in the first-line setting. PMID:22477726

  16. Fluorescently labeled bevacizumab in human breast cancer: defining the classification threshold

    Science.gov (United States)

    Koch, Maximilian; de Jong, Johannes S.; Glatz, Jürgen; Symvoulidis, Panagiotis; Lamberts, Laetitia E.; Adams, Arthur L. L.; Kranendonk, Mariëtte E. G.; Terwisscha van Scheltinga, Anton G. T.; Aichler, Michaela; Jansen, Liesbeth; de Vries, Jakob; Lub-de Hooge, Marjolijn N.; Schröder, Carolien P.; Jorritsma-Smit, Annelies; Linssen, Matthijs D.; de Boer, Esther; van der Vegt, Bert; Nagengast, Wouter B.; Elias, Sjoerd G.; Oliveira, Sabrina; Witkamp, Arjen J.; Mali, Willem P. Th. M.; Van der Wall, Elsken; Garcia-Allende, P. Beatriz; van Diest, Paul J.; de Vries, Elisabeth G. E.; Walch, Axel; van Dam, Gooitzen M.; Ntziachristos, Vasilis

    2017-07-01

    In-vivo fluorescently labelled drug (bevacizumab) breast cancer specimen where obtained from patients. We propose a new structured method to determine the optimal classification threshold in targeted fluorescence intra-operative imaging.

  17. A Phase II trial of tandutinib (MLN 518) in combination with bevacizumab for patients with recurrent glioblastoma.

    Science.gov (United States)

    Odia, Yazmin; Sul, Joohee; Shih, Joanna H; Kreisl, Teri N; Butman, John A; Iwamoto, Fabio M; Fine, Howard A

    2016-01-01

    A Phase II trial of bevacizumab plus tandutinib. We enrolled 41 recurrent, bevacizumab-naive glioblastoma patients for a trial of bevacizumab plus tandutinib. Median age was 55 and 71% were male. Treatment consisted of tandutinib 500 mg two-times a day (b.i.d.) and bevacizumab 10 mg/kg every 2 weeks starting day 15. Of 37 (90%) evaluable, nine (24%) had partial response. Median overall and progression-free survival was 11 and 4.1 months; progression-free survival at 6 months was 23%. All patients suffered treatment-related toxicities; common grade ≥3 toxicities were hypertension (17.1%), muscle weakness (17.1%), lymphopenia (14.6%) and hypophosphatemia (9.8%). Four of six with grade ≥3 tandutinib-related myasthenic-like muscle weakness had electromyography-proven neuromuscular junction pathology. Tandutinib with bevacizumab was as effective but more toxic than bevacizumab monotherapy.

  18. Molecular Drug Imaging: 89Zr-Bevacizumab PET in Children with Diffuse Intrinsic Pontine Glioma.

    Science.gov (United States)

    Jansen, Marc H; Veldhuijzen van Zanten, Sophie E M; van Vuurden, Dannis G; Huisman, Marc C; Vugts, Danielle J; Hoekstra, Otto S; van Dongen, Guus A; Kaspers, Gert-Jan L

    2017-05-01

    Predictive tools for guiding therapy in children with brain tumors are urgently needed. In this first molecular drug imaging study in children, we investigated whether bevacizumab can reach tumors in children with diffuse intrinsic pontine glioma (DIPG) by measuring the tumor uptake of 89 Zr-labeled bevacizumab by PET. In addition, we evaluated the safety of the procedure in children and determined the optimal time for imaging. Methods: Patients received 89 Zr-bevacizumab (0.1 mg/kg; 0.9 MBq/kg) at least 2 wk after completing radiotherapy. Whole-body PET/CT scans were obtained 1, 72, and 144 h after injection. All patients underwent contrast (gadolinium)-enhanced MRI. The biodistribution of 89 Zr-bevacizumab was quantified as SUVs. Results: Seven DIPG patients (4 boys; 6-17 y old) were scanned without anesthesia. No adverse events occurred. Five of 7 primary tumors showed focal 89 Zr-bevacizumab uptake (SUVs at 144 h after injection were 1.0-6.7), whereas no significant uptake was seen in the healthy brain. In 1 patient, multiple metastases all showed positive PET results. We observed inter- and intratumoral heterogeneity of uptake, and 89 Zr-bevacizumab uptake was present predominantly (in 4/5 patients) within MRI contrast-enhanced areas, although 89 Zr-bevacizumab uptake in these areas was variable. Tumor targeting results were quantitatively similar at 72 and 144 h after injection, but tumor-to-blood-pool SUV ratios increased with time after injection ( P = 0.045). The mean effective dose per patient was 0.9 mSv/MBq (SD, 0.3 mSv/MBq). Conclusion: 89 Zr-bevacizumab PET studies are feasible in children with DIPG. The data suggest considerable heterogeneity in drug delivery among patients and within DIPG tumors and a positive, but not 1:1, correlation between MRI contrast enhancement and 89 Zr-bevacizumab uptake. The optimal time for scanning is 144 h after injection. Tumor 89 Zr-bevacizumab accumulation assessed by PET scanning may help in the selection of

  19. Influence of Bevacizumab on Blood-Brain Barrier Permeability and O-(2-18F-Fluoroethyl)-l-Tyrosine Uptake in Rat Gliomas.

    Science.gov (United States)

    Stegmayr, Carina; Oliveira, Dennis; Niemietz, Nicole; Willuweit, Antje; Lohmann, Philipp; Galldiks, Norbert; Shah, N Jon; Ermert, Johannes; Langen, Karl-Josef

    2017-05-01

    Restoration of the blood-brain barrier (BBB) after antiangiogenic therapy of gliomas with bevacizumab may result in a decrease in contrast enhancement on MRI despite tumor progression. This so-called pseudoresponse is difficult to differentiate from a true tumor response with conventional MRI. Initial patient studies have indicated that PET using O -(2- 18 F-fluoroethyl)-l-tyrosine ( 18 F-FET) may be helpful for solving this diagnostic problem. This study was performed to investigate the effects of bevacizumab on BBB permeability and 18 F-FET uptake in a human xenograft model. Methods: Human U87 glioblastoma cells were implanted into the striatum of immunodeficient RNU rats. 18 F-FET PET scans and ex vivo autoradiography were performed in animals receiving a single high dose of bevacizumab (45 mg/kg 2 d before PET; n = 9) or in animals receiving 2 lower doses (10 mg/kg 9 and 2 d before PET; n = 10) to evaluate short-term and long-term effects on the BBB, respectively, and in control animals without bevacizumab treatment ( n = 8). Time-activity curves, slope, and tumor-to-brain ratios of 18 F-FET uptake (18-61 min after injection) were evaluated using a volume-of-interest analysis. After PET scanning, Evans blue dye (EBD) was injected into animals, and cryosections of the brains were evaluated by autoradiography, by histology, and for EBD fluorescence to assess BBB permeability. Results: Compared with the control, short-term bevacizumab therapy resulted in a trend toward BBB restoration ( P = 0.055) and long-term therapy resulted in a significant decrease ( P = 0.004) in BBB permeability, as assessed by EBD fluorescence. In contrast, no significant differences in tumor-to-brain ratios or slope of 18 F-FET uptake were observed in PET and autoradiography ( P > 0.05). Conclusion: 8 F-FET uptake in glioblastomas seems to be largely independent of BBB permeability and reflects the viability of tumor tissue during antiangiogenic therapy more reliably than contrast

  20. Efficacy of systemic diclofenac sodium on intravitreal concentration.

    Science.gov (United States)

    Panahi, Yunes; Naderi, Mostafa; Jadidi, Khosrow; Hoseini, Hadise; Abrishami, Mojtaba

    2018-02-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs), as an alternative, are replacing corticosteroids in ocular inflammatory diseases. Diclofenac has been used mainly topically, and recent focus has been on intravitreal delivery. Both of these methods have been shown to have complications in long-term application. To assess the efficacy of slow release oral diclofenac sodium on intravitreal concentration in experimental model of chemically injured eyes. In an experimental double-masked clinical trial, right eyes of 24 albino rabbits were chemically injured by 1 N NaOH. One hour after chemical injury, 10 cc suspension gavage containing 100 mg slow release diclofenac sodium was administered in all cases. 2, 4, 6, 12, 24, 48 h after gavage, vitreous samples were obtained in all cases. Intravitreal concentration of diclofenac sodium was evaluated in all samples using high-performance liquid chromatography (HPLC) method. Intravitreal diclofenac levels by oral intake were enhanced by the inflammation in all the measurements. In inflamed eyes, diclofenac concentration was ten times more than control eye (2.658 ± 0.344 vs. 0.242 ± 0.0279 and 1.617 ± 0.527 vs. 0.148 ± 0.095; in 2 and 4 h, respectively). After 6 h, diclofenac concentration was statistically different, although it reduced below 1 μg/ml. Diclofenac is delivered to the inflamed eye more than healthy eye. It seems that by oral diclofenac consumption, it is possible to make a significant intravitreal concentration.

  1. Dexamethasone intravitreal implants for diabetic macular edema refractory to ranibizumab monotherapy or combination therapy.

    Science.gov (United States)

    Gutiérrez-Benítez, L; Millan, E; Arias, L; Garcia, P; Cobos, E; Caminal, M

    2015-10-01

    To determine the effectiveness and local safety of dexamethasone intravitreal implants as a treatment in diabetic macular edema (DME) refractory to intravitreal injections of ranibizumab monotherapy or combination therapy. A retrospective study conducted on patients with DME refractory to ranibizumab monotherapy or combined with other treatments treated with dexamethasone intravitreal implants. The parameters analyzed were visual acuity (VA) by ETDRS (Early Treatment Diabetic Retinopathy Study) charts and foveal thickness by spectral-domain optical coherence tomography (SD-OCT) before the treatment, 2 months after treatment, and at the end of the follow-up. A total of 14 eyes of 14 patients were included, with a mean age of 64 years (SD: 9.5; range 41-78) and a mean follow-up of 7.6 months. The mean VA improved from 53 letters to 59 letters at 2 months (P=.03), and 57 at the end of the follow-up period (P=.3). The mean foveal thickness decreased from 502 μ to 304 μ at 2 months (P=.001), and 376 μ at the end of the follow-up period (P=.009). Further treatment with intravitreal dexamethasone was required in 43% of the patients, and 21% had increased intraocular pressure, which was controlled with topical medication. Intravitreal dexamethasone implant is an effective and locally safe treatment for the management of DME refractory to ranibizumab monotherapy or combined with other treatments. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  2. Contraindicated use of bevacizumab and toxicity in elderly patients with cancer.

    Science.gov (United States)

    Hershman, Dawn L; Wright, Jason D; Lim, Emerson; Buono, Donna L; Tsai, Wei Yann; Neugut, Alfred I

    2013-10-01

    Drugs are approved on the basis of randomized trials conducted in selected populations. However, once approved, these treatments are usually expanded to patients ineligible for the trial. We used the SEER-Medicare database to identify subjects older than 65 years with metastatic breast, lung, and colon cancer, diagnosed between 2004 and 2007 and undergoing follow-up to 2009, who received bevacizumab. We defined a contraindication as having at least two billing claims before bevacizumab for thrombosis, cardiac disease, stroke, hemorrhage, hemoptysis, or GI perforation. We defined toxicity as first development of one of these conditions after therapy. Among 16,085 metastatic patients identified, 3,039 (18.9%) received bevacizumab. Receipt of bevacizumab was associated with white race, later year of diagnosis, tumor type, and decreased comorbid conditions. Of patients who received bevacizumab, 1,082 (35.5%) had a contraindication. In multivariate analysis, receipt of bevacizumab with a contraindication was associated with black race (odds ratio [OR] = 2.6; 95% CI, 1.4 to 4.9), increased age, comorbidity, later year of diagnosis, and lower socioeconomic status. Patients with lung (OR = 1.7; 95% CI, 1.1 to 2.4) and colon cancer (OR = 1.4; 95% CI, 1.1 to 1.9) were more likely to have a contraindication. In the group with no contraindication, 30% had a complication after bevacizumab; black patients were more likely to have a complication than were white patients (OR = 1.9; 95% CI, 1.21 to 2.93). Our study demonstrates widespread use of bevacizumab among patients who had contraindications. Black patients were less likely to receive the drug, but those who did were more likely to have a contraindication. Efforts to understand toxicity and efficacy in populations excluded from clinical trials are needed.

  3. Neoadjuvant Therapy of DOF Regimen Plus Bevacizumab Can Increase Surgical Resection Ratein Locally Advanced Gastric Cancer

    Science.gov (United States)

    Ma, Junxun; Yao, Sheng; Li, Xiao-Song; Kang, Huan-Rong; Yao, Fang-Fang; Du, Nan

    2015-01-01

    Abstract Locally advanced gastric cancer (LAGC) is best treated with surgical resection. Bevacizumab in combination with chemotherapy has shown promising results in treating advanced gastric cancer. This study aimed to investigate the efficacy of neoadjuvant chemotherapy using the docetaxel/oxaliplatin/5-FU (DOF) regimen and bevacizumab in LAGC patients. Eighty LAGC patients were randomized to receive DOF alone (n = 40) or DOF plus bevacizumab (n = 40) as neoadjuvant therapy before surgery. The lesions were evaluated at baseline and during treatment. Circulating tumor cells (CTCs) were counted using the FISH test. Patients were followed up for 3 years to analyze the disease-free survival (DFS) and overall survival (OS). The total response rate was significantly higher in the DOF plus bevacizumab group than the DOF group (65% vs 42.5%, P = 0.0436). The addition of bevacizumab significantly increased the surgical resection rate and the R0 resection rate (P DOF plus bevacizumab group showed significantly greater reduction in CTC counts after neoadjuvant therapy in comparison with the DOF group (P = 0.0335). Although the DOF plus bevacizumab group had significantly improved DFS than the DOF group (15.2 months vs 12.3 months, P = 0.013), the 2 groups did not differ significantly in OS (17.6 ± 1.8 months vs 16.4 ± 1.9 months, P = 0.776. Cox proportional model analysis showed that number of metastatic lymph nodes, CTC reduction, R0 resection, and neoadjuvant therapy are independent prognostic factors for patients with LAGC. Neoadjuvant of DOF regimen plus bevacizumab can improve the R0 resection rate and DFS in LAGC. These beneficial effects might be associated with the reduction in CTC counts. PMID:26496252

  4. Synergistic anti-tumor effects of bevacizumab and tumor targeted polymerized VEGF siRNA nanoparticles.

    Science.gov (United States)

    Kim, Myung Goo; Jo, Sung Duk; Yhee, Ji Young; Lee, Beom Suk; Lee, So Jin; Park, Sung Gurl; Kang, Sun-Woong; Kim, Sun Hwa; Jeong, Ji Hoon

    2017-07-15

    A variety of VEGF inhibitors have been reported to treat cancers by suppressing tumor angiogenesis. Bevacizumab, a monoclonal VEGF antibody, was the first FDA approved anti-angiogenic agent for cancer treatments. However, bevacizumab shows modest therapeutic efficiency and often cause resistant problem in significant populations of cancer patients. To solve these problem, we investigated the therapeutic efficacy of siRNA drugs targeting VEGF and combination of the RNAi drug with bevacizumab for cancer treatments. For efficient VEGF siRNA delivery, chemically polymerized siRNAs were complexed with thiolated-glycol chitosan (psi(VEGF)/tGC). The poly-VEGF siRNA and thiolated-glycol chitosan formed stable nanoparticles via electrostatic interaction and chemical crosslinking, and showed high accumulation in tumor tissues resulting in efficient gene silencing. Both VEGF siRNA nanoparticles and bevacizumab had efficient therapeutic effects in tumor xenograft mouse models. Interestingly, most pronounced therapeutic efficacy was observed when the two distinct VEGF inhibitors were treated in combination revealing synergistic effects. The results showed that the psi(VEGF)/tGC nanoparticle mediated knockdown of VEGF exerts anti-tumor effects and the combination treatments with bevacizumab can extend the treatments options to conventional bevacizumab treatments for cancer therapy. Copyright © 2017. Published by Elsevier Inc.

  5. Exploration of the recurrence in radiation brain necrosis after bevacizumab discontinuation

    Science.gov (United States)

    Zhuang, Hongqing; Yuan, Xiangkun; Chang, Joe Y.; Song, Yongchun; Wang, Junjie; Yuan, Zhiyong; Wang, Xiaoguang; Wang, Ping

    2016-01-01

    Objective: The aim of the paper was to investigate the recurrence and its causes of radiation brain necrosis following bevacizumab discontinuation. Methods: This study included 14 patients with radiation brain necrosis (confirmed through imaging) after stereotactic radiotherapy for a primary or metastatic brain tumor and who received bevacizumab treatment from June 2011 through December 2014. The patients received bevacizumab at 5 mg/kg, q3-4w, for at least 3 cycles. The T1 signal intensity from enhanced MRI images was used as the evaluation criteria for the brain necrosis treatment efficacy. Results: brain necrosis improved in 13 of the 14 cases (92.9%). However, during follow-up, 10 of the 13 responsive patients (76.9%) exhibited a recurrence in brain necrosis, and a multiple linear regression analysis shows that brain necrosis recurrence was related to the follow-up time after the initial bevacizumab treatment discontinuation. Conclusion: bevacizumab produced good short-term effects for radiation brain necrosis; however, most of the patients would recurrence after bevacizumab is discontinued. Thus, brain necrosis was irreversible. PMID:26934327

  6. PROPHYLACTIC PERIPHERAL LASER AND FLUORESCEIN ANGIOGRAPHY AFTER BEVACIZUMAB FOR RETINOPATHY OF PREMATURITY.

    Science.gov (United States)

    Garcia Gonzalez, Jose M; Snyder, Laura; Blair, Michael; Rohr, Ashley; Shapiro, Michael; Greenwald, Mark

    2018-04-01

    To report reactivation rate after bevacizumab treatment for retinopathy of prematurity (ROP) in eyes with classic ROP (CROP) versus aggressive posterior ROP (APROP) and to report peripheral fluorescein angiography findings in these eyes. Retrospective chart review was conducted on consecutive infants treated with bevacizumab for ROP, followed by fluorescein angiography and prophylactic laser to persistent avascular retina. Sixty-four eyes of 33 patients were included. Mean gestational age was 25 weeks with mean birth weight of 674 g. Mean follow-up was 125 weeks post-menstrual age (PMA). Reactivation requiring treatment after initial bevacizumab was more common in eyes with APROP (8/16) than with CROP (2/48; P < 0.0001). At mean 73 weeks PMA, eyes with APROP had more avascular retina (mean 4.4 disk diameters vs. 2.6 disk diameters; P = 0.0004) and higher percentage of leakage (11/11 eyes vs. 22/38 eyes; P = 0.01) on fluorescein angiography than in eyes with CROP. Unfavorable outcome occurred in 1 of 16 eyes with APROP and in no eyes with CROP. No eye that underwent prophylactic laser after bevacizumab had a poor structural outcome. In our study, bevacizumab-treated eyes with APROP have a higher likelihood of recurrence and larger area of persistent nonperfusion than in eyes with CROP. Treatment of ROP with bevacizumab followed by prophylactic laser has a low rate of unfavorable structural outcome.

  7. Greater efficacy of intracavitary infusion of bevacizumab compared to traditional local treatments for patients with malignant cavity serous effusion.

    Science.gov (United States)

    Chen, Dawei; Song, Xinyu; Shi, Fang; Zhu, Hui; Wang, Haiyong; Zhang, Nasha; Zhang, Yan; Kong, Li; Yu, Jinming

    2017-05-23

    Intracavitary infusion of bevacizumab is one effective treatment for malignant serous cavity effusion (MSCE). In this study, we retrospectively evaluated the efficacy of local treatments in 996 advanced cancer patients with MSCE who received paracentesis and intracavitary bevacizumab, or chemotherapy, biological response modifiers, or simple puncture to drain the effusion. The median progression-free survival (PFS) time in patients treated with bevacizumab was 189 days (range, 13-522 days), which was longer than in patients who received one of the other three treatments (p bevacizumab was advantageous for patients with malignant pleural, pericardial, or peritoneal effusions. The median PFS in patients receiving intracavitary bevacizumab did not significantly differ from that of patients receiving a combination of intracavitary and intravenous bevacizumab. Thus the efficacy did not depend on whether patients received intravenous bevacizumab. Only mild related adverse events were observed in all cases, and they did not differ between groups. Proteinuria (severity grade bevacizumab, but no obvious symptoms were observed. Thus, intracavitary infusion of bevacizumab was effective for controlling MSCE without apparent toxicity.

  8. Ocular silicon distribution and clearance following intravitreal injection of porous silicon microparticles

    Science.gov (United States)

    Nieto, Alejandra; Hou, Huiyuan; Sailor, Michael J.; Freeman, William R.; Cheng, Lingyun

    2013-01-01

    Porous silicon (pSi) microparticles have been investigated for intravitreal drug delivery and demonstrated good biocompatibility. With the appropriate surface chemistry, pSi can reside in vitreous for months or longer. However, ocular distribution and clearance pathway of its degradation product, silicic acid, are not well understood. In the current study, rabbit ocular tissue was collected at different time point following fresh pSi (day 1, 5, 9, 16, and 21) or oxidized pSi (day 3, 7, 14, 21, and 35) intravitreal injection. In addition, dual-probe simultaneous microdialysis of aqueous and vitreous humor was performed following a bolus intravitreal injection of 0.25 mL silicic acid (150 μg/mL) and six consecutive microdialysates were collected every 20 min. Silicon was quantified from the samples using inductively coupled plasma-optical emission spectroscopy. The study showed that following the intravitreal injection of oxidized pSi, free silicon was consistently higher in the aqueous than in the retina (8.1 ± 6.5 vs. 3.4 ± 3.9 μg/mL, p = 0.0031). The area under the concentration-time curve (AUC) of the retina was only about 24% that of the aqueous. The mean residence time was 16 days for aqueous, 13 days for vitreous, 6 days for retina, and 18 days for plasma. Similarly, following intravitreal fresh pSi, free silicon was also found higher in aqueous than in retina (7 ± 4.7 vs. 3.4 ± 4.1 μg/mL, p = 0.014). The AUC for the retina was about 50% of the AUC for the aqueous. The microdialysis revealed the terminal half-life of free silicon in the aqueous was 30 min and 92 min in the vitreous; the AUC for aqueous accounted for 38% of the AUC for vitreous. Our studies indicate that aqueous humor is a significant pathway for silicon egress from the eye following intravitreal injection of pSi crystals. PMID:24036388

  9. Safety of bevacizumab in clinical practice for recurrent ovarian cancer: A retrospective cohort study

    Science.gov (United States)

    SELLE, FRÉDÉRIC; EMILE, GEORGE; PAUTIER, PATRICIA; ASMANE, IRÈNE; SOARES, DANIELE G.; KHALIL, AHMED; ALEXANDRE, JEROME; LHOMMÉ, CATHERINE; RAY-COQUARD, ISABELLE; LOTZ, JEAN-PIERRE; GOLDWASSER, FRANÇOIS; TAZI, YOUSSEF; HEUDEL, PIERRE; PUJADE-LAURAINE, ERIC; GOUY, SÉBASTIEN; TREDAN, OLIVIER; BARBAZA, MARIE O.; ADY-VAGO, NORA; DUBOT, CORALINE

    2016-01-01

    The poor outcome of patients with recurrent ovarian cancer constitutes a continuous challenge for decision-making in clinical practice. In this setting, molecular targets have recently been identified, and novel compounds are now available. Bevacizumab has been introduced for the treatment of patients with ovarian cancer and is, to date, the most extensively investigated targeted therapy in this setting. However, potential toxicities are associated with the use of this monoclonal antibody. These toxicities have been reported in clinical trials, and can also be observed outside of trials. As limited data is currently available regarding the safety of bevacizumab treatment in daily clinical practice, the current retrospective study was designed to evaluate this. Data from 156 patients with recurrent ovarian cancer who had received bevacizumab treatment between January 2006 and June 2009 were retrospectively identified from the institutional records of five French centers. In contrast to clinical trials, the patients in the present study were not selected and had a heterogeneous profile according to their prior medical history, lines of treatment prior to bevacizumab introduction and number of relapses. The results first confirm the effect of heavy pretreatment on the occurrence of serious and fatal adverse events in clinical practice, as previously reported for clinical trials and for other retrospective cohort studies. Importantly, the data also demonstrates, for the first time, that medical history of hypertension is an independent predictive risk factor for the development of high-grade hypertension during bevacizumab treatment. These results thus suggest that treating physicians must consider all risk factors for managing bevacizumab toxicity prior to its introduction. Such risk factors include the time of bevacizumab introduction, a patient's history of hypertension and a low incidence of pre-existing obstructive disease. PMID:26998090

  10. Bevacizumab May Differentially Improve Ovarian Cancer Outcome in Patients with Proliferative and Mesenchymal Molecular Subtypes.

