Efficacy of intra-meibomian gland injection of the anti-VEGF agent bevacizumab for the treatment of meibomian gland dysfunction with lid-margin vascularity

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Jiang X

2018-05-01

Full Text Available Xiaodan Jiang,* Yuexin Wang,* Huibin Lv, Yan Liu, Mingzhou Zhang, Xuemin Li Department of Ophthalmology, Peking University Third Hospital, Beijing, China *These authors contributed equally to this work Purpose: To investigate the efficacy of a novel treatment – intra-meibomian gland (MG injection of the anti-VEGF agent bevacizumab – for MG dysfunction (MGD with eyelid-margin vascularity. Methods: A total of 26 eyes from 13 patients diagnosed with MGD and eyelid-margin vascularity were included in our study. Patients received intra-meibomian gland injections of bevacizumab (150 µL, 2.5 mg/0.1 mL at multiple sites with a 29 G needle where telangiectasia was severe. The Ocular Surface Disease Index (OSDI, tear film, tear-breakup time (TBUT, eyelid-margin features, MG features, conjunctiva, and corneal staining were assessed at 1 day before injection and 1 week, 1 month, and 3 months after injection. Blood pressure, best-corrected visual acuity, intraocular pressure, and slit lamp examinations were performed to assure the safety of patients at 1 day before and 1 day, 1 week, 1 month, and 3 months after injection. Results: Lid-margin vascularity, conjunctival injection, expressed secretion quality, expressivity of the MG, TBUT, corneal staining, and OSDI were significantly improved 1 week, 1 month, and 3 months after injection compared to baseline values. Lid-margin vascularity, conjunctival injection, meibomian gland expressivity, TBUT, and OSDI continued to improve; the greatest improvements were observed at 1 month and sustained for 3 months. Spearman’s correlation analysis indicated that age and sex significantly influenced TBUT improvement. Females and older patients tended to have shorter baseline TBUT that followed a different trend from that of males and younger patients during postinjection visits, revealed by subgroup analysis. No local or systemic side effects were observed at follow-up visits. Conclusion: This study is the first to

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

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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...... these membranes. After a single injection, bevacizumab did not exhibit a size reducing effect on CNV, but it was still present in the membranes 14 days after intravitreal injection....

A case of recipient bed melt and wound dehiscence after penetrating keratoplasty and subconjunctival injection of bevacizumab.

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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.

Wound Dehiscence and Device Migration after Subconjunctival Bevacizumab Injection with Ahmed Glaucoma Valve Implantation.

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Miraftabi, Arezoo; Nilforushan, Naveed

2016-01-01

To report a complication pertaining to subconjunctival bevacizumab injection as an adjunct to Ahmed Glaucoma Valve (AGV) implantation. A 54-year-old woman with history of complicated cataract surgery was referred for advanced intractable glaucoma. AGV implantation with adjunctive subconjunctival bevacizumab (1.25 mg) was performed with satisfactory results during the first postoperative week. However, 10 days after surgery, she developed wound dehiscence and tube exposure. The second case was a 33-year-old man with history of congenital glaucoma and uncontrolled IOP who developed AGV exposure and wound dehiscence after surgery. In both cases, for prevention of endophthalmitis and corneal damage by the unstable tube, the shunt was removed and the conjunctiva was re-sutured. The potential adverse effect of subconjunctival bevacizumab injection on wound healing should be considered in AGV surgery.

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

Effects of topical bevacizumab application on early bleb failure after trabeculectomy: observational case series

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Klos-Rola J

2013-09-01

Full Text Available Justyna Klos-Rola, Maria Tulidowicz-Bielak, Tomasz Zarnowski Department of Ophthalmology, Medical University of Lublin, Lublin, Poland Background: The aim of this study was to evaluate the influence of topical bevacizumab on the formation and function of filtering blebs in eyes with early bleb failure after antiglaucoma surgery. Methods: Of all patients who underwent mitomycin-augmented trabeculectomy for glaucoma in the Department of Ophthalmology at the Medical University in Lublin, Poland, between March 2009 and March 2010, a total of 21 eyes from 20 patients with injected filtration bleb 9.8 ± 4.7 days after surgery were included in this observational case series. All patients were treated with standard steroid therapy and topical bevacizumab 5 mg/mL five times a day for 20.9 ± 9.8 days. Patients were followed up every other day, and a full eye examination was performed 14, 30, 60, and 180 days after initiation of treatment. Blebs were evaluated for vascularity by slit-lamp examination with concomitant photographic documentation and intraocular pressure measurement. Results: Elevated functional bleb with significantly reduced vascularity was present in 16 eyes, and was flat and nonfunctional in five eyes. Intraocular pressure in all eyes decreased from a mean of 26.6 ± 9.6 mmHg before surgery to 14.6 ± 7.7 mmHg and 15.8 ± 8.3 mmHg at 2 and 6 months after surgery, respectively. Filtration bleb leak was noted in three eyes while on treatment with bevacizumab. Conclusion: Topical application of bevacizumab might favor functional bleb formation after trabeculectomy in eyes with a high risk of failure. Keywords: glaucoma, trabeculectomy, bleb failure, bevacizumab

A protocol for the retina surgeon’s safe initial intravitreal injections

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Ronald EP Frenkel

2010-11-01

Full Text Available Ronald EP Frenkel1,2, Shamim A Haji1,2, Melvin La1, Max PC Frenkel1, Angela Reyes11Eye Research Foundation, Stuart, FL, USA; 2East Florida Eye Institute, Stuart, FL, USAPurpose: To determine the safety of a surgeon’s initial consecutive intravitreal injections using a specific protocol and to review the complications that may be attributed to the injection procedure.Design: A retrospective chart review.Participants: Fifty-nine patients (30 females, 29 males received intravitreal injections of pegaptanib, bevacizumab, or ranibizumab as part of their treatment for neovascular age-related macular degeneration. The average patient age was 80 years. Twenty-two patients were diagnosed with or suspected of having glaucoma. Each patient received an average of 5.8 injections.Methods: The charts of 59 patients who received a total of 345 intravitreal injections (104 pegaptanib, 74 bevacizumab, 167 ranibizumab were reviewed. All injections were performed in an office-based setting. Povidone–iodine, topical antibiotics, and eye speculum were used as part of the pre injection procedure. Vision and intraocular pressure were evaluated immediately following each injection.Main outcome measures: Incidence of post injection complications, including but not limited to endophthalmitis, retinal detachment, traumatic cataract, and vitreous hemorrhage.Results: There were no cases of endophthalmitis, toxic reactions, traumatic cataracts, retinal detachment, or vitreous hemorrhage. There was one case each of lid swelling, transient floaters, retinal pigment epithelial tear, corneal edema, and corneal abrasion. There were five cases of transient no light perception following pegaptanib injections.Conclusion: The incidence of serious complications was very low for the intravitreal injections given. A surgeon’s initial intravitreal injections may be performed with a very high degree of safety using this protocol.Keywords: intravitreal injection, post injection

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

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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.

Clinical study on the incidence of vancomycin intraocular injection in treatment with suppurative endophthalmitis

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Yi-Qin Duan

2015-05-01

Full Text Available AIM:To estimate the clinical significance of the microculture of humor and vitreous and vancomycin intraocular injection in treatment of suppurative endophthalmitis associated with intraocular foreign bodies.METHODS: Totally 65 patients with penetrating eye trauma and retained intraocular foreign bodies in emergency operation and intraocular injection from January 2012 to September 2014 were regarded as the study group, another 62 patients with penetrating eye trauma and retained intraocular foreign bodies in emergency operation without intraocular injection before August 2011 were regarded as the control group. Aqueous humor and vitreous humor were taken from each patient of the study group and the control group for bacteria and fungus cultivation. The study group was treated with 1mg vancomycin intraocular injection after operation, while the control group was not. RESULTS: The incidence of endophthalmitis in the control group was 16%(10 cases, while in the study group was 3%(2 cases, with significant difference between two groups(x2=6.32, PP>0.05. The positive rate of vitreous humor germiculture in study group was 14%(9 cases, and the incidence of endophthalmitis was 3%. The positive rate of vitreous humor germiculture in control group was 11%(7 casesand the incidence of endophthalmitis was 16%, with significant differences between two groups(PCONCLUSION: Intraocular foreign bodies treated with emergency operation and vancomycin intraocular injections can decrease the incidence of suppurative endophthalmitis and have a good vision prognosis for the second stage of operation.

Intraocular Pressure Increases After Intraarticular Knee Injection With Triamcinolone but Not Hyaluronic Acid.

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Taliaferro, Kevin; Crawford, Alexander; Jabara, Justin; Lynch, Jonathan; Jung, Edward; Zvirbulis, Raimonds; Banka, Trevor

2018-03-09

Intraarticular steroid injections are a common first-line therapy for severe osteoarthritis, which affects an estimated 27 million people in the United States. Although topical, oral, intranasal, and inhalational steroids are known to increase intraocular pressure in some patients, the effect of intraarticular steroid injections on intraocular pressure has not been investigated, to the best of our knowledge. If elevated intraocular pressure is sustained for long periods of time or is of sufficient magnitude acutely, permanent loss of the visual field can occur. How does intraocular pressure change 1 week after an intraarticular knee injection either with triamcinolone acetonide or hyaluronic acid? A nonrandomized, nonblinded prospective cohort study was conducted at an outpatient, ambulatory orthopaedic clinic. This study compared intraocular pressure elevation before and 1 week after intraarticular knee injection of triamcinolone acetonide versus hyaluronic acid for management of primary osteoarthritis of the knee. Patients self-selected to be injected in their knee with either triamcinolone acetonide or hyaluronic acid before being informed of the study. The primary endpoint was intraocular pressure elevation of ≥ 7 mm Hg 1 week after injection. This cutoff is determined as the minimum significant pressure change in the ophthalmology literature recognized as an intermediate responder to steroids. Intraocular pressure was measured using a handheld Tono-Pen® applanation device. This device is frequently used in intraocular pressure measurement in clinical and research settings; 10 sequential measurements are obtained and averaged with a confidence interval. Only measurements with a 95% confidence interval were used. Over a 6-month period, a total of 96 patients were approached to enroll in the study. Sixty-two patients out of 96 approached (65%) agreed. Thirty-one (50%) were injected with triamcinolone and 31 (50%) were injected with hyaluronic acid. Patients

Wound dehiscence and device migration after subconjunctival bevacizumab injection with Ahmed glaucoma valve implantation

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Arezoo Miraftabi; Naveed Nilforushan

2016-01-01

Purpose: To report a complication pertaining to subconjunctival bevacizumab injection as an adjunct to Ahmed Glaucoma Valve (AGV) implantation. Case Report: A 54-year-old woman with history of complicated cataract surgery was referred for advanced intractable glaucoma. AGV implantation with adjunctive subconjunctival bevacizumab (1.25 mg) was performed with satisfactory results during the first postoperative week. However, 10 days after surgery, she developed wound dehiscence and tube exposur...

Serious adverse events and visual outcomes of rescue therapy using adjunct bevacizumab to laser and surgery for retinopathy of prematurity. The Indian Twin Cities Retinopathy of Prematurity Screening database Report number 5.

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Jalali, Subhadra; Balakrishnan, Divya; Zeynalova, Zarifa; Padhi, Tapas Ranjan; Rani, Padmaja Kumari

2013-07-01

To report serious adverse events and long-term outcomes of initial experience with intraocular bevacizumab in retinopathy of prematurity (ROP). Consecutive vascularly active ROP cases treated with bevacizumab, in addition to laser and surgery, were analysed retrospectively from a prospective computerised ROP database. Primary efficacy outcome was regression of new vessels. Secondary outcomes included the anatomic and visual status. Serious systemic and ocular adverse events were documented. 24 ROP eyes in 13 babies, received single intraocular bevacizumab for severe stage 3 plus after failed laser (seven eyes), stage 4A plus (eight eyes), and stage 4B/5 plus (nine eyes). Drug was injected intravitreally in 23 eyes and intracamerally in one eye. New vessels regressed in all eyes. Vision salvage in 14 of 24 eyes and no serious neurodevelopmental abnormalities were noted up to 60 months (mean 30.7 months) follow-up. Complications included macular hole and retinal breaks causing rhegmatogenous retinal detachment (one eye); bilateral, progressive vascular attenuation, perivascular exudation and optic atrophy in one baby, and progression of detachment bilaterally to stage 5 in one baby with missed follow-up. One baby who received intracameral injection developed hepatic dysfunction. One eye of this baby also showed a large choroidal rupture. Though intraocular bevacizumab, along with laser and surgery salvaged vision in many otherwise progressive cases of ROP, vigilance and reporting of serious adverse events is essential for future rationalised use of the drug. We report one systemic and four ocular adverse events that require consideration in future use of the drug.

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

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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

Intracameral bevacizumab as an adjunct to trabeculectomy: a 1-year prospective, randomised study.

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Vandewalle, Evelien; Abegão Pinto, Luís; Van Bergen, Tine; Spielberg, Leigh; Fieuws, Steffen; Moons, Lieve; Spileers, Werner; Zeyen, Thierry; Stalmans, Ingeborg

2014-01-01

To investigate the efficacy and safety of a single intracameral bevacizumab injection to improve the outcome of trabeculectomy. A 12-month, prospective, randomised, double-masked, placebo-controlled trial. Patients with medically uncontrolled open-angle glaucoma scheduled for a primary trabeculectomy were recruited and randomised to receive 50 µL of either bevacizumab (1.25 mg) or placebo (balanced salt solution) peroperatively. Absolute success was defined as intraocular pressure (IOP) ≤18 mm Hg and >5 mm Hg with at least 30% reduction from baseline and no loss of light perception. Success through the use of additional medical and/or surgical IOP-lowering treatments was defined as qualified success. 138 patients completed a 12-month follow-up, 69 of whom were in the bevacizumab treated group. IOP at 1 year postoperatively was significantly lower than baseline (placebo: 25.6±9.9 mm Hg vs 11.5±3.9 mm Hg, p<0.01; bevacizumab: 24.8±8.1 mm Hg vs 11.9±3.8 mm Hg, p<0.01), with no difference between treatment groups (p=0.69). However, absolute success was higher in the bevacizumab group (71% vs 51%, p=0.02), with the need for IOP-lowering interventions (needlings) being lower in this group (12% vs 33%, p=0.003). Complication rates were low and comparable between groups. Peroperative administration of intracameral bevacizumab significantly reduces the need for additional interventions during the follow-up of patients undergoing trabeculectomy.

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

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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.

Single intravitreal bevacizumab injection effects on contrast sensitivity in macular edema from branch retinal vein occlusion

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Rony Carlos Preti

2012-02-01

Full Text Available PURPOSE: To evaluate the effect of a single intravitreal bevacizumab injection on visual acuity, contrast sensitivity and optical coherence tomography-measured central macular thickness in eyes with macular edema from branch retinal vein occlusion. METHODS: Seventeen eyes of 17 patients with macular edema from unilateral branch retinal vein occlusion were treated with a single bevacizumab injection. Patients were submitted to a complete evaluation including best corrected visual acuity, contrast sensitivity and optical coherence tomography measurements before treatment and one and three months after injection. Visual acuity, contrast sensitivity and optical coherence tomography measurements were compared to baseline values. RESULTS: Mean visual acuity measurement improved from 0.77 logMAR at baseline to 0.613 logMAR one month after injection (P=0.0001 but worsened to 0.75 logMAR after three months. Contrast sensitivity test demonstrated significant improvement at spatial frequencies of 3, 6, 12 and 18 cycles/degree one month after injection and at the spatial frequency of 12 cycles/degree three months after treatment. Mean ± standard deviation baseline central macular thickness (552 ± 150 µm reduced significantly one month (322 ± 127 µm, P=0.0001 and three months (439 ± 179 µm, P=0.01 after treatment. CONCLUSIONS: Bevacizumab injection improves visual acuity and contrast sensitivity and reduces central macular thickness one month after treatment. Visual acuity returns to baseline levels at the 3-month follow-up, but some beneficial effect of the treatment is still present at that time, as evidenced by optical coherence tomography-measured central macular thickness and contrast sensitivity measurements.

Clinical, legal and ethical implications of the intra-ocular (off-label) use of bevacizumab (avastin)--a South African perspective.

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Jansen, Rita-Marié; Gouws, Chris

2009-06-01

Choroidal neovascularisation is a potentially visually devastating element of various forms of eye pathology. Recent research has focused on neurovascular age-related macular degeneration (AMD) as a cause. AMD can be classified as being exudative (wet) or atrophic (dry). Wet AMD is characterised by a pathological process in which new blood vessels develop in the choroids, causing leakage of fluid and haemorrhage under the retina and leading to localised serous detachment and loss of central vision. Vascular endothelial growth factor (VEGF) stimulates growth of neovascular membranes. Treatments have until recently yielded disappointing results. Ophthalmologists are using intra-ocular injections of bevacizumab (Avastin), an anti-VEGF, to treat AMD. Avastin appears to be safe and effective in the short term, but its intra-ocular administration is entirely off-label. Avastin is registered for treating metastatic colorectal and breast cancer. The off-label use of medication is an important part of mainstream, legitimate medical practice worldwide. Lawyers representing plaintiffs injured by drugs increasingly encounter off-label use claims. From a legal/ethical point of view the off-label use of medication represents a delicate balance between the statutory regulation of medication and a physician's prerogative to prescribe medication that in his or her medical opinion will be beneficial to the patient. The main reason for the controversy created by the off-label use of Avastin is that there are anti-VEGF drugs on the market that have formal approval for the treatment of AMD (and other eye conditions). Lucentis, for example, is extremely expensive, with treatment cost approximately 50 times that of Avastin. Many patients suffering from AMD and macular oedema cannot afford the registered product. The off-label use of Avastin has passed the innovative or experimental stages, as ophthalmologists have used it regularly and openly for a long time, with good success. Such use

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

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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.

An intravenous microdose of bevacizumab for the treatment of pigment epithelial detachment associated to age-related macular degeneration refractory to intravitreal bevacizumab: a case report.

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Wu, Lihteh; Evans, Teodoro

2011-01-01

The purpose of this study was to report the visual and anatomical outcomes of an intravenous microdose of 10 mg of bevacizumab in a patient with a vascularized pigment epithelial detachment (PED) associated with exudative age-related macular degeneration refractory to several intravitreal bevacizumab injections. Interventional case report and literature review. A 62-year-old female patient with a PED secondary to age-related macular degeneration was treated with 9 consecutive intravitreal injections of 2.5 mg of bevacizumab. Despite an initial response where the PED decreased in size, the subretinal fluid reabsorbed and the visual acuity improved; after the seventh injection, the PED started to grow in size again causing a drop in visual acuity. After an intravenous injection of 10 mg of bevacizumab, the patient experienced an improvement in visual acuity and a flattening of her PED. An intravenous injection of a microdose of bevacizumab appears to have resolved the PED with a sustained improvement of visual acuity.

Fibrous membranes in diabetic retinopathy and bevacizumab.

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Pattwell, David M; Stappler, Theodor; Sheridan, Carl; Heimann, Heinrich; Gibran, Syed K; Wong, David; Hiscott, Paul

2010-01-01

The purpose of this study was to determine the histopathologic characteristics of bevacizumab-treated human proliferative diabetic retinopathy (PDR) membranes with particular regard to membrane vasculature as a step toward addressing the effects of the drug on PDR membranes. Intravitreous injection of bevacizumab, an antivascular endothelial growth factor monoclonal antibody, has recently been advocated as an adjunct in surgery for PDR. In this context, a clinically observed decrease in PDR epiretinal membrane vascularity (vascular regression) occurs from 24 hours to 48 hours after injection, but the exact mechanisms of drug action are unknown. A consecutive series of seven PDR membrane specimens that had been removed sequentially from seven bevacizumab-treated patients were studied retrospectively. The membrane specimens were examined using light microscopic methods, including immunohistochemistry. Five of the seven membranes were clinically avascular (one contained "ghost" vessels) and did not hemorrhage during excision. Of these 5 specimens, which included 1 removed 7 days after a total of 6 intravitreous injections of 1.25 mg bevacizumab, 4 contained histologically detectable capillaries (1 did not). These blood vessels were lined by endothelial cells as determined by immunohistochemistry for the endothelial markers CD31 and CD34. The two remaining membranes were clinically and histologically still vascularized despite bevacizumab treatment. All the specimens also contained smooth muscle actin-containing fibroblastic cells within the collagenous stroma. The findings do not support the concept that the clinical phenomenon of vascular regression in PDR membranes after bevacizumab injection in the vitreous is resulting from obliteration of the membrane blood vessels. Another mechanism appears to be involved in at least some patients, possibly a vasoconstrictive response. Such a mechanism might explain reversal of the effects of bevacizumab that has been reported

Intravitreal bevacizumab in pigmented rabbit eyes: histological analysis 90 days after injection Bevacizumabe intravítreo em olhos de coelhos não albinos: análise histológica 90 dias após a injeção

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João Carlos Diniz Arraes

2009-10-01

Full Text Available PURPOSE: To evaluate bevacizumab toxicity in neurosensorial retina and retinal pigment epithelium in pigmented rabbit eyes by means of histological studies. METHODS: Thirty eyes of fifteen rabbits were distributed into three groups: sham group (S, that received a 0.1 ml balanced saline solution (BSS intravitreal injection (10 eyes; group 1, that received a 1.25 mg (0.1 ml bevacizumab intravitreal injection (10 eyes; and group 2, that received a 2.5 mg (0.1 ml bevacizumab intravitreal injection (10 eyes. Rabbits were sacrificed 90 days after the procedure and both eyes of each rabbit were enucleated. A histological examination of neurosensorial retina and retinal pigmented epithelium (RPE was performed. Its morphological features and layer thickness were also analyzed. RESULTS: No histological differences in neurosensorial retina or in retinal pigmented epithelium were found and layer thickness did not differ significantly between balanced saline solution-injected eyes and bevacizumab-injected eyes. CONCLUSION: After a 90-day follow-up period, a single 1.25 or 2.5 mg bevacizumab intravitreal injection did not lead to toxic damage in the neurosensorial retina and retinal pigment epithelium of pigmented rabbit eyes, and it appears to be a safe procedure for retinal neovascular diseases.OBJETIVOS: Avaliar a toxicidade do bevacizumabe na retina neurossensorial e epitélio pigmentado da retina (EPR em olhos de coelhos não albinos pelos estudos histológicos. MÉTODOS: Trinta olhos de 15 coelhos foram distribuídos em três grupos: 10 olhos no grupo placebo (P, que recebeu uma injeção intravítrea de 0,1 ml de solução salina balanceada (SSB; 10 olhos no grupo 1, que recebeu uma injeção intravítrea de 1,25 mg (0,1 ml de bevacizumabe; e 10 olhos no grupo 2, que recebeu uma injeção intravítrea de 2,5 mg (0,1 ml de bevacizumabe. Os coelhos tiveram seus dois olhos enucleados sob anestesia geral e submetidos à eutanásia 90 dias após a inje

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, 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.

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

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 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. PMID:27330272

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

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

Comparison of the effects of intravitreal bevacizumab and dexamethasone in experimental posterior penetrating eye injury

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Ayse Oner

2018-04-01

Full Text Available AIM: To compare the effects of intravitreal anti-vascular endothelial growth factor (VEGF and dexamethasone in an experimental rabbit model of posterior penetrating ocular injury. METHODS: Thirty white New Zealand rabbits were included in the study. A posterior penetrating ocular injury was performed at the superotemporal quadrant. They were randomly divided into three groups. The rabbits in group 1 received intravitreal dexamethasone, in group 2 they received intravitreal bevacizumab and those in group 3 received intravitreal physiological saline solution in both eyes. All eyes were examined ophthalmologically on the 1st, 3rd, 7th, 14th and 28th days following the injury and the clinical findings were scored. On the day 28, the eyes were enucleated, evaluated and scored macroscopically, histopathologically and scanning electron microscopically. RESULTS: The median clinical score on the 14th and 28th days and the median macroscopic score of the dexamethasone group was significantly better than that of control (P=0.004, 0.018. Dexamethasone group was also better than that of bevacizumab group but the differences did not reach statistical significance. Retinal detachment rate was 8.3%, 16.6% and 12.5% in the dexamethasone group, bevacizumab group and control group, respectively (P=0.476. More extensive fibrocelluler proliferations were observed in controls compared with dexamethasone and bevacizumab groups. But these differences did not reach the statistical significance (P=0.538. In scanning electron microscopy all groups showed fibreous stalk and dense collagen fibrils in vitreous. CONCLUSION: This study shows that intravitreal injection of both dexamethasone and bevacizumab may reduce the intraocular fibrous proliferation after an experimental posterior penetrating ocular injury in rabbits.