    Science.gov (United States)

    Kommoss, Stefan; Winterhoff, Boris; Oberg, Ann L; Konecny, Gottfried E; Wang, Chen; Riska, Shaun M; Fan, Jian-Bing; Maurer, Matthew J; April, Craig; Shridhar, Viji; Kommoss, Friedrich; du Bois, Andreas; Hilpert, Felix; Mahner, Sven; Baumann, Klaus; Schroeder, Willibald; Burges, Alexander; Canzler, Ulrich; Chien, Jeremy; Embleton, Andrew C; Parmar, Mahesh; Kaplan, Richard; Perren, Timothy; Hartmann, Lynn C; Goode, Ellen L; Dowdy, Sean C; Pfisterer, Jacobus

    2017-07-15

    Purpose: Recent progress in understanding the molecular biology of epithelial ovarian cancer has not yet translated into individualized treatment for these women or improvements in their disease outcome. Gene expression has been utilized to identify distinct molecular subtypes, but there have been no reports investigating whether or not molecular subtyping is predictive of response to bevacizumab in ovarian cancer. Experimental Design: DASL gene expression arrays were performed on FFPE tissue from patients enrolled on the ICON7 trial. Patients were stratified into four TCGA molecular subtypes. Associations between molecular subtype and the efficacy of randomly assigned therapy with bevacizumab were assessed. Results: Molecular subtypes were assigned as follows: 122 immunoreactive (34%), 96 proliferative (27%), 73 differentiated (20%), and 68 mesenchymal (19%). In univariate analysis patients with tumors of proliferative subtype obtained the greatest benefit from bevacizumab with a median PFS improvement of 10.1 months [HR, 0.55 (95% CI, 0.34-0.90), P = 0.016]. For the mesenchymal subtype, bevacizumab conferred a nonsignificant improvement in PFS of 8.2 months [HR 0.78 (95% CI, 0.44-1.40), P = 0.41]. Bevacizumab conferred modest improvements in PFS for patients with immunoreactive subtype (3.8 months; P = 0.08) or differentiated subtype (3.7 months; P = 0.61). Multivariate analysis demonstrated significant PFS improvement in proliferative subtype patients only [HR, 0.45 (95% CI, 0.27-0.74), P = 0.0015]. Conclusions: Ovarian carcinoma molecular subtypes with the poorest survival (proliferative and mesenchymal) derive a comparably greater benefit from treatment that includes bevacizumab. Validation of our findings in an independent cohort could enable the use of bevacizumab for those patients most likely to benefit, thereby reducing side effects and healthcare cost. Clin Cancer Res; 23(14); 3794-801. ©2017 AACR . ©2017 American Association for Cancer Research.

  11. Cellular stress response in human Müller cells (MIO-M1) after bevacizumab treatment.

    Science.gov (United States)

    Matsuda, Monique; Krempel, Paloma Gava; Marquezini, Mônica Valeria; Sholl-Franco, Alfred; Lameu, Amanda; Monteiro, Mário Luiz R; Miguel, Nádia Campos de Oliveira

    2017-07-01

    Bevacizumab, an anti-vascular endothelial growth factor (VEGF) agent, is widely used in the treatment of retinal vascular diseases. However, due to the essential role Müller cell derived-VEGF plays in the maintenance of retinal neurons and glial cells, cell viability is likely to be affected by VEGF inhibition. We therefore evaluated the effect of bevacizumab-induced VEGF inhibition on Müller cells (MIO-M1) in vitro. MIO-M1 cells were cultured for 12 or 24 h in media containing bevacizumab at 0.25 or 0.5 mg/mL. Controls were cultured in medium only. Cell viability was determined with the trypan blue exclusion test and MTT assay. Caspase-3, beclin-1, glial fibrillary acidic protein (GFAP) and vimentin content were quantified by immunohistochemistry. Gene expression was evaluated by real-time quantitative PCR. Treatment with bevacizumab did not reduce MIO-M1 cell viability, but increased metabolic activity at 24 h (0.5 mg/mL) and induced apoptosis and autophagy, as shown by the increased caspase-3 levels at 12 h (0.25 and 0.5 mg/mL) and the increased beclin levels at 24 h (0.5 mg/mL). Caspase-3 mRNA was upregulated at 12 h and downregulated at 24 h in cells treated with bevacizumab at 0.25 mg/mL. Bevacizumab treatment was also associated with structural protein abnormalities, with decreased GFAP and vimentin content and upregulated GFAP and vimentin mRNA expression. Although bevacizumab did not significantly affect MIO-M1 cell viability, it led to metabolic and molecular changes (apoptosis, autophagy and structural abnormalities) suggestive of significant cellular toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Effect of bevacizumab on acetic acid-induced ulcerative colitis in rats.

    Science.gov (United States)

    Ozsoy, Zeki; Ozsoy, Seyma; Gevrek, Fikret; Demir, Emre; Benli, Ismail; Daldal, Emin; Yenidogan, Erdinc

    2017-08-01

    The aim of this study was to examine the effect of intraperitoneally administered bevacizumab on colitis induced by acetic acid. An experimental model of acetic acid-induced colitis was introduced in rats. After the induction of colitis, bevacizumab was administered intraperitoneally at two different daily doses of low (2.5 mg/kg) or high (5 mg/kg) concentration. Control groups were included for colitis and bevacizumab. After 7 d, the rats were sacrificed, and colonic tissues were harvested for macroscopic and microscopic examination of colonic damage. Tumor necrosis factor alpha, interleukin 1 beta (IL-1β), IL-6, myeloperoxidase, malondialdehyde, glutathione, and superoxidismutase values were measured biochemically. There was no statistically significant macroscopic improvement in damage to the colon tissues (P > 0.05). The severity of inflammation was significantly reduced (0.98 ± 0.22) in the low-dose bevacizumab-treated rat group compared with the control group (P bevacizumab-treated rat group was not statistically significant (1.40 ± 0.33). In addition, although there was no significant change in the myeloperoxidase levels biochemically, IL-6 and malondialdehyde levels decreased in the low-dose treatment group (P = 0.014, P = 0.002, respectively). A significant decrease was found at both treatment doses in IL-1β (P bevacizumab were observed to have a protective effect in an experimental colitis model, and the dosage of 2.5 mg/kg bevacizumab was found to have a more prominent effect. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Efficacy and Safety of Intracameral Bevacizumab for Treatment of Neovascular Glaucoma.

    Science.gov (United States)

    Ha, Jun Young; Lee, Tae Hee; Sung, Mi Sun; Park, Sang Woo

    2017-12-01

    To evaluate the long-term efficacy and safety of intracameral bevacizumab in patients with neovascular glaucoma. This retrospective study included 26 eyes of 26 neovascular glaucoma patients who received intracameral bevacizumab injection between January 2013 and May 2015, and were followed-up for at least 1 year. All patients were treated with topical and/or systemic intraocular pressure (IOP)-lowering medications, intracameral bevacizumab, and panretinal photocoagulation (PRP). The main outcome measures were changes in visual acuity, IOP, and neovascularization of the iris (NVI) and the anterior chamber angle (NVA). To assess the safety of intracameral bevacizumab, corneal endothelial changes were also determined using specular microscopy. Patients whose IOP was uncontrolled received IOP-lowering surgery. Clinical factors associated with IOP-lowering surgery were also investigated. In all patients, intracameral bevacizumab resulted in a rapid and marked reduction of IOP, NVI, and NVA within 1 week. At 12 months after initial injection, 19 of 26 eyes (73%) underwent IOP-lowering surgery. The average interval between initial injection and surgical treatment was 33.6 ± 26.9 days. Baseline IOP (p = 0.018), NVA grade (p = 0.029), and incomplete PRP (p = 0.005) were identified as predictive factors for IOP-lowering surgery. During the follow-up period, there were no statistically significant corneal endothelial changes after intracameral bevacizumab injection. During 1 year of follow-up after intracameral bevacizumab, the procedure was found to be safe for the corneal endothelium. However, the IOP-lowering effect was transient, and 73% of patients eventually required IOP-lowering surgery. Predictive factors for IOP-lowering surgery were high baseline IOP and NVA grade, and incomplete PRP. © 2017 The Korean Ophthalmological Society

  14. Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Dellas, Kathrin; Dunst, Jürgen; Höhler, Thomas; Reese, Thomas; Würschmidt, Florian; Engel, Erik; Rödel, Claus; Wagner, Wolfgang; Richter, Michael; Arnold, Dirk

    2013-01-01

    Preoperative radiochemotherapy (RCT) with 5-FU or capecitabine is the standard of care for patients with locally advanced rectal cancer (LARC). Preoperative RCT achieves pathological complete response rates (pCR) of 10-15%. We conducted a single arm phase II study to investigate the feasibility and efficacy of addition of bevacizumab and oxaliplatin to preoperative standard RCT with capecitabine. Eligible patients had LARC (cT3-4; N0/1/2, M0/1) and were treated with preoperative RCT prior to planned surgery. Patients received conventionally fractionated radiotherapy (50.4 Gy in 1.8 Gy fractions) and simultaneous chemotherapy with capecitabine 825 mg/m 2 bid (d1-14, d22-35) and oxaliplatin 50 mg/m 2 (d1, d8, d22, d29). Bevacizumab 5 mg/kg was added on days 1, 15, and 29. The primary study objective was the pCR rate. 70 patients with LARC (cT3-4; N0/1, M0/1), ECOG < 2, were enrolled at 6 sites from 07/2008 through 02/2010 (median age 61 years [range 39–89], 68% male). At initial diagnosis, 84% of patients had clinical stage T3, 62% of patients had nodal involvement and 83% of patients were M0. Mean tumor distance from anal verge was 5.92 cm (± 3.68). 58 patients received the complete RCT (full dose RT and full dose of all chemotherapy). During preoperative treatment, grade 3 or 4 toxicities were experienced by 6 and 2 patients, respectively: grade 4 diarrhea and nausea in one patient (1.4%), respectively, grade 3 diarrhea in 2 patients (3%), grade 3 obstipation, anal abscess, anaphylactic reaction, leucopenia and neutropenia in one patient (1.4%), respectively. In total, 30 patients (46%) developed postoperative complications of any grade including one gastrointestinal perforation in one patient (2%), wound-healing problems in 7 patients (11%) and bleedings in 2 patients (3%). pCR was observed in 12/69 (17.4%) patients. Pathological downstaging (ypT < cT and ypN ≤ cN) was achieved in 31 of 69 patients (44.9%). All of the 66 operated patients had a R0 resection

  15. Intravenous Drug Use-Associated Scopulariopsis Endophthalmitis Treated with Systemic and Intravitreal Voriconazole

    Directory of Open Access Journals (Sweden)

    Joseph J. Raevis

    2018-01-01

    Full Text Available Purpose: To report a case of intravenous (i.v. heroin use-associated endogenous endophthalmitis caused by Scopulariopsis fungal species, and its response to intravitreal and oral voriconazole treatments. Patient: A 21-year-old-female with chronic hepatitis C and i.v. heroin use presented with subacute decreased vision to hand motion in her left eye. Results: Endogenous fungal endophthalmitis caused by Scopulariopsis was confirmed by vitreous biopsy. The patient improved clinically after vitrectomy with intravitreal voriconazole and 3 weeks of oral voriconazole. The final vision was 20/60 after 6 months. Conclusions: Scopulariopsis is a rare cause of endophthalmitis, and is often difficult to treat due to its resistance to commonly used antifungals. This case is the first report of Scopulariopsis endophthalmitis secondary to i.v. drug use.

  16. Patients' experiences of nursing actions during intravitreal treatment for wet age-related macular degeneration

    OpenAIRE

    Rönn Emsfors, Åsa; Elgán, Carina

    2015-01-01

    Purpose: The aim was to identify and describe nursing actions performed by nursing staff in which patients with wet age-related macular degeneration (AMD) experience good nursing care. Method: An explorative and descriptive qualitative design based on the Critical incident technique (CIT) was used. A strategic sample of 16 patients, aged 61-87 years (eleven women and five men) with wet AMD who received intravitreal treatment were interviewed. Results: Two main areas of good nursing care was i...

  17. Survey: technique of performing intravitreal injection among members of the Brazilian Retina and Vitreous Society (SBRV

    Directory of Open Access Journals (Sweden)

    Helio F. Shiroma

    2015-02-01

    Full Text Available Purpose: To evaluate and describe the precautions involved in the technique of intravitreal injection of antiangiogenic drugs adopted by the ophthalmologists who are members of the Brazilian Society of Retina and Vitreous (SBRV. Methods: A questionnaire containing 22 questions related to precautions taken before, during, and after intravitreal injection was sent electronically to 920 members of SBRV between November 15, 2013 and April 31, 2014. Results: 352 responses (38% were obtained. There was a predominance of men (76% from the southwest region of Brazil (51%. The professional experience varied between 6 and 15 years after medical specialization (50%. Most professionals (76% performed an average of 1 to 10 intravitreal injections a week, and 88% of the procedures were performed in the operating room using povidone iodine (99%, sterile gloves, and blepharostat (94%. For inducing topical anesthesia, usage of anesthetic eye drops was the most used technique (65%. Ranibizumab (Lucentis® was the most common drug (55%, and age-related macular degeneration (AMD was the most treated disease (57%. Regarding the complications treated, 6% of the ophthalmologists had treated at least one case of retinal detachment, 20% had treated cases of endophthalmitis, 9% had treated cases of vitreous hemorrhage, and 12% had encountered cases of crystalline lens touch. Conclusion: Intravitreal injection is a procedure routinely performed by retina specialists and has a low incidence of complications. Performing the procedure in the operating room using an aseptic technique was preferred by most of the respondents. Ranibizumab was the most used drug, and AMD was the most treated disease.

  18. Efficacy of intravitreal ranibizumab injection combined with macular grid photocoagulation for diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Hu-Lin Jiang

    2014-07-01

    Full Text Available AIM:To evaluate the clinical efficacy of intravitreal injection of ranibizumab combined with macular grid photocoagulation for diabetic macular edema(DME.METHODS:Totally 60 eyes(60 patientswith DME were randomly divided into 2 groups: 30 eyes of simple injection group underwent intravitreal injection of ranibizumab, and 30 eyes of combined treatment group underwent intravitreal injection of ranibizumab and macular grid photocoagulation 1wk later. The best corrected visual acuity(BCVA, central macular thickness(CMTmeasured by optical coherence tomography(OCTand postoperative complications were observed.RESULTS:In simple injection group, the BCVA after operation were separately 0.390±0.075(4wk, 0.367±0.088(8wkand 0.319±0.064(12wk,the CMT after operation were separately 221.63±112.34μm(4wk, 337.73±99.56μm(8wkand 432.92±100.46μm(12wk, which were much better than pre-operation. But during follow-up, the BCVA presented down trend and the CMT was on the rise slowly. In combined treatment group, the BCVA after operation were separately 0.385±0.036(4wk, 0.382±0.079(8wkand 0.377±0.097(12wk,the CMT after operation were separately 249.77±106.55μm(4wk, 270.40±92.88μm(8wkand 275.84±97.34μm(12wk, which were satisfactory and steady during follow-up, better than simple injection group(PCONCLUSION:Intravitreal injection of ranibizumab can effectively improve visual acuity and decrease central foveal thickness for patients with DME, combining with macular grid photocoagulation can ensure therapeutic effects steady and permanent.

  19. Short-term efficacy of intravitreal conbercept in treatment-naive patients with polypoidal choroidal vasculopathy

    Directory of Open Access Journals (Sweden)

    Peng Y

    2018-02-01

    Full Text Available Yuting Peng, Xiongze Zhang, Miaoling Li, Bing Liu, Lan Mi, Chengguo Zuo, Feng Wen State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China Introduction: To evaluate the functional and morphological outcomes of intravitreal conbercept monotherapy in patients with polypoidal choroidal vasculopathy (PCV. Materials and methods: In this retrospective, observational case series study, we reviewed medical records of 48 eyes (48 patients with naive PCV that were treated with a series of 3 monthly intravitreal injections of 0.5 mg of conbercept followed by as-needed injections (3+pro re nata. All patients completed at least 6 months of monthly follow-up. Changes in the best-corrected visual acuity, optical coherence tomography, and indocyanine green angiography were retrospectively evaluated. Results: At 6 months, the mean best-corrected visual acuity significantly improved from 0.89±0.35 (20/160 in Snellen equivalent at baseline to 0.58±0.26 (Snellen equivalent of 20/80; P<0.001, and 60.42% (29/48 of eyes had an improvement of three lines of vision; the mean central retinal thickness significantly decreased from 333.56±171.04 µm at baseline to 187.65±54.46 µm (P<0.001, and 93.75% (45/48 achieved a dry macula. At 3 months, 6 of 32 eyes (18.75% showed partial regression of branching vascular network, 14 of 32 (43.75% patients showed complete resolution of polyps. The mean number of injections was 3.4±0.9 through 6 months. No conbercept-related systemic or ocular adverse effects were observed. Conclusion: Intravitreal injection of conbercept using “3+pro re nata” regimen significantly improved visual acuity and anatomical outcomes in treatment-naive patients with PCV. Keywords: conbercept, intravitreal injection, PCV, short-term efficacy, “3+PRN”

  20. Distribution of [35S] taurine in mouse retina after intravitreal and intravascular injection

    International Nuclear Information System (INIS)

    Pourcho, R.G.

    1977-01-01

    The distribution of [ 35 S] taurine in mouse retinae was studied by autoradiographic techniques after either intravitreal or intravascular injection. The route of injection did not affect the final localization. The major sites of label accumulation were the outer nuclear layer, the inner nuclear layer, and Mueller cell processes adjacent to the vitreal surface. The distribution was consistent with the interpretation that taurine was localized within two cellular compartments of mouse retina, photoreceptor cells and Mueller cells. (author)

  1. Transformational change: nurses substituting for ophthalmologists for intravitreal injections – a quality-improvement report

    Directory of Open Access Journals (Sweden)

    Michelotti MM

    2014-04-01

    Full Text Available Monica M Michelotti,1 Salwa Abugreen,2 Simon P Kelly,1 Jiten Morarji,1 Debra Myerscough,2 Tina Boddie,2 Ann Haughton,1 Natalie Nixon,2 Brenda Mason,1 Evangelos Sioras11Ophthalmology Department, Royal Bolton Hospital NHS Foundation Trust, Bolton, UK; 2Ophthalmology Department, East Lancashire NHS Trust, Blackburn, UKBackground: The dramatic increase in need for anti-vascular endothelial growth factor (anti-VEGF intravitreal therapy in the treatment of retinal disease and the absence of an equivalent increase in ophthalmologists to undertake such intravitreal injections created a patient-safety risk. Timing of intravitreal therapy (IVT is critical to prevent vision loss and local clinics lacked capacity to treat patients appropriately. We aimed to improve capacity for IVT by nurse injections.Materials and methods: A multidisciplinary prospective service-improvement process was undertaken at two adjacent general hospitals in the northwest of England. IVT injections by nurses were a principal component of solution development. After we had obtained appropriate institutional approval, experienced ophthalmic nurses were trained, supervised, and assessed to undertake IVT. Ophthalmologists directly supervised the first 200 injections, and a retina specialist was always on site.Results: Nurses undertook 3,355 intravitreal injections between June 2012 and November 2013, with minor adverse events (0.3% subconjunctival hemorrhage and corneal abrasion. There were no patient complaints at either hospital.Conclusion: Experienced ophthalmic nurses quickly learned how to perform such injections safely. IVT by nurses was well accepted by patients and staff. Hospital A trained three nurses sequentially for improved flexibility in scheduling. Novel use of appropriately trained nonmedical staff can improve efficiency and access in an overburdened service with time-sensitive disease. Retinal assessment was undertaken by ophthalmologists only. Improved access to IVT

  2. Monitoring the effects of bevacizumab beyond progression in a murine colorectal cancer model: a functional imaging approach

    NARCIS (Netherlands)

    Heijmen, L.; Punt, C. J. A.; ter Voert, E. G. W.; de Geus-Oei, L. F.; Heerschap, A.; Bussink, J.; Sweep, C. G. J.; Zerbi, V.; Oyen, W. J. G.; Span, P. N.; Boerman, O.; van Laarhoven, H. W. M.

    2013-01-01

    Clinical studies have shown that bevacizumab beyond progression to first line therapy is beneficial for overall survival in advanced stage colorectal cancer. We studied the utility of several functional imaging modalities to assess the efficacy of bevacizumab beyond progression (BBP). All BALB/c

  3. Bevacizumab in combination with cetuximab and irinotecan after failure of cetuximab and irinotecan in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Larsen, Finn Ole; Pfeiffer, Per; Nielsen, Dorte

    2011-01-01

    The efficacy and safety of concurrent administration of irinotecan with the two monoclonal antibodies cetuximab and bevacizumab as fourth line therapy in heavily pretreated patients with metastatic colorectal cancer were evaluated.......The efficacy and safety of concurrent administration of irinotecan with the two monoclonal antibodies cetuximab and bevacizumab as fourth line therapy in heavily pretreated patients with metastatic colorectal cancer were evaluated....

  4. Cytotoxicity and genotoxicity of intravitreal adalimumab administration in rabbit retinal cells

    Directory of Open Access Journals (Sweden)

    Álcio Coutinho de Paula

    2015-04-01

    Full Text Available Purpose: To assess the cytotoxicity and genotoxicity of intravitreal adalimumab treatment in an animal experimental model using cytological and molecular techniques. Methods: Eighteen rabbits were randomly assigned to three groups: control, adalimumab treatment, and placebo. Cytotoxicity on retinal cells was evaluated using flow cytometry assays to determine the level of apoptosis and necrosis. Genotoxicity was evaluated by comet assays to assess DNA damage, and quantitative real-time polymerase chain reaction (qPCR was used to evaluate expression of apoptosis-inducing caspases (8 and 3. Results: No cytotoxicity or genotoxicity was observed in any of the two treatment groups (adalimumab and placebo following intravitreal administration compared with the control group. Flow cytometry analysis revealed that more than 90% of the cells were viable, and only a low proportion of retinal cells presented apoptotic (~10% or necrotic (<1% activity across all groups. Molecular damage was also low with a maximum of 6.4% DNA degradation observed in the comet assays. In addition, no increase in gene expression of apoptosis-inducing caspases was observed on retinal cells by qPCR in both the adalimumab and placebo groups compared with the control group. Conclusion: The use of adalimumab resulted in no detectable cytotoxicity or genotoxicity on retinal cells for up to 60 days upon administration. These results therefore indicate that adalimumab may be a safe option for intravitreal application to treat ocular inflammatory diseases in which TNF-α is involved.

  5. Treatment of CNV secondary to presumed ocular histoplasmosis with intravitreal aflibercept 2.0 mg injection.

    Science.gov (United States)

    Walia, Harpreet S; Shah, Gaurav K; Blinder, Kevin J

    2016-04-01

    To assess the efficacy and safety of intravitreal aflibercept injection in the treatment of CNV secondary to presumed ocular histoplasmosis syndrome (POHS). To assess safety of intravitreal aflibercept for the treatment of CNV secondary to presumed ocular histoplasmosis syndrome. Masked, open-label, prospective study. Five subjects will receive 2.0 mg aflibercept injection every 8 weeks with 3 initial monthly doses over a 12 month period. No adverse systemic or ocular were reported. At month six, the mean visual acuity improved by 7.8 ETDRS letters, mean central subfoveal thickness decreased by 38.8 microns and mean OCT volume decreased by 0.076 mm3 . At month twelve, the mean visual acuity improved by 12.4 ETDRS letters, mean central subfoveal thickness decreased by 34.6 microns and mean OCT volume decreased by 0.576 mm3. The use of intravitreal 2.0 mg aflibercept injection for the treatment of CNV secondary to presumed ocular histoplasmosis syndrome yielded no systemic or ocular adverse events and produced improvement in visual acuity and reduction of OCT thickness and volume. Copyright © 2016 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  6. Effect of photodynamic therapy combined with intravitreal ranibizumab injection on circumscribed choroidal hemangioma

    Directory of Open Access Journals (Sweden)

    Yu-Shun Xue

    2017-02-01

    Full Text Available AIM:To investigate the effect of photodynamic therapy(PDTcombined with intravitreal injection of ranibizumab on circumscribed choroidal hemangioma(CCH. METHODS:A retrospective study was performed for 6 eyes(6 casesdiagnosed as CCH. Before treatment, OCT examination showed macular cystoid edema and retinal neurepithelium layer detachment in all patients. All patients underwent photodynamic therapy, then intravitreal injection of ranibizumab 0.5mg(0.05mLwere administered at 48h after PDT. The best corrected visual acuity(BCVA, examination of the ocular fundus, fundus photography, fluorescence fundus angiography(FFA, indocyanine green angiography(ICGA, eye B ultrasonic and optical coherence tomography(OCTwere performed respectively at 1, 3 and 6mo after treatment. RESULTS:The patients were followed up for 4 to 10mo, the final vision of follow-up increased than before, it was raised 7 lines. The images of ICGA revealed hypofluorescence or no leakage in focal area. Eye B ultrasonic showed that hemangioma shrunk or faded. The images of ICGA revealed macular region retinal reattached well and edema disappeared completely. Mean flow-up was 6mo postoperative. There had no evidence of recurrence. CONCLUSION:For CCH patients, hemangioma got smaller obviously by PDT. Intravitreal ranibizumab injection promote effusion absorption under the retina. Combining use of the two therapies could improve visual acuity in a short-term.

  7. Low Visceral Fat Content Is a Negative Predictive Marker for Bevacizumab in Metastatic Colorectal Cancer.

    Science.gov (United States)

    Miyamoto, Yuji; Oki, Eiji; Emi, Yasunori; Tokunaga, Shoji; Shimokawa, Mototsugu; Ogata, Yutaka; Akagi, Yoshito; Sakamoto, Yasuo; Tanaka, Takaho; Saeki, Hiroshi; Maehara, Yoshihiko; Baba, Hideo

    2018-01-01

    This study aimed to clarify the predictive impact of visceral fat on response to bevacizumab in patients with metastatic colorectal cancer (mCRC). Pretreatment computed tomography was used to measure visceral fat area (VFA) and patients with mCRC receiving first-line chemotherapy with/without bevacizumab were divided by median VFA value into two groups: high VFA and low VFA. In the bevacizumab-treated group, patients with low VFA had significantly shorter overall survival (OS) than patients with high VFA in univariate (median=21.1 vs. 38.9 months; hazard ratio=1.70, 95% confidence interval=1.06-2.70, p=0.03) and multivariate analysis (hazard ratio=1.85, 95% confidence interval=1.15-3.03, p=0.01). No significant differences were seen in OS between groups treated with chemotherapy alone. The VFA had a marginally significant modifying effect on the relationship between bevacizumab and OS (p for interaction=0.07). Our findings provide the first evidence that a low VFA might be a negative predictive marker for response to bevacizumab in patients with mCRC. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  8. Toxicity and efficacy of lomustine and bevacizumab in recurrent glioblastoma patients

    DEFF Research Database (Denmark)

    Jakobsen, J N; Urup, T; Grunnet, K

    2018-01-01

    The combination of lomustine and bevacizumab is a commonly used salvage treatment for recurrent glioblastoma (GBM). We investigated the toxicity and efficacy of lomustine plus bevacizumab (lom-bev) in a community-based patient cohort and made a comparison to another frequently used combination...... therapy consisting of irinotecan plus bevacizumab (iri-bev). Seventy patients with recurrent GBM were treated with lomustine 90 mg/m2 every 6 weeks and bevacizumab 10 mg/kg every 2 weeks. Toxicity was registered and compared to the toxicity observed in 219 recurrent GBM patients who had previously been...... treated with irinotecan 125 mg/m2 and bevacizumab 10 mg/kg every 2 weeks. The response rate was 37.1% for lom-bev and 30.1% for iri-bev. Median progression-free survival (PFS) was 23 weeks for lom-bev and 21 weeks for iri-bev (p = 0.9). Overall survival (OS) was 37 weeks for lom-bev and 32 weeks for iri...

  9. Aflibercept in diabetic macular edema refractory to previous bevacizumab: outcomes and predictors of success.

    Science.gov (United States)

    Laiginhas, Rita; Silva, Marta Inês; Rosas, Vitor; Penas, Susana; Fernandes, Vitor Adriano; Rocha-Sousa, Amândio; Carneiro, Ângela; Falcão-Reis, Fernando; Falcão, Manuel Sousa

    2018-01-01

    To evaluate functional and anatomical outcomes after aflibercept in patients with diabetic macular edema (DME) with poor response to bevacizumab. We retrospectively reviewed patients with DME recalcitrant to bevacizumab who were switched to aflibercept between January and December 2015. All patients had a minimal follow-up of three months before the conversion and underwent at least three injections of bevacizumab. Functional outcome consisted in best corrected visual acuity (VA). Anatomical outcomes were demonstrated through central macular thickness (CMT) measured by optical coherence tomography. Forty-nine eyes of 34 subjects were reviewed. Mean VA improved from 0.55 ± 0.32 logMAR to 0.46 ± 0.33 logMAR (p = 0.038). Mean CMT decreased from 473 ± 146 μm to 349 ± 85 μm (p bevacizumab exposure did not correlate with different outcomes. The variation of VA in response to aflibercept was significantly superior in the group with poorer VA before the switch (mean variation of -0.097 ± 0.21 logMAR) when compared to eyes with VA bevacizumab exposure. Pre-switch CMT was a predictor of anatomical changes after aflibercept.

  10. Intranasal bevacizumab in the treatment of HHT -related epistaxis: a systematic review.

    Science.gov (United States)

    Stokes, P; Rimmer, J

    2018-03-01

    Hereditary haemorrhagic telangiectasia (HHT) remains a difficult disease for the ENT specialist to manage. Affected patients often report recurrent epistaxis as the most debilitating symptom. The pathogenesis of the disease is due to genetic mutations affecting angiogenesis. For this reason, the anti-angiogenic therapy bevacizumab has gained popularity in the local treatment of epistaxis in patients with HHT. A systematic review of the efficacy of bevacizumab in local treatment of epistaxis in patients with HHT based on epistaxis duration, frequency, severity and impact on quality of life. A systematic search was performed using the PubMed, MEDLINE and EMBASE databases. The Preferred Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies that measured the efficacy of intranasal bevacizumab treatment of epistaxis in patients with HHT were included for qualitative analysis. Thirteen studies (four randomised controlled trials, three prospective studies, three retrospective studies, one case series and two case reports) with a total of 357 patients were included. Local administration (either by submucosal injection or topically) did not have a significant impact on epistaxis duration, frequency, severity or quality of life compared to placebo or other local treatments. The available evidence suggests that intranasal bevacizumab treatment does not have a significant effect on epistaxis in patients with HHT. There are several limitations that require further investigation to confidently rule out local bevacizumab as an effective therapy in HHT related epistaxis.

  11. A prospective study of XELIRI plus bevacizumab as a first-line therapy in Japanese patients with unresectable or recurrent colorectal cancer (KSCC1101).

    Science.gov (United States)

    Ando, Koji; Emi, Yasunori; Suenaga, Toyokuni; Hamanoue, Masahiro; Maekawa, Soichiro; Sakamoto, Yasuo; Kai, Seiichiro; Satake, Hironaga; Shimose, Takayuki; Shimokawa, Mototsugu; Saeki, Hiroshi; Oki, Eiji; Sakai, Kenji; Akagi, Yoshito; Baba, Hideo; Maehara, Yoshihiko

    2017-10-01

    This study was designed to evaluate the efficacy and toxicity of XELIRI plus bevacizumab for the treatment of Japanese patients with unresectable or recurrent colorectal cancer (CRC). This was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated unresectable or recurrent CRC, presence of measurable lesions, ≥20 years of age, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients received bevacizumab (7.5 mg/kg on day 1) and XELIRI (irinotecan 200 mg/m 2 on day 1 plus capecitabine 800 mg/m 2 b.i.d. on days 1-14) every 3 weeks. The primary endpoint was the objective tumor response rate. A total of 36 patients were enrolled in this study from July 2011 to September 2012. One patient did not fulfill the eligibility criteria and one patient withdrew their consent before the start of the treatment protocol. The confirmed objective response rate was 58.8% (95% CI 35.1-70.2%). The median progression-free survival was 9.6 months (95% CI 5.1-11.1 months) and the median overall survival was 23.1 months (95% CI 11.3-36.7 months). The grade ≥3 adverse events that were frequently encountered in this study were neutropenia (31.4%), leukopenia (22.9%), diarrhea (22.9%), anemia (20.0%), anorexia (20.0%) and febrile neutropenia (17.2%). The frequency of grade 3/4 adverse events, such as neutropenia and leukopenia, was much higher in patients with a UGT1A1 polymorphism. A first-line therapy comprising XELIRI plus bevacizumab yielded a promising response rate. However, careful attention should be given to adverse clinical events in Japanese patients receiving treatment with unresectable or recurrent CRC.

  12. Cost-Effectiveness of Bevacizumab and Ranibizumab for Newly Diagnosed Neovascular Macular Degeneration (An American Ophthalmological Society Thesis)

    Science.gov (United States)

    Stein, Joshua D.; Newman-Casey, Paula Anne; Mrinalini, Tavag; Lee, Paul P.; Hutton, David W.

    2013-01-01

    Purpose: To determine the most cost-effective treatment for patients with newly diagnosed neovascular macular degeneration: monthly or as-needed bevacizumab injections, or monthly or as-needed ranibizumab injections. Methods: Using a Markov model with a 20-year time horizon, we compared the incremental cost-effectiveness of treating a hypothetical cohort of 80-year-old patients with newly diagnosed neovascular macular degeneration using monthly bevacizumab, as-needed bevacizumab, monthly ranibizumab, or as-needed ranibizumab. Data came from the Comparison of Age-Related Macular Degeneration Treatment Trial (CATT), the Medicare Fee Schedules, and the medical literature. Results: Compared with as-needed bevacizumab, the incremental cost-effectiveness ratio of monthly bevacizumab is $242,357 per quality-adjusted life year (QALY). Monthly ranibizumab gains an additional 0.02 QALYs vs monthly bevacizumab at an incremental cost-effectiveness ratio of more than $10 million per QALY. As-needed ranibizumab was dominated by monthly bevacizumab. In sensitivity analyses assuming a willingness to pay of $100,000 per QALY, the annual risk of serious vascular events would have to be at least 2.5 times higher with bevacizumab than that observed in the CATT trial for as-needed ranibizumab to have an incremental cost-effectiveness ratio of bevacizumab experienced declining vision by one category (eg, from 20/25–20/40 to 20/50–20/80) after 2 years but all patients receiving ranibizumab retained their vision level, as-needed ranibizumab would have an incremental cost-effectiveness ratio of $97,340 per QALY. Conclusion: Even after considering the potential for differences in risks of serious adverse events and therapeutic effectiveness, bevacizumab confers considerably greater value than ranibizumab for the treatment of neovascular macular degeneration. PMID:24167325

  13. The impact of bevacizumab in metastatic colorectal cancer with an intact primary tumor: Results from a large prospective cohort study.

    Science.gov (United States)

    Lee, Belinda; Wong, Hui-Li; Tacey, Mark; Tie, Jeanne; Wong, Rachel; Lee, Margaret; Nott, Louise; Shapiro, Jeremy; Jennens, Ross; Turner, Natalie; Tran, Ben; Ananda, Sumitra; Yip, Desmond; Richardson, Gary; Parente, Phillip; Lim, Lionel; Stefanou, Greg; Burge, Matthew; Iddawela, Mahesh; Power, Jeremy; Gibbs, Peter

    2017-08-01

    Debate continues regarding the benefits versus risks of initial resection of the primary tumor in metastatic colorectal cancer (mCRC) patients with an asymptomatic primary tumor. Although the benefit of the anti-vascular endothelial growth factor agent bevacizumab alongside first-line chemotherapy in mCRC is established, the impact of bevacizumab on the intact primary tumor (IPT) is less well understood. Data from an Australian mCRC registry were used to assess the impact of bevacizumab-based regimens in the presence of an IPT, to see if this differs from effects in resected primary tumor (RPT) patients and to understand the safety profile of bevacizumab in patients with IPT. Progression-free survival (PFS), overall survival (OS) and safety endpoints were analyzed. Of 1204 mCRC patients, 826 (69%) were eligible for inclusion. Bevacizumab use was similar in both arms (IPT (64%) versus RPT (70%)); compared with chemotherapy alone, bevacizumab use was associated with significantly longer PFS (IPT: 8.5 months vs 4.7 months, P = 0.017; RPT: 10.8 months vs 5.8 months, P Bevacizumab use in an IPT was associated with more GI perforations (4.5% vs 1.8%, P = 0.210) but less frequent bleeding (1.5% vs 5.3%, P = 0.050) and thrombosis (1.5% vs 2.7%, P = 0.470), versus chemotherapy alone. Median survival was equivalent between patients that did or did not experience bevacizumab-related adverse events - 20.0 months versus 19.9 months, hazard ratio = 0.98, P = 0.623. 1 CONCLUSIONS: The addition of bevacizumab significantly improved survival outcomes in mCRC with an IPT. The occurrence of bevacizumab-related adverse events did not significantly impact survival outcomes. © 2016 John Wiley & Sons Australia, Ltd.

  14. Bevacizumab in the treatment of NSCLC: patient selection and perspectives

    Directory of Open Access Journals (Sweden)

    Russo AE

    2017-12-01

    Full Text Available Alessia E Russo,1 Domenico Priolo,1 Giovanna Antonelli,1 Massimo Libra,2 James A McCubrey,3 Francesco Ferraù1 1Medical Oncology Department, San Vincenzo Hospital, Taormina (Messina, Italy; 2Laboratory of Translational Oncology & Functional Genomics, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy; 3Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA Abstract: Non-small-cell lung cancer (NSCLC represents about 85% of all lung cancers, and more than half of NSCLCs are diagnosed at an advanced stage. Chemotherapy has reached a plateau in the overall survival curve of about 10 months. Therefore, in last decade novel targeted approaches have been developed to extend survival of these patients, including antiangiogenic treatment. Vascular endothelial growth factor (VEGF signaling pathway plays a dominant role in stimulating angiogenesis, which is the main process promoting tumor growth and metastasis. Bevacizumab (bev; Avastin® is a recombinant humanized monoclonal antibody that neutralizes VEGF’s biologic activity through a steric blocking of its binding with VEGF receptor. Currently, bev is the only antiangiogenic agent approved for the first-line treatment of advanced or recurrent nonsquamous NSCLC in “bev-eligible” patients. The ineligibility to receive bev is related to its toxicity. In the pivotal trials of bev in NSCLC, fatal bleeding events including pulmonary hemorrhage were observed with rates higher in the chemotherapy-plus-bev group. Therefore, in order to reduce the incidence of severe pulmonary hemorrhage, numerous exclusion criteria have been characteristically applied for bev such as central tumor localization or tumor cavitation, use of anticoagulant therapy, presence of brain metastases, age of patients (elderly. Subsequent studies designed to evaluate the safety of bev have demonstrated that this agent is safe and

  15. Retinoblastoma Control With Primary Intra-arterial Chemotherapy: Outcomes Before and During the Intravitreal Chemotherapy Era.

    Science.gov (United States)

    Shields, Carol L; Alset, Adel E; Say, Emil Anthony T; Caywood, Emi; Jabbour, Pascal; Shields, Jerry A

    2016-09-01

    To compare outcomes of intra-arterial chemotherapy for retinoblastoma as primary therapy before (Era I) and during (Era II) the intravitreal chemotherapy era. In this retrospective interventional case series at a tertiary referral center, 66 eyes of 66 patients with untreated unilateral retinoblastoma were used. intraarterial chemotherapy into the ophthalmic artery under fluoroscopic guidance was performed using melphalan in every case, with additional topotecan as necessary. Intravitreal chemotherapy using melphalan and/or topotecan was employed as needed for active vitreous seeding. Globe salvage was measured based on the International Classification of Retinoblastoma (ICRB) during two eras. The two eras encompassed 2008 to 2012 (intraarterial chemotherapy alone, Era I) and 2012 to 2015 (intraarterial chemotherapy plus intravitreal chemotherapy, Era II). Over this period, there were 66 patients with unilateral untreated retinoblastoma treated with primary intra-arterial chemotherapy. A comparison of features (Era I vs Era II) revealed no significant difference in mean patient age (24 vs 24 months), ICRB groups, mean largest tumor diameter (19 vs 17 mm), mean largest tumor thickness (10 vs 10 mm), vitreous seed presence (56% vs 59%), subretinal seed presence (67% vs 62%), retinal detachment (70% vs 66%), or vitreous hemorrhage (0% vs 5%). There was no significant difference in mean number of intra-arterial chemotherapy cycles (3 vs 3.1) or intraarterial chemotherapy dosages. Following therapy, there was a significant difference (Era I vs Era II) in the need for enucleation overall (44% vs 15%, P = .012), especially for group E eyes (75% vs 27%, P = .039). Four of the eyes that initiated therapy in Era I later required intravitreal chemotherapy during Era II. The enucleation rate was 0% for groups B and C in both eras and non-significant for group D (23% vs 13%). There were no patients with stroke, seizure, limb ischemia, extraocular tumor extension, secondary

  16. Treatment of experimental autoimmune uveoretinitis with intravitreal injection of infliximab encapsulated in liposomes.

    Science.gov (United States)

    Zhang, Rui; Qian, Jiang; Li, Xiaofeng; Yuan, Yifei

    2017-12-01

    To evaluate the safety and efficacy of intravitreal injection of liposomes encapsulating infliximab in experimental autoimmune uveoretinitis (EAU) rats. Liposomes containing infliximab were prepared and characterised for mean particle size, entrapment efficiency, polydispersity index (PDI) and zeta potential. In vitro release profile and the stability of infliximab-lip were evaluated. EAU rats were intravitreally injected with saline, infliximab, infliximab-lip or unloaded liposomes. Clinical signs and ocular histological sections were graded. Infliximab concentrations were determined with competitive ELISA. Safety of the intravitreal injections was evaluated by electroretinography (ERG) and histopathological examination. Retinal biodistribution and clearance of rhodamine-conjugated liposomes containing infliximab were evaluated with a laser scanning confocal microscope. The mean particle size of infliximab liposomes was 351.3±58 nm and entrapment efficiency was 90.65%±2.68%. PDI and zeta potential of infliximab liposomes were 0.386 and -20.8±9.78 mV, respectively. Stability test data showed that the infliximab-lip was stable for 60 days at room temperature. In EAU rats, intravitreal injection of infliximab and infliximab-lip greatly reduced intraocular inflammation determined by clinical scores and histopathological analyses (n=4). The mean concentrations of infliximab decreased quickly in infliximab injection group and were lower than those in infliximab-lip injection group (n=4 eyes, pinfliximab-lip in ERG (n=4 rats, p>0.05) and histopathological sections compared with normal rats. Confocal microscopy showed that fluorescent liposomes were observed in almost every layer of the retina and remained detectable for >30 days after injection. Intravitreal injection of liposomal infliximab can prolong the persistence of the drug in vitreous body and demonstrated a satisfactory safety and significant therapeutic potentials in EAU. The use of biodegradable

  17. Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Staunstrup, Line Maersk; Michaelsen, Signe Regner

    2017-01-01

    Background: Bevacizumab combined with chemotherapy produces clinical durable response in 25-30% of recurrent glioblastoma patients. This group of patients has shown improved survival and quality of life. The aim of this study was to investigate changes in gene expression associated with response...... and resistance to bevacizumab combination therapy.Methods: Recurrent glioblastoma patients who had biomarker-accessible tumor tissue surgically removed both before bevacizumab treatment and at time of progression were included. Patients were grouped into responders (n = 7) and non-responders (n = 14). Gene......-responders 1 gene was significantly differentially expressed. In responders, this approach revealed 256 significantly differentially expressed genes (72 down-and 184 up-regulated genes at the time of progression). Genes differentially expressed in responders revealed a shift towards a more proneural and less...