Effect of Intravitreal Injection of Bevacizumab on Acute Central Serous Chorioretinopathy Patients Who Visited Feiz Hospital during 2014–2015 Period

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Akhlaghi, Mohamad Reza; Nasrollahi, Cobra; Namgar, Seyed Mohamad; Kianersi, Farzan; Dehghani, Ali Reza; Arefpour, Reza

2017-01-01

Background: Aim of this clinical trial is the evaluation of the effect of intravitreal injection of bevacizumab on acute central serous chorioretinopathy (CSC). Materials and Methods: In a nonrandomized clinical trial, 36 CSC eyes (with the patients underwent posterior and anterior segment examinations as well as complete eye examination to evaluate the best spectacle-corrected visual acuity (BSCVA). Then, optical coherence tomography was performed to confirm the diagnosis. The patients were divided to the two groups each of 18 subjects, which 18 patients received intravitreal injection of bevacizumab (1.25 mg) and the rest of them did not receive any treatment (control group). The patients were health checked by the end of the 1st and 3rd months. Significance level was considered as P the BSCVA, no significant difference in visual improvement was observed in baseline vision compared to each other (P = 0.481). There was also no significant difference in the vision of intervention and control groups 1 and 3 months after injection (P = 0.379 and P = 0.557). A significant decrement existed in the intervention group compared with the control group in the maximum central macular thickness at 1 month after injection (P = 0.001); however, the difference was not significant when comparing the two groups at baseline and 3 months after injection (P = 0.925 and P = 0.338). Conclusion: In general, according to the results of this study, intravitreal injection of bevacizumab was not effective in improvement of patients with acute CSC, although it had no side effects. PMID:29142888

A protocol for the retina surgeon's safe initial intravitreal injections.

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Frenkel, Ronald E P; Haji, Shamim A; La, Melvin; Frenkel, Max P C; Reyes, Angela

2010-11-10

To determine the safety of a surgeon's initial consecutive intravitreal injections using a specific protocol and to review the complications that may be attributed to the injection procedure. A retrospective chart review. Fifty-nine patients (30 females, 29 males) received intravitreal injections of pegaptanib, bevacizumab, or ranibizumab as part of their treatment for neovascular age-related macular degeneration. The average patient age was 80 years. Twenty-two patients were diagnosed with or suspected of having glaucoma. Each patient received an average of 5.8 injections. The charts of 59 patients who received a total of 345 intravitreal injections (104 pegaptanib, 74 bevacizumab, 167 ranibizumab) were reviewed. All injections were performed in an office-based setting. Povidone-iodine, topical antibiotics, and eye speculum were used as part of the pre injection procedure. Vision and intraocular pressure were evaluated immediately following each injection. Incidence of post injection complications, including but not limited to endophthalmitis, retinal detachment, traumatic cataract, and vitreous hemorrhage. There were no cases of endophthalmitis, toxic reactions, traumatic cataracts, retinal detachment, or vitreous hemorrhage. There was one case each of lid swelling, transient floaters, retinal pigment epithelial tear, corneal edema, and corneal abrasion. There were five cases of transient no light perception following pegaptanib injections. The incidence of serious complications was very low for the intravitreal injections given. A surgeon's initial intravitreal injections may be performed with a very high degree of safety using this protocol.

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

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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.

Effect of Intravitreal Injection of Bevacizumab on Acute Central Serous Chorioretinopathy Patients who Visited Feiz Hospital during 2014–2015 Period

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Mohamad Reza Akhlaghi

2017-01-01

Full Text Available Background: Aim of this clinical trial is the evaluation of the effect of intravitreal injection of bevacizumab on acute central serous chorioretinopathy (CSC. Materials and Methods: In a nonrandomized clinical trial, 36 CSC eyes (with <1-month disease history were examined. Initially, all the patients underwent posterior and anterior segment examinations as well as complete eye examination to evaluate the best spectacle-corrected visual acuity (BSCVA. Then, optical coherence tomography was performed to confirm the diagnosis. The patients were divided to the two groups each of 18 subjects, which 18 patients received intravitreal injection of bevacizumab (1.25 mg and the rest of them did not receive any treatment (control group. The patients were health checked by the end of the 1st and 3rd months. Significance level was considered as P < 0.05. Results: In the BSCVA, no significant difference in visual improvement was observed in baseline vision compared to each other (P = 0.481. There was also no significant difference in the vision of intervention and control groups 1 and 3 months after injection (P = 0.379 and P = 0.557. A significant decrement existed in the intervention group compared with the control group in the maximum central macular thickness at 1 month after injection (P = 0.001; however, the difference was not significant when comparing the two groups at baseline and 3 months after injection (P = 0.925 and P = 0.338. Conclusion: In general, according to the results of this study, intravitreal injection of bevacizumab was not effective in improvement of patients with acute CSC, although it had no side effects.

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.

The effect of intravitreal bevacizumab injection before Ahmed valve implantation in patients with neovascular glaucoma.

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Kang, Jung Youb; Nam, Ki Yup; Lee, Sang Joon; Lee, Seung Uk

2014-08-01

To evaluate the effect of intravitreal bevacizumab (IVB) before Ahmed valve implantation for treatment of neovascular glaucoma (NVG). This study is a retrospective, comparative, consecutive case series. The study group consisted of 27 eyes of 26 patients with NVG who underwent an Ahmed valve implantation. Thirteen eyes were treated with Ahmed valve implantation alone (control group), and 14 eyes were treated with a combination of preoperative IVB injection and Ahmed valve implantation (IVB group). Visual acuity, intraocular pressure (IOP), number of anti-glaucoma medications, surgical complications, and success rate were compared between the two groups. There were no significant differences in preoperative characteristics between the two groups. Visual acuity at 1, 2 weeks, and 1 month after surgery were significantly better in the IVB group (p = 0.038, 0.034, and 0.032, respectively). Hyphema associated with Ahmed valve implantation occurred significantly less in the IVB group (p = 0.016). On the other hand, the mean IOP and number of anti-glaucoma medications at all follow-up periods were similar between the two groups. Kaplan-Meier survival analysis showed the probability of success 6 months after surgery as 71.4 % in the IVB group and 84.6 % in the control group. No significant difference in success rate was found between the groups (p = 0.422). IVB before Ahmed valve implantation for treatment of NVG reduced the incidence of hyphema. In this retrospective study, IVB provided better visual outcome in the early postoperative periods but did not significantly improve mean IOP, number of anti-glaucoma medications, or success rate.

Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes

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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...

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

Comparison of grid laser, intravitreal triamcinolone, and intravitreal bevacizumab in the treatment of diffuse diabetic macular edema.

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Sobaci, Güngör; Ozge, Gökhan; Erdurman, Cüneyt; Durukan, Hakan A; Bayraktar, Zeki M

2012-01-01

To compare the effects of grid laser (GL), intravitreal bevacizumab (IVB), and intravitreal triamcinolone acetonide (IVTA) in diffuse diabetic macular edema (DDME). One hundred and twenty-six patients (126 eyes) treated with GL (modified grid), IVTA (4 mg), and IVB (1.25 mg) injections, matched for best corrected visual acuity (BCVA) and OCT-based central macular thickness at presentation, were enrolled. Primary outcome measure was change in best corrected logMAR visual acuity at 1-year follow-up. Rates of visual stabilization (within ±0.2 logMAR of baseline BCVA) (71.4, 83.3, 78.6%, respectively) were not different between the groups (p = 0.41) at 12-month follow-up. Higher rates of anatomical and functional success, however, were evident in IVB and IVTA groups within 6 months of treatment (p < 0.05 for both). No severe adverse effects except higher intraocular pressure (10 mm Hg from baseline) in one third (14 eyes) of the IVTA cases, who required trabeculectomy in 2 (4.8%) eyes, were observed. Intraocular injections may give favorable results within the first 6 months, and after 6 months, GL results seem to be more favorable in the treatment of treatment-naïve, acute, nonischemic, and center-involving DDME. Copyright © 2011 S. Karger AG, Basel.

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

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Finger, Paul T.; Chin, Kimberly J.

2012-01-01

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.

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

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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.

Corneal injection track:an unusual complication of intraocular lens implantation and review

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Julie Y.C. Lok

2015-06-01

Full Text Available Phacoemulsification is the main gold standard for cataract operation in the developed world together with foldable intraocular lens (IOL implantation by injection, allowing for stable wound construction and less postoperative astigmatism. It is a safe procedure with high success rate with the advancement in machines, improvement of IOL injection systems and further maturation of surgeons’ techniques. Despite the large number of operations performed every day, foldable IOL injection leading to an intra-stromal corneal track is a very rare complication. We report a case of this unusual finding in a 70-year-old gentleman who has undergone cataract operation in November 2011 in our hospital and will review on the complications related to foldable IOL injection.

Comparison of glare in YAG-damaged intraocular lenses: injection-molded versus lathe-cut.

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Bath, P E; Dang, Y; Martin, W H

1986-11-01

A comparative analysis of YAG laser intraocular lens (IOL) damage was undertaken on injection-molded and lathe-cut IOLs. Damage sites were evaluated with polarized light. A consistent positive polarization was observed in the damage sites of lathe-cut IOLs. A consistent negative polarization was observed in the damage sites of injection-molded IOLs. The presence of positive polarization in IOL damage sites may be correlated with increased potential for glare. Results and clinical implications are discussed.

Subconjunctival bevacizumab to augment trabeculectomy with mitomycin C in the management of failed glaucoma surgery

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Saeed AM

2014-09-01

Full Text Available Ahmed M Saeed, Tarek Tawfeek AboulNasrOphthalmology Department, Benha University, Egypt Purpose: To provide a feasible solution to the problem of failed glaucoma surgery. The aim was to evaluate the efficacy and safety of the additional effects of a combined surgical approach. This approach augments the application of trabeculectomy with mitomycin C (MMC by adding subconjunctival bevacizumab injection. The results were compared with those of trabeculectomy with only adjunctive MMC. Methods: A randomized controlled prospective clinical trial included 28 eyes diagnosed with failed scarred bleb of a previous trabeculectomy. The eyes were divided into two equal groups: combined group A, “trabeculectomy with adjunctive MMC and subconjunctival bevacizumab,” and control group B, “trabeculectomy with adjunctive MMC only.” The main outcome results included the cumulative probability of surgical success, intraocular pressure (IOP values, and number of IOP-lowering medications needed to achieve the target IOP.Results: Group A achieved a cumulative probability of complete success of 0.769 and of qualified success of 0.231 at the end of the 24 month study period; group B achieved cumulative probabilities of 0.538 and 0.308, respectively. Group A achieved a lower mean IOP value than group B, with fewer antiglaucoma drugs at all postoperative visits, but this lower value did not reach a statistically significant level (P>0.05. There was no statistically significant difference between both groups regarding best corrected visual acuity, visual field parameters, operative and/or postoperative complications, and additional interventions. No significant adverse effects were caused by this combined approach.Conclusion: Bevacizumab was not found to add much to the favorable long-term outcome of conventional trabeculectomy with MMC as a solution to the problem of scarred failed bleb. Keywords: glaucoma, bevacizumab, mitomycin C, failed trabeculectomy

Neo-Vascular Glaucoma: Etiology and Outcome of Treatment in Lagos

African Journals Online (AJOL)

tulyasys

therapy of ocular medications, intraocular bevacizumab injections and retinal laser photocoagulation treatments showed an average IOP reduction of 19 mmHg [Table 5]. However, the remaining 11 patients who came for follow-up but did not receive either intravitreal bevacizumab or PRP showed different paern of IOP.

Effect of pegaptanib sodium 0.3 mg intravitreal injections (Macugen) in intraocular pressure

DEFF Research Database (Denmark)

Boyer, David S; Goldbaum, Mauro; Leys, Anita M

2014-01-01

OBJECTIVE: To assess the rate of pegaptanib-associated sustained intraocular pressure (IOP) elevation. METHODS: A posthoc analysis was conducted on all IOP measurements, except the immediate 30-min postinjection, from all subjects randomised to pegaptanib 0.3 mg or sham injections continuously in...

Image-guided intraocular injection using multimodality optical coherence tomography and fluorescence confocal scanning laser ophthalmoscopy in rodent ophthalmological models

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Terrones, Benjamin D.; Benavides, Oscar R.; Leeburg, Kelsey C.; Mehanathan, Sankarathi B.; Levine, Edward M.; Tao, Yuankai K.

2018-02-01

Intraocular injections are routinely performed for delivery of anti-VEGF and anti-inflammatory therapies in humans. While these injections are also performed in mice to develop novel models of ophthalmic diseases and screen novel therapeutics, the injection location and volume are not well-controlled and reproducible. We overcome limitations of conventional injections methods by developing a multimodality, long working distance, non-contact optical coherence tomography (OCT) and fluorescence confocal scanning laser ophthalmoscopy (cSLO) system for retinal imaging before and after injections. Our OCT+cSLO system combines a custom-built spectraldomain OCT engine (875+/-85 nm) with 125 kHz line-rate with a modified commercial cSLO with a maximum frame-rate of 30 fps (512 x 512 pix.). The system was designed for an overlapping OCT+cSLO field-of-view of 1.1 mm with a 7.76 mm working distance to the pupil. cSLO excitation light sources and filters were optimized for simultaneous GFP and tdTomato imaging. Lateral resolution was 3.02 µm for OCT and 2.74 μm for cSLO. Intravitreal injections of 5%, 10%, and 20% intralipid with Alex Fluor 488 were manually injected intraocularly in C57BL/6 mice. Post-injection imaging showed structural changes associated with retinal puncture, including the injection track, a retinal elevation, and detachment of the posterior hyaloid. OCT enables quantitative analysis of injection location and volumes whereas complementary cSLO improves specificity for identifying fluorescently labeled injected compounds and transgenic cells. The long working distance of our non-contact OCT+cSLO system is uniquely-suited for concurrent imaging with intraocular injections and may be applied for imaging of ophthalmic surgical dynamics and real-time image-guided injections.

Intravitreal bevacizumab as therapy for refractory neovascular glaucoma secondary to iris metastasis of breast carcinoma

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Stephanie Vale

2018-03-01

Conclusions & importance: A single intravitreal bevacizumab injection may be sufficient to achieve palliative control of neovascular glaucoma secondary to iris breast cancer metastasis. To our knowledge, this is the first case report in which a single intravitreal bevacizumab injection was used for the effective management of this condition.

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.

Intravitreal bevacizumab injections versus dexamethasone implant for treatment-naïve retinal vein occlusion related macular edema

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Laine I

2017-11-01

Full Text Available Ilkka Laine,1–3 Juha-Matti Lindholm,1,2 Petteri Ylinen,1,4 Raimo Tuuminen1,2,5 1Helsinki Retina Research Group, University of Helsinki, Helsinki, 2Unit of Ophthalmology, Kymenlaakso Central Hospital, Kotka, Finland; 3Department of Automation and Electrical Engineering, Aalto University, Helsinki, Finland; 4Department of Ophthalmology, Helsinki University Hospital, Helsinki, Finland; 5The Insurance Centre, Patient Insurance Centre, Helsinki, Finland Purpose: To compare the short-term effects of three monthly intravitreal bevacizumab (IVB injections to single dexamethasone (DEX implantation in treatment-naïve patients with cystoid macular edema (CME secondary to branch (BRVO and central retinal vein occlusion (CRVO.Design: A retrospective single-center study.Subjects: A total of 135 eyes of 135 patients with BRVO (n=83 and CRVO (n=52.Methods: Changes in clinical parameters were recorded before treatment and at the first and third month after commencement of IVB (n=121 and DEX (n=14.Main outcome measures: Central retinal thickness (CRT, intraocular pressure (IOP, and best-corrected visual acuity (BCVA.Results: The baseline parameters were comparable between IVB and DEX groups. After the first month, CRT decreased by 131.3±42.9 µm in IVB and by 266.9±48.3 µm in DEX (mean ± SEM; p=0.047. IOP change was –0.29±0.39 mmHg in IVB and +3.70±2.34 mmHg in DEX (p=0.005. IOP elevation to ≥25 mmHg and ≥5 mmHg from the baseline was observed in two of the DEX- and in none of the IVB-treated eyes (p=0.010. After the third month, no differences regarding CRT and IOP were observed between the treatment modalities. Moreover, BCVA gain was comparable between IVB (0.37±0.05 logarithm of minimum angle of resolution [logMAR] units and DEX (0.33±0.30 logMAR units groups.Conclusion: DEX was associated with faster resolution of CME, but had greater probability for short-term IOP elevation when compared to IVB. After the third month, treatments were

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.

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

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

Fellow Eye Macular Edema Improvement after Intravitreal Bevacizumab for Radiation Retinopathy

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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.

Comparison of Neuroprotective Effect of Bevacizumab and Sildenafil following Induction of Stroke in a Mouse Model

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Ivan Novitzky

2016-01-01

Full Text Available To evaluate the effect of bevacizumab and sildenafil on stroke parameters in a mouse model, middle cerebral artery occlusion was induced in male C57Bl/6 mice using an intra-arterial filament method. The filament was removed after 60 minutes, and the mice were immediately given a single intraperitoneal injection of saline, bevacizumab, or sildenafil. An additional group of mice (n=7 received bevacizumab 6 h after MCAO induction. The mice were euthanized 24 hours later and evaluated for infarct area and brain edema using triphenyltetrazolium chloride staining and ImageJ. In the saline-treated mice (n=16, total stroke volume was 19.20±6.38 mm3, mean penumbra area was 4.5±2.03 mm3, and hemispheric asymmetry was 106.5%. Corresponding values in the bevacizumab group (n=19 were 17.79±5.80 mm3, 7.3±3.5 mm3, and 108.6%; in the delayed (6 h bevacizumab injected mice (n=7 they were 9.80±8.00 mm3, 2.4±2.0 mm3, and 98.2%; and in the sildenafil group (n=16 they were 18.42±5.41 mm3, 5.7±2.02 mm3, and 109.9%. The bevacizumab group had a significantly larger mean penumbra area when given immediately and smaller total stroke area in both groups than the saline- (p=0.03 and sildenafil-treated (p=0.003 groups. Only delayed bevacizumab group had reduced edema. Bevacizumab, injected immediately or delayed after injury, exerts a neuroprotective/salvage effect, whereas immediate treatment with sildenafil does not. Inflammation may play a role in the neuroprotective effect.

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

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J. Fernando Arevalo

2011-01-01

Full Text Available 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.

Comparison of Intravitreal Bevacizumab and Intravitreal Diclofenac in the Treatment of Diabetic Macular Edema: a 6-month Follow-up.

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Faghihi, Hooshang; Yahyapour, Hanif; Mahmoudzadeh, Raziyeh; Faghihi, Shahin

2017-01-01

The aim of this study was to compare the effect of intravitreal diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with that of bevacizumab, a well-known anti-vascular endothelial growth factor (VEGF) drug, in the treatment of diabetic macular edema (DME). Diclofenac was chosen in this study because it has both features of NSAIDs and corticosteroids by inhibiting the cyclooxygenase (COX) and lipoxygenase pathways, respectively. In this non-randomized comparative interventional case series, 64 eyes from 32 patients with bilateral naïve DME were selected and every eye was randomly assigned to intravitreal injection of bevacizumab (IVB) or diclofenac (IVD). After exclusion of some patients because of short follow-up duration or less than two intravitreal injections, finally, 52 eyes from 26 patients were analyzed. Of those, 26 eyes received 500 µg/0.1 mL IVD and 26 eyes received 1.25 mg IVB. After 6 months of follow-up, the results indicated that visual acuity was significantly improved from 0.50 ± 0.13 in IVB and 0.52 ± 0.12 LogMAR in IVD at baseline to 0.2 ± 0.1 and 0.29 ± 0.07, respectively. Central macular thickness (CMT) and macular volume were measured based on spectral-domain optical coherence tomography (OCT) at month 1, 3, and 6. Both groups showed a significant reduction in CMT and macular volume from baseline but there was no significant difference between the IVB and IVD groups. Interestingly, IVD, but not IVB, decreased intraocular pressure (IOP), which is a desirable effect. There was no serious complication due to injections. This study sheds light into the long-term effects of NSAIDs and may support the idea that inflammation suppression by NSAIDs may have the same results as anti-VEGF administration.

Targeting Src family kinases inhibits bevacizumab-induced glioma cell invasion.

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Deborah Huveldt

Full Text Available Anti-VEGF antibody therapy with bevacizumab provides significant clinical benefit in patients with recurrent glioblastoma multiforme (GBM. Unfortunately, progression on bevacizumab therapy is often associated with a diffuse disease recurrence pattern, which limits subsequent therapeutic options. Therefore, there is an urgent need to understand bevacizumab's influence on glioma biology and block it's actions towards cell invasion. To explore the mechanism(s of GBM cell invasion we have examined a panel of serially transplanted human GBM lines grown either in short-term culture, as xenografts in mouse flank, or injected orthotopically in mouse brain. Using an orthotopic xenograft model that exhibits increased invasiveness upon bevacizumab treatment, we also tested the effect of dasatinib, a broad spectrum SFK inhibitor, on bevacizumab-induced invasion.We show that 1 activation of Src family kinases (SFKs is common in GBM, 2 the relative invasiveness of 17 serially transplanted GBM xenografts correlates strongly with p120 catenin phosphorylation at Y228, a Src kinase site, and 3 SFK activation assessed immunohistochemically in orthotopic xenografts, as well as the phosphorylation of downstream substrates occurs specifically at the invasive tumor edge. Further, we show that SFK signaling is markedly elevated at the invasive tumor front upon bevacizumab administration, and that dasatinib treatment effectively blocked the increased invasion induced by bevacizumab.Our data are consistent with the hypothesis that the increased invasiveness associated with anti-VEGF therapy is due to increased SFK signaling, and support testing the combination of dasatinib with bevacizumab in the clinic.

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

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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.

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.

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

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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.

Effect of pegaptanib sodium 0.3 mg intravitreal injections (Macugen) in intraocular pressure: posthoc analysis from VISION study

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Boyer, David S.; Goldbaum, Mauro; Leys, Anita M.; Starita, Carla; Blumenkranz, M.; Buyse, M.; Goldberg, M.; Gragoudas, E. S.; Miller, J.; Schwartz, S. D.; Singerman, L.; Yannuzzi, L.; Adamis, A. P.; Guyer, D. R.; O'Shaughnessy, D.; de Gronckel, S.; Fesneau, G.; Quinaux, E.; Tremolet, D.; Wang, K.; Brailey, A.; Finman, J.; Ting, N.; Bressler, N. M.; Bressler, S. B.; Denblow, R.; Schein, O. D.; Seabrook, S.; Solomon, S.; Schachat, A. P.; Philips, D.; Altaweel, M.; Davis, M. D.; Blodi, Ba; Danis, R. P.; Ip, M. S.; Hiner, C.; Elledge, J.; Webster, M.; Hannan, C.; Ficken, J.; Alexander, S.; Neider, M.; Wabers, H.; Vargo, P.; Lambert, E.; Kastorff, L.; Carr, A.; Shkiele, A.; Schlingemann, R. O.

2014-01-01

Objective To assess the rate of pegaptanib-associated sustained intraocular pressure (IOP) elevation. Methods A posthoc analysis was conducted on all IOP measurements, except the immediate 30-min postinjection, from all subjects randomised to pegaptanib 0.3 mg or sham injections continuously in the

In vitro induction of protein complexes between bevacizumab, VEGF-A¹⁶⁵ and heparin: explanation for deposits observed on endothelial veins in monkey eyes.

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Julien, Sylvie; Biesemeier, Antje; Schraermeyer, Ulrich

2013-04-01

By investigating the effects of intravitreal bevacizumab on retinal vessels of monkeys, we found that bevacizumab accumulated locally at high concentration within individual blood vessels. It formed electron-dense fibrous deposits between endothelial cells and erythrocytes or granulocytes inducing retinal vein thrombosis. To better characterise the observed deposits, we investigated in vitro whether these deposits result from a complex between bevacizumab, vascular endothelial growth factor (VEGF)-A(165) and heparin. Cynomolgus monkeys were intravitreally injected with 1.25 mg bevacizumab. The eyes were enucleated between 1 and 14 days after injection and investigated by electron microscopy and immunohistochemistry. Human umbilical vein endothelial cells (HUVEC) were incubated with bevacizumab, VEGF-A(165) and heparin at different concentrations. Treatments with ranibizumab served as control. Bevacizumab and ranibizumab were detected immunohistochemically using Cy-3 or immunogold labelled antibodies. Treated animals showed bevacizumab locally at high concentration within retinal blood vessels. Electron-dense deposits inside retinal vessels and between erythrocytes were detected in three out of four treated monkeys. In vitro, many globular aggregates heavily stained with anti-human IgG were only observed with equimolar amounts (240 nM) of bevacizumab and VEGF-A(165) and 0.2 U/ml heparin and not after ranibizumab treatment. The immunogold labelling specifically localised ultrastructurally the complexes formed between bevacizumab, VEGF-A(165) and heparin at the surfaces of HUVEC cells. Heparin promotes bevacizumab immune complex deposition on to endothelial cells. Our in vitro results could explain the presence of deposits observed on endothelial veins in monkey eyes intravitreally injected with bevacizumab.

The effect of bevacizumab (Avastin) treatment on epistaxis in hereditary hemorrhagic telangiectasia.

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Simonds, Jana; Miller, Frank; Mandel, Jess; Davidson, Terence M

2009-05-01

Determine the effectiveness of treating epistaxis in hereditary hemorrhagic telangiectasia (HHT) with potassium titanyl phosphate (KTP) laser cautery combined with submucosal injection of 100 mg of bevacizumab. Retrospective pilot study. Bevacizumab was injected throughout the nasal cavity following KTP laser treatment in 10 patients (bevacizumab/KTP group) and compared to nine patients previously treated with KTP laser alone (KTP group). Epistaxis frequency and severity, blood transfusion requirement, intravenous iron supplementation, emergency department visit frequency, and quality of life within 1 month and 1 year pre- and postsurgery were analyzed. Benefit was defined as less than three nosebleeds per week, with less than 10 minutes to stop each nosebleed, and no blood transfusions. The pre- and postsurgery data were analyzed within and between the two groups. The groups were comparable in age and gender. Significant benefit was found in frequency of epistaxis (P epistaxis is superior to KTP laser treatment alone. It significantly decreases frequency and severity of nosebleeds and blood transfusion requirements, and significantly improves work ability and quality of life.

Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial.

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Wells, John A; Glassman, Adam R; Ayala, Allison R; Jampol, Lee M; Bressler, Neil M; Bressler, Susan B; Brucker, Alexander J; Ferris, Frederick L; Hampton, G Robert; Jhaveri, Chirag; Melia, Michele; Beck, Roy W

2016-06-01

To provide 2-year results comparing anti-vascular endothelial growth factor (VEGF) agents for center-involved diabetic macular edema (DME) using a standardized follow-up and retreatment regimen. Randomized clinical trial. Six hundred sixty participants with visual acuity (VA) impairment from DME. Randomization to 2.0-mg aflibercept, 1.25-mg repackaged (compounded) bevacizumab, or 0.3-mg ranibizumab intravitreous injections performed up to monthly using a protocol-specific follow-up and retreatment regimen. Focal/grid laser photocoagulation was added after 6 months if DME persisted. Visits occurred every 4 weeks during year 1 and were extended up to every 4 months thereafter when VA and macular thickness were stable. Change in VA, adverse events, and retreatment frequency. Median numbers of injections were 5, 6, and 6 in year 2 and 15, 16, and 15 over 2 years in the aflibercept, bevacizumab, and ranibizumab groups, respectively (global P = 0.08). Focal/grid laser photocoagulation was administered in 41%, 64%, and 52%, respectively (aflibercept vs. bevacizumab, P 0.10, for pairwise comparisons). Anti-Platelet Trialists' Collaboration (APTC) events occurred in 5% with aflibercept, 8% with bevacizumab, and 12% with ranibizumab (global P = 0.047; aflibercept vs. bevacizumab, P = 0.34; aflibercept vs. ranibizumab, P = 0.047; ranibizumab vs. bevacizumab, P = 0.20; global P = 0.09 adjusted for potential confounders). All 3 anti-VEGF groups showed VA improvement from baseline to 2 years with a decreased number of injections in year 2. Visual acuity outcomes were similar for eyes with better baseline VA. Among eyes with worse baseline VA, aflibercept had superior 2-year VA outcomes compared with bevacizumab, but superiority of aflibercept over ranibizumab, noted at 1 year, was no longer identified. Higher APTC event rates with ranibizumab over 2 years warrants continued evaluation in future trials. Copyright © 2016 American Academy of Ophthalmology. All rights

Survey of Intraocular Antibiotics Prophylaxis Practice after Open Globe Injury in China.

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Bingsheng Lou

Full Text Available To elucidate the Chinese practice of intraocular antibiotics administration for prophylaxis after open globe injury.A cross-sectional questionnaire survey was performed online by scanning a Quickmark (QR code with smartphones at the 20th Chinese National Conference of Ocular Trauma in November 2014.A total of 153 (30.6% of all participators at the conference responded. Of the respondents, 20.9% were routinely administered with prophylactic intraocular injection of antibiotics at the conclusion of the primary eye repair, and 56.9% were used only in cases with high risk of endophthalmitis development. The intraocular route of delivery was mainly included with intracameral injection (47.9% and intravitreal injection (42.0%. Cephalosporins (53.8% and vancomycin (42.0% were the main choices of antibiotic agents, followed by fluoroquinolones (24.3%, and aminoglycosides (13.4%. Only 21.9% preferred a combination of two or more two drugs routinely. In addition, significantly more respondents from the referral eye hospital (92.7% replied using intraocular antibiotics injection for prophylaxis compared to those respondents from the primary hospital (69.4% (p = 0.001, Fisher's exact test.Intraocular antibiotics injection for post-traumatic endophthalmitis prophylaxis is widely used in China. However, the choice of antibiotic agents and the intraocular route of delivery vary. A well-designed clinical trial is needed to establish a standardized protocol of intraocular antibiotics administration for post-traumatic endophthalmitis prophylaxis.

Accelerating repaired basement membrane after bevacizumab treatment on alkali-burned mouse cornea

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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

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

Multimodality optical coherence tomography and fluorescence confocal scanning laser ophthalmoscopy for image-guided feedback of intraocular injections in mouse models

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Benavides, Oscar R.; Terrones, Benjamin D.; Leeburg, Kelsey C.; Mehanathan, Sankarathi B.; Levine, Edward M.; Tao, Yuankai K.

2018-02-01

Rodent models are robust tools for understanding human retinal disease and function because of their similarities with human physiology and anatomy and availability of genetic mutants. Optical coherence tomography (OCT) has been well-established for ophthalmic imaging in rodents and enables depth-resolved visualization of structures and image-based surrogate biomarkers of disease. Similarly, fluorescence confocal scanning laser ophthalmoscopy (cSLO) has demonstrated utility for imaging endogenous and exogenous fluorescence and scattering contrast in the mouse retina. Complementary volumetric scattering and en face fluorescence contrast from OCT and cSLO, respectively, enables cellular-resolution longitudinal imaging of changes in ophthalmic structure and function. We present a non-contact multimodal OCT+cSLO small animal imaging system with extended working distance to the pupil, which enables imaging during and after intraocular injection. While injections are routinely performed in mice to develop novel models of ophthalmic diseases and screen novel therapeutics, the location and volume delivered is not precisely controlled and difficult to reproduce. Animals were imaged using a custom-built OCT engine and scan-head combined with a modified commercial cSLO scan-head. Post-injection imaging showed structural changes associated with retinal puncture, including the injection track, a retinal elevation, and detachment of the posterior hyaloid. When combined with imagesegmentation, we believe OCT can be used to precisely identify injection locations and quantify injection volumes. Fluorescence cSLO can provide complementary contrast for either fluorescently labeled compounds or transgenic cells for improved specificity. Our non-contact OCT+cSLO system is uniquely-suited for concurrent imaging with intraocular injections, which may be used for real-time image-guided injections.

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

Combination of Laser Photocoagulation and Intravitreal Bevacizumab in Aggressive Posterior Retinopathy of Prematurity.

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Altinsoy, Halil Ibrahim; Mutlu, Fatih Mehmet; Güngör, Riza; Sarici, S Ümit

2010-03-09

The response to combined laser photocoagulation and a single intravitreal injection of 0.75 mg bevacizumab to each eye on separate days in two patients with aggressive, posterior retinopathy of prematurity (ROP) is described. Combined treatment resulted in regression of zone-1 disease in Case 1, which had no retinal detachment. However, no significant regression or unfavorable anatomic response was observed in the second case with retinal detachment. Although the combination of laser photocoagulation and intravitreal bevacizumab injection seems to be well tolerated, inducing prompt regression of agressive zone-1 ROP without retinal detachment, further controlled studies with long-term follow-up are necessary for their use in the treatment of ROP with for potentially dangerous growth factor inhibitors in premature babies. Copyright 2010, SLACK Incorporated.

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

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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

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

Use of subconjunctival injections of 5-fluorouracil to rescue and prolong intraocular pressure reduction for a failing Ahmed glaucoma implant.

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Kaplowitz, Kevin; Khodadadeh, Sarah; Wang, Samantha; Lee, Daniel; Tsai, James C

2017-06-01

5-Fluorouracil (5-FU) has been well described for a failing trabeculectomy bleb, but not for aqueous shunts. We sought to determine whether subconjunctival 5-FU prolongs the intraocular pressure (IOP) efficacy of Ahmed shunts. We included all patients with Ahmed FP-7 implantation by one surgeon at Yale University. Patients with  21 on >2 medications. Five-milligram (0.1 cc) injections were made over the plate. The control group consisted of Ahmed FP-7 patients without injections. The main outcome measure was IOP. Secondary outcome was success (IOP Ahmed shunts. Outcomes between eyes receiving injections and controls were statistically similar.

Intravitreal bevacizumab has initial clinical benefit lasting eight weeks in eyes with neovascular age-related macular degeneration

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P William Conrad

2008-06-01

Full Text Available P William Conrad, David N Zacks, Mark W JohnsonDepartment of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USAPurpose: To determine whether the effect of a single initial intravitreal injection of bevacizumab for neovascular age-related macular degeneration (AMD persists for 8 weeks.Methods: We reviewed the records of 25 consecutive patients with neovascular AMD treated with intravitreal bevacizumab. Patients were included (n = 15 if follow up data were available from 4 and 8 week visits after a single initial injection. Additionally, optical coherence tomography (OCT images were graded qualitatively in a masked fashion by a single reader.Results: Baseline mean visual acuity was 20/200, improving to 20/125 at 4 weeks (p = 0.0153 and 20/100 at 8 weeks (p = 0.0027. Mean central retinal thickness was 316 ± 107 µm at baseline and decreased to 223 ± 70 µm and 206 ± 45 µm at 4 and 8 weeks post-injection, respectively (p = 0.0003 and 0.0005. By masked OCT grading, macular fluid was resolved in 10/15 (66.7% and 11/15 (73.3% eyes at 4 and 8 weeks, respectively, and 3/15 (20% eyes had continued reduction in residual macular fluid between 4 and 8 weeks.Conclusions: A single initial bevacizumab injection has persistent clinical benefit lasting 8 weeks in most eyes with neovascular AMD. Results of prospective randomized studies are needed before changes in treatment regimens can be recommended.Keywords: age-related macular degeneration, bevacizumab, choroidal neovascular membrane, optical coherence tomography

Intravitreous injection of bevacizumab, tissue plasminogen activator, and gas in the treatment of submacular hemorrhage in age-related macular degeneration.

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Guthoff, Rainer; Guthoff, Tanja; Meigen, Thomas; Goebel, Winfried

2011-01-01

To investigate the benefit of adding bevacizumab to intravitreal recombinant tissue plasminogen activator (rTPA) and gas as initial therapy in subretinal hemorrhage and choroidal neovascularization because of age-related macular degeneration. Thirty-eight consecutive patients with recent (1-31 days) subretinal hemorrhage who were treated with intravitreal rTPA and gas (26 patients) or with intravitreal bevacizumab, rTPA, and gas (12 patients) were included in this retrospective analysis. In all patients, a standardized antivascular endothelial growth factor therapy was followed. Testing of best-corrected visual acuity, biomicroscopy, and fundus examination were performed at 4 weeks and 7 months. The mean pretreatment best-corrected visual acuity in the rTPA/gas group was 0.08 ± 0.09 and 0.12 ± 0.13 in the bevacizumab/rTPA/gas group. After 4 weeks, it was significantly higher in the bevacizumab/rTPA/gas group (0.25 ± 0.26) than in the rTPA/gas (0.08 ± 0.1) group (P gas group (0.07 ± 0.07 vs. 0.24 ± 0.35; P gas) versus 50% (bevacizumab/rTPA/gas). Stabilization (0 ± 2 lines) or improvement of best-corrected visual acuity was obtained in 62% (rTPA/gas) versus 84% (bevacizumab/rTPA/gas). From our retrospective pilot study, there is a strong indication that the addition of intravitreal bevacizumab is safe and superior to the displacement of submacular hemorrhages alone with rTPA and gas.

Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings.

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Lepore, Domenico; Quinn, Graham E; Molle, Fernando; Baldascino, Antonio; Orazi, Lorenzo; Sammartino, Maria; Purcaro, Velia; Giannantonio, Carmen; Papacci, Patrizia; Romagnoli, Costantino

2014-11-01

To compare the structural outcome at 9 months of eyes treated with intravitreal injection of bevacizumab with fellow eyes treated with conventional laser photoablation in zone I type 1 retinopathy of prematurity (ROP). Single randomized controlled trial. All inborn babies with type 1 zone I ROP at a single institution were included in the study. One eye was randomized to receive an intravitreal injection of 0.5 mg bevacizumab; the fellow eye received conventional laser photoablation. Digital fundus photographs and fluorescein angiography (FA) using the RetCam (Clarity Medical Systems Inc., Pleasanton, CA) were performed before treatment and 9 months after treatment. Presence of retinal and choroidal abnormalities on FA at 9 months. Thirteen infants were enrolled; 1 died 3 months after birth. One laser-treated eye progressed to stage 5 retinal detachment. The remaining 23 eyes had favorable structural results at the 9-month follow-up and provided FA results. At 9 months of age, all eyes treated with a bevacizumab injection were noted to have abnormalities at the periphery (large avascular area, abnormal branching, shunt) or the posterior pole (hyperfluorescent lesion, absence of foveal avascular zone). These posterior and peripheral lesions were not observed in the majority of the lasered eyes. This study documents significant vascular and macular abnormalities of eyes in the bevacizumab group. Long-lasting implications of these abnormalities for visual function of the child need to be studied. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Neodymium: YAG laser damage threshold. A comparison of injection-molded and lathe-cut polymethylmethacrylate intraocular lenses.

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Wilson, S E; Brubaker, R F

1987-01-01

The possibility that injection-molded intraocular lenses (IOLs) with imperfections called iridescent clefts could have a decreased threshold to neodymium: YAG (Nd:YAG) laser-induced damage was investigated. Thresholds for Nd:YAG laser-induced damage were determined for injection-molded and lathe-cut polymethylmethacrylate lenses. When aimed at a membrane in contact with a posterior convex surface, the average thresholds were 0.96 +/- 0.18 mJ (Standard deviation [SD]) and 1.80 +/- 0.55 mJ, respectively. The difference was significant at P = 0.001. When injection-molding polymethylmethacrylate was used to make lathe-cut IOLs, very few iridescent clefts were present, and the threshold to Nd:YAG laser-induced damage was 0.94 +/- 0.25 mJ. Iridescent clefts are therefore produced during the injection-molding process but they do not lower the threshold to Nd:YAG laser-induced damage. Rather, the reduced threshold in injection-molded lenses is most probably a result of the polymethylmethacrylate used in their manufacture. Clinically, iridescent clefts in a lens suggest that it has been manufactured by an injection-molding process and that Nd:YAG laser posterior capsulotomy must be performed at the lowest possible energy level to avoid damage.

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.

Vitreous changes after intravitreal bevacizumab monotherapy for retinopathy of prematurity: a case series.

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Shoeibi, Nasser; Hosseini, Seyedeh Maryam; Banaee, Touka; Ansari-Astaneh, Mohammad-Reza; Abrishami, Majid; Ahmadieh, Hamid

2018-01-01

Reporting a special clinical finding after intravitreal bevacizumab monotherapy for retinopathy of prematurity. In a retrospective case series, the clinical courses of five premature infants with similar vitreous changes after a single dose of intravitreal bevacizumab (IVB) injection without additional laser therapy were reported. The mean post-conceptional age at IVB injection was 39.8 ± 2.2 (range 37-43) weeks. Localized vitreous syneresis and linear fibrotic vitreous condensation occurred 8.2 ± 2.3 weeks after IVB monotherapy in our patients (15.5% of injections). The mean last post injection visit was 61.6 ± 5.3 weeks (post-conceptional age). Further regression and complete retinal vascularization occurred in all patients. Thread-like vitreous condensation with localized vitreous liquefaction may be related to involutional ROP disease itself, combined to anti VEGF therapy and may be a predictor factor for further regression and retinal vascularization. The case series describes a successful response to anti-VEGF monotherapy with no further complications.

Intranasal bevacizumab in the treatment of HHT -related epistaxis: a systematic review.

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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.

Effect of bevacizumab on angiogenesis and growth of canine osteosarcoma cells xenografted in athymic mice.

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Scharf, Valery F; Farese, James P; Coomer, Alastair R; Milner, Rowan J; Taylor, David P; Salute, Marc E; Chang, Myron N; Neal, Dan; Siemann, Dietmar W

2013-05-01

Objective-To investigate the effects of bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, on the angiogenesis and growth of canine osteosarcoma cells xenografted in mice. Animals-27 athymic nude mice. Procedures-To each mouse, highly metastasizing parent osteosarcoma cells of canine origin were injected into the left gastrocnemius muscle. Each mouse was then randomly allocated to 1 of 3 treatment groups: high-dose bevacizumab (4 mg/kg, IP), low-dose bevacizumab (2 mg/kg, IP), or control (no treatment). Tumor growth (the number of days required for the tumor to grow from 8 to 13 mm), vasculature, histomorphology, necrosis, and pulmonary metastasis were evaluated. Results-Mice in the high-dose bevacizumab group had significantly delayed tumor growth (mean ± SD, 13.4 ± 3.8 days; range, 9 to 21 days), compared with that for mice in the low-dose bevacizumab group (mean ± SD, 9.4 ± 1.5 days; range, 7 to 11 days) or control group (mean ± SD, 7. 2 ± 1.5 days; range, 4 to 9 days). Mice in the low-dose bevacizumab group also had significantly delayed tumor growth, compared with that for mice in the control group. Conclusions and Clinical Relevance-Results indicated that bevacizumab inhibited growth of canine osteosarcoma cells xenografted in mice, which suggested that vascular endothelial growth factor inhibitors may be clinically useful for the treatment of osteosarcoma in dogs. Impact for Human Medicine-Canine osteosarcoma is used as a research model for human osteosarcoma; therefore, bevacizumab may be clinically beneficial for the treatment of osteosarcoma in humans.

Reversal of cerebral radiation necrosis with bevacizumab treatment in 17 Chinese patients

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Wang Yang

2012-08-01

Full Text Available Abstract Background Bevacizumab has been suggested as a new treatment modality for cerebral radiation necrosis due to its ability to block the effects of vascular endothelial growth factor (VEGF in leakage-prone capillaries, though its use still remains controversial in clinical practice. Methods The use of bevacizumab in 17 patients with symptomatic cerebral radiation necrosis poorly controlled with dexamethasone steroid treatments was examined between March 2010 and January 2012. Bevacizumab therapy was administered for a minimum of two cycles (7.5 mg/kg, at two-week interval with a median of four bevacizumab injections. Changes in bi-dimensional measurements of the largest radiation necrosis lesions were observed by gadolinium-enhanced and T2-weighted magnetic resonance imaging (MRI. Additionally, dexamethasone dosage, Karnofsky performance status (KPS, adverse event occurrence and associated clinical outcomes were recorded for each patient. Results MRI analysis revealed that the average reduction was 54.9% and 48.4% in post-gadolinium and T2-weighted sequence analysis, respectively. Significant clinical neurological improvements were expressed in 10 patients according to KPS values. Dexamethasone reduction was achieved four weeks after initiation of bevacizumab in all patients, with four patients successfully discontinuing dexamethasone treatment. Mild to moderate bevacizumab-related adverse events, such as fatigue, proteinuria and hypertension were observed in three patients. Upon follow-up at 4 to 12 months, 10 patients showed clinical improvement, and 7 patient deaths occurred from tumor progression (5 patients, recurrent necrosis (1 patient, and uncontrolled necrosis-induced edema (1 patient. Conclusions These findings suggest bevacizumab as a promising treatment for cerebral radiation necrosis induced by common radiation therapies, including external beam radiotherapy (EBRT, stereotactic radiosurgery (SRS, and fractionated stereotactic

Macular Hole Progression after Intravitreal Bevacizumab for Hemicentral Retinal Vein Occlusion

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Manish Nagpal

2011-01-01

Full Text Available Macular edema secondary to retinal vein occlusion is commonly being treated with off-label intravitreal bevacizumab with good outcomes. A significant reduction in macular edema and improvement in visual acuity is seen following such a treatment with no serious adverse effects. In the reported case, a full-thickness macular hole was noticed one month after intravitreal bevacizumab for macular edema secondary to hemicentral retinal vein occlusion. On a detailed review of the pre- and postoptical coherence tomography scans, it was realized that there was a preexisting stage 2-3 macular hole which was masked by the hemorrhages and edema at the fovea and the macular hole had progressed following the injection.

Ocular trace metal kinetics and toxicology. I. The distribution of intravitreally injected 67Cu++ within intraocular compartments and its loss from the globe

International Nuclear Information System (INIS)

Bito, L.Z.; Baroody, R.A.

1987-01-01

Radioactive copper (67Cu++) was injected into the center of the vitreous body of rabbits. The relatively rapid initial loss of 67Cu from the vitreous was associated with its accumulation in intraocular tissues. At 24 hr, 20% of the injected 67Cu was found in the retina, representing the highest 67Cu concentration among all ocular tissues, and this high 67Cu concentration was maintained in this tissue throughout the 10-day observation period. Significant amounts of 67Cu were not detected in the aqueous humor at any time. About one-half of the injected 67Cu was lost from the whole globe in 5 days, but the remaining Cu was retained in the globe during the next 5 days. Eyes that received a large dose of CuSO4 in addition to the tracer showed decreased 67Cu activity in the retina and a slight increase in the aqueous humor. Endotoxin-induced ocular inflammation decreased the rate of 67Cu loss from the vitreous, reduced its accumulation by the retina, and increased 67Cu entry into the aqueous humor. It is concluded that 67Cu is retained in the vitreous and the globe due to its binding by, and/or uptake into, intraocular tissues, especially the retina. Cu does not effectively enter the anterior chamber from the vitreous, apparently due to its effective removal by the ciliary processes, thus ruling out the possibility of identifying the existence of Cu-containing intraocular foreign bodies in the posterior segment of the eye by analysis of Cu in the aqueous humor

Ultra-low dose of intravitreal bevacizumab in retinopathy of prematurity.

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Şahin, A; Gürsel-Özkurt, Z; Şahin, M; Türkcü, F M; Yıldırım, A; Yüksel, H

2018-05-01

We aimed to investigate the effectivity of the 0.0625 mg dose of bevacizumab in patients with retinopathy of prematurity (ROP) and compare the results with 0.625 mg dose of intravitreal bevacizumab (IVB) injection. The medical records of the patients with type 1 ROP who received IVB monotherapy were retrospectively reviewed. Demographic and clinical characteristics of the patients were recorded. The patients were classified into two groups with respect to received dose of bevacizumab as follows: group F (n = 46) (full dose of bevacizumab-0.625 mg/0.025 ml) and group L (n = 45) (low dose (one tenth) of bevacizumab-0.0625 mg/0.025 ml). Both treatment dose regimens have similar outcomes. Moreover, the mean retinal vascularization time seemed to be significantly higher in group F compared to group L, 168 ± 65 and 97 ± 29 days, respectively (p < 0.001). Disappearance of plus sign is observed earlier in group F (2.45 ± 1.7 vs 3.66 ± 2.46 days, respectively, p = 0.03). The low dose (0.0625 mg) of IVB treatment was effective as full (0.625 mg) dose in ROP treatment. Moreover, our results showed that low-dose treatment might provide faster retinal vascularization than the regular used dose. On the other hand, disappearance of the plus sign takes longer time in patients treated with low dose compared to eyes treated with full dose of IVB that should be taken into account.