  18. Bevacizumab chemotherapy for management of pulmonary and laryngotracheal papillomatosis in a child.

    Science.gov (United States)

    Zur, Karen B; Fox, Elizabeth

    2017-07-01

    Recurrent laryngeal papillomatosis (RRP) can be a devastating condition for a child to endure, and pulmonary involvement may have terminal consequences. Adjuvant therapies have been trialed and reported over the years; however, these chemotherapy options have not been successful. Bevacizumab (Avastin, Genetech Inc., South San Francisco, CA) is a vascular endothelial factor (VEGF) inhibitor that has shown promise in the management of papillomatosis. Most research has focused on intralesional injections of this antiangiogenic drug. The systemic use of bevacizumab is not as well described. This is a case report of a 12-year-old female diagnosed with severe laryngotracheal papillomatosis near birth who underwent a tracheostomy tube placement at 1 year of age. She required weekly debridements to prevent tracheal obstruction. When lung involvement was diagnosed at 1 year of age, cidofovir was started intravenously. Over the course of the past 10 years, the patient was managed with celecoxib (Celebrex, Pfizer, New York, NY), anti-reflux medications, zithromycin, propranolol, Gardasil (Merck and Co., Kenilworth, NJ), and a 7-year course of interferon-alpha. Intravenous bevacizumab was started when the patient's pulmonary status deteriorated. There was remarkable improvement in her laryngotracheal disease within 6 weeks of therapy. Following 3 months of bevacizumab, the patient's disease was completely resolved at the laryngeal level and nearly gone in the trachea, and she was decannulated. A computed scan was performed following 5 months of intravenous bevacizumab, and the pulmonary RRP nodules completely resolved. The patient had no major or minor complication from the chemotherapy to date. Systemic Bevacizumab is a promising modality of adjuvant therapy for significant papillomatosis. Laryngoscope, 127:1538-1542, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  19. Effectiveness of bevacizumab and cetuximab in metastatic colorectal cancer across selected public hospitals in Queensland.

    Science.gov (United States)

    Chapman, Suzannah J; McKavanagh, Daniel; Burge, Matthew E; McPherson, Ian; Walpole, Euan; Hollingworth, Samantha A

    2017-10-01

    Metastatic colorectal cancer has a large burden of disease in Australia. Medical therapy is fundamental to extending survival and improving quality of life. The benefits of two costly medicines, bevacizumab and cetuximab, used in Australia remain unclear. The aim of this study was to retrospectively examine the use of these two medicines in metastatic colorectal cancer across five public hospitals in south east Queensland and to compare clinical outcomes to those of published clinical trials. We extracted data from the chemotherapy prescribing database for patients planned for bevacizumab or cetuximab therapy between 2009 and 2013. Median overall survival was estimated using Kaplan-Meier methods. There were 490 bevacizumab-containing protocols planned and 292 patients received at least one dose of bevacizumab. Median overall survival was 17.2 months (95% confidence interval [CI], 15.4-19.3). Of 208 planned cetuximab-containing protocols, 134 patients received at least one dose of cetuximab. Median overall survival was 9.1 months (95% CI, 7.6-12.0). Thirty-day mortality rates from date of first dose were 0.7% for bevacizumab and 7.5% for cetuximab. Overall survival of patients receiving bevacizumab and cetuximab was consistent with clinical trials, providing some assurance that benefits seen in trials are observed in usual practice. This study provides a methodology of using routinely collected health data for clinical monitoring and research. Because of the high cost of these medicines and the lack of toxicity data in this study, further analysis in the postmarketing setting should be explored. © 2016 John Wiley & Sons Australia, Ltd.

  20. A phase II trial evaluating the feasibility of adding bevacizumab to standard osteosarcoma therapy.

    Science.gov (United States)

    Navid, Fariba; Santana, Victor M; Neel, Michael; McCarville, M Beth; Shulkin, Barry L; Wu, Jianrong; Billups, Catherine A; Mao, Shenghua; Daryani, Vinay M; Stewart, Clinton F; Kunkel, Michelle; Smith, Wendene; Ward, Deborah; Pappo, Alberto S; Bahrami, Armita; Loeb, David M; Reikes Willert, Jennifer; Rao, Bhaskar N; Daw, Najat C

    2017-10-01

    Increased vascular endothelial growth factor (VEGF) expression in osteosarcoma correlates with a poor outcome. We conducted a phase II trial to evaluate the feasibility and efficacy of combining bevacizumab, a monoclonal antibody against VEGF, with methotrexate, doxorubicin and cisplatin (MAP) in patients with localized osteosarcoma. Eligible patients received two courses of MAP chemotherapy before definitive surgery at week 10. Bevacizumab (15 mg/kg) was administered 3 days before starting chemotherapy then on day 1 of weeks 3 and 5 of chemotherapy. After surgery, patients received MAP for a total of 29 weeks; bevacizumab was added every 2 or 3 weeks on day 1 of chemotherapy at least 5 weeks after surgery. Group sequential monitoring rules were used to monitor for unacceptable bevacizumab-related targeted toxicity (grade 4 hypertension, proteinuria or bleeding, grade 3 or 4 thrombosis/embolism, and grade 2-4 major wound complications). Thirty-one patients (median age 12.8 years) with localized osteosarcoma were enrolled. No unacceptable targeted toxicities were observed except for wound complications (9 minor and 6 major), which occurred in 15 patients; none required removal of prosthetic hardware or amputation. The estimated 4-year event-free survival (EFS) rate and overall survival rate were 57.5 ± 10.0% and 83.4 ± 7.8%, respectively. Eight (28%) of 29 evaluable patients had good histologic response (bevacizumab to MAP for localized osteosarcoma is feasible but frequent wound complications are encountered. The observed histologic response and EFS do not support further evaluation of bevacizumab in osteosarcoma. © 2017 UICC.

  1. Preoperative bevacizumab and volumetric recovery after resection of colorectal liver metastases.

    Science.gov (United States)

    Margonis, Georgios Antonios; Buettner, Stefan; Andreatos, Nikolaos; Sasaki, Kazunari; Pour, Manijeh Zargham; Deshwar, Ammar; Wang, Jane; Ghasebeh, Mounes Aliyari; Damaskos, Christos; Rezaee, Neda; Pawlik, Timothy M; Wolfgang, Christopher L; Kamel, Ihab R; Weiss, Matthew J

    2017-12-01

    While preoperative treatment is frequently administered to CRLM patients, the impact of chemotherapy, with or without bevacizumab, on liver regeneration remains controversial. The early and late regeneration indexes were defined as the relative increase in liver volume (RLV) within 2 and 9 months from surgery. Regeneration rates of the preoperative treatment groups were compared. Preoperative chemotherapy details and volumetric data were available for 185 patients; 78 (42.2%) received preoperative chemotherapy with bevacizumab (Bev+), 46 (24.8%) received chemotherapy only (Bev-), and 61 (33%) received no chemotherapy. Patients in the Bev+ and Bev- groups received similar chemotherapy cycles (4 [3-6] vs 4 [4-6]; P = 0.499). Despite the comparable clinicopathological characteristics and Resected Volume/Total Liver Volume (TLV) at surgery (P = 0.944) of both groups, Bev+ group had higher early and late regeneration (17.2% vs 4.3%; P = 0.035 and 14.0% vs 9.4%; P = 0.091, respectively). Of note, early and late regeneration rates (3.7% and 10.9% vs 6.6% and 5.5%, respectively) were comparable between the no chemotherapy and Bev- groups (all P > 0.05). In multivariable analysis -adjusted for gender, age, portal vein embolization, preoperative chemotherapy, resected liver volume, tumor number, postoperative chemotherapy, fibrosis, steatosis- bevacizumab independently predicted early liver regeneration (P = 0.019). Our findings suggest that preoperative bevacizumab administered along with chemotherapy was associated with enhanced volumetric restoration. Interestingly, this effect was more pronounced among patients who received oxaliplatin-based regimens and bevacizumab compared to those treated with irinotecan-based regimens and bevacizumab. © 2017 Wiley Periodicals, Inc.

  2. Dicer and Drosha expression and response to Bevacizumab-based therapy in advanced colorectal cancer patients.

    Science.gov (United States)

    Vincenzi, Bruno; Zoccoli, Alice; Schiavon, Gaia; Iuliani, Michele; Pantano, Francesco; Dell'aquila, Emanuela; Ratta, Raffaele; Muda, Andrea Onetti; Perrone, Giuseppe; Brunelli, Chiara; Correale, Pierpaolo; Riva, Elisabetta; Russo, Antonio; Loupakis, Fotios; Falcone, Alfredo; Santini, Daniele; Tonini, Giuseppe

    2013-04-01

    The miRNA-regulating enzymes Dicer and Drosha exhibit aberrant expression in several cancer types. Dicer and Drosha play a crucial role during the angiogenetic process in vitro and, for Dicer, in vivo. We aimed to investigate the potential role of Dicer and Drosha in predicting response to Bevacizumab-based therapy in advanced colorectal cancer (CRC) patients. Dicer and Drosha mRNA levels were analysed in formalin-fixed paraffin-embedded specimens from patients affected by advanced CRC treated with or without Bevacizumab-containing regimens (n=116 and n=50, respectively) and from patients with diverticulosis as control group (n=20). The experimental data were obtained using qRT-PCR, analysed comparing Dicer and Drosha expression levels in tumour samples versus normal mucosa and then compared to clinical outcome. The tumour samples from Bevacizumab-treated patients showed a significantly higher Drosha expression (P<.001) versus normal mucosa, while Dicer levels did not differ. Intriguingly, we found that low Dicer levels predicted a longer progression-free survival (PFS) (P<.0001) and overall survival (OS) (P=.009). In addition, low Dicer levels were associated with better response to Bevacizumab-based treatments versus high Dicer levels (1.7% complete responses and 53.4% partial responses versus 0% and 32.7%, respectively; P=.0067). Multivariate analysis identified three independent predictors of improved OS: high performance status (PS) (relative risk (RR) 1.45; P=.011), lower organs involvement (RR 0.79; P=.034) and low Dicer expression (RR 0.71; P=.008). Conversely, Drosha levels were not associated with prognosis and outcome associated with treatment. In non-Bevacizumab-treated patients, Dicer and Drosha expression did not correlate with outcome. These findings suggest that low Dicer mRNA levels seem to be independent predictors of favourable outcome and response in patients affected by advanced CRCs treated with Bevacizumab-based therapy. Copyright © 2012

  3. Prognostic factors in recurrent glioblastoma patients treated with bevacizumab.

    Science.gov (United States)

    Schaub, Christina; Tichy, Julia; Schäfer, Niklas; Franz, Kea; Mack, Frederic; Mittelbronn, Michel; Kebir, Sied; Thiepold, Anna-Luisa; Waha, Andreas; Filmann, Natalie; Banat, Mohammed; Fimmers, Rolf; Steinbach, Joachim P; Herrlinger, Ulrich; Rieger, Johannes; Glas, Martin; Bähr, Oliver

    2016-08-01

    The value of bevacizumab (BEV) in recurrent glioblastoma is unclear. Imaging parameters and progression-free survival (PFS) are problematic endpoints. Few data exist on clinical factors influencing overall survival (OS) in unselected patients with recurrent glioblastoma exposed to BEV. We retrospectively analyzed 174 patients with recurrent glioblastoma treated with BEV at two German brain tumor centers. We evaluated general patient characteristics, MGMT status, pretreatment, concomitant oncologic treatment and overall survival. Karnofsky performance score, number of prior chemotherapies, number of prior recurrences and combined treatment with irinotecan (IRI) were significantly associated with OS in univariate analysis. We did not find differences in OS related to sex, age, histology, MGMT status, prior surgical treatment or number of prior radiotherapies. Combined treatment with IRI and higher KPS both remained significantly associated with prolonged survival in multivariate analysis, but patients receiving IRI co-treatment had less advanced disease. Grouping into clinically relevant categories revealed an OS of 16.9 months from start of BEV in patients with first recurrence and KPS ≥ 80 % (n = 25). In contrast, in patients with second recurrence and KPS < 80 %, OS was 3.6 months (n = 27). Our observational data support an early use of BEV in patients with good performance status. The benefit of co-treatment with IRI in our cohort seems to be the result of biased patient recruitment.

  4. Autophagy-related polymorphisms predict hypertension in patients with metastatic colorectal cancer treated with FOLFIRI and bevacizumab: Results from TRIBE and FIRE-3 trials.

    Science.gov (United States)

    Berger, Martin D; Yamauchi, Shinichi; Cao, Shu; Hanna, Diana L; Sunakawa, Yu; Schirripa, Marta; Matsusaka, Satoshi; Yang, Dongyun; Groshen, Susan; Zhang, Wu; Ning, Yan; Okazaki, Satoshi; Miyamoto, Yuji; Suenaga, Mitsukuni; Lonardi, Sara; Cremolini, Chiara; Falcone, Alfredo; Heinemann, Volker; Loupakis, Fotios; Stintzing, Sebastian; Lenz, Heinz-Josef

    2017-05-01

    The most frequent bevacizumab-related side-effects are hypertension, proteinuria, bleeding and thromboembolism. To date, there is no biomarker that predicts anti-VEGF-associated toxicity. As autophagy inhibits angiogenesis, we hypothesised that single-nucleotide polymorphisms (SNPs) within autophagy-related genes may predict bevacizumab-mediated toxicity in patients with metastatic colorectal cancer (mCRC). Patients with mCRC treated with first-line FOLFIRI and bevacizumab in two phase III randomised trials, namely the TRIBE trial (n = 219, discovery cohort) and the FIRE-3 trial (n = 234, validation cohort) were included in this study. Patients receiving treatment with FOLFIRI and cetuximab (FIRE-3, n = 204) served as a negative control. 12 SNPs in eight autophagy-related genes (ATG3/5/8/13, beclin 1, FIP200, unc-51-like kinase 1, UVRAG) were analysed by PCR-based direct sequencing. The FIP200 rs1129660 variant showed significant associations with hypertension in the TRIBE cohort. Patients harbouring any G allele of the FIP200 rs1129660 SNP showed a significantly lower rate of grade 2-3 hypertension compared with the A/A genotype (3% versus 15%, odds ratio [OR] 0.17; 95% confidence interval [CI], 0.02-0.73; P = 0.009). Similarly, G allele carriers of the FIP200 rs1129660 SNP were less likely to develop grade 2-3 hypertension than patients with an A/A genotype in the FIRE-3 validation cohort (9% versus 20%, OR 0.43; 95% CI, 0.14-1.11; P = 0.077), whereas this association could not be observed in the control cohort (12% versus 9%, OR 1.40; 95% CI, 0.45-4.04; P = 0.60). This is the first report demonstrating that polymorphisms in the autophagy-related FIP200 gene may predict hypertension in patients with mCRC treated with FOLFIRI and bevacizumab. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Biomarkers in tissue from patients with upper gastrointestinal cancers treated with erlotinib and bevacizumab

    DEFF Research Database (Denmark)

    Rohrberg, Kristoffer Staal; Pappot, Helle; Lassen, Ulrik

    2011-01-01

    Malignancies in the upper gastrointestinal (UGI) tract are amongst the most aggressive cancers and only few treatment options exist. We have recently analysed data from a phase II trial where patients with UGI cancers were treated with erlotinib and bevacizumab. The combination therapy could......: 1.0-1.9). EGFR expression and KRAS mutation status were not correlated to response or survival. We conclude that VEGF-A and VEGFR-2 could potentially be predictive markers in patients with UGI cancers treated with erlotinib and bevacizumab....

  6. Pretreatment of RPE Cells with Lutein Can Mitigate Bevacizumab-Induced Increases in Angiogenin and bFGF.

    Science.gov (United States)

    Vilà, Natàlia; Coblentz, Jacqueline; Moreira-Neto, Carlos; Bravo-Filho, Vasco; Zoroquiain, Pablo; Burnier, Miguel N

    2017-01-01

    To determine whether pretreatment of retinal pigmented epithelial (RPE) cells with lutein can affect the response of cells to bevacizumab therapy. One human RPE cell line (ARPE-19) was used for all experiments. The cells were treated with lutein in different concentrations (0.01, 0.1, 1, 10, or 100 μg/ml). After 24 h, all plates were treated with bevacizumab (0.25 mg/ml). Media were harvested 24 h later for sandwich ELISA-based angiogenesis arrays. A Quantibody Human Angiogenesis Array was used in order to quantify the secretion of the following 10 proangiogenic cytokines: angiogenin, ANG2, EGF, bFGF, HB-EGF, PDGF-BB, leptin, PIGF, HGF and VEGF. Treatment with bevacizumab alone led to a significant decrease in VEGF, as well as a significant increase in angiogenin and bFGF. Pretreatment with 0.1 and 1.0 μg/ml of lutein led to significant decreases in both bFGF and angiogenin following treatment with bevacizumab compared to bevacizumab treatment alone. Lutein alone did not modify the secretion of proangiogenic cytokines. Pretreatment of human RPE cells in culture with specific doses of lutein prior to bevacizumab treatment mitigated the increase in bFGF and angiogenin caused by bevacizumab monotherapy. © 2016 S. Karger AG, Basel.

  7. Mechanisms of action of the anti-VEGF monoclonal antibody bevacizumab on chronic lymphocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Jakub Bogusz

    2013-03-01

    Full Text Available Introduction: Chronic lymphocytic leukemia (CLL remains incurable; therefore searching for new therapeutic strategies in this disease is necessary. An important mechanism of tumor development is neoangiogenesis. A potent antiangiogenic factor, bevacizumab (Avastin, AVA, has been poorly explored in CLL so far. In the current study we assessed cytotoxic activity of AVA alone or in combinations with drugs routinely used in this disease.Matherials and Methods: Cells isolated from 60 CLL patients were treated with AVA alone or in combination with anti-CD20 monoclonal antibody (MoAb, rituximab (RIT, anti-CD52 MoAb, alemtuzumab (ALT, 2-CdA (2-chlorodeoxyadenosine, FA (fludarabine, MAF (mafosfamide or RAPA (rapamycin. Cytotoxicity was assessed by propidium iodide staining. Apoptosis was evaluated using annexin-V and TUNEL assays. Additionally, a drop of mitochondrial potential (DYm as well as expression of apoptosis-regulating proteins Bax, Bak, Bid, Bad, Bcl-2, Mcl-2, XIAP, FLIP, Akt and Bcl-2-A1 were determined by flow cytometry.Results: At the dose of 40 μg/ml, after 48 hours of incubation, AVA induced significant cytotoxicity against CLL cells. The drug triggered apoptosis, with activation of caspase-3 and -9, but not caspase-8, along with a drop of DYm. Incubation with AVA induced significant overexpression of proapoptotic Bak and Bad as well as downregulation of antiapoptotic Mcl-2 and Akt proteins. Combination of AVA with RIT, ALT or RAPA significantly increased cytotoxicity when compared with the effects of single drugs.Discussion: In conclusion, this is the first report showing proapoptotic activity of AVA against CLL cells. Combination of AVA with RIT, ALT or RAPA may be a promising therapeutic strategy, which requires confirmation in further studies.

  8. Concurrent Stereotactic Radiosurgery and Bevacizumab in Recurrent Malignant Gliomas: A Prospective Trial

    Energy Technology Data Exchange (ETDEWEB)

    Cabrera, Alvin R. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Cuneo, Kyle C. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Desjardins, Annick [Department of Surgery, Duke University, Durham, North Carolina (United States); Sampson, John H. [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Department of Surgery, Duke University, Durham, North Carolina (United States); McSherry, Frances; Herndon, James E. [Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina (United States); Peters, Katherine B. [Department of Surgery, Duke University, Durham, North Carolina (United States); Allen, Karen [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Hoang, Jenny K. [Department of Radiology, Duke University, Durham, North Carolina (United States); Chang, Zheng; Craciunescu, Oana [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Vredenburgh, James J.; Friedman, Henry S. [Department of Surgery, Duke University, Durham, North Carolina (United States); Kirkpatrick, John P., E-mail: john.kirkpatrick@dm.duke.edu [Department of Radiation Oncology, Duke University, Durham, North Carolina (United States); Department of Surgery, Duke University, Durham, North Carolina (United States)

    2013-08-01

    Purpose: Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. Methods and Materials: Fifteen patients with recurrent MG, treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen, were enrolled in this prospective trial. Lesions <3 cm in diameter were treated in a single fraction, whereas those 3 to 5 cm in diameter received 5 5-Gy fractions. BVZ was administered immediately before SRS and 2 weeks later. Neurocognitive testing (Mini-Mental Status Exam, Trail Making Test A/B), Functional Assessment of Cancer Therapy-Brain (FACT-Br) quality-of-life assessment, physical exam, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed immediately before SRS and 1 week and 2 months following completion of SRS. The primary endpoint was central nervous system (CNS) toxicity. Secondary endpoints included survival, quality of life, microvascular properties as measured by DCE-MRI, steroid usage, and performance status. Results: One grade 3 (severe headache) and 2 grade 2 CNS toxicities were observed. No patients experienced grade 4 to 5 toxicity or intracranial hemorrhage. Neurocognition, quality of life, and Karnofsky performance status did not change significantly with treatment. DCE-MRI results suggest a significant decline in tumor perfusion and permeability 1 week after SRS and further decline by 2 months. Conclusions: Treatment of recurrent MG with concurrent SRS and BVZ was not associated with excessive toxicity in this prospective trial. A randomized trial of concurrent SRS/BVZ versus conventional salvage therapy is needed to establish the efficacy of this approach.