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.

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...

Acceleration of tendon healing using US guided intratendinous injection of bevacizumab: First pre-clinical study on a murine model

International Nuclear Information System (INIS)

Dallaudière, Benjamin; Lempicki, Marta; Pesquer, Lionel; Louedec, Liliane; Preux, Pierre Marie; Meyer, Philippe; Hess, Agathe; Durieux, Marie Hèlène Moreau; Hummel, Vincent; Larbi, Ahmed; Deschamps, Lydia

2013-01-01

Purpose: Tendinopathy shows early disorganized collagen fibers with neo-angiogenesis on histology. Peri-tendinous injection of corticosteroid is the commonly accepted strategy despite the abscence of inflammation in tendinosis. The aim of our study was to assess the potential of intratendinous injection of an anti-angiogenic drug (bevacizumab, AA) to treat tendinopathy in a murine model of patellar and Achilles tendinopathy, and to evaluate its local toxicity. Materials and method: Forty rats (160 patellar and Achilles tendons) were used for this study. We induced tendinosis (T+) in 80 tendons by injecting under ultrasonography (US) guidance Collagenase 1 ® (day 0 = D0, patellar = 40 and Achilles = 40). Clinical examination and tendon US were performed at D3, immediately followed by either AA (AAT+, n = 40) or physiological serum (PST+, n = 40, control) US-guided intratendinous injection. Follow-up at D6 and D13 using clinical, US and histology, and comparison between the 2 groups were performed. To study AA toxicity we compared the 80 remaining normal tendons (T−) after injecting AA in 40 (AAT−). Results: All AAT+ showed a better joint mobilization compared to PST+ at D6 (p = 0.004) with thinner US tendon diameters (p < 0.004), and less disorganized collagen fibers and neovessels on histology (p < 0.05). There was no difference at D13 regarding clinical status, US tendon diameter and histology (p > 0.05). Comparison between AAT− and T− showed no AA toxicity on tendon (p = 0.18). Conclusion: Our study suggests that high dose mono-injection of AA in tendinosis, early after the beginning of the disease, accelerates tendon's healing, with no local toxicity

Acceleration of tendon healing using US guided intratendinous injection of bevacizumab: First pre-clinical study on a murine model

Energy Technology Data Exchange (ETDEWEB)

Dallaudière, Benjamin, E-mail: bendallau64@hotmail.fr [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Inserm U698, Hôpital universitaire Bichat, Paris (France); Université de Médecine Paris Diderot (France); Lempicki, Marta [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Université de Médecine Paris Diderot (France); Pesquer, Lionel [Centre d’Imagerie Ostéo Articulaire, Clinique du Sport de Bordeaux-Mérignac (France); Louedec, Liliane [Inserm U698, Hôpital universitaire Bichat, Paris (France); Preux, Pierre Marie [Laboratoire de Biostatistiques, Faculté de médecine, Limoges (France); Meyer, Philippe [Centre d’Imagerie Ostéo Articulaire, Clinique du Sport de Bordeaux-Mérignac (France); Hess, Agathe [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Université de Médecine Paris Diderot (France); Durieux, Marie Hèlène Moreau [Centre d’Imagerie Ostéo Articulaire, Clinique du Sport de Bordeaux-Mérignac (France); Hummel, Vincent; Larbi, Ahmed [Service de Radiologie, Hôpital universitaire Bichat, Paris (France); Deschamps, Lydia [Service d’ Anatomopathologie, Hôpital universitaire Bichat, Paris (France); and others

2013-12-01

Purpose: Tendinopathy shows early disorganized collagen fibers with neo-angiogenesis on histology. Peri-tendinous injection of corticosteroid is the commonly accepted strategy despite the abscence of inflammation in tendinosis. The aim of our study was to assess the potential of intratendinous injection of an anti-angiogenic drug (bevacizumab, AA) to treat tendinopathy in a murine model of patellar and Achilles tendinopathy, and to evaluate its local toxicity. Materials and method: Forty rats (160 patellar and Achilles tendons) were used for this study. We induced tendinosis (T+) in 80 tendons by injecting under ultrasonography (US) guidance Collagenase 1{sup ®} (day 0 = D0, patellar = 40 and Achilles = 40). Clinical examination and tendon US were performed at D3, immediately followed by either AA (AAT+, n = 40) or physiological serum (PST+, n = 40, control) US-guided intratendinous injection. Follow-up at D6 and D13 using clinical, US and histology, and comparison between the 2 groups were performed. To study AA toxicity we compared the 80 remaining normal tendons (T−) after injecting AA in 40 (AAT−). Results: All AAT+ showed a better joint mobilization compared to PST+ at D6 (p = 0.004) with thinner US tendon diameters (p < 0.004), and less disorganized collagen fibers and neovessels on histology (p < 0.05). There was no difference at D13 regarding clinical status, US tendon diameter and histology (p > 0.05). Comparison between AAT− and T− showed no AA toxicity on tendon (p = 0.18). Conclusion: Our study suggests that high dose mono-injection of AA in tendinosis, early after the beginning of the disease, accelerates tendon's healing, with no local toxicity.

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

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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.

Role of bevacizumab in uterine leiomyosarcoma.

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Bogani, Giorgio; Ditto, Antonino; Martineli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Fonatella, Caterina; Sanfilippo, Roberta; Leone Roberti Maggiore, Umberto; Ferrero, Simone; Lorusso, Domenica; Raspagliesi, Francesco

2018-06-01

In the recent years, angiogenetic inhibitors have emerged for the treatment of several malignancies. In particular, bevacizumab has proved to be effective in many types of cancers (including sarcoma), but the limitations of antiangiogenic therapy have been shown in practice. Here, we sought to review the current evidence on the role and efficacy of bevacizumab in patients affected by uterine leiomyosarcoma. On April 2017, Literature was searched in order to identify studies reporting outcomes of patients affected either by early stage or advanced/recurred uterine leiomyosarcoma undergoing treatment with bevacizumab, alone or in combination with other chemotherapeutic regimens. Searching the literature data of 69 patients affected by metastatic, unresectable uterine leiomyosarcoma were retrieved; on the contrary, no data regarding the use of bevacizumab in patients with early-stage uterine leiomyosarcoma was published. Current evidence suggested that the addiction of bevacizumab to standard treatment modality does not increase grade 3 or worse toxicity (assessed by CTCAE). Pooled data regarding response rate suggested that 35%, 28%, 26% and 11% of patients experienced objective cure (complete + partial response), stable disease, progressive disease and unknown response, respectively. Data from the only one randomized controlled trial suggested that objective cure rate does not differ from standard chemotherapy treatment, thus limiting the indication to add bevacizumab in patients affected by metastatic, unresectable uterine leiomyosarcoma. The current evidence does not justify the use of bevacizumab into clinical practice. Further randomized studies testing the role of bevacizumab are warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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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

Insight into 144 patients with ocular vascular events during VEGF antagonist injections

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Shami M

2012-03-01

Full Text Available Ahmad M Mansour1, Maha Shahin2, Peter K Kofoed3, Maurizio B Parodi4, Michel Shami5, Stephen G Schwartz6, Collaborative Anti-VEGF Ocular Vascular Complications GroupDepartment of Ophthalmology, 1American University of Beirut, Beirut, Lebanon, Rafic Hariri University Hospital, Beirut, Lebanon; 2Mansoura University, Mansoura City, Egypt; 3Glostrup Hospital, University of Copenhagen, Denmark, National Eye Clinic, Kennedy Center, Glostrup, Denmark; 4University Vita-Salute, Scientific Institute San Raffaele, Milan, Italy; 5Texas Tech University Health Sciences Center, Lubbock, TX, USA; 6Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Naples and Miami, FL, USAAim: To record ocular vascular events following injections of vascular endothelium growth factor (VEGF antagonists.Methods: Collaborative multicenter case series (48 cases, literature reviews (32 cases, and reports to the FDA (64 cases of patients that had vascular occlusions during anti-VEGF therapy were collected and analyzed.Results: A total of 144 cases of ocular vascular events were identified, with these diagnosed a median of 15 days after anti-VEGF injection. The majority of patients had pre-existing risk factors for cardiovascular events and nine patients had a prior history of glaucoma. Mean visual acuity dropped by 6.4 lines with severe visual loss after injection to NLP (five eyes, LP (six eyes, and HM (two eyes. The overall risk of ocular vascular events following a VEGF antagonist injection was 0.108% in the general population and 2.61% in the diabetic population. Mean retinal arterial constriction after intravitreal bevacizumab in 13 eyes was 21% (standard deviation = 27%, and mean retinal venous constriction was 8% (standard deviation = 30%.Conclusion: Ocular vascular events are rare during anti-VEGF therapy, but can lead to severe visual loss and may be caused by a number of factors including the vasoconstrictor effect of the drug, a post-injection rise

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

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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

Nanoparticles in porous microparticles prepared by supercritical infusion and pressure quench technology for sustained delivery of bevacizumab.

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

2013-12-02

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 Fluor 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.

Safety of cupping during bevacizumab therapy.

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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.

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

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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.

Bevacizumab treatment for retinopathy of prematurity in South Africa

African Journals Online (AJOL)

Retinopathy of prematurity (ROP) is a growing problem in South. Africa (SA), as it is .... detected in the serum of both infants and adults after intraocular injection,[7] ... use of anti-VEGF agents to treat macular degeneration, diabetic retinopathy ...

Bevacizumab treatment reduces retinal neovascularization in a mouse model of retinopathy of prematurity

Institute of Scientific and Technical Information of China (English)

Fei; Feng; Yan; Cheng; Qing-Huai; Liu

2014-01-01

·AIM: To evaluate the effect of different bevacizumab concentrations on retinal neovascularization in a retinopathy of prematurity(ROP) mouse model.·METHODS: A total of 60 of C57BL/6 J mice were exposed to 75% ±2% oxygen from postnatal d7 to postnatal d12. Fifteen nonexposed mice served as negative controls(group A). On d12, 30 mice(group C)were injected with 2.5 μg intravitreal bevacizumab(IVB),30 mice(group D) were injected with 1.25 μg IVB in one eye. The contralateral eyes were injected with balanced salt solution(BSS)(control group =group B). The adenosine diphosphatase(ADPase) histochemical technique was used for retinal flat mount to assess the oxygen-induced changes of retinal vessels.Neovascularization was quantified by counting the endothelial cell proliferation on the vitreal side of the inner limiting membrane of the retina. Histological changes were examined by light microscopy. The mRNA levels of vascular endothelial growth factor(VEGF) were quantified by Real-time PCR. Western-blotting analysis was performed to examine the expression of P-VEGFR.· RESULTS: Comparing with the control group B,regular distributions and reduced tortuosity of vessels were observed in our retinal flat mounts in groups C and D. The endothelial cell count per histological section was lower in groups C(P <0.0001) and D(P <0.0001) compared with the control group B. Histological evaluation showed no retinal toxicity in any group. In all oxygen treated groups VEGF mRNA expression was significantly increased as compared to age-matched controls. No significant change in VEGF mRNA expression could be achieved in either of the treatments or the oxygen controls. The results of the Western blot were consistent with that of the Real-time PCR analysis.·CONCLUSION: An intravitreal injection of bevacizumab is able to reduce angioproliferative retinopathy in a mouse model for oxygen-induced retinopathy.

Effect of intravitreal bevacizumab on diabetic macular edema with hard exudates

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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

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.

A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

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Wang, Yang; Wang, Enmin; Pan, Li; Dai, Jiazhong; Zhang, Nan; Wang, Xin; Liu, Xiaoxia; Mei, Guanghai; Sheng, Xiaofang

2014-09-01

Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain

Correlation of bevacizumab-induced hypertension and outcomes of metastatic colorectal cancer patients treated with bevacizumab: a systematic review and meta-analysis.

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Cai, Jun; Ma, Hong; Huang, Fang; Zhu, Dichao; Bi, Jianping; Ke, Yang; Zhang, Tao

2013-11-28

With the wide application of targeted drug therapies, the relevance of prognostic and predictive markers in patient selection has become increasingly important. Bevacizumab is commonly used in combination with chemotherapy in the treatment of metastatic colorectal cancer. However, there are currently no predictive or prognostic biomarkers for bevacizumab. Several clinical studies have evaluated bevacizumab-induced hypertension in patients with metastatic colorectal cancer. This meta-analysis was performed to better determine the association of bevacizumab-induced hypertension with outcome in patients with metastatic colorectal cancer, and to assess whether bevacizumab-induced hypertension can be used as a prognostic factor in these patients. We performed a systematic review and meta-analysis on seven published studies to investigate the relationship between hypertension and outcome of patients with metastatic colorectal cancer treated with bevacizumab. Our primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and overall response rate (ORR). Hazard ratios (HRs) for PFS and OS were extracted from each trial, and the log of the relative risk ratio (RR) was estimated for ORR. The occurrence of bevacizumab-induced hypertension in patients was highly associated with improvements in PFS (HR = 0.57, 95% CI: 0.46-0.72; P hypertension. Bevacizumab-induced hypertension may represent a prognostic factor in patients with metastatic colorectal cancer.

WHAT HAPPENS TO INTRAOCULAR PRESSURE AFTER PERIBULBAR ANAESTHESIA?

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Krishnamoorthy Segharipuram Ranganathan

2017-08-01

Full Text Available BACKGROUND Most of intraocular surgeries are done under local anaesthesia. The peribulbar anaesthesia provides adequate anaesthesia and akinesia. There is no reported intraoperative and/or postoperative amaurosis. The peribulbar anaesthesia provides adequate anaesthesia and akinesia. The disadvantages of it are the larger quantity of the aesthetic agent. Increasing the bulk load on the globe and a reported rise of intraocular pressure. MATERIALS AND METHODS A study of fifty cases was conducted in patients who received peribulbar anaesthesia undergoing cataract extraction with intraocular lens implantation and their intraocular pressures were noted and studied after giving the peribulbar anaesthesia all given by the same surgeon. RESULTS This study did show that the peribulbar anaesthesia increases the intraocular pressure in all the cases. The external ocular compression indeed helps to dissipate the anaesthetic load thereby reducing the enormous rise in IOP, which is only expected if you recollect the fact that the eyeball occupies one sixth of the total volume of the orbit that is 5 mL and 30 mL. The volume of peribulbar anaesthesia (6 mL does add its effects to increase the IOP. Hence, a properly planned post peribulbar compression helps to minimise the transient rise in IOP. CONCLUSION Summarising the study, it is better to give peribulbar injection initially followed by external ocular compression after a delay of at least 2 to 5 minutes. It is also advised that an initial compression maybe given in slightly risk cases, so that the peribulbarinduced rise may not be alarming. The anaesthetic solution maybe fragmented and the second injection maybe delayed by 5 minutes or omitted if good akinesia and anaesthesia are achieved already.

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.

Rate of Post-traumatic Endophthalmitis with or without Injection of Balanced Salt Solution

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Nasrin Rafati

2013-01-01

Full Text Available Purpose: In a study complementing a previous multicenter randomized clinical trial on prophylactic injection of intraocular antibiotics during primary repair of penetrating eye injuries (PEIs, we sought to determine whether needle entrance and injection of balanced salt solution (BSS, per se, could increase the rate of acute post-traumatic bacterial endophthalmitis (APBE. Methods: Patients randomized to the BSS injection arm (n=167 of the Traumatic Endophthalmitis Trial, and eligible patients who had refused enrollment and received no intraocular injections during primary repair (n=111 were compared for the development of APBE. Results: APBE occurred in 8 of 167 (4.8% eyes in the BSS group and in 5 of 111 (4.5% eyes in the non-injection group (P=0.91. Retained intraocular foreign bodies were present in 46 eyes including 25 (15% eyes in the BSS injection group and 21 (18.9% eyes in the non-injection group (P=0.38. Logistic regression analysis showed no significant difference between BSS injected and non-injected eyes in terms of APBE (P=0.69. However, the presence of intraocular foreign bodies was strongly associated with the risk of endophthalmitis (P<0.001, OR=14.1, 95% CI: 4.1-48.5. Conclusion: Needle entrance and intraocular injection of BSS during primary repair of PEIs does not increase the risk of APBE.

Comparison of structural outcome between intravitreal bevacizumab and laser treatment for type 1 retinopathy of prematurity after long-term follow-up

Institute of Scientific and Technical Information of China (English)

Yen-Yi Chen; Yun-Ju Chen; Yung-Ray Hsu; Fang-Ting Chen; Jia-Kang Wang

2016-01-01

Background:To compare the structural outcome of intravitreal bevacizumab (IVB) and laser treatment for type 1 retinopathy of prematurity (ROP). Methods: This is a retrospective comparative study. From December 2002 to April 2009, patients with type 1 ROP according to criteria of Early Treatment of Retinopathy of Prematurity (ETROP) study were treated by peripheral retinal diode laser photocoagulation in nearly confluent pattern. From May 2009 to January 2015, we performed IVB for patients with type 1 ROP. The patients were closely followed until disappearance of retinal neovascularization in the laser group and regression of avascular zone in the bevacizumab group. The demographical data, postmenstrual age (PMA) for treatment, and fundus ifndings were recorded by chart review. The difference between laser and bevacizumab groups was compared by Studentt-test and Fisher exact test. Results: We collected 43 patients (86 eyes) with type 1 ROP, including 30 male and 13 female infants. Their mean gestation age and birth body weight (BBW) were 27.5 weeks and 1,034 gm. Zone I and zone II disease were found in 8 and 35 patients. The mean PMA for treatment was 37.3 weeks. The mean follow-up period was 54.4 months. Laser treatment was administered in 26 patients, and bevacizumab injection for 17 infants. Single session of laser was performed in all patients of laser group without recurrence of retinal neovascularization. Complete regression of ROP was found in 15 infants of bevacizumab group following the ifrst IVB. Four eyes in two patients (2/17, 11.7%) had recurrence of ROP and received additional injections and adjuvant laser treatment. There was no unfavorable anatomical results such as retinal detachment or macular ectopia or complications such as cataract or endophthalmitis in either bevacizumab or laser management. Conclusions: Laser therapy and IVB were both effective treatments for type 1 ROP to cause favorable anatomical outcomes. Single session of laser ablation

MRI and intraocular tamponade media

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Manfre, I. (Dept. of Neuroradiology, Inst. of Neurosurgery, Univ. of Catania (Italy)); Fabbri, G. (Dept. of Neuroradiology, Inst. of Neurosurgery, Univ. of Catania (Italy)); Avitabile, T. (Inst. of Ophthalmology, Univ. of Catania (Italy)); Biondi, P. (Inst. of Ophthalmology, Univ. of Catania (Italy)); Reibaldi, A. (Inst. of Ophthalmology, Univ. of Catania (Italy)); Pero, G. (Dept. of Neuroradiology, Inst. of Neurosurgery, Univ. of Catania (Italy))

1993-05-01

Thirteen patients who underwent surgery for retinal detachment and injection of intraocular tamponade media (silicone oil, flurosilicone oil, or perfluoro-carbon liquid) underwent magnetic resonance imaging (MRI), using spin-echo T1- and T2-weighted images. The ophthalmic tamponade media showed different signal intensity, according to their chemical structure. Unlike ophthalmoscopy or ultrasonography, MRI showed no oil-related artefact, making possible recognition of recurrent retinal detachment. (orig.)

MRI and intraocular tamponade media

International Nuclear Information System (INIS)

Manfre, I.; Fabbri, G.; Avitabile, T.; Biondi, P.; Reibaldi, A.; Pero, G.

1993-01-01

Thirteen patients who underwent surgery for retinal detachment and injection of intraocular tamponade media (silicone oil, flurosilicone oil, or perfluoro-carbon liquid) underwent magnetic resonance imaging (MRI), using spin-echo T1- and T2-weighted images. The ophthalmic tamponade media showed different signal intensity, according to their chemical structure. Unlike ophthalmoscopy or ultrasonography, MRI showed no oil-related artefact, making possible recognition of recurrent retinal detachment. (orig.)

Analytical and functional similarity of Amgen biosimilar ABP 215 to bevacizumab.

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Seo, Neungseon; Polozova, Alla; Zhang, Mingxuan; Yates, Zachary; Cao, Shawn; Li, Huimin; Kuhns, Scott; Maher, Gwendolyn; McBride, Helen J; Liu, Jennifer

ABP 215 is a biosimilar product to bevacizumab. Bevacizumab acts by binding to vascular endothelial growth factor A, inhibiting endothelial cell proliferation and new blood vessel formation, thereby leading to tumor vasculature normalization. The ABP 215 analytical similarity assessment was designed to assess the structural and functional similarity of ABP 215 and bevacizumab sourced from both the United States (US) and the European Union (EU). Similarity assessment was also made between the US- and EU-sourced bevacizumab to assess the similarity between the two products. The physicochemical properties and structural similarity of ABP 215 and bevacizumab were characterized using sensitive state-of-the-art analytical techniques capable of detecting small differences in product attributes. ABP 215 has the same amino acid sequence and exhibits similar post-translational modification profiles compared to bevacizumab. The functional similarity assessment employed orthogonal assays designed to interrogate all expected biological activities, including those known to affect the mechanisms of action for ABP 215 and bevacizumab. More than 20 batches of bevacizumab (US) and bevacizumab (EU), and 13 batches of ABP 215 representing unique drug substance lots were assessed for similarity. The large dataset allows meaningful comparisons and garners confidence in the overall conclusion for the analytical similarity assessment of ABP 215 to both US- and EU-sourced bevacizumab. The structural and purity attributes, and biological properties of ABP 215 are demonstrated to be highly similar to those of bevacizumab.

The use of intravitreal anti-vascular endothelial growth factor injection and its complications in Chiang Mai University Hospital.

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Kunavisarut, Paradee; Saenpen, Nithiracht; Ittipunkul, Nimitr; Patikulsila, Direk; Choovuthayakorn, Janejit; Watanachai, Nawat; Pathanapitoon, Kessara

2013-11-01

To report the use of intravitreal (IVT) injections of anti-vascular endothelial growth factor agents (anti-VEGF) and its complications. The authors performed a retrospective review of consecutive patients treated with IVT injection of anti-VEGF between May 2006 and December 2010 at Chiang Mai University Hospital. Demographic data and complications were registered. The present study included 1,006 eyes of 878 patients. Mean age was 60 years (range 1 month to 91 years). Mean follow-up time was 12 months (range 1 month to 54 months). Total injections were 2,077 given as 47, 210, 399, 575, and 846 injection per year between 2006 and 2010, respectively. Anti-VEGF agents were bevacizumab (1,878; 90.42%), ranibizumab (190; 9.15%), and pegaptanib (9; 0.43%). Indications for injection based on primary diagnosis were neovascular macular degeneration (38.5%), diabetic retinopathy (38%), and retinal vein occlusion (15.9%). The incidence of endophthalmitis was 0.048% (1/2,077) for all injections and 0.053% (1/1878)for bevacizumab. The use of IVT injections of anti-VEGF is increasing, especially the use of bevacizumab. Incidence of ocular and systemic complications after IVT injection of anti- VEGF was low with no significant difference among the three anti-VEGFs agents.

Influence of gross saponins from tribulus terrestris L on SOD activity and MDA content for chronic high intraocular pressure in rabbit

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Nuo Li

2013-05-01

Full Text Available AIM:To observe influence of gross saponins from tribulus terrestris L(GSTTon SOD activity and MDA content for chronic high intraocular pressure in rabbit, and discusses the retina oxidative damage inhibition on chronic high intraocular pressure model of rabbit. METHODS:Totally 24 healthy New Zealand rabbits were randomly divided into 4 groups: normal control group(A group; high intraocular pressure model blank group(B group; high intraocular pressure model with GSTT treated group(C group; high intraocular pressure model with Erigeron brevicapas hand mass(EBHMtreated group(D group. High intraocular pressure model was induced by 20g/L methylcellulose injection into the anterior chamber in B group, C group and D group. D group was injected 5 mg/kg GSTT and C group was injected 4.5mg/kg EBHM and measured intraocular pressure with Schiotz tonometer every day for 4 weeks. The retina tissue superoxide dismutase(SODand maleic dialdehyde(MDAcontent were detected 28 days later. RESULTS: After glaucoma model of rabbit eyes were established, the intraocular pressure during observation period was maintained in 32-39mmHg; High intraocular pressure model blank group and normal control group, EBHM treatment group, GSTT treatment group were compared, the differences of retina MDA, SOD content had statistical significance(P0.05; EBHM treatment group, GSTT treatment group and normal control group were compared, the content of MDA in the retina was still slightly higher(P<0.05, the content of SOD slightly lower(P<0.05 CONCLUSION: GSTT can effectively improve the retina SOD activity of chronic high intraocular pressure in rabbit and reduce the content of MDA, which has a protective effect of persistent high intraocular retinal oxidative stress.