  9. Simultaneous application of bevacizumab and anti-CTGF antibody effectively suppresses proangiogenic and profibrotic factors in human RPE cells

    Science.gov (United States)

    Bagheri, Abouzar; Ahmadieh, Hamid; Samiei, Shahram; Sheibani, Nader; Astaneh, Shamila Darvishalipour; Kanavi, Mozhgan Rezaei; Mohammadian, Azam

    2015-01-01

    Purpose Retinal pigment epithelial (RPE) cells play key roles in the development of choroidal neovascularization and subsequent fibrosis. We investigated the impact of bevacizumab, antihuman vascular endothelial growth factor (VEGF) antibody, and anticonnective tissue growth factor (anti-CTGF) neutralizing antibody, individually or in combination, on proangiogenic and profibrotic properties of RPE cells. Methods Primary cultures of human RPE cells were incubated with different concentrations of bevacizumab (0.25, 0.5, and 0.8 mg/ml) and/or anti-CTGF (10 μg/ml), and cell proliferation and apoptosis were determined. Expression and activity of proangiogenic and profibrotic genes including matrix metalloproteinases (MMP)-2 and 9, VEGFA, CTGF, vascular endothelial growth factor receptor-1 (VEGFR-1), cathepsin D, tissue inhibitor of metalloproteinases (TIMP) −1 and −2, and alpha smooth muscle actin (α-SMA) were assessed with slot blot, real-time RT–PCR, and zymography. Results Bevacizumab alone inhibited proliferation of RPE cells while anti-CTGF or bevacizumab and anti-CTGF combined had no inhibitory effect in this regard. Bevacizumab increased MMP-2, MMP-9, and cathepsin D but decreased VEGFA and VEGFR-1 expression. The CTGF level was increased by using 0.25 mg/ml bevacizumab but decreased at the 0.8 mg/ml concentration of bevacizumab. Treatment with anti-CTGF antibody decreased MMP-2 expression whereas combined treatment with bevacizumab and anti-CTGF resulted in decreased expression of MMP-2, TIMP-1, cathepsin D, VEGFA, CTGF, and α-SMA in the treated cultures. Conclusions Treatment of RPE cells with the combination of bevacizumab and anti-CTGF could effectively suppress the proangiogenic and profibrotic activity of RPE cells. PMID:25883524

  10. Evaluation of acute locoregional toxicity in patients with breast cancer treated with adjuvant radiotherapy in combination with bevacizumab.

    Science.gov (United States)

    Goyal, Sharad; Rao, Malay S; Khan, Atif; Huzzy, Lien; Green, Camille; Haffty, Bruce G

    2011-02-01

    Preclinical studies have shown that bevacizumab combined with radiotherapy (RT) induces a radiosensitizing effect. Published reports regarding the safety of combination therapy involving bevacizumab and RT are lacking. The purpose of this study was to analyze acute locoregional toxicity in patients with breast cancer receiving concurrent bevacizumab plus RT. After institutional review board approval was obtained, patients with breast cancer who received bevacizumab were identified; these patients were then cross-referenced with patients receiving RT. Toxicity was scored by the Common Terminology Criteria for Adverse Events. Patients were matched 1:1 with those who did not receive bevacizumab. Statistical analysis was performed to analyze toxicity between the two groups. Fourteen patients were identified to have received bevacizumab plus RT. All patients received bevacizumab during RT without delay or treatment breaks; there were no RT treatment breaks in all patients. No patient receiving bevacizumab plus RT experienced ≥Grade 3 toxicity; 3 matched control patients experienced a Grade 3 skin reaction. There was no difference in fatigue, radiation fibrosis, pneumonitis, or lymphedema between the two groups. Five patients (35%) developed reduction in ejection fraction; 2 with right-sided and 3 with left-sided treatment. Patients with left-sided treatment experienced a persistent reduction in ejection fraction compared with those receiving right-sided treatment. Concurrent bevacizumab and RT did not increase acute locoregional toxicity in comparison with matched control patients who did not receive RT alone. The addition of concurrent RT when treating the intact breast, chest wall, and associated nodal regions in breast cancer seems to be safe and well tolerated. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Bevacizumab did not reduce the risk of anemia associated with chemotherapy: an up-to-date meta-analysis.

    Science.gov (United States)

    Wang, Zuo-Pei; Zhang, Hai-Feng; Zhang, Feng; Hu, Bao-Li; Wei, Hai-Tao; Guo, Yong-Yuan

    2015-05-01

    The risk of anemia due to bevacizumab-based chemotherapy has not been well described, and new randomized controlled trials (RCTs) have been reported in recent years. We therefore conducted an up-to-date meta-analysis of RCTs to fully characterize the risk of anemia with bevacizumab. We carried out an electronic search of Medline, Embase, and The Cochrane Central Register of Controlled Trials to investigate the effects of RCTs on bevacizumab treatment on cancer patients up to October 2014, and random or fixed-effect meta-analytical models were used to assess the risk ratio (RR) of anemia due to the use of bevacizumab according to the heterogeneity of included studies. A total of 13,173 patients were included in this analysis from 18 RCTs. Among those patients receiving bevacizumab and chemotherapy, the incidences of all-grade and high-grade (grade 3 and above) anemia were 24% (95% confidence interval (CI) 13-41%) and 4.0% (95% CI 3.0-6.0%), respectively. Bevacizumab-containing therapy did not significantly decreased the risk of developing all-grade anemia (RR 0.872, 95% CI 0.739-1.029, P = 0.104) and high-grade anemia (RR 0.850, 95% CI 0.720-1.002, P = 0.053), which is not in agreement with previous meta-analysis. On subgroup analysis, we did not find significant risk differences based on bevacizumab dosage, tumor types, and concomitant drugs. When stratified by dose level, a significantly decreased risk of high-grade anemia with bevacizumab was obtained in a lower dose level (2.5 mg/kg/week, RR 0.773, 95% CI 0.611-0.978, P = 0.031) compared to control group. Bevacizumab did not significantly reduce the risk of anemia with chemotherapy in cancer patients.

  12. Toxoplasma gondii: an atypical presentation of toxoplasma as optic disc swelling and hemispherical retinal vein occlusion treated with intravitreal clindamycin.

    Science.gov (United States)

    Wong, Roger; dell'Omo, Roberto; Marino, Michele; Hussein, Badrul; Okhravi, Narciss; Pavesio, Carlos E

    2009-06-01

    To present a case of toxoplasmosis with an atypical presentation and treated successfully with intravitreal clindamycin. A young Brazilian woman presented with panuveitis and disc swelling with associated hemispheric vascular occlusion in one eye. The presumed diagnosis was of a papillitis with vasculitis due to an unknown inflammatory condition. Following treatment with intravenous corticosteroids, macular star appeared 1 week after treatment. On the 2nd week, a focus of retinitis appeared, and the patient was started on antitoxoplasma treatment. This was poorly tolerated, and the patient was injected with intravitreal clindamycin. Inflammation eventually settled and an organized lesion typical of toxoplasma chorioretinitis was observed. We describe an unusual presentation and the detrimental effects of toxoplasmosis in an otherwise immunocompetent subject. As the patient was not tolerating systemic antitoxoplasma treatment, intravitreal injection was administered and proved to be effective and well tolerated.

  13. In vitro inhibitory effects of palonosetron hydrochloride, bevacizumab and cyclophosphamide on purified paraoxonase-I (hPON1) from human serum.

    Science.gov (United States)

    Türkeş, Cüneyt; Söyüt, Hakan; Beydemir, Şükrü

    2016-03-01

    In this study, we investigated the effects of the drugs, palonosetron hydrochloride, bevacizumab and cyclophosphamide, on human serum paraoxonase-I (hPON1) enzyme activity in in vitro conditions. The enzyme was purified ∼231-fold with 34.2% yield by using ammonium sulphate precipitation, DEAE-Sephadex A-50 ion-exchange chromatography and Sephadex G-200 gel-filtration chromatography from human serum. hPON1 exhibited a single protein band on the SDS polyacrylamide gel electrophoresis. The inhibition studies were performed on paraoxonase activity of palonosetron hydrochloride, bevacizumab and cyclophosphamide. Ki constants were found as 0.033±0.001, 0.054±0.003 mM and 3.419±0.518 mM, respectively. Compared to the inhibition rates of the drugs, palonosetron hydrochloride has the maximum inhibition rate. However, inhibition mechanisms of the drugs were determined as noncompetitive by Lineweaver-Burk curves. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. KRAS mutation and primary tumor location do not affect efficacy of bevacizumab-containing chemotherapy in stagae IV colorectal cancer patients.

    Science.gov (United States)

    Sun, De-Cong; Shi, Yan; Wang, Yan-Rong; Lv, Yao; Yan, Huan; Mao, Hui; Wang, Zhi-Kuan; Wu, Zhi-Yong; Shi, Wei-Wei; Dai, Guang-Hai

    2017-10-30

    This study aims to investigate the efficacy of bevacizumab-combined chemotherapy (BCC) in Chinese stage IV colorectal cancer (CRC), and analyze the relationship between clinicopathological features with survival. Patients with stage IV CRC treated with BCC were analyzed retrospectively. 217 metastatic CRC (mCRC) patients were collected, out of which79 were right-sided CRCs and 138 were left-sided ones. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2, single agent chemotherapy, poor/mucous/signet ring cell component, second-and further-line of bevacizumab administration, multiple metastasis sites had comparatively worse survival. Among 141 patients with known KRAS status, 55 patients harbored KRAS mutation and 86 had wild type KRAS. The ORR and DCR were 41.9% and 78.9%, respectively, in patients with wild type KRAS, while ORR and DCR was 38.7% and 77.9%, respectively, in patients with KRAS mutation. The median PFS of patients with wild type and mutant KRAS were 8.38, and9.59 months, respectively; whereas the OS was 23.00 and 21.26 months, respectively for mCRC patients with wild-type and mutant KRAS. Cumulatively, our study indicated that BCC was effective and beneficial for Chinese stage IV CRC patients. KRAS mutation status and tumor location were not a prognostic factor for survival.

  15. A case of recipient bed melt and wound dehiscence after penetrating keratoplasty and subconjunctival injection of bevacizumab.

    Science.gov (United States)

    Bhasin, Purendra; Gujar, Prateek; Bhasin, Priyamvada

    2012-11-01

    We describe a case of recipient bed melt and wound dehiscence after uneventful penetrating keratoplasty and subconjunctival injection of bevacizumab. Three weeks postoperatively, the patient presented with limbal ischemia, recipient bed melt, and wound dehiscence corresponding to the area of bevacizumab injection. The melt was managed by application of cyanoacrylate glue along with bandage contact lens. Although the graft survived, there was a problem in re-epithelization. This case highlights the need for further studies to elucidate the therapeutic dose, side effects, and correct timing of using bevacizumab with respect to corneal transplant surgery.

  16. Bevacizumab, temozolomide, and radiotherapy for newly diagnosed glioblastoma: comprehensive safety results during and after first-line therapy

    Science.gov (United States)

    Saran, Frank; Chinot, Olivier L.; Henriksson, Roger; Mason, Warren; Wick, Wolfgang; Cloughesy, Timothy; Dhar, Sunita; Pozzi, Emanuela; Garcia, Josep; Nishikawa, Ryo

    2016-01-01

    Background The proposed use of bevacizumab with radiotherapy/temozolomide for newly diagnosed glioblastoma raised potential safety concerns. Bevacizumab has been linked with stroke, bleeding events, and wound-healing complications in other tumor types; these events are of particular concern for glioblastoma (highly vascular tumors that are usually resected). Published data on the interaction of bevacizumab with radiotherapy/temozolomide are also limited. We report safety data from a phase III randomized trial (Avastin in Glioblastoma), focusing on these considerations. Methods Eligible patients received: radiotherapy and temozolomide plus bevacizumab/placebo, 6 cycles; a 4-week treatment break; temozolomide plus bevacizumab/placebo, 6 cycles; and bevacizumab/placebo until progression. Data on adverse events (AEs) were collected throughout. Results Bevacizumab-treated patients (n = 461) had a longer median safety follow-up time (12.3 vs 8.5 mo), and a higher proportion completed 6 cycles of maintenance temozolomide (64.6% vs 36.9%) versus placebo (n = 450). The incidences of relevant AEs (bevacizumab vs placebo, respectively) were: arterial thromboembolic events (5.9% vs 1.6%); cerebral hemorrhage (3.3% vs 2.0%); wound-healing complications (6.9% vs 4.7%); thrombocytopenia (34.1% vs 27.3%); radiotherapy-associated skin injury (8.2% vs 9.3%); alopecia (39.0% vs 36.0%); gastrointestinal perforation (including gastrointestinal abscesses and fistulae, 1.7% vs 0.4%); and radiotherapy-associated injury (0.4% vs 0.0%). Overall, 15.8% and 23.8% of bevacizumab- and placebo-treated patients had surgery (including biopsy) after progression. Within 30 days of postprogression surgery, AE incidence was 10.9% (bevacizumab) and 23.4% (placebo). Conclusion The safety profile was consistent with that expected from radiotherapy/temozolomide plus bevacizumab. The increased AE incidence with bevacizumab did not impact patients' ability to receive standard-of-care treatment or to undergo

  17. Effect of intravitreal triamcinolone acetonide injection on central macular thickness in diabetic patients having phacoemulsification.

    Science.gov (United States)

    Ahmadabadi, Hooshang Faghihi; Mohammadi, Massood; Beheshtnejad, Hooshang; Mirshahi, Ahmad

    2010-06-01

    To assess the effect of intraoperative intravitreal injection of triamcinolone acetonide on the central macular thickness, visual outcomes, and development of cystoid macular edema (CME) after phacoemulsification in diabetic patients. Farabi Eye Hospital, Tehran, Iran. In this prospective randomized controlled study, patients with diabetes were randomly assigned to a treatment group, which received an intravitreal injection of triamcinolone acetonide at the end of phacoemulsification, and a control group, which had routine phacoemulsification. Visual acuity, center-point thickness, central 1.0 mm subfield mean thickness, CME development, and diabetic retinopathy progression were compared between the 2 groups 1, 3, and 6 months postoperatively. The treatment group comprised 20 eyes and the control group, 21 eyes. There was no statistically significant difference between the 2 groups in the mean corrected distance visual acuity at any follow-up examination (P>.05). The mean change in center-point thickness and central 1.0 mm subfield mean thickness was statistically significantly lower in the treatment group than in the control group at all follow-up visits (P<.05). Four eyes in the control group and no eye in the treatment group developed CME (P = .059). Three eyes (15%) in the treatment group developed an intraocular pressure rise that was managed by topical medication. Intravitreal injection of triamcinolone reduced the amount of increase in center-point thickness and central 1.0 mm subfield mean thickness after phacoemulsification in eyes of diabetic patients. Although it also reduced the incidence of CME, it had no effect on visual acuity gain. (c) 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  18. Pharmacokinetics and tolerance study of intravitreal injection of dexamethasone-loaded nanoparticles in rabbits

    Directory of Open Access Journals (Sweden)

    Linhua Zhang

    2009-09-01

    Full Text Available Linhua Zhang1, Yue Li2, Chao Zhang1, Yusheng Wang2, Cunxian Song11Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China; 2Department of Ophthalmology, Institute of Ophthalmology of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaAbstract: The aim of the study was to investigate the tolerance and pharmacokinetics of dexamethasone (DEX-loaded poly(lactic acid–co-glycolic acid nanoparticles (DEX-NPs in rabbits after intravitreal injection. The DEX-NPs were prepared and characterized in terms of morphology, particle size and size distribution, encapsulation efficiency, and in vitro release. Ophthalmic investigations were performed, including fundus observation and photography, intraocular pressure measurement, and B-scan ocular ultrasonography. There were no abnormalities up to 50 days after administration of DEX-NPs in rabbits. The DEX concentrations in plasma and the ocular tissues such as the cornea, aqueous humor, lens, iris, vitreous humor, and chorioretina were determined by high-pressure liquid chromatography. The DEX-NPs maintained a sustained release of DEX for about 50 days in vitreous and provided relatively constant DEX levels for more than 30 days with a mean concentration of 3.85 mg/L-1. Based on the areas under the curve, the bioavailability of DEX in the experimental group was significantly higher than that in the control group injected with regular DEX. These results suggest that intravitreal injection of DEX-NPs lead to a sustained release of DEX with a high bioavailability, providing a basis for a novel approach to the treatment of posterior segment diseases.Keywords: dexamethasone, nanoparticles, intravitreal injection, pharmacokinetics

  19. Results of Intravitreal Ranibizumab Treatment for Exudative Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Umut Karaca

    2012-01-01

    Full Text Available Pur po se: To evaluate the efficacy and safety of intravitreal ranibizumab injection for exudative age-related macular degeneration. Ma te ri al and Met hod: In this study, we included forty-eight eyes of 43 age-related macular degeneration patients followed for at least twelve months. Mean age was 73.65±8.93 years and mean follow-up time was 14.2 months. All patients received three consecutive monthly intravitreal ranibizumab injections and then were followed up with clinical examination and optic coherence tomography monthly. Re-injection was executed as needed. Re sults: Twenty patients were male (46.5% and twenty-three patients were female (53.5%. The average number of ranibizumab injection was 3.7 (3-7 per eye. Twenty-six lesions (54.2% were classic (predominantly and minimally and twenty-two (45.8% were occult. Mean best-corrected visual acuity was 46.8 letters with ETDRS chart at the initial examination and 55.5 letters at twelfth month. Mean central foveal thickness decreased from 320 microns to 269 microns. There was a statistically significant improvement in visual acuity and central foveal thickness. On the other hand, this improvement was not significant between lesion types. During follow-up, there were no systemic or serious ocular complications determined. Dis cus si on: Intravitreal ranibizumab injection is safe and effective, both anatomically and functionally, for age-related macular degeneration. (Turk J Ophthalmol 2012; 42: 25-9

  20. Predictors of 1-year visual outcome in neovascular age-related macular degeneration following intravitreal ranibizumab treatment

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; la Cour, Morten; Sander, Birgit

    2013-01-01

    Purpose: To describe predictors of visual outcome in patients treated with intravitreal ranibizumab for choroidal neovascularisation (CNV) in age-related macular degeneration (AMD). Methods: Retrospective review of 279 patients with CNV in AMD who fulfilled MARINA/ANCHOR study eligibility criteria...... and were treated with repeated intravitreal injections of ranibizumab 0.5 mg in routine clinical practice, beginning with three initial injections at 4-week intervals followed by individualized retreatment for the subsequent 9 months. Study parameters included best-corrected visual acuity (BCVA...

  1. Peristence of triamcinolone crystals after intra-vitreal injection: Benign crystalline hyaloidopathy

    Directory of Open Access Journals (Sweden)

    Rafik Zarifa

    2013-01-01

    Full Text Available We report a case of unusually long persistence of triamcinolone crystals after intra-vitreal injection. Crystals were noted on fundus examination predominantly confined to the posterior pole. Optical coherence tomography localized the crystals to the posterior hyaloidal surface. Over 6 years of follow-up the patient has retained good visual acuity and no observable changes in the retina. As the condition clinically resembles both crystalline maculopathy and asteroid hyalosis, we suggest the term ′drug-induced benign crystalline hyaloidopathy′.

  2. Pharmacokinetics of intravitreal glial cell line-derived neurotrophic factor: experimental studies in pigs

    DEFF Research Database (Denmark)

    Ejstrup, Rasmus; Kiilgaard, J F; Tucker, B A

    2010-01-01

    a retinal ganglion cell line (RGC5) bioassay. Indirect ophthalmoscopy, intraocular pressure assessment, and fundus photography were performed before enucleation. There was initial variability in the cGDNF, but after 24h GDNF was cleared in a monoexponential fashion with a half-life of 37 h (CL 33-43 h......The purpose of this study was to establish the intravitreal (ITV) pharmacokinetics of glial cell line-derived neurotrophic factor (GDNF) and observe possible complications after ITV injection. Twenty Danish landrace pigs and 34 eyes were included in the study; 30 were injected with 100 ng of GDNF...

  3. Pharmacokinetics of intravitreal glial cell line-derived neurotrophic factor: experimental studies in pigs

    DEFF Research Database (Denmark)

    Ejstrup, Rasmus; Kiilgaard, J F; Tucker, B A

    2010-01-01

    The purpose of this study was to establish the intravitreal (ITV) pharmacokinetics of glial cell line-derived neurotrophic factor (GDNF) and observe possible complications after ITV injection. Twenty Danish landrace pigs and 34 eyes were included in the study; 30 were injected with 100 ng of GDNF...... a retinal ganglion cell line (RGC5) bioassay. Indirect ophthalmoscopy, intraocular pressure assessment, and fundus photography were performed before enucleation. There was initial variability in the cGDNF, but after 24h GDNF was cleared in a monoexponential fashion with a half-life of 37 h (CL 33-43 h...

  4. Pharmacokinetics of intravitreal 5-flurouracil prodrugs in silicone oil. Experimental studies in pigs

    DEFF Research Database (Denmark)

    Laugesen, Caroline S; Steffansen, Bente; Scherfig, Erik

    2005-01-01

    PURPOSE: To examine the in vivo pharmacokinetics of intravitreal 5-Fluorouracil (5-FU) following tamponade with 5-FU prodrug silicone oil formulations. METHOD: Two different alkoxycarbonyl 5-FU prodrugs denoted C12 and C18 were synthesized and formulated as silicone oil suspensions. A total of 26...... vitreal 5-FU never reached 1 microg/ml during the 7 days these experiments lasted. A mathematical model is presented that can explain the measured data if the clearance of 5-FU from the vitreous water phase follows first order kinetics with a half-life of 20 min. CONCLUSION: These experiments...

  5. Wound healing complications in brain tumor patients on Bevacizumab.

    Science.gov (United States)

    Ladha, Harshad; Pawar, Tushar; Gilbert, Mark R; Mandel, Jacob; O-Brien, Barbara; Conrad, Charles; Fields, Margaret; Hanna, Teresa; Loch, Carolyn; Armstrong, Terri S

    2015-09-01

    Bevacizumab (BEV) is commonly used for treating recurrent glioblastoma (GBM), and wound healing is a well-established adverse event. Retrospective analysis of GBM patients with and without wound healing complications while on BEV treatment is reported. 287 patients identified, majority were males (60 %) with median age of 52.5 years. 14 cases identified with wound healing problems, related to either craniotomy (n = 8) or other soft tissue wounds (n = 6). Median duration of BEV treatment to complication was 62 days (range 6-559). Majority received 10 mg/kg (n = 11) and nine (64.3 %) were on corticosteroids, with median daily dose of 6 mg (range 1-16 mg) for median of 473 days before starting BEV. For dehisced craniotomy wounds, median time for starting BEV from last surgery was 29 days (range 27-345). Median time from starting BEV to developing wound complication was 47 days (range 16-173). Seven (87.5 %) had infected wounds requiring antibiotics, hospitalization. Four (50 %) required plastic surgery. BEV stopped and safely resumed in 6 (75 %) patients; median delay was 70 days (range 34-346). Soft tissue wounds included decubitus ulcer, dehisced striae, herpes simplex, trauma to hand and back, and abscess. Median time from starting BEV to wound issues was 72 days (range 6-559). Five (83.3 %) were infected, requiring antibiotics. While three (50 %) required hospitalization, none required plastic surgery. Treatment stopped in five (83.3 %) and restarted in two (median delay 48 days, range 26-69). Wound healing complications are uncommon but associated with significant morbidity. Identifying those at risk and contributing factors warrants further investigation.

  6. [Comparison of anti-angiogenic effect in vitro between ranibizumab and bevacizumab].

    Science.gov (United States)

    Souto, Alexandre Cupello; Maricato, Juliana Terzi; Denapoli, Priscila Martins Andrade; Sallum, Juliana Maria Ferraz; Han, Sang Won

    2011-01-01

    To evaluate the comparative in-vitro antiangiogenic effect of Bevacizumab and Ranibizumab. Endothelial venous umbilical cells culture (ECV304) cultivated in F12 media with addition of 10% Fetal Bovine Serum, were plaqued and treated with clinically relevant concentrations of Bevacizumab and Ranibizumab just after the scratch done in the middle of the culture (scratch methodology). Measurements of the linear size of the area free of cell proliferation were done 24, 48 and 72 hours after the scratch day point. All the experiments were done in triplicate and statistical analysis were done with T-student test. Inhibitory effect was observed just at the concentrations of 0.5 and 0.7 mg/ml in both drugs. At 0.7 mg/ml, Ranibizumab demonstrated a more potent proliferative inhibitory effect than Bevacizumab. At the same concentration, Ranibizumab was three times more potent than Ranibizumab. Inhibitory effect was observed just in the first 24 hours for both drugs. Ranibizumab demonstrates an increased effect when compared to Bevacizumab and this is related more to the different molar rate of each drug than related to a real better proliferative inhibitory effect.

  7. Bevacizumab with or after chemotherapy for platinum-resistant recurrent ovarian cancer

    DEFF Research Database (Denmark)

    Bamias, A; Gibbs, E; Khoon Lee, C

    2017-01-01

    Background: In the open-label randomized phase III AURELIA trial, adding bevacizumab to chemotherapy for platinum-resistant ovarian cancer (PROC) significantly improved progression-free survival and response rate versus chemotherapy alone, but not overall survival (OS). We explored the effect of ...

  8. Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide

    DEFF Research Database (Denmark)

    Hasselbalch, Benedikte; Lassen, Ulrik; Hansen, Steinbjørn

    2010-01-01

    The aim of this clinical trial was to investigate safety and efficacy when combining cetuximab with bevacizumab and irinotecan in patients with recurrent primary glioblastoma multiforme (GBM). Patients were included with recurrent primary GBM and progression within 6 months of ending standard tre...

  9. Capecitabine and bevacizumab in heavily pre-treated patients with advanced colorectal cancer

    DEFF Research Database (Denmark)

    Larsen, Finn Ole; Boisen, Mogens Karsbøl; Fromm, Anne-Lene Gunge

    2012-01-01

    No standard treatment exists for patients with metastatic colorectal cancer who have progressed after treatment with 5-fluorouracil (5-FU), oxaliplatin, irinotecan and an anti-EGFR antibody. The efficacy and safety of bevacizumab and capecitabine in heavily pre-treated patients with metastatic...

  10. Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab

    Science.gov (United States)

    Mitsuhashi, Atsushi; Goto, Hisatsugu; Saijo, Atsuro; Trung, Van The; Aono, Yoshinori; Ogino, Hirokazu; Kuramoto, Takuya; Tabata, Sho; Uehara, Hisanori; Izumi, Keisuke; Yoshida, Mitsuteru; Kobayashi, Hiroaki; Takahashi, Hidefusa; Gotoh, Masashi; Kakiuchi, Soji; Hanibuchi, Masaki; Yano, Seiji; Yokomise, Hiroyasu; Sakiyama, Shoji; Nishioka, Yasuhiko

    2015-01-01

    Bevacizumab exerts anti-angiogenic effects in cancer patients by inhibiting vascular endothelial growth factor (VEGF). However, its use is still limited due to the development of resistance to the treatment. Such resistance can be regulated by various factors, although the underlying mechanisms remain incompletely understood. Here we show that bone marrow-derived fibrocyte-like cells, defined as alpha-1 type I collagen-positive and CXCR4-positive cells, contribute to the acquired resistance to bevacizumab. In mouse models of malignant pleural mesothelioma and lung cancer, fibrocyte-like cells mediate the resistance to bevacizumab as the main producer of fibroblast growth factor 2. In clinical specimens of lung cancer, the number of fibrocyte-like cells is significantly increased in bevacizumab-treated tumours, and correlates with the number of treatment cycles, as well as CD31-positive vessels. Our results identify fibrocyte-like cells as a promising cell biomarker and a potential therapeutic target to overcome resistance to anti-VEGF therapy. PMID:26635184

  11. When Combined with Chemotherapy, Bevacizumab Is Associated with Increased Risk of Death

    Science.gov (United States)

    Cancer patients who receive the targeted therapy bevacizumab (Avastin) in combination with chemotherapy are at increased risk of serious side effects that may lead to death, according to a meta-analysis of 16 clinical trials that was published February 2,

  12. MTR-18 Predictive Biomarkers Of Bevacizumab Response In Recurrent Glioblastoma Patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Michaelsen, Signe Regner; Olsen, Lars Rønn

    2015-01-01

    Bevacizumab (BEV) plus chemotherapy has shown activity in recurrent glioblastoma (GBM). However, the prognosis varies and only one third of patients have a durable clinical response to BEV combination therapy. Recent findings from a randomized phase-3 study (AVAglio) indicate that patients...

  13. Development and validation of a prognostic model for recurrent glioblastoma patients treated with bevacizumab and irinotecan

    DEFF Research Database (Denmark)

    Urup, Thomas; Dahlrot, Rikke Hedegaard; Grunnet, Kirsten

    2016-01-01

    BACKGROUND: Predictive markers and prognostic models are required in order to individualize treatment of recurrent glioblastoma (GBM) patients. Here, we sought to identify clinical factors able to predict response and survival in recurrent GBM patients treated with bevacizumab (BEV) and irinotecan...

  14. Biomarkers in Recurrent Grade III Glioma Patients Treated with Bevacizumab and Irinotecan

    DEFF Research Database (Denmark)

    Toft, Anders; Urup, Thomas; Christensen, Ib Jarle

    2018-01-01

    -free survival, overall survival, and response to bevacizumab and irinotecan therapy. Significant factors from univariate screening are included in multivariate analysis. Biomarkers previously advanced as predictive or prognostic in the first-line setting did not affect outcome in this patient cohort. Based...

  15. Accelerating repaired basement membrane after bevacizumab treatment on alkali-burned mouse cornea

    Science.gov (United States)

    Lee, Koon-Ja; Lee, Ji-Young; Lee, Sung Ho; Choi, Tae Hoon

    2013-01-01

    To understand the corneal regeneration induced by bevacizumab, we investigated the structure changes of stroma and basement membrane regeneration. A Stick soaked in 0.5 N NaOH onto the mouse cornea and 2.5 mg/ml of bevacizumab was delivered into an alkali-burned cornea (2 μl) by subconjunctival injections at 1 hour and 4 days after injury. At 7 days after injury, basement membrane regeneration was observed by transmission electron microscope. Uneven and thin epithelial basement membrane, light density of hemidesmosomes, and edematous collagen fibril bundles are shown in the alkali-burned cornea. Injured epithelial basement membrane and hemidesmosomes and edematous collagen fibril bundles resulting from alkali-burned mouse cornea was repaired by bevacizumab treatment. This study demonstrates that bevacizumab can play an important role in wound healing in the cornea by accelerating the reestablishment of basement membrane integrity that leads to barriers for scar formation. [BMB Reports 2013; 46(4): 195-200] PMID:23615260

  16. Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin 
in Patients with IIIa Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Songliang ZHANG

    2015-06-01

    Full Text Available Background and objective Bevacizumab has showed its efficacy in advanced non-squamous lung cancer. The aim of this study is to assess the safety of bevacizumab plus pemetrexed and carboplatin neoadjuvant chemotherapy in patients with lung adenocarcinoma. Methods 25 patients with IIIa lung adenocarcinoma undergoing lobectemy or pneumonectomy with mediastinal lymphadenectomy after induction bevacizumab (Bev plus pemetrexed/carboplatin (PC were selected. Toxicity of chemotherapy and postoperative complications were analyzed. Results Grade 3 or 4 neoadjuvant-related adverse events included fatigue (3 patients, neutropenia (3 patients, hypertension (1 patient. The adverse events thought to be related to bevacizumab included epistaxis in 2 patients (grade 1: 1; grade 2: 1 and hypertension in 3 patients (grade 1: 2; grade 3: 1. Postoperative complications included pneumonia in 2 patients, bronchial stump insufficiency in 1 case, atelectasis in 2 cases, and arrhythmia in 1 case. Hemorrhage events, thromboembolic events and wound-healing problems were not observed in the perioperative period. Conclusion The treatment modality of neoadjuvant Bev-PC appears to be safe and tolerant in patients with stage IIIa lung adenocarcinoma.

  17. Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab-based treatment response in metastatic colorectal cancer

    Science.gov (United States)

    Prager, Gerald W; Braemswig, Kira H; Martel, Alexandra; Unseld, Matthias; Heinze, Georg; Brodowicz, Thomas; Scheithauer, Werner; Kornek, Gabriela; Zielinski, Christoph C

    2014-01-01

    Carcinoembryonic antigen (CEA) affects tumorigenesis by enhancing tumor cell survival and by inducing tumor angiogenesis. This study aimed to evaluate baseline CEA serum levels to predict bevacizumab-based therapy effect and survival in patients with metastatic colorectal cancer (mCRC). Two hundred and ninety eight mCRC patients receiving chemotherapy plus either bevacizumab or cetuximab were analyzed in a retrospective study. Disease control (DC), progression-free survival (PFS), and overall survival were assessed and related to pretreatment CEA serum levels. Patients with baseline CEA serum levels below the statistical median of 26.8 ng/mL (group I) were compared with patients with higher CEA levels (group II). The cetuximab-based treatment cohort was analyzed for specificity assessment of CEA to predict the anti-vascular endothelial growth factor effect in mCRC. Baseline CEA serum levels inversely correlated with therapeutic response in patients receiving bevacizumab-based treatment (disease control rate, 84% vs 60%), inversely correlated with median PFS leading to a median PFS benefit of 2.1 months for patients in group I when compared with group II, as well as inversely correlated with median overall survival (37.5 months vs 21.4 months). In an independent cohort of 129 patients treated with cetuximab-based therapy, no association of therapeutic response or PFS with CEA serum levels was found. As expected, baseline CEA levels were prognostic for mCRC. These data give first evidence that baseline serum CEA levels might constitute an important predictor for the efficacy of first-line bevacizumab-based therapy in patients with mCRC. Previously, we found that CEA induces angiogenesis independent of VEGF. The data presented here now give first evidence that baseline serum CEA levels in patients might constitute an important predictor for the efficacy of first-line bevacizumab-based therapy for metastatic colorectal cancer. PMID:24850362

  18. Bevacizumab treatment in the elderly patient with metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Di Bartolomeo M

    2015-01-01

    Full Text Available Maria Di Bartolomeo,1 Claudia Maggi,1 Francesca Ricchini,1 Filippo Pietrantonio,1 Roberto Iacovelli,1 Filippo de Braud,1 Alessandro Inno2 1Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, 2Department of Medical Oncology, Sacro Cuore-Don Calabria Hospital, Negrar, Italy Abstract: Metastatic colorectal cancer (mCRC, like many cancers, is primarily a disease of elderly people. Despite this prevalence, such patients are often excluded from randomized trials or represent a minority of enrolled patients. Moreover, the criteria for establishing benefit or side effects of treatment strategies in this population are uncertain and not well recognized. Bevacizumab improves the outcome of mCRC when used in combination with standard first-line and second-line chemotherapy and beyond the first disease progression when given with a chemotherapy backbone different from that used in the precedent line. The particular toxicity profile of this antiangiogenesis agent (in particular hypertension, thromboembolic events, hemorrhage, and renal failure may discourage its use in elderly patients with comorbidities. Data from subgroup analyses of randomized trials and the results of recent cohort studies suggest a significant benefit from the addition of bevacizumab to standard chemotherapy for elderly patients comparable with that observed in younger patients, except for the increased risk for thromboembolic events. Age alone should not be a barrier to use of bevacizumab, and further research with a more complete geriatric assessment should investigate the role of bevacizumab in elderly patients with mCRC to avoid undertreatment of this patient population due to a ­historical conservative approach. Keywords: bevacizumab, elderly, metastatic colorectal cancer, antivascular treatment, review

  19. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer

    NARCIS (Netherlands)

    van Cutsem, Eric; Vervenne, Walter L.; Bennouna, Jaafar; Humblet, Yves; Gill, Sharlene; van Laethem, Jean-Luc; Verslype, Chris; Scheithauer, Werner; Shang, Aijing; Cosaert, Jan; Moore, Malcolm J.

    2009-01-01

    Treatment with gemcitabine provides modest benefits in patients with metastatic pancreatic cancer. The addition of erlotinib to gemcitabine shows a small but significant improvement in overall survival (OS) versus gemcitabine alone. Phase II results for bevacizumab plus gemcitabine provided the

  20. Bevacizumab Plus Radiosurgery for Nonsquamous Non-Small Cell Lung Cancer Patients with Brain Metastases: Safe Combination?

    Science.gov (United States)

    Guinde, Julien; Carron, Romain; Tomasini, Pascale; Greillier, Laurent; Régis, Jean; Barlesi, Fabrice

    2017-11-01

    In the context of bronchial cancers, the brain is one of the most frequent sites for metastases. Local treatments of these metastases have evolved and are often combined to obtain greater efficiency, while the main objective remains to reduce the symptoms. Radiosurgery is currently used as a primary option for patients harboring few numbers of small to middle-sized brain metastases. In nonsquamous non-small cell lung cancer (NSCLC), chemotherapy is often associated with bevacizumab. Our goal was to assess the safety of this early combination. Six patients with advanced nonsquamous NSCLC were treated with radiosurgery for the management of their brain metastases (n = 40), followed within bevacizumab. No systemic or cerebral adverse event of grade 3 (intratumoral or parenchymal hemorrhage) or unexpected toxicity secondary to bevacizumab has been indexed. Radiosurgery may be safely combined with bevacizumab quite early on for patients with nonsquamous NSCLC with brain metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Intravitreal injection of the chimeric phage endolysin Ply187 protects mice from Staphylococcus aureus endophthalmitis.

    Science.gov (United States)

    Singh, Pawan Kumar; Donovan, David M; Kumar, Ashok

    2014-08-01

    The treatment of endophthalmitis is becoming very challenging due to the emergence of multidrug-resistant bacteria. Hence, the development of novel therapeutic alternatives for ocular use is essential. Here, we evaluated the therapeutic potential of Ply187AN-KSH3b, a chimeric phage endolysin derived from the Ply187 prophage, in a mouse model of Staphylococcus aureus endophthalmitis. Our data showed that the chimeric Ply187 endolysin exhibited strong antimicrobial activity against both methicillin-sensitive S. aureus and methicillin-resistant S. aureus (MRSA) strains, as evidenced by MIC determinations, reductions in turbidity, and disruption of biofilms. Moreover, exposure of S. aureus to Ply187 for up to 10 generations did not lead to resistance development. The intravitreal injection of chimeric Ply187 (at 6 or 12 h postinfection) significantly improved the outcome of endophthalmitis, preserved retinal structural integrity, and maintained visual function as assessed by electroretinogram analysis. Furthermore, phage lysin treatment significantly reduced the bacterial burden and the levels of inflammatory cytokines and neutrophil infiltration in the eyes. These results indicate that the intravitreal administration of a phage lytic enzyme attenuates the development of bacterial endophthalmitis in mice. To the best of our knowledge, this is the first study demonstrating the therapeutic use of phage-based antimicrobials in ocular infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  2. Retinal toxicity of intravitreally injected plain and liposome formulation of fluconazole in rabbit eye

    Directory of Open Access Journals (Sweden)

    Velpandian Thirumurthy

    2006-01-01

    Full Text Available Purpose: Candidal endophthalmitis is a sight-threatening ocular infection that most frequently occurs as a complication of candidemia. Fluconazole has been effective against Candida albicans in various animal models. Our objective was to evaluate retinal toxicity of plain and liposome formulation of fluconazole at various dose levels after intravitreal injection. Materials and Methods: Twelve New Zealand albino rabbits weighing 2-2.5 kg were used. Two rabbits were used for every dose level. Liposome formulation containing 100 and 200 µg of fluconazole in sterile phosphate buffer solution and plain fluconazole at concentrations of 100, 200, 400 and 800 µg in 0.1 ml of sterile normal saline were injected intravitreally into the right eyes. The left eyes received 0.1 ml normal saline or 0.1 ml of liposome formulation without fluconazole. One week later, the animals were sacrificed, their eyes enucleated and processed for light microscopy and scanning electron microscopy. Results: It showed that plain fluconazole at a concentration of 100 µg and above caused retinal changes, with disorganization of the photoreceptor outer segments. However, liposome formulation of fluconazole (200 µg/0.1 ml did not show any significant microscopic changes of the retina. Conclusion: The liposome formulation decreased the retinal toxicity of fluconazole up to the studied concentration of 200 µg/0.1 ml.

  3. Role of optical coherence tomography angiography in myopic choroidal neovascularization after intravitreal injections of Ranibizumab

    Directory of Open Access Journals (Sweden)

    Meng Cai

    2017-10-01

    Full Text Available AIM: To investigate the change of myopic choroidal neovascularization treated by ranibizumab and evaluate their value in monitoring the effect of anti- vascular endothelial growth factor(VEGFtherapy.METHODS: The study enrolled 30 patients(30 eyesdiagnosed with myopic choroidal neovascularization. All affected eyes were treated with intravitreal ranibizumab 0.05mL(10mg/mL. Best corrected visual acuity(BCVA, non-contact tonometer, ophthalmoscope, fundus fluorescein angiograph(FFAand OCTA were evaluated monthly until 6mo. The changes of BCVA and central macular thickness(CMTwere compared at 1, 3 and 6mo after treatment.RESULTS: All patients received an average of 1.70±0.65 injections. BCVA was 0.96±0.17(LogMARbefore therapy, and BCVA 1, 3 and 6mo after treatment respectively improved by 0.23±0.09, 0.34±0.07, 0.38±0.11. The differences were significant(t=5.461, 8.191, 8.894; Pt=12.007, 13.360, 9.531; PCONCLUSION: Intravitreal ranibizumab for CNV secondary to pathologic myopia is effective and safe; OCTA is a noninvasive and time-saving new technology, and it also is a promising tool for clinicians to make preliminary diagnosis and assess treatment efficacy in the follow-up visits.

  4. Intravitreal Triamcinolone Acetonide for Macular Edema in HLA-B27 Negative Ankylosing Spondylitis

    Directory of Open Access Journals (Sweden)

    M.M. Moschos

    2010-12-01

    Full Text Available We report a case of a human leukocyte antigen B27 (HLA-B27-negative patient with cystoid macular edema (CME and ankylosing spondylitis (AS after treatment with triamcinolone acetonide. The patient complained of deterioration of visual acuity of the right eye during the last 10 days. At presentation visual acuity of the right eye was 0.2, and the ophthalmic examination did not reveal any sign of active uveitis. Fluorescein angiography (FA and ocular coherent tomography (OCT showed CME. The left eye was normal with a visual acuity of 0.9. Eight weeks after intravitreal injection of triamcinolone acetonide, visual acuity improved to 0.8 and OCT revealed regression of macular edema. Six months later no recurrence was observed. Our case report indicates for the first time that CME may occur in AS independently of the presence of HLA-B27 and intraocular inflammation. Intravitreal use of triamcinolone acetonide can reduce macular edema and restore visual acuity.

  5. Clinical study of Conbercept intravitreal injection for the treatment of wet age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Xu-Ting He

    2015-09-01

    Full Text Available AIM: To observe the clinical curative effect of conbercept intravitreal injection for the treatment of wet age-related macular degeneration.METHODS: Sixty patients with wet age related macular degeneration were randomly divided into treatment group 30 cases and control group 30 cases according to the random number table. The treatment group was injected with Conbercept 0.05mL, the control group was injected with triamcinolone acetonide 0.1mL. The best corrected visual acuity(BCVAwas performed before and after 1d, 1 and 3mo after treatment, and the thickness of macular was detected by optical coherence tomography(OCT. The complications of patients were observed after 1d, 1 and 3mo,including inflammatory reaction, corneal edema, anterior chamber, high intraocular pressure, etc.RESULTS:In treatment group 1d, 1 and 3mo after treatment, eyesight was improved significantly better than the control group(PPCONCLUSION: Intravitreal injection of Conbercept in the treatment of wet age-related macular degeneration can improve the curative effect.

  6. CLINICAL AND ELECTROPHYSIOLOGICAL EVALUATION AFTER INTRAVITREAL ZIV-AFLIBERCEPT FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

    Science.gov (United States)

    de Oliveira Dias, João Rafael; de Andrade, Gabriel Costa; Kniggendorf, Vinicius Ferreira; Novais, Eduardo Amorim; Maia, André; Meyer, Carsten; Watanabe, Sung Eun Song; Farah, Michel Eid; Rodrigues, Eduardo Büchele

    2017-08-01

    To evaluate the 6-month safety and efficacy of ziv-aflibercept intravitreal injections for treating exudative age-related macular degeneration. Fifteen patients with unilateral exudative age-related macular degeneration were enrolled. The best-corrected visual acuity was measured and spectral domain optical coherence tomography was performed at baseline and monthly. Full-field electroretinography and multifocal electroretinography were obtained at baseline and 4, 13, and 26 weeks after the first injection. All patients received three monthly intravitreal injections of ziv-aflibercept (1.25 mg) followed by as-needed treatment. Between baseline and 26 weeks, the mean logMAR best-corrected visual acuity improved (P = 0.00408) from 0.93 ± 0.4 (20/200) to 0.82 ± 0.5 (20/160) logarithm of the minimum angle of resolution, respectively; the central retinal thickness decreased significantly (P = 0.0007) from 490.3 ± 155.1 microns to 327.9 ± 101.5 microns; the mean total macular volume decreased significantly (P macular responses within the first central 15° showed significantly (P macular volume from baseline to 26 weeks. No retinal toxicity on full-field electroretinography or adverse events occurred during the follow-up period.