Computational modeling of intraocular gas dynamics

International Nuclear Information System (INIS)

Noohi, P; Abdekhodaie, M J; Cheng, Y L

2015-01-01

The purpose of this study was to develop a computational model to simulate the dynamics of intraocular gas behavior in pneumatic retinopexy (PR) procedure. The presented model predicted intraocular gas volume at any time and determined the tolerance angle within which a patient can maneuver and still gas completely covers the tear(s). Computational fluid dynamics calculations were conducted to describe PR procedure. The geometrical model was constructed based on the rabbit and human eye dimensions. SF_6 in the form of pure and diluted with air was considered as the injected gas. The presented results indicated that the composition of the injected gas affected the gas absorption rate and gas volume. After injection of pure SF_6, the bubble expanded to 2.3 times of its initial volume during the first 23 h, but when diluted SF_6 was used, no significant expansion was observed. Also, head positioning for the treatment of retinal tear influenced the rate of gas absorption. Moreover, the determined tolerance angle depended on the bubble and tear size. More bubble expansion and smaller retinal tear caused greater tolerance angle. For example, after 23 h, for the tear size of 2 mm the tolerance angle of using pure SF_6 is 1.4 times more than that of using diluted SF_6 with 80% air. Composition of the injected gas and conditions of the tear in PR may dramatically affect the gas absorption rate and gas volume. Quantifying these effects helps to predict the tolerance angle and improve treatment efficiency. (paper)

Epithelial Downgrowth after Intraocular Surgery Treated with Intracameral 5-Fluorouracil

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Nina Ni

2015-01-01

Full Text Available Purpose. To present the clinical and histopathologic correlation of two cases of epithelial downgrowth (EDG after prior intraocular surgery. Methods. Observational case reports. Results. We present two cases of EDG occurring after intraocular surgery. In both cases, after two anterior chamber injections of 5-fluorouracil (5FU, the area of EDG initially regressed. In Case 1, a limited area of EDG eventually recurred, and penetrating keratoplasty with cryotherapy was curative. In Case 2, subsequent corneal edema required Descemet-stripping automated endothelial keratoplasty, and the patient remained clinically free of EDG without further treatment. Conclusion. Intracameral 5FU may have a role in the treatment of EDG after intraocular surgery, though its precise utilization and impact remain to be defined.

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

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.

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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

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

Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis.

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Nagai, Toshihiro; Sato, Masato; Kobayashi, Miyuki; Yokoyama, Munetaka; Tani, Yoshiki; Mochida, Joji

2014-09-18

Angiogenesis is an important factor in the development of osteoarthritis (OA). We investigated the efficacy of bevacizumab, an antibody against vascular endothelial growth factor and an inhibitor of angiogenesis, in the treatment of OA using a rabbit model of anterior cruciate ligament transection. First, we evaluated the response of gene expression and histology of the normal joint to bevacizumab treatment. Next, in a rabbit model of OA induced by anterior cruciate ligament transection, we used macroscopic and histological evaluations and real-time polymerase chain reaction (PCR) to examine the responses to intravenous (systemic) administration of bevacizumab (OAB IV group). We also investigated the efficacy of intra-articular (local) administration of bevacizumab in OA-induced rabbits (OAB IA group). Histologically, bevacizumab had no negative effect in normal joints. Bevacizumab did not increase the expression of genes for catabolic factors in the synovium, subchondral bone, or articular cartilage, but it increased the expression of collagen type 2 in the articular cartilage. Macroscopically and histologically, the OAB IV group exhibited a reduction in articular cartilage degeneration and less osteophyte formation and synovitis compared with the control group (no bevacizumab; OA group). Real-time PCR showed significantly lower expression of catabolic factors in the synovium in the OAB IV group compared with the OA group. In articular cartilage, expression levels of aggrecan, collagen type 2, and chondromodulin-1 were higher in the OAB IV group than in the OA group. Histological evaluation and assessment of pain behaviour showed a superior effect in the OAB IA group compared with the OAB IV group 12 weeks after administration of bevacizumab, even though the total dosage given to the OAB IA group was half that received by the OAB IV group. Considering the dosage and potential adverse effects of bevacizumab, the local administration of bevacizumab is a more

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.

Intraocular lens fabrication

Energy Technology Data Exchange (ETDEWEB)

Salazar, Mike A. (Albuquerque, NM); Foreman, Larry R. (Los Alamos, NM)

1997-01-01

This invention describes a method for fabricating an intraocular lens made rom clear Teflon.TM., Mylar.TM., or other thermoplastic material having a thickness of about 0.025 millimeters. These plastic materials are thermoformable and biocompatable with the human eye. The two shaped lenses are bonded together with a variety of procedures which may include thermosetting and solvent based adhesives, laser and impulse welding, and ultrasonic bonding. The fill tube, which is used to inject a refractive filling material is formed with the lens so as not to damage the lens shape. A hypodermic tube may be included inside the fill tube.

Towards optimizing the sequence of bevacizumab and nitrosoureas in recurrent malignant glioma.

Science.gov (United States)

Wiestler, Benedikt; Radbruch, Alexander; Osswald, Matthias; Combs, Stephanie E; Jungk, Christine; Winkler, Frank; Bendszus, Martin; Unterberg, Andreas; Platten, Michael; Wick, Wolfgang; Wick, Antje

2014-03-01

Studies on the monoclonal VEGF-A antibody bevacizumab gave raise to questions regarding the lack of an overall survival benefit, the optimal timing in the disease course and potential combination and salvage therapies. We retrospectively assessed survival, radiological progression type on bevacizumab and efficacy of salvage therapies in 42 patients with recurrent malignant gliomas who received bevacizumab and nitrosourea sequentially. 15 patients received bevacizumab followed by nitrosourea at progression and 27 patients vice versa. Time to treatment failure, defined as time from initiation of one to failure of the other treatment, was similar in both groups (9.6 vs. 9.2 months, log rank p = 0.19). Progression-free survival on nitrosoureas was comparable in both groups, while progression-free survival on bevacizumab was longer in the group receiving bevacizumab first (5.3 vs. 4.1 months, log rank p = 0.03). Survival times were similar for patients with grade III (n = 9) and grade IV (n = 33) tumors. Progression-free survival on bevacizumab for patients developing contrast-enhancing T1 progression was longer than for patients who displayed a non-enhancing T2 progression. However, post-progression survival times after bevacizumab failure were not different. Earlier treatment with bevacizumab was not associated with better outcome in this series. The fact that earlier as compared to later bevacizumab treatment does not result in a different time to treatment failure highlights the challenge for first-line or recurrence trials with bevacizumab to demonstrate an overall survival benefit if crossover of bevacizumab-naïve patients after progression occurs.

177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma.

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Camacho, Ximena; Calzada, Victoria; Fernandez, Marcelo; Alonso, Omar; Chammas, Roger; Riva, Eloisa; Gambini, Juan Pablo; Cabral, Pablo

2017-01-01

Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several types, including melanoma. Bevacizumab is a humanized monoclonal antibody directed against VEGF. To radiolabel Bevacizumab with 177-Lutetium as a potential radioimmunotherapy agent for melanoma. Bevacizumab was derivatized with DOTA-NHS-ester at 4 ºC for 18 h. DOTABevacizumab was radiolabeled with 177LuCl3 (15 MBq/mg) at 37 ºC for 1 h. The studies were performed in healthy and B16F1 tumor-bearing C57BL/6J mice at 24 and 48 h (n = 5). Scinthigraphic imaging studies were performed at 24 h to determine the radiochemical stability, targeting specificity and pharmacokinetics of the 177Lutetium-labeled antibody. DOTA-Bevacizumab was efficiently labeled with 177LuCl3 at 37 °C. The in-vitro stability of labeled product was optimal over 72 h. In-vivo biodistribution studies showed a high liver and tumor uptake of 177Lu-DOTA-Bevacizumab, with tumor-to-muscle ratios of 11.58 and 6.37 at 24 and 48 h p.i. Scintigraphic imaging of melanoma tumor-bearing C57BL/6J mice showed liver and a high tumor selective uptake of 177Lu-DOTA-Bevacizumab at 24 h. Our results support the potential role of 177Lu-DOTA-Bevacizumab as a novel radioimmunotherapy agent for melanoma. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for Melanoma disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Intraocular 6-hydroxydopamine prevents the persistent estrus induced by continuous light.

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Shimizu, K; Hokano, M

1985-01-15

Following the intraocular injection of 6-hydroxydopamine, which can destroy the retinal dopaminergic neurons, female rats showed a normal estrous cycle in LD 12:12 but not a persistent estrus in continuous light.

Periodontal disease in a patient receiving Bevacizumab: a case report

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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.

Pharmacokinetics and efficacy of intraocular flurbiprofen.

Science.gov (United States)

Blazaki, S; Tsika, C; Tzatzarakis, M; Naoumidi, E; Tsatsakis, A; Tsatsanis, C; Tsilimbaris, Miltiadis K

2017-12-01

Intravitreal delivery of non-steroidal anti-inflammatory drugs could be an effective way to treat macular edema caused by posterior segment inflammation. In this study, we evaluated the intravitreal bioavailability and anti-inflammatory efficacy of flurbiprofen in rabbit eyes. For pharmacokinetics, 0.1 ml of 7.66 mg/ml flurbiprofen solution was injected intravitreally and vitreous drug levels were analyzed at specific time points using LC-MS technique. For efficacy, 100 ng lipopolysaccharide of E.coli was injected intravitreally in rabbits to induce inflammation. The animals were separated in three groups and received intraocular flurbiprofen, dexamethasone and PBS to serve as control. Complete ocular examination and total cell count in aqueous fluid were determined to evaluate the extent of inflammation. Eyes were then enucleated for histopathology analysis. The efficacy in the uveitis model was determined by clinical signs of inflammation, total leukocyte count and histology findings. No adverse events were observed during pharmacokinetic assessment. No signs of inflammation, hemorrhage or retina detachment were detected. The recovery of flurbiprofen from vitreous samples was 92.6%. The half-life of flurbiprofen was estimated to be 1.92 h with an elimination constant rate (K) of 0.36. Treatment with intraocular injections of flurbiprofen and dexamethasone significantly reduced total leukocyte count in a manner comparable to dexamethasone [reduction of 96.84% (p flurbiprofen injection compared to control eyes. Flurbiprofen is effective in suppressing inflammation in this experimental uveitis model. In our experimental setting, intravitreal flurbiprofen seem to have a therapeutic result comparable to dexamethasone. However, the half-life of the drug remains short, necessitating further research to prolong its presence in the vitreous cavity.

Comparing the Effectiveness of Bevacizumab to Ranibizumab in Patients with Exudative Age-Related Macular Degeneration. The BRAMD Study.

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A M E Schauwvlieghe

Full Text Available To compare the effectiveness of bevacizumab and ranibizumab in the treatment of exudative age-related macular degeneration (AMD.Multicentre, randomized, controlled, double-masked clinical trial in 327 patients. The non-inferiority margin was 4 letters.Patients ≥ 60 years of age with primary or recurrent sub- or juxtafoveal choroidal neovascularization (CNV secondary to AMD with a total area of CNV < 12 disc areas and a best corrected visual acuity (BCVA score between 20 and 78 letters on an EDTRS like chart in the study eye.Monthly intravitreal injections with 1.25 mg bevacizumab or 0.5 mg ranibizumab were given during one year. Intention to treat with last observation carried forward analysis was performed.Primary outcome was the change in BCVA in the study eye from baseline to 12 months.The mean gain in BCVA was 5.1 (±14.1 letters in the bevacizumab group (n = 161 and 6.4 (±12.2 letters in the ranibizumab group (n = 166 (p = 0.37. The lower limit of the 95% confidence interval of the difference in BCVA gain was 3.72. The response to bevacizumab was more varied; 24% of patients showed a gain of ≥15 letters, 11% a loss of ≥15 letters and 65% a gain or loss < 15 letters compared to 19%, 5% and 76% respectively for ranibizumab (p = 0.038. No significant differences in absolute CRT and CRT change (p = 0.13 or in the presence of subretinal or intraretinal fluid (p = 0.14 and 0.10, respectively were observed. However, the presence of any fluid on SD-OCT (subretinal and/or intraretinal differed significantly (p = 0.020, with definite fluid on SD-OCT in 45% of the patients for bevacizumab versus 31% for ranibizumab. The occurrence of serious adverse events and adverse events was similar, with 34 SAEs and 256 AEs in the bevacizumab group and 37 SAEs and 299 AEs in the ranibizumab group (p = 0.87 and p = 0.48, respectively.Bevacizumab was not inferior to ranibizumab. The response to bevacizumab was more varied with higher percentages of both

Bevacizumab (Avastin® no tratamento da membrana neovascular coroidal secundária à degeneração macular relacionada à idade: relato de caso Bevacizumab (Avastin® in treatment of choroidal neovascularization secondary to age-related macular degeneration: a case report

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Tiago Eugênio Faria e Arantes

2007-12-01

Full Text Available As drogas anti-angiogênicas foram introduzidas recentemente no arsenal terapêutico das membranas neovasculares coroidais. O objetivo deste relato é descrever um caso de membranas neovasculares coroidais oculta com extenso descolamento do epitélio pigmentado da retina, tratada com bevacizumab (Avastin® intravítrea. A eficácia da medicação foi avaliada por meio da acuidade visual e de exames complementares (angiografia fluoresceínica, videoangiografia com indocianina verde e tomografia de coerência óptica. Após três injeções intravítreas de bevacizumab, obteve-se uma resposta anatômica e visual satisfatória, denotando benefícios da droga, apesar do extenso descolamento do epitélio pigmentado da retina associada a membranas neovasculares coroidais oculta.The antiangiogenic drugs have been recently introduced in the therapeutic armamentarium of choroidal neovascularization. The purpose of this report is to describe a case of occult choroidal neovascularization with extensive retinal pigment epithelial detachment treated with intravitreal bevacizumab (Avastin®. The efficacy of the medication was evaluated by means of visual acuity and complementary exams (fluorescein angiography, indocyanine green video angiography and optical coherence tomography. After three intravitreal injections of bevacizumab a satisfactory anatomic and visual response was achieved, showing benefits of the drug, despite the extensive retinal pigment epithelial detachment associated with occult choroidal neovascularization.

Intraocular lens fabrication

Energy Technology Data Exchange (ETDEWEB)

Salazar, M.A.; Foreman, L.R.

1997-07-08

This invention describes a method for fabricating an intraocular lens made from clear Teflon{trademark}, Mylar{trademark}, or other thermoplastic material having a thickness of about 0.025 millimeters. These plastic materials are thermoformable and biocompatable with the human eye. The two shaped lenses are bonded together with a variety of procedures which may include thermosetting and solvent based adhesives, laser and impulse welding, and ultrasonic bonding. The fill tube, which is used to inject a refractive filling material is formed with the lens so as not to damage the lens shape. A hypodermic tube may be included inside the fill tube. 13 figs.

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

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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 bevac......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...

A Crossover Design for Comparative Efficacy: A 36-Week Randomized Trial of Bevacizumab and Ranibizumab for Diabetic Macular Edema.

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Wiley, Henry E; Thompson, Darby J S; Bailey, Clare; Chew, Emily Y; Cukras, Catherine A; Jaffe, Glenn J; Lee, Richard W J; Loken, Erin K; Meyerle, Catherine B; Wong, Wai; Ferris, Frederick L

2016-04-01

To investigate the comparative efficacy of bevacizumab (Avastin) and ranibizumab (Lucentis; both Genentech, Inc, South San Francisco, CA) for diabetic macular edema (DME) using a crossover study design. Randomized, double-masked, 36-week, 3-period crossover clinical trial. Fifty-six subjects with DME involving the center of the macula in one or both eyes. Monthly intravitreous injections of bevacizumab (1.25 mg) or ranibizumab (0.3 mg). Comparison of mean changes in visual acuity and central retinal thickness, tested using a linear mixed-effects model. Based on the linear mixed-effects model, the 3-month estimated mean improvement in visual acuity was 5.3 letters for bevacizumab and 6.6 letters for ranibizumab (difference, 1.3 letters; P = 0.039). Estimated change in optical coherence tomography (OCT) central subfield mean thickness (CSMT) was -89 μm for bevacizumab and -137 μm for ranibizumab (difference, 48 μm; P < 0.001). Incorporating cumulative treatment benefit, the model yielded a predicted 36-week (9-month) average improvement in visual acuity of 7.1 letters (95% confidence interval [CI], 5.0-9.2) for bevacizumab and 8.4 letters (95% CI, 6.3-10.5) for ranibizumab, and a change in OCT CSMT of -128 μm (95% CI, -155 to -100) for bevacizumab and -176 μm (95% CI, -202 to -149) for ranibizumab. There was no significant treatment-by-period interaction (i.e., treatment difference was constant in all 3 periods), nor was there a significant differential carryover effect from one period to the next. This trial demonstrated a statistically significant but small relative clinical benefit of ranibizumab compared with bevacizumab for treatment of DME, using a markedly reduced sample size relative to a full comparative efficacy study. The effects on visual acuity and central retinal thickness for the 2 drugs are consistent with those reported at 1 year for the concurrent parallel-group trial by the Diabetic Retinopathy Clinical Research Network testing bevacizumab

Evolution of Choroidal Neovascular Membrane in Best Disease after Single Intravitreal Bevacizumab. Case Report.

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Celea, Christiana; Pop, Mihai; Avidis-Zamfiroiu, Nicoleta; Celea, Cristian

2015-03-01

Best's disease is a hereditary form of macular dystrophy that starts in childhood and progresses until visual symptoms occur. In evolution it can be complicated with choroidal neovascularization, condition very rare in children. We report an important visual improvement in a 8-year-old caucasian girl after successful treatment with one intravitreal bevacizumab injection. There are few cases reported in literature (1-7), and the patient presented here have important particularities: one of the youngest children ever-mentioned with this complication, the third-member of her family with this disease and the first patient who didn't receive a second intravitreal bevacizumab at six weeks after first treatment, even though BCVA was lower than expected. The girl accused decrease of vision in the RE for the past 3-4 months. BCVA at presentation was 1/10. After 6 weeks from the intravitreal treatment, BCVA improved, but not very satisfactory (5/10). Because fundus and OCT aspects were encouraging, we waited another 4 weeks before the second injection. BCVA doubled in this period (8/10). Visual acuity, fundus and OCT aspects stabilized for 18 months of follow-up. We note that choroidal neovascular membrane associated with Best's disease can appear at such young children, this fact being very important in the phase of diagnosis, when the clinician should also take in consideration this possibility. Another important idea underlined here is the long-term efficacy of a single intravitreal anti-VEGF injection and also the no-need for imminent, fast re-treatment when the fundus and OCT aspects are encouraging through the follow-up.

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.

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.

Tachyphylaxis Following Intravitreal Bevacizumab for Exudative Age-Related Macular Degeneration

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Forooghian, Farzin; Cukras, Catherine; Meyerle, Catherine B.; Chew, Emily Y.; Wong, Wai T.

2009-01-01

Purpose To describe tachyphylaxis to intravitreal bevacizumab (IVB) in patients with exudative age-related macular degeneration (AMD). Methods We retrospectively reviewed the records of 59 consecutive patients treated with IVB at the National Eye Institute over a 14 month period, and identified cases demonstrating loss of treatment efficacy as revealed by spectral domain optical coherence tomography. We defined tachyphylaxis as a loss of therapeutic response to IVB 28±7 days after administration in an eye which had previously demonstrated a therapeutic response in the same time interval. Results Five patients (6 eyes) were identified as developing tachyphylaxis following repeated treatment with IVB. High-dose IVB (2.50mg) did not restore therapeutic response in these patients. Bilateral tachyphylaxis to IVB was seen following an episode of unilateral post-injection anterior uveitis. After the first treatment of IVB, the median time taken to develop tachyphylaxis was 100 weeks (range: 31-128 weeks), and the median number of IVB treatments to the development of tachyphylaxis was 8 treatments (range: 5-10). Conclusion Tachyphylaxis can occur following long-term intravitreal use of bevacizumab in patients with AMD. The precise mechanism of tachyphylaxis is unclear, but both local and/or systemic factors may be involved. PMID:19516114

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

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

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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.

Takotsubo cardiomyopathy in two men receiving bevacizumab for metastatic cancer

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Thérèse H Franco

2008-10-01

Full Text Available Thérèse H Franco, Ahmed Khan, Vishal Joshi, Beje ThomasDepartment of Internal Medicine, University of Connecticut, Farmington, CT, USAAbstract: Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF. It is a novel chemotherapeutic agent currently approved as part of combination chemotherapy for metastatic colorectal cancer, non-small cell lung cancer, and breast cancer (Hurwitz et al 2004; Sandler et al 2006; Traina et al 2007. Arterial thrombosis, including cerebral infarction, transient ischemic attacks, myocardial infarction, and angina are common, occurring in 4.4% of patients whose regimen includes bevacizumab (versus 1.9% on regimen without bevacizumab (Genetech, Inc. 2008. This series will review two cases of patients exposed to bevacizumab who subsequently developed ST elevations on electrocardiogram (ECG and elevated cardiac biomarkers. Both patients underwent cardiac catheterization, which demonstrated apical ballooning and akinesis in a distribution discordant with the observed (noncritical atherosclerotic lesions. Both patients had recovery of left ventricular function within 30 days. The clinical presentation, including ECGs and findings on catheterization as well as the rapid recovery of ventricular function, is consistent with the diagnosis of takotsubo cardiomyopathy. Takotsubo cardiomyopathy was first described in 1991, but the pathophysiology and exact mechanism of injury remain largely unknown. These two cases are notable for their occurrence in men and the association with treatment of metastatic cancer including bevacizumab.Keywords: vascular endothelial growth factor, bevacizumab, metastatic cancer, chemotherapy, takotsubo, cardiomyopathy

Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme

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Lassen, Ulrik; Sorensen, Morten; Gaziel, Tine Bernhardtsen

2013-01-01

standard temozolomide chemoradiotherapy and bevacizumab-containing second-line therapy, received temsirolimus (25 mg i.v.) on days 1 and 8 and bevacizumab (10 mg/kg) on day 8, every two weeks. Assessments were performed every eight weeks. Blood samples for biomarkers were collected weekly for the first...... eight weeks and at progression. The primary end-point was median progression-free survival (PFS) and secondary end-points were radiographic response, overall survival (OS), and safety of the bevacizumab-temsirolimus combination. RESULTS: Thirteen patients were included, whereof three went off....../10), infection (1/10), hypertension (1/10), and hyperglycemia (1/10). CONCLUSION: Temsirolimus can be safely administered in combination with bevacizumab. This study failed to detect activity of such a combination in patients with progressive GBM beyond bevacizumab therapy....

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

Effect of bevacizumab on radiation necrosis of the brain

International Nuclear Information System (INIS)

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

Safety of bilateral same-day intravitreal injections of anti-vascular endothelial growth factor agents

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Ruão M

2017-02-01

Full Text Available Miguel Ruão,1 María Andreu-Fenoll,2 Rosa Dolz-Marco,2 Roberto Gallego-Pinazo2 1Department of Ophthalmology, Centro Hospitalar Entre Douro e Vouga, Santa Maria da Feira, Portugal; 2Unit of Macula, Department of Ophthalmology, University and Polytechnic Hospital La Fe, Valencia, Spain Purpose: The aim was to evaluate the safety of bilateral same-day injections with intravitreal antiangiogenic drugs for macular diseases.Methods: Cross-sectional retrospective review of unilateral and bilateral same-day antiangiogenic injections was conducted between January 2011 and March 2016 in the Unit of Macula, University and Polytechnic Hospital La Fe (Valencia, Spain. A total of 8,172 injections were administered, among which 6,560 were unilateral and 1,612 were bilateral injections. Patients were included in the study regardless of the diagnosis. Ranibizumab and aflibercept were the antiangiogenic drugs used. The presence of endophthalmitis or retinal detachment was evaluated.Results: A total of 1 (0.012% culture-proven endophthalmitis and 19 (0.233% acute intraocular inflammations were registered. In the unilateral injections group, there were 18 (0.274% acute intraocular inflammations and 1 (0.015% culture-proven endophthalmitis. One (0.062% of the 1,612 bilateral same-day injections had a unilateral acute intraocular inflammation, and there were no culture-proven endophthalmitis in this group.Conclusion: Bilateral same-day injections are more convenient for patients and their caregivers than the unilateral injections administered on different days. In our study, the prevalence of culture-proven endophthalmitis and acute intraocular inflammation was lower in the bilateral injections than in the unilateral group. These data support the idea that bilateral same-day injections are a safe and valid treatment to use in our clinical practice. Keywords: bilateral, intravitreal, injections, anti-VEGF, endophthalmitis

Bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle.