  7. Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and intravitreal chemotherapy

    Science.gov (United States)

    Shields, C L; Fulco, E M; Arias, J D; Alarcon, C; Pellegrini, M; Rishi, P; Kaliki, S; Bianciotto, C G; Shields, J A

    2013-01-01

    In this report, we explore retinoblastoma diagnostic accuracy and review chemotherapy alternatives for retinoblastoma using intravenous, intra-arterial, periocular, and intravitreal routes. A review of 2775 patients referred for management of retinoblastoma, disclosed 78% with confirmed retinoblastoma and 22% with simulating lesions, termed pseudoretinoblastomas. Children ≤2 years old showed leading pseudoretinoblastomas of persistent fetal vasculature, Coats disease, and vitreous haemorrhage, whereas those >5 years showed simulators of Coats, toxocariasis, and familial exudative vitreoretinopathy. The diagnosis of retinoblastoma should be established before planning therapeutic strategy. Chemotherapy strategy depends on tumour laterality and stage of disease. If bilateral retinoblastoma, intravenous chemotherapy (IVC) is important as first-line therapy for control of intraocular disease, prevention of metastasis, and reduction in prevalence of pinealoblastoma and long-term second malignant neoplasms. Bilateral groups D and E retinoblastoma receive additional subtenon's carboplatin boost for improved local control. If unilateral disease is present, then intra-arterial chemotherapy (IAC) is often considered. IAC can be salvage therapy following chemoreduction failure. Unilateral retinoblastoma of groups D and E are managed with enucleation or globe-conserving IVC and/or IAC. Intravitreal chemotherapy is cautiously reserved for recurrent vitreous seeds following other therapies. In conclusion, the strategy for retinoblastoma management with chemotherapy depends on tumour laterality and stage of disease. Bilateral retinoblastoma is most often managed with IVC and unilateral retinoblastoma with IAC, but if advanced stage, combination IVC plus IAC or enucleation. PMID:22995941

  8. DEPLOYMENT OF SIX SIGMA METHODOLOGY TO REDUCE COMPLICATIONS IN INTRAVITREAL INJECTIONS

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    İbrahim SAHBAZ

    2014-04-01

    Full Text Available The purpose of this study is to show how a private eye care center in Turkey initiated Six Sigma principles to reduce the number of complications encountered during and after intravitreal injections. Data were collected for 30-months. To analyse the complications among 229 injections administered on 106 patients, main tools of Six Sigma’s Define-Measure-Analyze-Improve-Control (DMAIC improvement cycle such as SIPOC table, Fishbone Diagram and, Failure, Mode and Effect Analysis were implemented. Sources and root causes of seven types of complications were identified and reported. For a successful intravitreal injection, experience of the retina specialist, attention of the retina specialist and patient’s ocular pathology were determined to be the “critical few” factors whereas, sterilization and hygiene, dosage of drug/agent and chemical properties of drug/agent were found to be the “trivial many”factors. The most frequently occuring and the complication with the highest hazard score was found to be subconjunctival haemorrhage. The process sigma level of the process was measured to be 3.2657. The surgical team concluded that six of the complications (out of seven should be significantly reduced by taking the necessary preventative measures.

  9. Biomechanical Properties of the Internal Limiting Membrane after Intravitreal Ocriplasmin Treatment.

    Science.gov (United States)

    Vielmuth, Franziska; Schumann, Ricarda G; Spindler, Volker; Wolf, Armin; Scheler, Renate; Mayer, Wolfgang J; Henrich, Paul B; Haritoglou, Christos

    2016-01-01

    To assess the stiffness of the human internal limiting membrane (ILM) and evaluate potential changes of mechanical properties following intravitreal ocriplasmin injection for vitreomacular traction. This is an interventional comparative case series of 12 surgically excised ILM specimens consecutively obtained from 9 eyes of 9 patients after unsuccessful pharmacologic vitreolysis with ocriplasmin. During the same time period, 16 specimens from 13 other eyes without ocriplasmin treatment were harvested during vitrectomy and served as controls. All patients presented with macular holes or vitreomacular traction and underwent vitrectomy with ILM peeling either with or without brilliant blue (BB) staining. All specimens were analyzed using atomic force microscopy with scan regions of 25 × 25 μm. In all specimens, both the retinal side and vitreal side of the ILM were analyzed. Atomic force microscopy revealed no significant differences in elasticity of ILM specimens removed from eyes with or without ocriplasmin treatment. Undulated areas of the retinal side presented stiffer than the vitreal side of the ILM. Topographical mapping of both the vitreal and retinal side of the ILM showed no apparent alteration of the morphology in ocriplasmin-treated eyes compared to untreated eyes. Staining with BB resulted in an increase of tissue stiffness. Intravitreal injection of ocriplasmin does not change biomechanical properties of the human ILM. There is no evidence of a potential enzymatic effect of ocriplasmin interfering with the stiffness of this basement membrane. © 2016 S. Karger AG, Basel.

  10. Intravitreal dexamethasone implant for cystoid macular edema and inflammation after scleral buckling.

    Science.gov (United States)

    Bonfiglio, Vincenza; Fallico, Matteo R; Russo, Andrea; De Grande, Vittorio; Longo, Antonio; Uva, Maurizio G; Reibaldi, Michele; Avitabile, Teresio

    2015-07-30

    Cystoid macular edema may occur following scleral buckling and therefore deteriorate the visual outcome. Inflammation may be the major causative factor in the development of postoperative cystoid macular edema. This case demonstrates the effectiveness of a dexamethasone implant as a treatment after the onset of choroidal inflammation and cystoid macular edema 6 months following scleral buckling and having visual acuity restored. A 59-year-old phakic woman treated with scleral buckling for macula-off retinal detachment presented 2 months after surgery with cystoid macular edema with choroidal inflammation. Optical coherence tomography and fluorescein angiography were performed. From the time of the diagnosis, the patient's condition had been nonresponsive to medical therapy and only partially responsive to sub-Tenon triamcinolone acetonide. An intravitreal implant with a sustained release of 0.7 mg dexamethasone was implanted. Following an intravitreal injection with a dexamethasone implant, the macular edema subsided completely and optical coherence tomography showed decreased foveal thickness from 510 μm to 220 μm. Choroidal fluorescein leakage disappeared. Best-corrected visual acuity improved from 0.70 to 0.20 logMAR, a condition maintained throughout the 6 months of follow-up. Cystoid macular edema and choroidal inflammation are difficult to treat, but the improvement observed in this case of post scleral buckling macular edema and choroidal inflammation showed how a dexamethasone implant proved to be useful during the 6-month follow-up.

  11. Efficient production of a bioactive Bevacizumab monoclonal antibody using the 2A self-cleavage peptide in transgenic rice callus

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    Lei Chen

    2016-08-01

    Full Text Available Bevacizumab, a humanized monoclonal antibody (mAb targeting to the vascular endothelial growth factor (VEGF, has been widely used in clinical practice for the treatment of multiple cancers. Bevacizumab was mostly produced by the mammalian cell expression system. We here reported the first plant-derived Bevacizumab by using transgenic rice callus as an alternative gene expression system. Codon-optimized Bevacizumab light chain (BLC and heavy chain (BHC genes were designed, synthesized as a polyprotein with a 2A self-cleavage linker peptide from the Foot-and-mouth disease virus (FMDV, cloned into a plant binary vector under a constitutive maize ubiquitin promoter, and transformed into rice nuclear genome through Agrobacterium-mediated transformation. Southern blot and western blot analyses confirmed the integration and expression of BLC and BHC genes in transgenic rice callus. Enzyme linked immunosorbent assay (ELISA analysis indicated that the rice-derived Bevacizumab mAb was biologically active and the recombinant mAb was expressed at high levels (160.7-242.8 mg kg-1FW in transgenic rice callus. The mAb was purified by using protein A affinity chromatography and the purified antibody was tested for its binding affinity with its target hVEGF antigen by ELISA. Rice callus produced Bevacizumab and a commercial Bevacizumab (Avastin were shown to have similar binding affinity to hVEGF. These results indicated that rice callus produced Bevacizumab could have similar biological activity and might potentially be used as a cost-effective biosimilar molecule in future cancer treatment.

  12. Large-volume low apparent diffusion coefficient lesions predict poor survival in bevacizumab-treated glioblastoma patients

    Science.gov (United States)

    Zhang, Myron; Gulotta, Bryanna; Thomas, Alissa; Kaley, Thomas; Karimi, Sasan; Gavrilovic, Igor; Woo, Kaitlin M.; Zhang, Zhigang; Arevalo-Perez, Julio; Holodny, Andrei I.; Rosenblum, Marc; Young, Robert J.

    2016-01-01

    Background Glioblastomas treated with bevacizumab may develop low-signal apparent diffusion coefficient (low-ADC) lesions, which may reflect increased tumor cellularity or atypical necrosis. The purpose of this study was to examine the relationship between low-ADC lesions and overall survival (OS). We hypothesized that growing low-ADC lesions would be associated with shorter OS. Methods We retrospectively identified 52 patients treated with bevacizumab for the first (n = 42, 81%) or later recurrence of primary glioblastoma, who had low-ADC lesions and 2 post-bevacizumab scans ≤90 days apart. Low-ADC lesion volumes were measured, and normalized 5th percentile histogram low-ADC values were recorded. Using OS as the primary endpoint, semiparametric Cox models were fitted to ascertain univariate and multivariate hazard ratios (HRs) with significance at P = .05. Results Median OS was 9.1 months (95% CI = 7.2–14.3). At the second post-bevacizumab scan, the volume of the low-ADC lesion (median: 12.94 cm3) was inversely associated with OS, with larger volumes predicting shorter OS (HR = 1.014 [95% CI = 1.003–1.025], P = .009). The percent change in low-ADC volume (median: 6.8%) trended toward increased risk of death with growing volumes (P = .08). Normalized 5th percentile low-ADC value and its percent change were not associated with OS (P > .51). Also correlated with shorter OS were the pre-bevacizumab nonenhancing volume (P = .025), the first post-bevacizumab enhancing volume (P = .040), and the second post-bevacizumab enhancing volume (P = .004). Conclusions The volume of low-ADC lesions at the second post-bevacizumab scan predicted shorter OS. This suggests that low-ADC lesions may be considered important imaging markers and included in treatment decision algorithms. PMID:26538618

  13. Mechanisms Controlling the Effects of Bevacizumab (Avastin) on the Inhibition of Early but Not Late Formed Corneal Neovascularization

    Science.gov (United States)

    Chu, Hsiao-Sang; Lin, Chung-Tien; Chow, Lu-Ping; Chen, Chih-Ta; Hu, Fung-Rong

    2014-01-01

    Purpose To evaluate the effects and underlying mechanisms of early and late subconjunctival injection of bevacizumab on the inhibition of corneal neovascularization (NV). Methods Corneal NV was induced by closed eye contact lens wear followed by a silk suture tarsorrhaphy in rabbits. Weekly subconjunctival injections of bevacizumab (5.0 mg) for 1 month were started immediately (early treatment group) or 1 month after induction of corneal NV with continuous induction (late treatment group). The severity of corneal NV was evaluated. Immunostaining was used to evaluate the intracorneal diffusion of bevacizumab, and the existence of pericytes and smooth muscle cells around the NV. The expression of AM-3K, an anti-macrophage antibody, vascular endothelial growth factor (VEGF) with its receptors (VEGFR1 and VEGFR2), and vascular endothelial apoptosis were also evaluated. Western blot analysis was performed to quantify the expression level of VEGF, VEGFR1 and VEGFR2 on corneal epithelium and stroma in different groups. Results Early treatment with bevacizumab inhibited corneal NV more significantly than late treatment. Intracorneal diffusion of bevacizumab was not different among different groups. Immunostaining showed pericytes and smooth muscle cells around newly formed vessels as early as 2 weeks after induction. Immunostaining and Western blot analysis showed that VEGF, VEGFR1, and VEGFR2 on corneal stroma increased significantly in no treatment groups and late treatment groups, but not in early treatment group. Bevacizumab significantly inhibited macrophage infiltration in the early but not late treatment group. Sporadic vascular endothelial apoptosis was found at 4 weeks in the late but not early treatment group. Conclusions Early but not late injection of bevacizumab inhibited corneal NV. Late injection of bevacizumab did not alter macrophage infiltration, and can't inhibit the expression of VEGF, VEGFR1, and VEGFR2 on corneal vessels. The inhibition of corneal NV

  14. Efficacy of bevacizumab therapy in recurrent malignant gliomas in relation to the prior recurrence pattern or tumor location.

    Science.gov (United States)

    Matsuda, Masahide; Ishikawa, Eiichi; Yamamoto, Tetsuya; Akutsu, Hiroyoshi; Takano, Shingo; Matsumura, Akira

    2017-06-01

    Although promising preliminary results have been widely observed with bevacizumab for recurrent malignant gliomas, many unanswered questions remain to be resolved to achieve an optimal outcome. No predictive biomarkers of a survival benefit from bevacizumab have been established, and no consensus exists about the response or survival benefit regarding the prior recurrence pattern or tumor location. Here we retrospectively analyzed the clinical benefit from bevacizumab for recurrent malignant gliomas in relation to the prior recurrence pattern or tumor location. Thirty-one consecutive patients with recurrent malignant gliomas who were treated with bevacizumab were investigated. The treatment response and survival benefit from bevacizumab were analyzed in association with age, sex, Karnofsky performance status, prior pathological diagnosis, prior recurrence pattern, primary location of tumor, recurrence status, and expression of angiogenic and hypoxic markers. The group with leptomeningeal dissemination had a significantly shorter median overall survival with bevacizumab (OS Bev) (6.0months, 95% confidence interval (CI) 1.4-10.7) compared to those in the local/distant group (11.8months, 95% CI 6.1-17.4). The median OS Bev of the infratentorial tumor group and supratentorial tumor group were 9.2months (95% CI 5.0-13.4) and 10.4months (95% CI 6.6-14.3), respectively. With multivariate analysis, the prior recurrence pattern was the only independent prognostic factor of OS Bev . Patients with leptomeningeal dissemination of recurrent malignant glioma experienced minimal benefit from bevacizumab. Therefore, in the context of cost effectiveness, bevacizumab is not recommended for patients with leptomeningeal dissemination. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Neoadjuvant Therapy of DOF Regimen Plus Bevacizumab Can Increase Surgical Resection Ratein Locally Advanced Gastric Cancer: A Randomized, Controlled Study.

    Science.gov (United States)

    Ma, Junxun; Yao, Sheng; Li, Xiao-Song; Kang, Huan-Rong; Yao, Fang-Fang; Du, Nan

    2015-10-01

    Locally advanced gastric cancer (LAGC) is best treated with surgical resection. Bevacizumab in combination with chemotherapy has shown promising results in treating advanced gastric cancer. This study aimed to investigate the efficacy of neoadjuvant chemotherapy using the docetaxel/oxaliplatin/5-FU (DOF) regimen and bevacizumab in LAGC patients.Eighty LAGC patients were randomized to receive DOF alone (n = 40) or DOF plus bevacizumab (n = 40) as neoadjuvant therapy before surgery. The lesions were evaluated at baseline and during treatment. Circulating tumor cells (CTCs) were counted using the FISH test. Patients were followed up for 3 years to analyze the disease-free survival (DFS) and overall survival (OS).The total response rate was significantly higher in the DOF plus bevacizumab group than the DOF group (65% vs 42.5%, P = 0.0436). The addition of bevacizumab significantly increased the surgical resection rate and the R0 resection rate (P DOF plus bevacizumab group showed significantly greater reduction in CTC counts after neoadjuvant therapy in comparison with the DOF group (P = 0.0335). Although the DOF plus bevacizumab group had significantly improved DFS than the DOF group (15.2 months vs 12.3 months, P = 0.013), the 2 groups did not differ significantly in OS (17.6 ± 1.8 months vs 16.4 ± 1.9 months, P = 0.776. Cox proportional model analysis showed that number of metastatic lymph nodes, CTC reduction, R0 resection, and neoadjuvant therapy are independent prognostic factors for patients with LAGC.Neoadjuvant of DOF regimen plus bevacizumab can improve the R0 resection rate and DFS in LAGC. These beneficial effects might be associated with the reduction in CTC counts.

  16. Bevacizumab Modulation of the Interaction Between the MCF-7 Cell Line and the Chick Embryo Chorioallantoic Membrane

    OpenAIRE

    COMŞA, ŞERBAN; POPESCU, ROXANA; AVRAM, ŞTEFANA; CEAUȘU, RALUCA AMALIA; CÎMPEAN, ANCA MARIA; RAICA, MARIUS

    2017-01-01

    Aim: To evaluate the interaction between MCF-7 breast cancer cells and the chick embryo chorioallantoic membrane (CAM) and the ability of bevacizumab to modulate this process. Materials and Methods: We implanted MCF-7 cells onto CAM and repeatedly added bevacizumab to a subset of eggs. We then evaluated the morphological and immunohistochemical profiles of CAM and MCF-7. Results: MCF-7 cells entered the mesoderm and stimulated the mesenchymal cells to acquire vasculogenic and myofibroblastoid...

  17. Assessment of the effect of intravitreal triamcinolone acetonide on the chorioretinal and vitreous inflammatory reaction to cryotherapy in rabbits

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    Eugênio Santana de Figueirêdo

    2012-10-01

    Full Text Available PURPOSE: To evaluate the inflammatory response in the choroid, retina and vitreous in rabbit eyes underwent cryotherapy followed by intravitreal triamcinolone acetonide and to compare with those underwent cryotherapy followed by intravitreal injection of saline solution. METHODS: This is a prospective case-control study. Surgical procedures were performed in eleven rabbits. Two animals were excluded because they did not complete the postoperative period or had intraoperative or postoperative complications. All rabbits underwent superior temporal peritomy and transscleralcryotherapy in both eyes. After cryotherapy, animals received intravitreal injection of triamcinolone acetonide in one eye and saline solution in the fellow eye. Animals were sacrificed seven days after the procedure and their eyes were enucleated. Histological sections of eyeballs were prepared and the vitreous humor was aspirated. The count of inflammatory cells was performed by light microscopy. RESULTS: Histological sections of both eyes of nine rabbits were analyzed. Inflammatory cells were found only in the choroid. There was no statistically significant difference in the number of inflammatory cells between the two groups, regardless of cell type analyzed. CONCLUSION: This study showed no statistically significant difference between the use or absence of intravitreal triamcinolone acetonide in the inflammatory response to cryotherapy in rabbit eyes. Studies with larger samples are needed to confirm the trend of this paper.

  18. INTEGRATION OF BEVACIZUMAB IN METASTATIC COLORECTAL CANCER CHEMOTHERAPY REGIMENS IN 2 CLINICAL CENTERS IN MOSCOW AND SAINT PETERSBURG

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    N. V. Dobrova

    2013-01-01

    Full Text Available The aim of this study was to estimate efficacy of first line chemotherapy with bevacizumab in metastatic colorectal cancer patients and investigate the impact of different prognostic factors on treatment outcome.Methods.During 2004–2008 48 colorectal cancer patients were included (29 in Russian N.N. Blokhin Cancer Research Center, 19 in St. Petersburg, who had unresectable distant metastases. Primary tumor was resected in 93.8 % patients. 52.1 % had rectal cancer. 87.5 % had liver metastases, 43.8 % had more than 1 organ affected. 66.7 % received chemotherapy with bevacizumab 5 mg/kg biweekly, 33.3 % received bevacizumab 7,5 mg/kg every 3 weeks. 62.5 % patients had oxaliplatin-based regimens, 35.4 % – only fluorpyrimidines, 2.1 % – chemotherapy with irinotecan.Results.Median time of bevacizumab use was 7.8 months. 60.3 % had objective response, 87.4 % had stable diseases during more than 6 months. Median progression-free survival (PFS was 11.5 months. Median overall survival (OS was 24.1 months.Conclusions.Survival and efficacy results are comparable to international experience. Combination of fluorpyrimidines with bevacizumab had comparable efficacy to combined chemotherapy regimens with no impact on quality of life. Integration of bevacizumab in combined treatment regimens reduced the impact of negative prognostic factors on PFS and OS. 

  19. Serum Nitric Oxide as a Predictive Biomarker for Bevacizumab in Non-small Cell Lung Cancer Patients.

    Science.gov (United States)

    Muto, Satoshi; Takagi, Hironori; Owada, Yuki; Inoue, Takuya; Watanabe, Yuzuru; Yamaura, Takumi; Fukuhara, Mitsuro; Okabe, Naoyuki; Matsumura, Yuki; Hasegawa, Takeo; Osugi, Jun; Hoshino, Mika; Higuchi, Mitsunori; Shio, Yutaka; Suzuki, Hiroyuki

    2017-06-01

    Reportedly, hypertension tends to be associated with response to bevacizumab therapy, because bevacizumab suppresses vascular nitric oxide production. In this study we examined the predictive value of nitric oxide in bevacizumab-treated non-small cell lung cancer (NSCLC) patients. Fifteen patients with advanced or recurrent NSCLC treated with bevacizumab-based regimens were evaluated retrospectively. Serum NOx (NO 2 - /NO 3 - ) was assayed by the Griess method. Serum nitric oxide levels were decreased after two courses of bevacizumab treatment in our responder group (p=0.02). According to the change in nitric oxide levels after the second course of treatment, median progression-free survival was 11.0 months in the group with decreased serum nitric oxide and 7.6 months in the group with increased serum nitric oxide (p=0.08). Serum nitric oxide levels could be a predictive biomarker for response to bevacizumab in NSCLC patients. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  20. Sinusoidal obstruction syndrome (veno-occlusive disease in a patient receiving bevacizumab for metastatic colorectal cancer: a case report

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    Agarwal Vijay

    2008-07-01

    Full Text Available Abstract Introduction We present the case of a patient with colon cancer who, while receiving bevacizumab, developed sinusoidal obstruction syndrome (veno-occlusive disease (SOSVOD. Certain antitumour agents such as 6-mercaptopurine and 6-thioguanine have also been reported to initiate hepatic SOSVOD in isolated cases. There have been no reports so far correlating bevacizumab with SOSVOD. Case presentation A 77-year-old man was being treated with oxaliplatin and a modified de Gramont regimen of 5-fluorouracil for metastatic colon cancer. Bevacizumab (7.5 mg/kg was added from the seventh cycle onwards. Protracted neutropenia and thrombocytopenia led to discontinuation of oxaliplatin after the ninth cycle. A computed tomography scan showed complete response and bevacizumab was continued for another 3 months, after which time the patient developed right hypochondrial pain, transudative ascites, splenomegaly and abnormal liver function tests. Upper gastrointestinal endoscopy showed oesophageal varices. Liver biopsy showed features considered to be consistent with SOSVOD. Bevacizumab was stopped and a policy of watchful waiting was adopted. He tolerated the acute damage to his liver and subsequently the ascites resolved and liver function tests normalised. Conclusion We need to be aware that bevacizumab can cause sinusoidal obstruction syndrome (veno-occlusive disease and that the occurrence of ascites should not be attributed to progressive disease without appropriate evaluation.