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Rusovici, Raluca; Patel, Chirag J; Chalam, Kakarla V

2013-01-01

The purpose of this study was to evaluate cell cycle changes in choroidal endothelial cells treated with varying doses of bevacizumab in the presence of a range of concentrations of vascular endothelial growth factor (VEGF). Bevacizumab, a drug widely used in the treatment of neovascular age-related macular degeneration, choroidal neovascularization, and proliferative diabetic retinopathy, neutralizes all isoforms of VEGF. However, the effect of intravitreal administration of bevacizumab on the choroidal endothelial cell cycle has not been established. Monkey choroidal endothelial (RF/6A) cells were treated with VEGF 50 ng/mL and escalating doses of bevacizumab 0.1-2 mg/mL for 72 hours. Cell cycle changes in response to bevacizumab were analyzed by flow cytometry and propidium iodide staining. Cell proliferation was measured using the WST-1 assay. Morphological changes were recorded by bright field cell microscopy. Bevacizumab inhibited proliferation of choroidal endothelial cells by stabilization of the cell cycle in G0/G1 phase. Cell cycle analysis of VEGF-enriched choroidal endothelial cells revealed a predominant increase in the G2/M population (21.84%, P, 0.01) and a decrease in the G0/G1 phase population (55.08%, P, 0.01). Addition of escalating doses of bevacizumab stabilized VEGF-enriched cells in the G0/G1 phase (55.08%, 54.49%, 56.3%, and 64% [P, 0.01]) and arrested proliferation by inhibiting the G2/M phase (21.84%, 21.46%, 20.59%, 20.94%, and 16.1% [P, 0.01]). The increase in G0/G1 subpopulation in VEGF-enriched and bevacizumab-treated cells compared with VEGF-enriched cells alone was dose-dependent. Bevacizumab arrests proliferation of VEGF-enriched choroidal endothelial cells by stabilizing the cell cycle in the G0/G1 phase and inhibiting the G2/M phase in a dose-dependent fashion.

Abdominal wall perforation in a patient with recurrent epithelial ovarian cancer after bevacizumab treatment

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Efnan Algin

2016-08-01

Full Text Available Bowel perforation is a rare but well-described complication of bevacizumab, a VEGF monoclonal antibody. However, bevacizumab associated abdominal wall perforation is a more serious complication. In here, a patient with recurrent epithelial ovarian cancer developing both bowel and abdominal wall perforation after bevacizumab treatment is reported with review of the literature to point out the clinical significance of this rare complication. To our knowledge, this is the first case with bevacizumab associated abdominal wall perforation.

Comparison of the effect of intravitreal bevacizumab and intravitreal fasudil on retinal VEGF, TNFα, and caspase 3 levels in an experimental diabetes model

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Fatih Çelik

2014-02-01

Full Text Available AIM: To evaluate the influence of an intravitreal injection of bevacizumab and fasudil on the retinal vascular endothelial growth factor (VEGF, tumor necrosis factor alpha (TNFα, and caspase 3 levels in a diabetic rabbit model.RESULTS: There was a statistically significant difference in the VEGF and caspase 3 levels between groups (P=0.005 and P =0.013, respectively, but the TNFα level did not differ significantly between groups (P=0.792. It was found that VEGF levels were significantly lower in Group 1 and Group 3 than in Group 2 using the Mann-Whitney U test with the Bonferroni correction (P=0.004 for both comparison. There was no statistically significant difference between other groups with regard to VEGF levels (the P value ranged between 0.015 and 0.886. Although the P values of the caspase 3 levels were 0.015 for Group 1 and Group 4, 0.038 for Group 2 and Group 3, and 0.018 for Group 3 and Group 4, these P values remained above the threshold P value of 0.0083, which was the statistically significant level for post hoc tests.CONCLUSION: An intravitreal injection of bevacizumab decreased both the VEGF level, which plays a role in angiogenesis, and the caspase 3 level, which plays a role in apoptosis. Although not as effective as bevacizumab, fasudil had a beneficial effect on the VEGF levels but significantly increased the caspase 3 levels.

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

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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.

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...

Toxicity and efficacy of lomustine and bevacizumab in recurrent glioblastoma patients

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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......-bev is a well-tolerated treatment for recurrent GBM, although hematological toxicity may be a dose limiting factor. No significant differences between lom-bev and iri-bev were observed with regard to PFS or OS. The differences in toxicity profiles between lom-bev and iri-bev could guide treatment decision...

Treatment of Corneal Neovascularization Using Anti-VEGF Bevacizumab

Directory of Open Access Journals (Sweden)

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.

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.

Evaulation of Incidence and Risk Factors for Intraocular Pressure Elevation After Intravitreal Triamcinolone Acetonide Injection

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Didar Uçar

2015-05-01

Full Text Available Objectives: To investigate the effect of intravitreal triamcinolone acetonide (IVTA used for the macular edema on intraocular pressure (IOP and to determine the risk factors for IOP elevation. Materials and Methods: This retrospective study included 93 eyes of 85 patients who had 4 mg intravitreal triamcinolone injection. Of the 85 patients, 56 (65.8% had diabetic macular edema, 22 (25.8% had branch retinal, and 7 (8.2% had central retinal vein occlusion. IOP changes after injection as well as the relation between IOP elevation and age, sex, lens status, etiology of macular edema, baseline IOP were evaluated. Results: Fourty-six male and 39 female patients with mean age 61.58±9.5 years were evaluated. IOP was recorded to be >24 mmHg in 30 eyes (32.2% at follow-up visit after an average of 7.5 weeks. Normalization of IOP with medication was achieved in all IOP elevated eyes. Fifteen of 29 eyes (51.7% with vein occlusion and 15 of 64 eyes (23.3% with diabetic macula edema had IOP elevation (p=0.01. Twenty-six of 73 phakic (35.6% and 4 of 20 pseudophakic eyes (20% had IOP >24 mmHg (p=0.16. There was no association between IOP elevation and sex (p=0.33. Baseline IOP was 16.47±2.8 mmHg in eyes which had elevated IOP and 14.78±2.4 mmHg in the remaining. There was significant relation between IOP elevation and baseline IOP level (p=0.01. Conclusion: Elevated IOP is common side effect after IVTA, but normalization is usually achieved by topical medication. Patients with baseline IOP ≥15 mmHg and vein occlusion have higher risk for IOP elevation. (Turk J Ophthalmol 2015; 45: 86-91

Intravitreal bevacizumab (Avastin for post laser anterior segment ischemia in aggressive posterior retinopathy of prematurity

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Shah Parag

2007-01-01

Full Text Available Aggressive posterior retinopathy of prematurity (formerly known as fulminate/type II/rush disease occurs in zone 1 or posterior zone 2. Treatment involves extensive near confluent laser ablation of a large area of avascular retina. Anterior segment ischemia is a rare complication that can occur due to injury to the long posterior ciliary arteries in the horizontal meridians during aggressive posterior laser treatment. The outcome of this rare complication is very poor. This case describes a favorable outcome of intravitreal injection of bevacizumab (Avastin in a case of anterior segment ischemia.

Timing of Administration of Bevacizumab Chemotherapy Affects Wound Healing Following Chest Wall Port Placement

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Erinjeri, Joseph P; Fong, Abigail J; Kemeny, Nancy E; Brown, Karen T; Getrajdman, George I; Solomon, Stephen B

2010-01-01

The risk of a wound dehiscence requiring chest wall port explant in patients treated with bevacizumab is inversely proportional to the interval between bevacizumab administration and port placement. There is significantly higher risk of wound dehiscence when the interval between bevacizumab administration and chest wall port placement is less than 14 days.

Managed hypertensive crisis induced by bevacizumab in patient with metastatic lung adenocarcinoma

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Gracova, K.; Dolakova, L.

2015-01-01

Purpose and objective: The aim of the casuistry is to present a case report of a patient with metastatic lung adenocarcinoma and describe the successful management of hypertensive crisis, which is one of the most common cardiovascular complications of bevacizumab therapy. Casuistry: We describe 82-year old patient with lung adenocarcinoma verified by cytology of fluidothorax. Patient started chemotherapy in the scheme of carboplatin + paclitaxel with addition of bevacizumab since the third cycle. We provided a CT-scan which described partial tumour regression after six cycles of chemotherapy and four cycles of bevacizumab. Before the first cycle of maintenance therapy with bevacizumab patient overcame hypertensive crisis with neurological symptomatology which reacted positively to standard antihypertensives added to the therapy. After the stabilization we continued oncological treatment until disease progression and post chemotherapeutic ischemic colitis occurrence. Conclusion: Arterial hypertension is a common adverse effect of treatment with VEGF inhibitors. Considering the fact that the hypertension may occur at any time during the treatment with bevacizumab, blood pressure should be measured before, during and after the infusion. This side effect is reversible. On the basis of several case studies a positive association between arterial hypertension and prolonged survival in cancer patients has been found, as a difference from those without arterial hypertension during the treatment. Antihypertensive treatment does not reduce the antitumor effect of bevacizumab treatment. (author)

Delivery of Intraocular Triamcinolone Acetonide in the Treatment of Macular Edema

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Brent Siesky

2012-03-01

Full Text Available Macular edema (ME is one of the eventual outcomes of various intraocular and systemic pathologies. The pathogenesis for ME is not yet entirely understood; however, some of the common risk factors for its development have been identified. While this investigation will not discuss the numerous etiologies of ME in detail, it appraises the two most widely studied delivery modalities of intraocular corticosteroids in the treatment of ME—intravitreal injection (IVI and sub-Tenon’s infusion (STI. A thorough review of the medical literature was conducted to identify the efficacy and safety of IVI and STI, specifically for the administration of triamcinolone acetonide (TA, in the setting of ME in an attempt to elucidate a preferred steroid delivery modality for treatment of ME.

Iodogen-mediated radiolabeling of Bevacizumab with I-123 for clinical applications

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Lemps, R. de; Desruet, M.; Bacot, S.; Ahmadi, M.; Ghezzi, C.; Desruet, M.; Fagret, D.; Berger, F.

2014-01-01

Bevacizumab is a monoclonal antibody, directed against vascular endothelial growth factor (VEGF), and is currently used in various types of cancers (breast, lung, colorectal). In order to administer to humans glioblastomas, we developed its iodine 123 radiolabeling for in vitro and in vivo studies subsequent. The aim of the study is to choose the best radioiodination conditions based on feasibility in a hospital radiopharmacy: Quick one step method under mild condition, reproducible, using materials for pharmaceutical use and in a closed-system. Method Bevacizumab was radiolabeled with "1"2"3I using Iodogen, the most widely used oxidants in direct labelling techniques for tyrosyl residues-containing compounds. We have been explored two crucial parameters for clinical transfer: the amount of oxidant required (50μg and 100μg) and the choice of the purification column (size exclusion column or anion exchange resin), respectively. Quality control was performed before and after purification of each condition in order to evaluate the radiochemical purity (RCP) and purification efficiency. The stability of the radiolabeled molecule is evaluated over time and also when the solution is diluted with unlabeled bevacizumab. Moreover, the in vitro stability of "1"2"3I-bevacizumab was determined in presence of human blood at 15, 30, 60 and 120 min. Labeling yield before purification was 96.5% for the first condition (50μg Iodogen) and 95.5% for the second one (100μg Iodogen). The radiochemical purity was 99.5% after purification on a size exclusion column and 99% after purification on anion exchange resin. The purification yield with size exclusion column is 75%, compared with 81% of the anionic exchange resin. The stability in the labeling medium of "1"2"3I-bevacizumab at 3, 6, 24 and 30 h after labeling showed a RCP at 100%, 93%, 99.8% and 99.8% for condition 1 so that it was found to be 99.2%, 100%, 99.3%, 99.5% for condition 2, respectively. In vitro incubation with

Reinduction of Bevacizumab in Combination with Pegylated Liposomal Doxorubicin in a Patient with Recurrent Glioblastoma Multiforme Who Progressed on Bevacizumab/Irinotecan

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Mohammed Almubarak

2008-01-01

Full Text Available Glioblastoma multiforme (GBM carries a dismal prognosis despite the current standard of multimodality treatments. Recent studies showed promising results to a regimen consisting of a VEGF inhibitor, (bevacizumab and a topoisomerase I inhibitor (irinotecan [BI] in recurrent GBM. However, those patients with GBM who progress on BI will succumb to their disease generally in a very short period of time. We report a case of a 56-year-old male patient with GBM who declined surgical resection and received chemoradiation with temozolomide. This treatment was withheld secondary to significant thrombocytopenia. Subsequently, he achieved stable disease for 10 months with a regimen consisting of thalidomide and tamoxifen before progressing. This was followed by bevacizumab with irinotecan [BI], for which he had a significant partial response for 8 months with subsequent progression. Reinducing the patient with bevacizumab in combination with a pegylated liposomal doxorubicin [PLD] (a topoisomerase II inhibitor demonstrated antitumor activity with significant shrinkage of contrast enhancing mass and peritumoral edema.

Sigmoid-vaginal fistula during bevacizumab treatment diagnosed by fistulography.

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Hayashi, C; Takada, S; Kasuga, A; Shinya, K; Watanabe, M; Kano, H; Takayama, T

2016-12-01

There have been several reports describing rectovaginal fistula development after bevacizumab treatment, and these fistulas were diagnosed by CT scan or colonoscopy. We report a case of sigmoid-vaginal fistula diagnosed by fistulography. The case is a 53-year-old woman who was treated for chronic myelogenous leukaemia and gynaecological cancers 8 years previously. At 52 years of age, she was diagnosed with colon cancer and had a partial colectomy performed. One year after surgery, colon cancer recurred, and she was treated with anticancer agents, including bevacizumab. During chemotherapy, she complained of a foul smelling discharge from the vagina. Fistulography revealed a sigmoid-vaginal fistula. This is the first report of vaginal fistulography performed on a patient who was treated with bevacizumab. Fistulography may be useful for detecting sigmoid-vaginal fistula. © 2016 John Wiley & Sons Ltd.

Intraocular pressure reduction and regulation system

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Baehr, E. F.; Burnett, J. E.; Felder, S. F.; Mcgannon, W. J.

1979-01-01

An intraocular pressure reduction and regulation system is described and data are presented covering performance in: (1) reducing intraocular pressure to a preselected value, (2) maintaining a set minimum intraocular pressure, and (3) reducing the dynamic increases in intraocular pressure resulting from external loads applied to the eye.

[Treatment of macular hematoma complicating AMD by vitrectomy, subretinal r-TPA injection, intravitreal injection of bevacizumab combined with gas tamponade: Report of 4 cases].

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Abboud, M; Benzerroug, M; Milazzo, S

2017-02-01

The occurrence of a subretinal hematoma in age-related macular degeneration (AMD) is a serious complication that can impact the visual prognosis with a poor functional recovery. The management of this complication remains controversial. Several therapeutic methods have been described. We report the results of four patients treated with a protocol combining: vitrectomy, subretinal injection of r-TPA 0.025mg/0.3ml, intravitreal injection of 0.05ml of bevacizumab and retinal tamponade with 20% SF6 gas. Our series consists of four patients with a submacular hematoma complicating AMD, included in succession between October 2013 and October 2014 and treated with the same treatment protocol and by the same surgeon. All patients underwent surgery within eight days after the onset of the macular hematoma. Patients with a consultation period longer than eight days did not undergo this treatment. Face down postoperative positioning was then carried out for seven days by the patients. We observed a shift in the macular hematoma in the four patients, which allowed the identification of secondary neovascularization responsible for the bleeding. The visual acuity improved in three patients from hand motion (HM) preoperatively to 2/10 at one month postoperatively. One patient maintained visual acuity 1/20 during the entire follow-up despite almost complete resorption of the subretinal hematoma. These visual acuities were stable at 6 months postoperatively. Macular subretinal hematoma can cause severe visual loss by several mechanisms. The blood accumulates between the neurosensory retina and the retinal pigment epithelium, which causes a toxic effect on the surrounding tissues, thus resulting in a loss of photoreceptors and cellular destruction in the pigment epithelium and choriocapillaris, evolving into a fibroglial scar. The therapeutic evaluation of this protocol in our series of four patients gives a favorable result. We observed an improvement in visual acuity in 3/4 of

Bevacizumab for Metastatic Colorectal Cancer: A Global Cost-Effectiveness Analysis.

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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.

Anti-angiogenic treatment (Bevacizumab) improves the responsiveness of photodynamic therapy in colorectal cancer.

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Peng, Cheng-Liang; Lin, Hua-Ching; Chiang, Wei-Lun; Shih, Ying-Hsia; Chiang, Ping-Fang; Luo, Tsai-Yueh; Cheng, Chun-Chia; Shieh, Ming-Jium

2018-06-09

Photodynamic therapy (PDT) is a new treatment utilizing the combined action of photosensitizers and light for the treatment of various cancers. The mechanisms for tumor destruction after PDT include direct tumor cell kill by singlet oxygen species (OS), indirect cell kill via vascular damage, and an elicited immune response. However, it has been reported that many cellular activators, including vascular endothelial growth factor (VEGF), are produced by tumor cells after PDT. In this study, we demonstrate that meta-tetra(hydroxyphenyl) chlorin (mTHPC)-based photodynamic therapy combined with bevacizumab (Avastin™), an anti-VEGF neutralizing monoclonal antibody that blocks the binding of VEGF to its receptor, can enhance the effectiveness of each treatment modality. We evaluated the efficacy of bevacizumab-based anti-angiogenesis in combination with PDT as well as the resulting VEGF levels in a mouse model of human colon cancer. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were performed to assess VEGF concentrations in the various treatment groups, and confocal imaging and high performance liquid chromatography (HPLC) analyses were used to measure the distribution and concentration of mTHPC in tumors. Our results demonstrate that combination of PDT followed by bevacizumab significantly elicits a greater tumor response whereas bevacizumab treatment prior to PDT led to a reduced tumor response. Immunostaining and ELISA analyses revealed a lower expression of VEGF in tumors treated with combination therapy of PDT followed by bevacizumab. However, bevacizumab treatment decreased the accumulation of mTHPC in tumors 24 h after administration, which complemented the results of decreased anti-tumor efficacy of bevacizumab followed by PDT. Copyright © 2018. Published by Elsevier B.V.

Intraocular (Eye) Melanoma—Health Professional Version

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Intraocular (uveal) melanoma of the uveal tract (iris, ciliary body, and choroid), though rare, is the most common primary intraocular malignancy in adults. Find evidence-based information on intraocular melanoma treatment.

[A case of intragastric wall abscess formation during bevacizumab combined chemotherapy].

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Mori, Ayano; Kogawa, Takahiro; Arihara, Youhei; Abe, Masakazu; Tamura, Fumito; Abe, Seiichirou; Kukitsu, Takehiro; Ihara, Hideyuki; Sumiyoshi, Tetsuya; Yoshizaki, Naoto; Kondou, Hitoshi; Tsuji, Yasushi

2013-05-01

A 38-year-old man was given a diagnosis of as sigmoid colon cancer and underwent sigmoid colectomy. Post-operative pathological staging was stage IIIb. He then underwent adjuvant chemotherapy. One year and 4 months after the surgery, CT scans revealed multiple liver and lung metastases. He was given mFOLFOX6+bevacizumab, which was changed later to FOLFIRI+bevacizumab. After these chemotherapies, he was admitted to the hospital due to sudden abdominal pain and high grade fever. Obstructive jaundice was initially diagnosed, but detailed study of initial CT revealed intragastric wall abscess. After the drainage of the abscess, his conditions improved. We speculated that the abscess formation was caused by mucosal damage due to bevacizumab.

Third-line therapy in recurrent glioblastoma: is it another chance for bevacizumab?

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Franceschi, Enrico; Lamberti, Giuseppe; Paccapelo, Alexandro; Di Battista, Monica; Genestreti, Giovenzio; Minichillo, Santino; Mura, Antonella; Bartolini, Stefania; Agati, Raffaele; Brandes, Alba A

2018-04-18

Standard glioblastoma therapy is long-lasting. Among second-line therapy, choices could be bevacizumab and nitrosoureas depending on National Agencies approval. There is no consensus on 3rd line therapy or clinical trials specifically designed for this setting. We reviewed our institutional database on all consecutive patients who received 3rd line therapy for glioblastoma. Data on 168 out of 1337 (12.6%) glioblastoma patients who underwent 3rd line therapy treatment were collected. Third line treatments were bevacizumab or chemotherapy (nitrosourea, temozolomide or carboplatin plus etoposide). Median progression free survival was 2.9 months and median survival time was 6.6 months from the start of 3rd line therapy. Bevacizumab significantly improved progression-free survival (4.7 vs. 2.6 months, p = .020) and survival from 3rd line start (8.0 vs. 6.0 months, p = .014) in respect to chemotherapy. Toxicity of grade ≥ 3 occurred in 13.7% of patients. In multivariate analysis, survival in 3rd line treatment depends on MGMT methylation (p = .006) and treatment with Bevacizumab (p = .011). Third line therapy in selected glioblastoma patients may be feasible and well tolerated. Bevacizumab improved outcome in 3rd line in respect to chemotherapy.

Motorized injector-assisted intrascleral intraocular lens fixation.

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Hung, Jia-Horung; Wang, Shih-Hao; Teng, Yu-Ti; Hsu, Sheng-Min

2017-03-01

For eyes with deficient capsular support, intraocular lens (IOL) implantation has long been a technical challenge. Recently, intrascleral fixation of the haptics of a three-piece posterior chamber IOL has become a popular option. In this procedure, externalization of the leading haptic during IOL injection is a stressful step. We present a modified technique to improve the ease and safety of this step. Our modified technique involves IOL injection with a motorized injector with several important modifications described here. With these modifications, a surgeon can easily maintain the correct orientation of the IOL in a well-controlled manner during IOL injection. The records of 13 patients who underwent this technique were retrospectively evaluated. Corrected-distance visual acuity improved significantly after surgery (pIOL decentration, or vitreous hemorrhage was noted during the follow-up period. In conclusion, the motorized injector-assisted intrascleral IOL fixation technique is a safe and effective alternative to the conventional procedure. This technique makes the process of leading haptic externalization easier and more controllable. Copyright © 2017. Published by Elsevier Taiwan.

Motorized injector-assisted intrascleral intraocular lens fixation

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Jia-Horung Hung

2017-03-01

Full Text Available For eyes with deficient capsular support, intraocular lens (IOL implantation has long been a technical challenge. Recently, intrascleral fixation of the haptics of a three-piece posterior chamber IOL has become a popular option. In this procedure, externalization of the leading haptic during IOL injection is a stressful step. We present a modified technique to improve the ease and safety of this step. Our modified technique involves IOL injection with a motorized injector with several important modifications described here. With these modifications, a surgeon can easily maintain the correct orientation of the IOL in a well-controlled manner during IOL injection. The records of 13 patients who underwent this technique were retrospectively evaluated. Corrected-distance visual acuity improved significantly after surgery (p<0.05. No postoperative retinal detachment, endophthalmitis, IOL decentration, or vitreous hemorrhage was noted during the follow-up period. In conclusion, the motorized injector-assisted intrascleral IOL fixation technique is a safe and effective alternative to the conventional procedure. This technique makes the process of leading haptic externalization easier and more controllable.

Intravitreally Injected Anti-VEGF Antibody Reduces Brown Fat in Neonatal Mice.

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Jo, Dong Hyun; Park, Sung Wook; Cho, Chang Sik; Powner, Michael B; Kim, Jin Hyoung; Fruttiger, Marcus; Kim, Jeong Hun

2015-01-01

Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants.

Intravitreally Injected Anti-VEGF Antibody Reduces Brown Fat in Neonatal Mice.

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Dong Hyun Jo

Full Text Available Anti-vascular endothelial growth factor (VEGF agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants.

The use of bevacizumab in a multilevel retinal hemorrhage secondary to retinal macroaneurysm: a 39-month follow-up case report

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Tsakpinis, Dimitrios; Nasr, Mayssa B; Tranos, Paris; Krassas, Nikos; Giannopoulos, Theodoros; Symeonidis, Chrysanthos; Dimitrakos, Stavros A; Konstas, Anastasios GP

2011-01-01

Purpose The evaluation of long-term visual outcome after the use of bevacizumab for the management of multilevel hemorrhage due to retinal arterial macroaneurysm (MA). Case report A 71-year-old hypertensive female presented with sudden reduction of visual acuity in her left eye (OS). Fundoscopy revealed an arterial macroaneurysm with preretinal and subretinal hemorrhage in the eye. Due to significant macular involvement, the patient received two intravitreal injections of bevacizumab within 2 months. Results Significant visual and anatomical recovery was observed 2 months later, which was confirmed by fluorescein angiography. At the end of a follow-up period (39 months) visual acuity and visual field were at normal levels. Conclusion Retinal MA is a relatively rare condition. Anti-vascular endothelial growth factor therapy appears a safe and effective treatment option for selected symptomatic individuals that may offer faster visual rehabilitation. Herein we report, for the first time, a 39-month follow-up of a retinal MA treated with anti-vascular endothelial growth factor therapy. PMID:22069349

The use of bevacizumab in a multilevel retinal hemorrhage secondary to retinal macroaneurysm: a 39-month follow-up case report

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Tsakpinis D

2011-10-01

Full Text Available Dimitrios Tsakpinis1, Mayssa B Nasr1,2, Paris Tranos3, Nikos Krassas1, Theodoros Giannopoulos2, Chrysanthos Symeonidis1, Stavros A Dimitrakos1, Anastasios GP Konstas212nd University Department of Ophthalmology, Papageorgiou Hospital; 2Glaucoma Unit, 1st University, Department of Ophthalmology, AHEPA Hospital, Thessaloniki, Greece; 3Retina Eye Center, Thessaloniki, GreecePurpose: The evaluation of long-term visual outcome after the use of bevacizumab for the management of multilevel hemorrhage due to retinal arterial macroaneurysm (MA.Case report: A 71-year-old hypertensive female presented with sudden reduction of visual acuity in her left eye (OS. Fundoscopy revealed an arterial macroaneurysm with preretinal and subretinal hemorrhage in the eye. Due to significant macular involvement, the patient received two intravitreal injections of bevacizumab within 2 months.Results: Significant visual and anatomical recovery was observed 2 months later, which was confirmed by fluorescein angiography. At the end of a follow-up period (39 months visual acuity and visual field were at normal levels.Conclusion: Retinal MA is a relatively rare condition. Anti-vascular endothelial growth factor therapy appears a safe and effective treatment option for selected symptomatic individuals that may offer faster visual rehabilitation. Herein we report, for the first time, a 39-month follow-up of a retinal MA treated with anti-vascular endothelial growth factor therapy.Keywords: arterial retinal macroaneurysm, anti-VEGF, bevacizumab, multilevel hemorrhage

[¹⁸F]fluorothymidine-positron emission tomography in patients with locally advanced breast cancer under bevacizumab treatment: usefulness of different quantitative methods of tumor proliferation.

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Marti-Climent, J M; Dominguez-Prado, I; Garcia-Velloso, M J; Boni, V; Peñuelas, I; Toledo, I; Richter, J A

2014-01-01

To investigate quantitative methods of tumor proliferation using 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT) PET in patients with breast cancer (BC), studied before and after one bevacizumab administration, and to correlate the [(18)F]FLT-PET uptake with the Ki67 index. Thirty patients with newly diagnosed, untreated BC underwent a [(18)F]FLT-PET before and 14 days after bevacizumab treatment. A dynamic scan centered over the tumor began simultaneously with the injection of [(18)F]FLT (385 ± 56 MBq). Image derived input functions were obtained using regions of interest drawn on the left ventricle (LV) and descending aorta (DA). Metabolite corrected blood curves were used as input functions to obtain the kinetic Ki constant using the Patlak graphical analysis (time interval 10-60 min after injection). Maximum SUV values were derived for the intervals 40-60 min (SUV40) and 50-60 min (SUV50). PET parameters were correlated with the Ki67 index obtained staining tumor biopsies. [(18)F]FLT uptake parameters decreased significantly (p<0.001) after treatment: SUV50=3.09 ± 1.21 vs 2.22 ± 0.96; SUV40=3.00 ± 1.18 vs 2.14 ± 0.95, Ki_LV(10-3)=52[22-116] vs 38[13-80] and Ki_DA(10-3)=49[15-129] vs 33[11-98]. Consistency interclass correlation coefficients within SUV and within Ki were high. Changes of SUV50 and Ki_DA between baseline PET and after one bevacizumab dose PET correlated with changes in Ki67 index (r-Pearson=0.35 and 0.26, p=0.06 and 0.16, respectively). [(18)F]FLT-PET is useful to demonstrate proliferative changes after a dose of bevacizumab in patients with BC. Quantification of tumor proliferation by means of SUV and Ki has shown similar results, but SUV50 obtained better results. A correlation between [(18)F]FLT changes and Ki67 index was observed. Copyright © 2013 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

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)

Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis

OpenAIRE

Nagai, Toshihiro; Sato, Masato; Kobayashi, Miyuki; Yokoyama, Munetaka; Tani, Yoshiki; Mochida, Joji

2014-01-01

Introduction Angiogenesis is an important factor in the development of osteoarthritis (OA). We investigated the efficacy of bevacizumab, an antibody against vascular endothelial growth factor and an inhibitor of angiogenesis, in the treatment of OA using a rabbit model of anterior cruciate ligament transection. Methods First, we evaluated the response of gene expression and histology of the normal joint to bevacizumab treatment. Next, in a rabbit model of OA induced by anterior cruciate ligam...

[Correlation of intraocular pressure variation after visual field examination with 24-hour intraocular pressure variations in primary open-angle glaucoma].

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Noro, Takahiko; Nakamoto, Kenji; Sato, Makoto; Yasuda, Noriko; Ito, Yoshinori; Ogawa, Shumpei; Nakano, Tadashi; Tsuneoka, Hiroshi

2014-10-01

We retrospectively examined intraocular pressure variations after visual field examination in primary open angle glaucoma (POAG), together with its influencing factors and its association with 24-hour intraocular pressure variations. Subjects were 94 eyes (52 POAG patients) subjected to measurements of 24-hour intraocular pressure and of changes in intraocular pressure after visual field examination using a Humphrey Visual Field Analyzer. Subjects were classified into three groups according to the magnitude of variation (large, intermediate and small), and 24-hour intraocular pressure variations were compared among the three groups. Factors influencing intraocular pressure variations after visual field examination and those associated with the large variation group were investigated. Average intraocular pressure variation after visual field examination was -0.28 ± 1.90 (range - 6.0(-) + 5.0) mmHg. No significant influencing factors were identified. The intraocular pressure at 3 a.m. was significantly higher in the large variation group than other two groups (p field examination. Increases in intraocular pressure during the night might be associated with large intraocular pressure variations after visual field examination.

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

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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

Intravitreal Bevacizumab and Triamcinolone for Treatment of Cystoid Macular Oedema Associated with Chronic Myeloid Leukaemia and Imatinib Therapy

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Eric K. Newcott

2015-01-01

Full Text Available Purpose. To evaluate the efficacy of intravitreal bevacizumab and triamcinolone in the treatment of cystoid macular oedema in a case with chronic myeloid leukaemia on imatinib treatment. Methods. We treated a 78-year-old man with bilateral cystoid macular oedema with intravitreal triamcinolone and subsequent bevacizumab in one eye and intravitreal bevacizumab, alone, in the fellow eye. Results. Serial intravitreal bevacizumab with and without triamcinolone treated cystoid macular oedema in both eyes and improved the vision. Conclusion. Intravitreal bevacizumab and triamcinolone could be viable options to treat cystoid macular oedema due to chronic myeloid leukaemia and imatinib therapy.

Bevacizumab in Treatment of High-Risk Ovarian Cancer—A Cost-Effectiveness Analysis

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Herzog, Thomas J.; Hu, Lilian; Monk, Bradley J.; Kiet, Tuyen; Blansit, Kevin; Kapp, Daniel S.; Yu, Xinhua

2014-01-01

Objective. The objective of this study was to evaluate a cost-effectiveness strategy of bevacizumab in a subset of high-risk advanced ovarian cancer patients with survival benefit. Methods. A subset analysis of the International Collaboration on Ovarian Neoplasms 7 trial showed that additions of bevacizumab (B) and maintenance bevacizumab (mB) to paclitaxel (P) and carboplatin (C) improved the overall survival (OS) of high-risk advanced cancer patients. Actual and estimated costs of treatment were determined from Medicare payment. Incremental cost-effectiveness ratio per life-year saved was established. Results. The estimated cost of PC is $535 per cycle; PCB + mB (7.5 mg/kg) is $3,760 per cycle for the first 6 cycles and then $3,225 per cycle for 12 mB cycles. Of 465 high-risk stage IIIC (>1 cm residual) or stage IV patients, the previously reported OS after PC was 28.8 months versus 36.6 months in those who underwent PCB + mB. With an estimated 8-month improvement in OS, the incremental cost-effectiveness ratio of B was $167,771 per life-year saved. Conclusion. In this clinically relevant subset of women with high-risk advanced ovarian cancer with overall survival benefit after bevacizumab, our economic model suggests that the incremental cost of bevacizumab was approximately $170,000. PMID:24721817

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

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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.

The Effect of Intravitreal Bevacizumab on Apoptosis of Rat Retina Cells

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Özcan Kayıkçıoğlu

2013-01-01

Full Text Available Pur po se: To investigate the apoptotic effects of intravitreal bevacizumab on rat retinal cells. Ma te ri al and Met hod: Thirty-six male adult Swiss albino rats were randomly divided into two groups. The first group was applied 0.25 mg bevacizumab in 0.01 ml saline, and the second group received the same amount of saline intravitreally. Each group was divided into 3 subgroups. The animals were sacrificed and their globes were enucleated at the 3rd, 24th, and 72nd hours of the experiment. Enucleated eyes were preserved for histological analysis, immunohistochemical analysis of caspase-3, caspase-8, caspase-9, Fas/Fas L, VEGF and VEGF receptors (Flt-1, Flk-1, and TUNEL staining. Re sults: Histological evaluation showed no sign of retinal toxicity in both groups. In TUNEL staining, TUNEL(+ cells were detected in all subgroups, but the number of positive cells was relatively lower in bevacizumab treatment group that reached statistically significant level at 24 and 72 hours of treatment (p<0.001. Immunohistochemical analysis revealed that in saline-treated subgroups, immunoreactivity was more pronounced for all apoptosis-inducing proteins compared to bevacizumab-treated group. Also immunoreactivity of VEGF was prominent in saline treated group. For VEGF receptors, staining was only positive for Flt-1 at the 3rd hour in the control group. Dis cus si on: Bevacizumab did not have apoptosis-inducing potential compared to saline solution in short term, which was documented with TUNEL and immunohistochemical staining. (Turk J Ophthalmol 2013; 43: 39-44

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

Safety and Efficacy of Bevacizumab With Hypofractionated Stereotactic Irradiation for Recurrent Malignant Gliomas

International Nuclear Information System (INIS)

Gutin, Philip H.; Iwamoto, Fabio M.; Beal, Kathryn; Mohile, Nimish A.; Karimi, Sasan; Hou, Bob L.; Lymberis, Stella; Yamada, Yoshiya; Chang, Jenghwa

2009-01-01

Purpose: Preclinical studies suggest that inhibition of vascular endothelial growth factor (VEGF) improves glioma response to radiotherapy. Bevacizumab, a monoclonal antibody against VEGF, has shown promise in recurrent gliomas, but the safety and efficacy of concurrent bevacizumab with brain irradiation has not been extensively studied. The objectives of this study were to determine the safety and activity of this combination in malignant gliomas. Methods and Materials: After prior treatment with standard radiation therapy patients with recurrent glioblastoma (GBM) and anaplastic gliomas (AG) received bevacizumab (10 mg/kg intravenous) every 2 weeks of 28-day cycles until tumor progression. Patients also received 30 Gy of hypofractionated stereotactic radiotherapy (HFSRT) in five fractions after the first cycle of bevacizumab. Results: Twenty-five patients (20 GBM, 5 AG; median age 56 years; median Karnofsky Performance Status 90) received a median of seven cycles of bevacizumab. One patient did not undergo HFSRT because overlap with prior radiotherapy would exceed the safe dose allowed to the optic chiasm. Three patients discontinued treatment because of Grade 3 central nervous system intratumoral hemorrhage, wound dehiscence, and bowel perforation. Other nonhematologic and hematologic toxicities were transient. No radiation necrosis was seen in these previously irradiated patients. For the GBM cohort, overall response rate was 50%, 6-month progression-free survival was 65%; median overall survival was 12.5 months, and 1-year survival was 54%. Discussion: Bevacizumab with HFSRT is safe and well tolerated. Radiographic responses, duration of disease control, and survival suggest that this regimen is active in recurrent malignant glioma.

Intravitreal injection therapy in the treatment of noninfectious uveitis.

Science.gov (United States)

Modorati, Giulio; Miserocchi, Elisabetta

2012-01-01

Uveitis is responsible for 5-20% of legal blindness in the United States and in Europe. In noninfectious uveitis, the most frequent uveitic complication that endangers sight is cystoid macular edema. Clinical characteristics, inflammation grading and visual acuity determine the choice of the correct therapy for each patient. We can utilize drugs either alone or in combination using different dosages and routes of administration. Intravitreal injection directly into the vitreous cavity leads to rapid therapeutic drug concentration in the retinal tissue and reduces systemic side effects. Intravitreally injected triamcinolone acetonide is the most powerful drug for the treatment of cystoid macular edema related to intraocular inflammation, but it also causes the most frequent and serious side effects. Due to the numerous side effects associated with the use of corticosteroids, there is a need to identify other anti-inflammatory agents with a better safety profile. Recent studies have demonstrated that intravitreal immunosuppressant injections of methotrexate or anti-VEGF agents may lead to fewer intraocular side effects, but also have a lower therapeutic activity for the reduction of macular edema. At present, intraocular anti-TNF-α drugs do not show promising results. As regards nonsteroidal anti-inflammatory drugs, further data are necessary to fully understand their efficacy and potential side effects. Copyright © 2012 S. Karger AG, Basel.

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.

Transarterial chemoembolization plus or minus intravenous bevacizumab in the treatment of hepatocellular cancer: A pilot study

International Nuclear Information System (INIS)

Britten, Carolyn D; Gomes, Antoinette S; Wainberg, Zev A; Elashoff, David; Amado, Rafael; Xin, Yan; Busuttil, Ronald W; Slamon, Dennis J; Finn, Richard S

2012-01-01

Stimulation of vascular endothelial growth factor (VEGF) has been observed following transarterial chemoembolization (TACE) in hepatocellular cancer (HCC) and may contribute to tumor regrowth. This pilot study examined whether intravenous (IV) bevacizumab, a monoclonal antibody against VEGF, could inhibit neovessel formation after TACE. 30 subjects with HCC undergoing TACE at a single academic institution were randomized with a computer-generated allocation in a one to one ratio to either bevacizumab at a dose of 10 mg/kg IV every 14 days beginning 1 week prior to TACE (TACE-BEV arm) or observation (TACE-O arm). Angiography was performed with TACE at day 8, and again at weeks 10 and 14. Repeat TACE was performed at week 14 if indicated. TACE-BEV subjects were allowed to continue bevacizumab beyond week 16. TACE-O subjects were allowed to cross-over to bevacizumab at week 16 in the setting of progressive disease. The main outcome measure was a comparison of neovessel formation by serial angiography. Secondary outcome measures were progression free survival (PFS) at 16 weeks, overall survival (OS), bevacizumab safety, and an analysis of VEGF levels before and after TACE with and without bevacizumab. Among the 30 subjects enrolled, 9 of 15 randomized to the TACE-O arm and 14 of 15 randomized to the TACE-BEV arm completed all 3 angiograms. At week 14, 3 of 9 (33%) TACE-O subjects and 2 of 14 (14%) TACE-BEV subjects demonstrated neovascularity. The PFS at 16 weeks was 0.19 in the TACE-O arm and 0.79 in the TACE-BEV arm (p = 0.021). The median OS was 61 months in the TACE-O arm and 49 months in the TACE-BEV arm (p = 0.21). No life-threatening bevacizumab-related toxicities were observed. There were no substantial differences in bevacizumab pharmacokinetics compared to historical controls. Bevacizumab attenuated the increase in VEGF observed post-TACE. IV bevacizumab was well tolerated in selected HCC subjects undergoing TACE, and appeared to diminish neovessel formation

Safety of bevacizumab in clinical practice for recurrent ovarian cancer: A retrospective cohort study

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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

Systematic review and economic evaluation of bevacizumab and cetuximab for the treatment of metastatic colorectal cancer.

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Tappenden, P; Jones, R; Paisley, S; Carroll, C

2007-03-01

To assess the clinical effectiveness and cost-effectiveness of bevacizumab and cetuximab in the treatment of individuals with metastatic colorectal cancer (CRC). Searches of main electronic databases were conducted in April and May 2005. For the assessment of bevacizumab, trials were included if they recruited participants with untreated metastatic CRC for first-line treatment. Only trials comparing bevacizumab in combination with irinotecan and/or established fluorouracil (5-FU)-containing or releasing regimens given as first-line therapy were included. For the assessment of cetuximab, trials were included if they recruited participants with epidermal growth-factor receptor-expressing metastatic CRC who had previously failed irinotecan-including therapy. Independent cost-effectiveness models of bevacizumab and cetuximab were developed using survival modelling methods. Adding bevacizumab to irinotecan in combination with 5-FU/folic acid (FA) plus irinotecan resulted in a statistically significant increase in median overall survival (OS) of 4.7 months. Adding bevacizumab to 5-FU/FA resulted in a non-significant increase in median OS of 3.7 months within one study and 7.7 months in another. Adding bevacizumab to irinotecan, fluorouracil and leucovorin (IFL) resulted in a statistically significant increase in median progression-free survival (PFS) of 4.4 months. Adding bevacizumab to 5-FU/FA resulted in a statistically significant increase in median PFS of 3.7 months, and a statistically significant increase in time to disease progression of 3.8 months compared to FU/FA alone. An overall tumour response rate of 44.8% was reported for bevacizumab plus IFL compared to 34.8% for IFL plus placebo. This addition was statistically significant. The addition of bevacizumab to 5-FU/FA resulted in a significant difference in tumour response rate within one study, but not another. Bevacizumab in combination with IFL or 5-FU/FA was observed to result in an increase of grade 3

Indications and Treatment Outcomes of Intravitreal Bevacizumab ...

African Journals Online (AJOL)

Bevacizumab and Ranibizumab for Retinal Diseases in Benin. City, Nigeria. Odarosa M. .... travel costs and risk of complications such as endophthalmitis and retinal detachment ... antiVEGF to be utilised considering reports of increased risk of.

Simultaneous application of bevacizumab and anti-CTGF antibody effectively suppresses proangiogenic and profibrotic factors in human RPE cells.

Science.gov (United States)

Bagheri, Abouzar; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Samiei, Shahram; Sheibani, Nader; Astaneh, Shamila Darvishalipour; Kanavi, Mozhgan Rezaei; Mohammadian, Azam

2015-01-01

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. 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. 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. Treatment of RPE cells with the combination of bevacizumab and anti-CTGF could effectively suppress the proangiogenic and profibrotic activity of RPE cells.

Inhibition of Corneal Neovascularization with the Combination of Bevacizumab and Plasmid Pigment Epithelium-Derived Factor-Synthetic Amphiphile INTeraction-18 (p-PEDF-SAINT-18 Vector in a Rat Corneal Experimental Angiogenesis Model

Directory of Open Access Journals (Sweden)

Ching-Hsein Chen

2013-04-01

Full Text Available Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonal antibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeability properties. In this study, we demonstrated that the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18 (p-PEDF-SAINT-18 has a favorable antiangiogenic effect on corneal NV. Four groups (Group A: 0 μg + 0 μg, B: 0.1 μg + 0.1 μg, C: 1 μg + 1 μg, and D: 10 μg + 10 μg of bevacizumab + p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus on the temporal side. Then, 1 μg of p-bFGF-SAINT-18 was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. The inhibition of NV was observed and quantified from days 1 to 60. Biomicroscopic examination, western blot analysis and immunohistochemistry were used to analyze the 18-kDa bFGF, 50-kDa PEDF and VEGF protein expression. No inhibition activity for normal limbal vessels was noted. Subconjunctival injection with the combination of bevacizumab and p-PEDF-SAINT-18 successfully inhibited corneal NV. The bFGF and PEDF genes were successfully expressed as shown by western blot analysis, and a mild immune response to HLA-DR was shown by immunohistochemistry. We concluded that the combination of bevacizumab and p-PEDF-SAINT-18 may have more potent and prolonged antiangiogenic effects, making it possible to reduce the frequency of subconjunctival.Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonalantibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeabilityproperties. In this study, we demonstrated that the combination of bevacizumaband plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18(p-PEDF-SAINT-18 has a favorable antiangiogenic effect on corneal NV. Four groups(Group A: 0 μg + 0 μg, B: 0.1 μg + 0.1 μg, C: 1 μg + 1 μg, and

Bevacizumab treatment in the elderly patient with metastatic colorectal cancer

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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

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.

Intraocular lymphoma

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Li-Juan Tang

2017-08-01

Full Text Available Intraocular lymphoma (IOL is a rare lymphocytic malignancy which contains two main distinct forms. Primary intraocular lymphoma (PIOL is mainly a sub-type of primary central nervous system lymphoma (PCNSL. Alternatively, IOL can originate from outside the central nervous system (CNS by metastasizing to the eye. These tumors are known as secondary intraocular lymphoma (SIOL. The IOL can arise in the retina, uvea, vitreous, Bruch’s membrane and optic nerve. There are predominantly of B-cell origin; however there are also rare T-cell variants. Diagnosis remains challenging for ophthalmologists and pathologists, due to its ability to masquerade as noninfectious or infectious uveitis, white dot syndromes, or occasionally as other metastatic cancers. Laboratory tests include flow cytometry, immunocytochemistry, interleukin detection (IL-10: IL-6, ratio >1, and polymerase chain reaction (PCR amplification. Methotrexate-based systemic chemotherapy with external beam radiotherapy and intravitreal chemotherapy with methotrexate are useful for controlling the disease, but the prognosis remains poor. Therefore, it is important to make an early diagnose and treatment. This review is focused on the clinical manifestations, diagnosis, treatment and prognosis of the IOL.

Feasibility of Vascular Endothelial Growth Factor Imaging in Human Atherosclerotic Plaque Using 89Zr-Bevacizumab Positron Emission Tomography

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Reza Golestani

2013-06-01

Full Text Available Intraplaque angiogenesis is associated with the occurrence of atherosclerotic plaque rupture. Cardiovascular molecular imaging can be used for the detection of rupture-prone plaques. Imaging with radiolabeled bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF-A, can depict VEGF levels corresponding to the angiogenic status in tumors. We determined the feasibility of 89Zr-bevacizumab imaging for the detection of VEGF in carotid endarterectomy (CEA specimens. Five CEA specimens were coincubated with 89Zr-bevacizumab and aspecific 111In-labeled IgG to determine the specificity of bevacizumab accumulation. In 11 CEA specimens, 89Zr-bevacizumab micro-positron emission tomography (PET was performed following 2 hours of incubation. Specimens were cut in 4 mm wide segments and were stained for VEGF and CD68. In each segment, the mean percent incubation dose per gram of tissue (%Inc/g and tissue to background ratio were determined. A 10-fold higher accumulation of 89Zr-bevacizumab compared to 111In-IgG uptake was demonstrated by gamma counting. The mean %Inc/ghot spot was 2.2 ± 0.9 with a hot spot to background ratio of 3.6 ± 0.8. There was a significant correlation between the segmental tissue to background uptake ratio and the VEGF score (ρ = .74, p < .001. It is feasible to detect VEGF tissue concentration within CEA specimens using 89Zr-bevacizumab PET. 89Zr-bevacizumab accumulation in plaques is specific and correlates with immunohistochemistry scores.