  1. Single-Chain Antibody Fragment VEGF Inhibitor RTH258 for Neovascular Age-Related Macular Degeneration

    DEFF Research Database (Denmark)

    Holz, Frank G; Dugel, Pravin U.; Weissgerber, Georges

    2016-01-01

    Purpose To assess the safety and efficacy of different doses of RTH258 applied as single intravitreal administration compared with ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (AMD). Design Six-month, phase 1/2, prospective, multicenter, double-masked, randomized...

  2. Bevacizumab for Metastatic Colorectal Cancer: A Global Cost-Effectiveness Analysis.

    Science.gov (United States)

    Goldstein, Daniel A; Chen, Qiushi; Ayer, Turgay; Chan, Kelvin K W; Virik, Kiran; Hammerman, Ariel; Brenner, Baruch; Flowers, Christopher R; Hall, Peter S

    2017-06-01

    In the U.S., the addition of bevacizumab to first-line chemotherapy in metastatic colorectal cancer (mCRC) has been demonstrated to provide 0.10 quality-adjusted life years (QALYs) at an incremental cost-effectiveness ratio (ICER) of $571,000/QALY. Due to variability in pricing, value for money may be different in other countries. Our objective was to establish the cost-effectiveness of bevacizumab in mCRC in the U.S., U.K., Canada, Australia, and Israel. We performed the analysis using a previously established Markov model for mCRC. Input data for efficacy, adverse events, and quality of life were considered to be generalizable and therefore identical for all countries. We used country-specific prices for medications, administration, and other health service costs. All costs were converted from local currency to U.S. dollars at the exchange rates in March 2016. We conducted one-way and probabilistic sensitivity analyses (PSA) to assess the model robustness across parameter uncertainties. Base case results demonstrated that the highest ICER was in the U.S. ($571,000/QALY) and the lowest was in Australia ($277,000/QALY). In Canada, the U.K., and Israel, ICERs ranged between $351,000 and $358,000 per QALY. PSA demonstrated 0% likelihood of bevacizumab being cost-effective in any country at a willingness to pay threshold of $150,000 per QALY. The addition of bevacizumab to first-line chemotherapy for mCRC consistently fails to be cost-effective in all five countries. There are large differences in cost-effectiveness between countries. This study provides a framework for analyzing the value of a cancer drug from the perspectives of multiple international payers. The cost-effectiveness of bevacizumab varies significantly between multiple countries. By conventional thresholds, bevacizumab is not cost-effective in metastatic colon cancer in the U.S., the U.K., Australia, Canada, and Israel. © AlphaMed Press 2017.

  3. Increased risk of hemorrhage in metastatic colorectal cancer patients treated with bevacizumab

    Science.gov (United States)

    Zhu, Xiaoqiang; Tian, Xianglong; Yu, Chenyang; Hong, Jie; Fang, Jingyuan; Chen, Haoyan

    2016-01-01

    Abstract Background: As an important antivascular endothelial growth factor monoclonal antibody, bevacizumab has been administrated for the treatment of cancer patients. Hemorrhage, one of the common adverse events of angiogenesis inhibitors, sometimes is also fatal and life-threatening. We aimed at determining the incidence and risk of hemorrhage associated with bevacizumab in patients with metastatic colorectal cancer (mCRC). Methods: We searched PubMed, EMBASE, and the Web of Science databases for relevant randomized controlled trials (RCTs). The overall incidence, overall relative risk (RR), and 95% confidence interval (CI) were calculated by using a random-effects or fixed-effects model based on the heterogeneity of selected trials. Results: A total of 10,555 mCRC patients from 12 RCTs were included in our study. The overall incidence of hemorrhage was 5.8% (95% CI 3.9%–7.8%). Bevacizumab significantly increased the overall risk of hemorrhage with an RR of 1.96 (95% CI 1.27–3.02). The RR of all-grade hemorrhage was 2.39 (95% CI 1.09–5.24) and 1.41 (95% CI 1.01–1.97) for high-grade hemorrhage. The risk of hemorrhage associated with bevacizumab was dose-dependent with an RR of 1.73 (95% CI 1.15–2.61) for 2.5 mg/kg/wk and 4.67 (95% CI 2.36–9.23) for 5 mg/kg/wk. More importantly, the RR of hemorrhage for treatment duration ( 6 months) based on subgroup analysis was 4.13 (95% CI 2.58–6.61) and 1.43 (95% CI 0.96–2.14), respectively. Conclusion: The addition of bevacizumab to concurrent antineoplastic in patients with mCRC significantly increased the risk of hemorrhage. The dose of bevacizumab may contribute to the risk of hemorrhage. And the 1st 6 months of treatment may be a crucial period when hemorrhagic events occur. PMID:27559943

  4. Safety and Efficacy of Stereotactic Radiosurgery and Adjuvant Bevacizumab in Patients With Recurrent Malignant Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Cuneo, Kyle C. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Vredenburgh, James J.; Sampson, John H.; Reardon, David A.; Desjardins, Annick; Peters, Katherine B.; Friedman, Henry S. [Department of Surgery, Duke University Medical Center, Durham, NC (United States); Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC (United States); Willett, Christopher G. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Kirkpatrick, John P., E-mail: john.kirkpatrick@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC (United States)

    2012-04-01

    Purpose: Patients with recurrent malignant gliomas treated with stereotactic radiosurgery (SRS) and multiagent systemic therapies were reviewed to determine the effects of patient- and treatment-related factors on survival and toxicity. Methods and Materials: A retrospective analysis was performed on patients with recurrent malignant gliomas treated with salvage SRS from September 2002 to March 2010. All patients had experienced progression after treatment with temozolomide and radiotherapy. Salvage SRS was typically administered only after multiple postchemoradiation salvage systemic therapies had failed. Results: 63 patients were treated with SRS for recurrent high-grade glioma; 49 patients had World Health Organization (WHO) Grade 4 disease. Median follow-up was 31 months from primary diagnosis and 7 months from SRS. Median overall survival from primary diagnosis was 41 months for all patients. Median progression-free survival (PFS) and overall survival from SRS (OS-SRS) were 6 and 10 months for all patients, respectively. The 1-year OS-SRS for patients with Grade 4 glioma who received adjuvant (concurrent with or after SRS) bevacizumab was 50% vs. 22% for patients not receiving adjuvant bevacizumab (p = 0.005). Median PFS for patients with a WHO Grade 4 glioma who received adjuvant bevacizumab was 5.2 months vs. 2.1 months for patients who did not receive adjuvant bevacizumab (p = 0.014). Karnofsky performance status (KPS) and age were not significantly different between treatment groups. Treatment-related Grade 3/4 toxicity for patients receiving and not receiving adjuvant BVZ was 10% and 14%, respectively (p = 0.58).On multivariate analysis, the relative risk of death and progression with adjuvant bevacizumab was 0.37 (confidence interval [CI] 0.17-0.82) and 0.45 (CI 0.21-0.97). KPS >70 and age <50 years were significantly associated with improved survival. Conclusions: The combination of salvage radiosurgery and bevacizumab to treat recurrent malignant

  5. Biophysical study of bevacizumab structure and bioactivity under thermal and pH-stresses.

    Science.gov (United States)

    Sousa, Flávia; Sarmento, Bruno; Neves-Petersen, Maria Teresa

    2017-07-15

    The evaluation of the structural stability and bioactivity of monoclonal antibodies (mAb) is a crucial step in the development of mAb therapeutic based products, since immunogenicity needs to be avoided. In the present work, a study was carried out to understand the changes on the structure and bioactivity of mAbs induced by different pH and temperature values. Structural changes of bevacizumab were monitored using fluorescence spectroscopy, circular dichroism (CD) and Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). The secondary and tertiary structural content was monitored at six different pH values and at room temperature, upon heating up to 85°C and upon cooling down to 20°C. Furthermore, the temperature induced conformational changes were continuously monitored from 20°C to 85°C using fluorescence spectroscopy and circular dichroism, allowing to monitor the melting temperature of the protein at different pH values. The results showed that the thermal denaturation of bevacizumab was irreversible at all pH value. The conformational changes induced by pH were higher at extreme pH values (5, 9 and 10) than neutral pH. Thermal stability studies showed that pH6 was the pH that confer bevacizumab the highest structural stability. These studies were confirmed by in vitro studies, where bevacizumab's bioactivity was measured by cell viability/proliferation at all pH values at room temperature, and it was found a higher bioactivity for pH6. Biophysical and biological studies were correlated in order to understand the importance of the modifications in bevacizumab structural content on its bioactivity. However, a decrease in bevacizumab's bioactivity was observed for pH8, 9 and 10. Overall, this work demonstrated the usefulness of the spectroscopy techniques for estimating the stability of therapeutic mAb during formulation development. Copyright © 2017. Published by Elsevier B.V.

  6. Suppression of oxidative phosphorylation confers resistance against bevacizumab in experimental glioma.

    Science.gov (United States)

    Eriksson, Jule A; Wanka, Christina; Burger, Michael C; Urban, Hans; Hartel, Ines; von Renesse, Janusz; Harter, Patrick N; Mittelbronn, Michel; Steinbach, Joachim P; Rieger, Johannes

    2017-11-27

    Although bevacizumab initially shows high response rates in gliomas and other tumours, therapy resistance usually develops later. Because anti-angiogenic agents are supposed to induce hypoxia, we asked whether rendering glioma cells independent of oxidative phosphorylation modulates their sensitivity against hypoxia and bevacizumab. LNT-229 glioma cells without functional mitochondria (rho 0 ) and control (rho + ) cells were generated. LNT-229 rho 0 -cells displayed reduced expression of oxidative phosphorylation-related genes and diminished oxygen consumption. Conversely, glycolysis was up-regulated in these cells, as shown by increased lactate production and stronger expression of glucose transporter-1 and lactate dehydrogenase-A. However, hypoxia-induced cell death in vitro was nearly completely abolished in the LNT-229 rho 0 -cells, these cells were more sensitive towards glucose restriction and the treatment with the glycolysis inhibitor 2-deoxy-D-glucose. In an orthotopic mouse xenograft experiment, bevacizumab induced hypoxia as reflected by elevated Hypoxia-inducible factor 1-alpha staining in both, rho + - and rho 0 -tumours. However, it prolonged survival only in the mice bearing rho + -tumours (74 days vs. 105 days, p = 0.024 log-rank test) and had no effect on survival in mice carrying LNT-229 rho 0 -tumours (75 days vs. 70 days, p = 0.52 log-rank test). Interestingly, inhibition of glycolysis in vivo with 2-deoxy-D-glucose re-established sensitivity of rho 0 -tumours against bevacizumab (98 days vs. 80 days, p = 0.0001). In summary, ablation of oxidative phosphorylation in glioma cells leads to a more glycolytic and hypoxia-resistant phenotype and is sufficient to induce bevacizumab-refractory tumours. These results add to increasing evidence that a switch towards glycolysis is one mechanism how tumour cells may evade anti-angiogenic treatments and suggest anti-glycolytic strategies as promising approaches to overcome bevacizumab

  7. Strategies for Improving Patient Comfort During Intravitreal Injections: Results from a Survey-Based Study.

    Science.gov (United States)

    Gomez, Jessica; Koozekanani, Dara D; Feng, Alex Z; Holt, Mitchell; Drayna, Paul; Mackley, Melissa R; van Kuijk, Frederik J G M; Beardsley, Robert M; Johnston, Richard H; Terry, Joseph M; Montezuma, Sandra R

    2016-12-01

    Many ocular diseases require intravitreal injections of pharmacological agents. Optimizing patients' experiences during injections is important to ensure compliance and maintenance of quality of life. The objective of this study was to identify strategies to help alleviate discomfort during intravitreal injections. A cross-sectional study surveying 128 patients during clinic visits between 2014 and 2015 in two outpatient Retina Clinics (one academic and one private). Patients receiving an intravitreal injection(s) for any retinal disorder were given a questionnaire with 10-yes/no responses for various potential strategies. Responses were stratified by sex, age (60 years) and total number of prior injections (0-9 injections, 10-20 injections and >20 injections). A total of 128 patients were surveyed: 59 males, 41 females and 28 with no sex specified. Our results identified four favorable strategies as those receiving more than 50% "yes" votes. These included the presence of technician/staff during the procedure, the use of a neck pillow, a verbal warning before the injection and performing injections in both eyes on the same day. Other specific strategies were identified for females, younger patients and those with greatest experience. These included: females preferred having their hand held during injections (P = 0.001) and using a stress ball (P = 0.000) when compared to males. Stratifying by age, patients 30-60 years old preferred having their hand held (P = 0.008) and background music (P = 0.007). Stratifying by prior injections, patients with >20 prior injections preferred having their hand held (P = 0.001), using a stress ball (P = 0.021) and, if necessary, having bilateral injections performed the same day to improve comfort (P = 0.037). Having an extra staff member present during the injection, having a neck pillow, having a verbal warning prior to injection and having both eyes injected on the same day were indicated as favorable strategies

  8. Clinical Variables for Prediction of the Therapeutic Effects of Bevacizumab Monotherapy in Nasopharyngeal Carcinoma Patients With Radiation-Induced Brain Necrosis.

    Science.gov (United States)

    Li, Yi; Huang, Xiaolong; Jiang, Jingru; Hu, Weihan; Hu, Jiang; Cai, Jinhua; Rong, Xiaoming; Cheng, Jinping; Xu, Yongteng; Wu, Rong; Luo, Jinjun; Tang, Yamei

    2018-03-01

    To identify the predictive and prognostic factors for a decrease or recurrence of brain edema in patients who developed radiation-induced brain necrosis (RN) after radiation therapy for nasopharyngeal carcinoma (NPC) and who received bevacizumab monotherapy. This was a retrospective study. The charts of 50 patients who were diagnosed with RN after radiation therapy for NPC, treated with bevacizumab, and followed up for 6 months were reviewed. Clinical data of these patients were collected, and their brain edema volume before bevacizumab administration, after bevacizumab administration, at 3-month follow-up, and at 6-month follow-up was evaluated on the basis of brain magnetic resonance imaging findings. The baseline serum vascular endothelial growth factor levels of 15 patients were measured by enzyme-linked immunosorbent assay. A random forests model was developed for statistical analysis. The median percentage of decrease in RN volume shown on T2-weighted fluid-attenuated inversion recovery images at the end of bevacizumab therapy was 72.6% (interquartile range, 34.5% to 89.5%; P < .001). Twelve of these 50 patients (24.0%) did not have an effective response, and 38 patients (76.0%) showed an effective response after bevacizumab administration. Fifteen of the 38 patients showed RN recurrence. According to the random forests model the maximum radiation dose of the temporal lobe (D max of the temporal lobe) was a highly ranked predictor for the therapeutic effect of bevacizumab. The duration between radiation therapy and bevacizumab treatment and the duration between radiation therapy and RN diagnosis were highly ranked predictors for RN recurrence after bevacizumab treatment. Prediction models for the therapeutic effect of bevacizumab in RN patients were developed, using the random forests model. Bevacizumab might be more effective in patients with a lower maximum radiation dose to the temporal lobe. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. A Case of Appendiceal Adenocarcinoma with Clinical Benefit from FOLFOX and Bevacizumab

    Directory of Open Access Journals (Sweden)

    Erin D. Powell

    2009-07-01

    Full Text Available A 44-year-old woman presented with lower abdominal pain and bilateral ovarian masses on ultrasound. Exploratory laparotomy revealed extensive peritoneal and intra-abdominal disease and an abnormal appendix. Bilateral salpingo-oophorectomy, infracolic omentectomy, ileocolic resection and primary anastomosis were performed. Final pathology revealed a primary appendiceal adenocarcinoma, poorly differentiated, of signet ring cell type. CT scan postoperatively revealed gross residual disease. The patient was treated with FOLFOX chemotherapy combined with bevacizumab. Repeat CT scan showed a decrease in residual disease and the patient clinically improved. After her treatment has been continued for 13 months, she remains clinically well and her CT scan shows sustained disease stability. Disseminated appendiceal carcinoma is generally considered to be refractory to 5-FU-based chemotherapy and, to our knowledge, this is the first reported case of a patient with appendiceal adenocarcinoma demonstrating clinical benefit and sustained stability of disease with combination chemotherapy plus bevacizumab.

  10. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7)

    DEFF Research Database (Denmark)

    Oza, Amit M; Cook, Adrian D; Pfisterer, Jacobus

    2015-01-01

    of the trial. METHODS: ICON7 was an international, phase 3, open-label, randomised trial undertaken at 263 centres in 11 countries across Europe, Canada, Australia and New Zealand. Eligible adult women with newly diagnosed ovarian cancer that was either high-risk early-stage disease (International Federation......), three grade 2 treatment-related events (cardiac failure, sarcoidosis, and foot fracture, all in bevacizumab-treated patients), and one grade 1 treatment-related event (vaginal haemorrhage, in a patient treated with standard chemotherapy) were reported. INTERPRETATION: Bevacizumab, added to platinum......-based chemotherapy, did not increase overall survival in the study population as a whole. However, an overall survival benefit was recorded in poor-prognosis patients, which is concordant with the progression-free survival results from ICON7 and GOG-218, and provides further evidence towards the optimum use...

  11. Effect of Bevacizumab Nasal Spray on Epistaxis Duration in Hereditary Hemorrhagic Telangectasia: A Randomized Clinical Trial.

    Science.gov (United States)

    Dupuis-Girod, Sophie; Ambrun, Alexis; Decullier, Evelyne; Fargeton, Anne-Emmanuelle; Roux, Adeline; Bréant, Valentine; Colombet, Bettina; Rivière, Sophie; Cartier, César; Lacombe, Pascal; Chinet, Thierry; Blivet, Sandra; Blondel, Jean-Hugues; Gilbert-Dussardier, Brigitte; Dufour, Xavier; Michel, Justin; Harle, Jean-Robert; Dessi, Patrick; Faure, Frédéric

    2016-09-06

    Epistaxis is the most frequent and disabling manifestation of hereditary hemorrhagic telangiectasia (HHT). The efficacy of intravenous bevacizumab (an anti-vascular endothelial growth factor monoclonal antibody) for epistaxis has been shown. However, the efficacy of intranasal bevacizumab has yet to be evaluated. To evaluate the efficacy of 3 different doses of bevacizumab administered as a nasal spray in a repeated manner for the duration of nosebleeds in patients with HHT. Randomized, multicenter, placebo-controlled, phase 2/3 clinical trial with dose selection at an intermediate analysis and prespecified stopping rules (nonbinding stopping for futility). Patients aged 18 years or older with a diagnosis of HHT were recruited from 5 French centers from April 2014 to January 2015 with a 6-month follow-up after the end of treatment. Participants had a history of self-reported nosebleeds with a monthly duration of more than 20 minutes in at least the 3 months prior to inclusion corroborated by epistaxis grids completed during the same preinclusion period. Eighty consecutive HHT patients were randomized and treated in the phase 2 study, with 4 parallel groups in a 1:1:1:1 ratio. One group received placebo (n = 21); the other 3 received bevacizumab nasal spray. Each bevacizumab group received a different dose of the drug (25 mg [n = 20], 50 mg [n = 20], or 75 mg [n = 19] per treatment) in 3 doses 14 days apart for a total treatment duration of 4 weeks, resulting in a total dose of 75 mg, 150 mg, and 225 mg in each treatment group. Mean monthly epistaxis duration for 3 consecutive months immediately after the end of the treatment. Of the 80 patients who were randomized (mean age, 60.47 [SD, 10.61] years; 37 women [46.25%]), 75 completed the study. Mean monthly epistaxis duration measured at 3 months was not significantly different in the 59 patients receiving bevacizumab in comparison with the placebo group (P = .57) or between the bevacizumab groups

  12. Subconjunctival and Orbital Silicone Oil Granuloma (Siliconoma Complicating Intravitreal Silicone Oil Tamponade

    Directory of Open Access Journals (Sweden)

    Jung Hye Lee

    2014-01-01

    Full Text Available A 30-year-old male, who underwent previous pars plana vitrectomy and silicone oil tamponade due to endogenous endophthalmitis originated from Klebsiella liver abscess, was referred for evisceration. At 2 months after vitrectomy with silicon oil tamponade, conjunctival chemosis and ocular pain were aggravated. Diffuse eyelid swelling and large subconjunctival mass with lipid droplets were noted. On MRI examination, subconjunctival mass and intra- and extraconal orbital mass around superior rectus muscle were observed. Excision of subconjunctival and orbital mass was performed. Histopathologic examination showed multiple silicone oil vacuoles surrounded by foreign body giant cells and fibrosis, which confirmed silicone oil granuloma. In a patient with suspicious melting sclera in diseases such as endophthalmitis, large silicone oil granuloma may be complicated in a rapid fashion after intravitreal silicone oil tamponade due to silicone oil leakage.

  13. Preoperative Radiation Therapy With Concurrent Capecitabine, Bevacizumab, and Erlotinib for Rectal Cancer: A Phase 1 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Das, Prajnan, E-mail: PrajDas@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Eng, Cathy [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez-Bigas, Miguel A.; Chang, George J.; Skibber, John M.; You, Y. Nancy [Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Maru, Dipen M. [Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Munsell, Mark F. [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Clemons, Marilyn V. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kopetz, Scott E.; Garrett, Christopher R.; Shureiqi, Imad [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Delclos, Marc E.; Krishnan, Sunil; Crane, Christopher H. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-02-01

    Purpose: The goal of this phase 1 trial was to determine the maximum tolerated dose (MTD) of concurrent capecitabine, bevacizumab, and erlotinib with preoperative radiation therapy for rectal cancer. Methods and Materials: Patients with clinical stage II to III rectal adenocarcinoma, within 12 cm from the anal verge, were treated in 4 escalating dose levels, using the continual reassessment method. Patients received preoperative radiation therapy with concurrent bevacizumab (5 mg/kg intravenously every 2 weeks), erlotinib, and capecitabine. Capecitabine dose was increased from 650 mg/m{sup 2} to 825 mg/m{sup 2} orally twice daily on the days of radiation therapy; erlotinib dose was increased from 50 mg orally daily in weeks 1 to 3, to 50 mg daily in weeks 1 to 6, to 100 mg daily in weeks 1 to 6. Patients underwent surgery at least 9 weeks after the last dose of bevacizumab. Results: A total of 19 patients were enrolled, and 18 patients were considered evaluable. No patient had grade 4 acute toxicity, and 1 patient had grade 3 acute toxicity (hypertension). The MTD was not reached. All 18 evaluable patients underwent surgery, with low anterior resection in 7 (39%), proctectomy with coloanal anastomosis in 4 patients (22%), posterior pelvic exenteration in 1 (6%), and abdominoperineal resection in 6 (33%). Of the 18 patients, 8 (44%) had pathologic complete response, and 1 had complete response of the primary tumor with positive nodes. Three patients (17%) had grade 3 postop