Cetuximab reduces the accumulation of radiolabeled bevacizumab in cancer xenografts without altering VEGF expression

NARCIS (Netherlands)

Heskamp, S.; Boerman, O.C.; Molkenboer-Kuenen, J.D.M.; Sweep, F.C.; Geurts-Moespot, A.; Engelhardt, M.S.; Graaf, W.T.A. van der; Oyen, W.J.G.; Laarhoven, H.W.M. van

2014-01-01

Introduction: 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

Tumor Volume Estimation and Quasi-Continuous Administration for Most Effective Bevacizumab Therapy.

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Sápi, Johanna; Kovács, Levente; Drexler, Dániel András; Kocsis, Pál; Gajári, Dávid; Sápi, Zoltán

2015-01-01

Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol. We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. In both cases, three groups were compared in the experiments. The first group did not receive therapy, the second group received one 200 μg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 μg bevacizumab every day (quasi-continuous therapy). Tumor volume measurement was performed by digital caliper and small animal MRI. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. The effectiveness of bevacizumab administration was examined by statistical analysis. In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). In the case of HT-29 adenocarcinoma, the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment (p = 0.038). When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper-measured data with the applied two-dimensional mathematical model. Our results

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.

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

A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme).

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Avallone, Antonio; Piccirillo, Maria Carmela; Aloj, Luigi; Nasti, Guglielmo; Delrio, Paolo; Izzo, Francesco; Di Gennaro, Elena; Tatangelo, Fabiana; Granata, Vincenza; Cavalcanti, Ernesta; Maiolino, Piera; Bianco, Francesco; Aprea, Pasquale; De Bellis, Mario; Pecori, Biagio; Rosati, Gerardo; Carlomagno, Chiara; Bertolini, Alessandro; Gallo, Ciro; Romano, Carmela; Leone, Alessandra; Caracò, Corradina; de Lutio di Castelguidone, Elisabetta; Daniele, Gennaro; Catalano, Orlando; Botti, Gerardo; Petrillo, Antonella; Romano, Giovanni M; Iaffaioli, Vincenzo R; Lastoria, Secondo; Perrone, Francesco; Budillon, Alfredo

2016-02-08

Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy. OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80% statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [(18)F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project. Overall this

Intraocular methotrexate can induce extended remission in some patients in noninfectious uveitis.

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Taylor, Simon R J; Banker, Alay; Schlaen, Ariel; Couto, Cristobal; Matthe, Egbert; Joshi, Lavnish; Menezo, Victor; Nguyen, Ethan; Tomkins-Netzer, Oren; Bar, Asaf; Morarji, Jiten; McCluskey, Peter; Lightman, Sue

2013-01-01

To assess the outcomes of the intravitreal administration of methotrexate in uveitis. Multicenter, retrospective interventional case series of patients with noninfectious uveitis. Thirty-eight eyes of 30 patients were enrolled, including a total of 54 intravitreal injections of methotrexate at a dose of 400 µg in 0.1 mL. The primary outcome measure was visual acuity. Secondary outcome measures included control of intraocular inflammation and cystoid macular edema, time to relapse, development of adverse events, and levels of systemic corticosteroid and immunosuppressive therapy. Methotrexate proved effective in controlling intraocular inflammation and improving vision in 30 of 38 eyes (79%). The side effect profile was good, with no reported serious ocular adverse events and only one patient having an intraocular pressure of >21 mmHg. Of the 30 eyes that responded to treatment, 8 relapsed, but 22 (73%) entered an extended period of remission, with the Kaplan-Meier estimate of median time to relapse for the whole group being 17 months. The eight eyes that relapsed were reinjected and all responded to treatment. One eye relapsed at 3 months, but 7 eyes again entered extended remission. Of the 14 patients on systemic therapy at the start of the study, 8 (57%) were able to significantly reduce this following intravitreal methotrexate injection. In patients with uveitis and uveitic cystoid macular edema, intravitreal MTX can effectively improve visual acuity and reduce cystoid macular edema and, in some patients, allows the reduction of immunosuppressive therapy. Some patients relapse at 3 to 4 months, but a large proportion (73%) enter an extended period of remission of up to 18 months. This larger study extends the results obtained from previous smaller studies suggesting the viability of intravitreal methotrexate as a treatment option in uveitis.

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

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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 

Bevacizumab for the Treatment of Gammaknife Radiosurgery-Induced Brain Radiation Necrosis.

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Ma, Yifang; Zheng, Chutian; Feng, Yiping; Xu, Qingsheng

2017-09-01

Radiation necrosis is one of the complications of Gammaknife radiosurgery. The traditional treatment of radiation necrosis carries a high risk of failure, Bevacizumab is an antiangiogenic monoclonal antibody against vascular endothelial growth factor, a known mediator of cerebral edema. It can be used to successfully treat brain radiation necrosis. Two patients with a history of small cell lung cancer presented with metastatic disease to the brain. They underwent Gammaknife radiosurgery to brain metastases. Several months later, magnetic resonance imaging showed radiation necrosis with significant surrounding edema. The patients had a poor response to treatment with dexamethasone. They were eventually treated with bevacizumab (5 mg/kg every 2 weeks, 7.5 mg/kg every 3 weeks, respectively), and the treatment resulted in significant clinical and radiographic improvement. Bevacizumab can be successfully used to treat radiation necrosis induced by Gammaknife radiosurgery in patients with cerebral metastases. It is of particular benefit in patients with poor reaction to corticosteroids and other medications.

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

Novel MET/TIE2/VEGFR2 inhibitor altiratinib inhibits tumor growth and invasiveness in bevacizumab-resistant glioblastoma mouse models

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Piao, Yuji; Park, Soon Young; Henry, Verlene; Smith, Bryan D.; Tiao, Ningyi; Flynn, Daniel L.

2016-01-01

Background Glioblastoma highly expresses the proto-oncogene MET in the setting of resistance to bevacizumab. MET engagement by hepatocyte growth factor (HGF) results in receptor dimerization and autophosphorylation mediating tumor growth, invasion, and metastasis. Evasive revascularization and the recruitment of TIE2-expressing macrophages (TEMs) are also triggered by anti-VEGF therapy. Methods We investigated the activity of altiratinib (a novel balanced inhibitor of MET/TIE2/VEGFR2) against human glioblastoma stem cell lines in vitro and in vivo using xenograft mouse models. The biological activity of altiratinib was assessed in vitro by testing the expression of HGF-stimulated MET phosphorylation as well as cell viability after altiratinib treatment. Tumor volume, stem cell and mesenchymal marker levels, microvessel density, and TIE2-expressing monocyte infiltration were evaluated in vivo following treatment with a control, bevacizumab alone, bevacizumab combined with altiratinib, or altiratinib alone. Results In vitro, HGF-stimulated MET phosphorylation was completely suppressed by altiratinib in GSC17 and GSC267, and altiratinib markedly inhibited cell viability in several glioblastoma stem cell lines. More importantly, in multiple xenograft mouse models, altiratinib combined with bevacizumab dramatically reduced tumor volume, invasiveness, mesenchymal marker expression, microvessel density, and TIE2-expressing monocyte infiltration compared with bevacizumab alone. Furthermore, in the GSC17 xenograft model, altiratinib combined with bevacizumab significantly prolonged survival compared with bevacizumab alone. Conclusions Together, these data suggest that altiratinib may suppress tumor growth, invasiveness, angiogenesis, and myeloid cell infiltration in glioblastoma. Thus, altiratinib administered alone or in combination with bevacizumab may overcome resistance to bevacizumab and prolong survival in patients with glioblastoma. PMID:26965451

Effectiveness of bevacizumab and cetuximab in metastatic colorectal cancer across selected public hospitals in Queensland.

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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.

Evaluation of Acute Locoregional Toxicity in Patients With Breast Cancer Treated With Adjuvant Radiotherapy in Combination With Bevacizumab

International Nuclear Information System (INIS)

Goyal, Sharad; Rao, Malay S.; Khan, Atif; Huzzy, Lien; Green, Camille; Haffty, Bruce G.

2011-01-01

Purpose: 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. Methods and Materials: 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. Results: Fourteen patients were identified to have received bevacizumab plus RT. All patients receivedbevacizumab 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. Conclusion: 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.

Massive Silicone Oil Migration into the Subconjunctival Space: A Leakage Mechanism Dilemma

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Jesús Téllez

2018-05-01

Full Text Available Purpose: To report a case in which an early, massive silicone oil migration into the subconjunctival space occurred in a patient after sutureless vitrectomy with the presence of a previously implanted pars plana glaucoma drainage device. Case Report: An 80-year-old man presented with neovascular glaucoma secondary to a proliferative diabetic retinopathy in his left eye. After an intracamerular bevacizumab injection and panretinal photocoagulation, a 23-gauge pars plana vitrectomy (PPV combined with a superotemporal Ahmed pars plana glaucoma valve implantation was performed. Afterwards, the patient underwent a new 23-gauge PPV for a dense vitreous hemorrhage. Intravitreal 1,000 centistokes silicone oil was placed to prevent recurrent intraocular bleeding. No sutures were performed. In the first postoperative month, a massive migration of silicone oil into the 360° subconjunctival space was noted until no intraocular silicone oil was observed. Conclusions: We discuss the possible leakage mechanisms in this particular case.

IS IT POSSIBLE TO USE BEVACIZUMAB BIOSIMILAR IN ALL INDICATIONS REGISTERED FOR ORIGINAL DRUG?

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S. V. Orlov

2016-01-01

Full Text Available The possibility of extrapolation of indications for biosimilars is one of the issues widely discussed in modern literature. Currently, the European Medicines Agency (EMA and the Food and Drug Administration (FDA have identified specific conditions under which for biosimilars extrapolation of indications is possible. In2015, athe first bioanalogue bevacizumab, (produced by JSC "BIOCAD", has been registered. The article provides summary of the pivotal clinical study of Bevacizumab bioanalogue conducted in patients with non-small cell lung cancer. The article includes detailed scientific justification for the extrapolation of data on the efficacy, safety and immunogenicity obtained in the pivotal study to other indications, registered for the original bevacizumab drug.

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.

Chemotherapy, Bevacizumab, and Cetuximab in Metastatic Colorectal Cancer

NARCIS (Netherlands)

Tol, Jolien; Koopman, Miriam; Cats, Annemieke; Rodenburg, Cees J.; Creemers, Geert J. M.; Schrama, Jolanda G.; Erdkamp, Frans L. G.; Vos, Allert H.; van Groeningen, Cees J.; Sinnige, Harm A. M.; Richel, Dirk J.; Voest, Emile E.; Dijkstra, Jeroen R.; Vink-Börger, Marianne E.; Antonini, Ninja F.; Mol, Linda; van Krieken, Johan H. J. M.; Dalesio, Otilia; Punt, Cornelis J. A.

2009-01-01

Background Fluoropyrimidine- based chemotherapy plus the anti - vascular endothelial growth factor ( VEGF) antibody bevacizumab is standard first- line treatment for metastatic colorectal cancer. We studied the effect of adding the anti - epidermal growth factor receptor ( EGFR) antibody cetuximab

The role of pili in Bacillus cereus intraocular infection.

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Callegan, Michelle C; Parkunan, Salai Madhumathi; Randall, C Blake; Coburn, Phillip S; Miller, Frederick C; LaGrow, Austin L; Astley, Roger A; Land, Craig; Oh, So-Young; Schneewind, Olaf

2017-06-01

Bacterial endophthalmitis is a potentially blinding intraocular infection. The bacterium Bacillus cereus causes a devastating form of this disease which progresses rapidly, resulting in significant inflammation and loss of vision within a few days. The outer surface of B. cereus incites the intraocular inflammatory response, likely through interactions with innate immune receptors such as TLRs. This study analyzed the role of B. cereus pili, adhesion appendages located on the bacterial surface, in experimental endophthalmitis. To test the hypothesis that the presence of pili contributed to intraocular inflammation and virulence, we analyzed the progress of experimental endophthalmitis in mouse eyes infected with wild type B. cereus (ATCC 14579) or its isogenic pilus-deficient mutant (ΔbcpA-srtD-bcpB or ΔPil). One hundred CFU were injected into the mid-vitreous of one eye of each mouse. Infections were analyzed by quantifying intraocular bacilli and retinal function loss, and by histology from 0 to 12 h postinfection. In vitro growth and hemolytic phenotypes of the infecting strains were also compared. There was no difference in hemolytic activity (1:8 titer), motility, or in vitro growth (p > 0.05, every 2 h, 0-18 h) between wild type B. cereus and the ΔPil mutant. However, infected eyes contained greater numbers of wild type B. cereus than ΔPil during the infection course (p ≤ 0.05, 3-12 h). Eyes infected with wild type B. cereus experienced greater losses in retinal function than eyes infected with the ΔPil mutant, but the differences were not always significant. Eyes infected with ΔPil or wild type B. cereus achieved similar degrees of severe inflammation. The results indicated that the intraocular growth of pilus-deficient B. cereus may have been better controlled, leading to a trend of greater retinal function in eyes infected with the pilus-deficient strain. Although this difference was not enough to significantly alter the severity

Neovascular Glaucoma Induced by Peripheral Retinal Ischemia in Neurofibromatosis Type 1: Management and Imaging Features

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Francesco Pichi

2013-04-01

Full Text Available Purpose: To report the case of a young patient affected by neurofibromatosis 1 (NF-1 with peripheral retinal ischemia-induced neovascular glaucoma and the peculiar spectral-domain optical coherence tomography (SD-OCT features. Material and Methods: A 13-year-old boy affected by NF-1, as diagnosed according to established criteria, was referred with a diagnosis of hypertensive uveitis in his left eye. He underwent a complete ophthalmic examination and comprehensive blood work with viral and immunological tests. The case was documented with fluorescein angiography (FA and SD-OCT. When the intraocular pressure (IOP of the left eye decreased and the cornea cleared, FA revealed retinal ischemia and leakage from pathologic retinal vessels. SD-OCT revealed foveal hypoplasia secondary to the complete absence of the retinal nerve fiber layer. Results: Peripheral retinal ischemia-induced neovascular glaucoma was diagnosed. The patient underwent Ahmed valve implantation to control his IOP, and subsequent retinal photocoagulation by argon laser and intravitreal bevacizumab injection were performed to control neovascularization. Discussion: Retinal ischemia in NF-1 might lead to neovascular glaucoma: lowering of the IOP with surgical implantation of an Ahmed valve, regression of neovascularization by argon laser panretinal photocoagulation and intravitreal injection of bevacizumab can be a helpful way to control such a complication.

Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer

NARCIS (Netherlands)

Tol, J.; Koopman, M.; Cats, A.; Rodenburg, C.J.; Creemers, G.J.M.; Schrama, J.G.; Erdkamp, F.L.G.; Vos, A.H.; van Groeningen, C.J.; Sinnige, H.A.M.; Richel, D.J.; Voest, E.E.; Dijkstra, J.R.; Vink-Börger, M.E.; Antonini, N.F.; Mol, L.; van Krieken, J.H.J.M.; Dalesio, O.; Punt, C.J.A.

2009-01-01

Background: Fluoropyrimidine- based chemotherapy plus the anti - vascular endothelial growth factor (VEGF) antibody bevacizumab is standard first- line treatment for metastatic colorectal cancer. We studied the effect of adding the anti - epidermal growth factor receptor (EGFR) antibody cetuximab to

Growth of Scytalidium sp. in a counterfeit bevacizumab bottle

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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.

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...... acceptable safety and is a clinically relevant choice of therapy in heavily pre-treated patients with recurrent high-grade brain tumours Udgivelsesdato: 2009...

Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab

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Ronald M Bukowski

2010-03-01

Full Text Available Ronald M BukowskiCleveland Clinic Taussig Cancer Center, CCF Lerner College of Medicine of CWRU Cleveland, OH, USAAbstract: The biology and pathogenesis of clear cell carcinoma of the kidney has been extensively investgated, and the role of von Hipple-Landau gene inactivation and tumor associated angiogenesis is now recognized. Development of vascular endothelial growth factor inhibitors and phase 3 clinical trials utilizing this class of agents has produced a new treatment paradigm for patients with metastatic renal cell carcinoma (RCC. One of the active regimens identified is the combination of bevacizumab and interferon-α. Recently published reports provided evidence of the clinical and biologic activity of this therapy. The current manuscript reviews the background and rationale for the activity of bevacizumab in RCC, and results from recent clinical trials with this agent alone or in combination with targeted agents or cytokines. The role of this therapy in contrast to other targeted agents is reviewed, and the potential utility as well as questions raised by recent studies are discussed.Keywords: metastatic renal cell carcinoma, bevacizumab, interferon-α

Effect on Intraocular Pressure of Switching from Latanoprost and Travoprost Monotherapy to Timolol Fixed Combinations in Patients with Normal-Tension Glaucoma

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Ryoko Igarashi

2014-01-01

Full Text Available Purpose. To evaluate the effect on intraocular pressure (IOP of switching from latanoprost and travoprost monotherapy to timolol fixed combinations in Japanese patients with normal-tension glaucoma (NTG. Methods. 27 NTG patients (54 eyes were compared IOP, superficial punctuate keratitis (SPK scores, and conjunctival injection scores in eyes treated with prostaglandin (PG or PG analog/beta-blocker (PG/b fixed-combination 6 months after the change in therapy. Results. The mean baseline intraocular pressure was 17.4±1.59 mmHg in eyes receiving PG therapy only and 17.4±1.69 mmHg in eyes switched to PG/b. Switching to fixed combination therapy from PG monotherapy, the mean IOP was 13.1±1.79 mmHg (P<0.001  (-24.71% reduction from baseline at 6 months. The mean conjunctival injection score was 0.69 for eyes on PG monotherapy and 0.56 for eyes on fixed combination therapy (P=0.028. The mean SPK scores were 0.46 and 0.53. This difference was not statistically significant (P=0.463. Conclusions. Switching from PG monotherapy to PG/b fixed combination therapy for NTG resulted in a greater intraocular pressure reduction than PG alone without increasing the number of instillations.

Efficacy and safety of bevacizumab for the treatment of advanced hepatocellular carcinoma: a systematic review of phase II trials.

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Ping Fang

Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is a common cancer associated with a poor prognosis. Bevacizumab is a monoclonal antibody that binds vascular endothelial growth factor, a mediator of tumor angiogenesis. Bevacizumab is currently under investigation as treatment for HCC. We performed a systematic review of the efficacy and safety of bevacizumab for the treatment of advanced HCC. METHODS: PubMed, the Cochrane Library, and Google Scholar were searched using the terms "bevacizumab AND hepatocellular carcinoma AND (advanced OR unresectable". Phase II trials of bevacizumab for the treatment of advanced HCC were included. Outcomes of interest included progression-free and overall survival (PFS and OS, tumor response, and toxicities. RESULTS: A total of 26 records were identified. Of these, 18 were excluded. Hence, eight trials involving 300 patients were included. Bevacizumab was given as monotherapy (n = 1 trial or in combination with erlotinib (n = 4 trials, capecitabine (n = 1 trial, capecitabine+oxaliplatin (n = 1 trial, or gemcitabine+oxaliplatin (n = 1 trial. Most trials (five of eight reported median PFS and OS between 5.3 months and 9.0 months and 5.9 and 13.7 months, respectively. The disease control rate was consistent in five of eight trials, ranging from 51.1% to 76.9%. The response and partial response rates ranged from 0 to 23.7%, but were around 20% in four trials. Only one patient had a complete response. Frequently reported Grade 3/4 toxicities were increased aspartate transaminase/alanine transaminase (13%, fatigue (12%, hypertension (10%, diarrhea (8%, and neutropenia (5%. Thirty patients experienced gastrointestinal bleeding (grade 1/2 = 18, grade 3/4 = 12, typically due to esophageal varices. CONCLUSIONS: Bevacizumab shows promise as an effective and tolerable treatment for advanced HCC. The reported efficacy of bevacizumab appears to compare favorably with that of sorafenib, the only currently

Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin 
in Patients with IIIa Lung Adenocarcinoma

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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.

Synthesis, radiolabeling and quality control of {sup 111}In-DOTA-bevacizumab for radioimmunoscintigraphy of VEGF receptors

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Khorami-Moghadam, A.; Jalilian, A.R.; Yavari, K.; Alirezapour, B.; Mazidi, M.; Mirzaii, M. [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of)

2013-11-01

In this study, bevacizumab was successively labeled with {sup 111}In-InCl{sub 3} after conjugation with DOTA-NHS-ester followed by molecular filtration and determination of the average number ofDOTAconjugated per mAb (6:1) by spectrophotometric method. Radiochemical purity (> 97%, measured by ITLC and HPLC), integrity of protein after radiolabeling (gel electrophoresis) and stability of {sup 111}In-DOTA-Bevacizumab (in final formulation, human serum, liver/kidney homogenates) were determined in 24-72 h as well as biodistribution studies in wild-type rats and human colon cancer (SW-480) bearing mice. The accumulation of the radiolabeled antibody was consistent with the former reported Bevacizumab conjugates. Significant tumor uptake (8%) was observed at 72 h p.i. Tumor/muscle uptake ratios were 2.6 (24 h), 9.74 (48 h) and 25 (72 h). {sup 111}In-DOTA-Bevacizumab was prepared as a SPECT molecular imaging agent for diagnosis and follow-up of vascular endothelial growth factor A (VEGF-A) expression in oncology. (orig.)

An overview of fotemustine in high-grade gliomas: from single agent to association with bevacizumab.

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Lombardi, Giuseppe; Farina, Patrizia; Della Puppa, Alessandro; Cecchin, Diego; Pambuku, Ardi; Bellu, Luisa; Zagonel, Vittorina

2014-01-01

Fotemustine is a third-generation nitrosourea showing efficacy in various types of tumors such as melanoma and glioma. We reviewed the most important studies on fotemustine treatment in glioma patients analyzing its pharmacological profile and its activity and safety. Fotemustine was used as single agent or in association with new targeted drugs such as bevacizumab; fotemustine was used both as first-line chemotherapy before temozolomide era and in refractory-temozolomide patients during temozolomide era. Finally, analyzing and comparing the activity and safety of fotemustine alone or in combination with bevacizumab versus other nitrosoureas such as lomustine, we may suggest that the combination treatment with bevacizumab and fotemustine may be active and tolerable in patients with high grade gliomas.

The effect of bevacizumab on vestibular schwannoma tumour size and hearing in patients with neurofibromatosis type 2

DEFF Research Database (Denmark)

Alanin, Mikkel Christian; Klausen, Camilla; Caye-Thomasen, Per

2015-01-01

-34). We observed a radiological response (≥20 % tumour shrinkage) in seven out of 18 tumours (39 %) in six out of 12 patients (50 %). Sustained radiological responses were maintained in six tumours (33 %) for more than 2 months. Three patients had objectively improved hearing and five patients reported...... been shown to induce tumour shrinkage and improve hearing. We retrospectively reviewed the effect of bevacizumab on hearing and VS tumour size in 12 consecutive NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every second week for 6 months; hereafter, bevacizumab 15 mg...

Effects of anti-vascular endothelial growth factor monoclonal antibody (bevacizumab on lens epithelial cells

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Jun JH

2016-06-01

Full Text Available Jong Hwa Jun,1 Wern-Joo Sohn,2 Youngkyun Lee,2 Jae-Young Kim21Department of Ophthalmology, School of Medicine, Dongsan Medical Center, Keimyung University, 2Department of Oral Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, South KoreaAbstract: The molecular and cellular effects of anti-vascular endothelial growth factor monoclonal antibody (bevacizumab on lens epithelial cells (LECs were examined using both an immortalized human lens epithelial cell line and a porcine capsular bag model. After treatment with various concentrations of bevacizumab, cell viability and proliferation patterns were evaluated using the water-soluble tetrazolium salt assay and 5-bromo-2'-deoxyuridine enzyme-linked immunosorbent assay, respectively. The scratch assay and Western blot analysis were employed to validate the cell migration pattern and altered expression levels of signaling molecules related to the epithelial–mesenchymal transition (EMT. Application of bevacizumab induced a range of altered cellular events in a concentration-dependent manner. A 0.1–2 mg/mL concentration demonstrated dose-dependent increase in proliferation and viability of LECs. However, 4 mg/mL decreased cell proliferation and viability. Cell migrations displayed dose-dependent retardation from 0.1 mg/mL bevacizumab treatment. Transforming growth factor-β2 expression was markedly increased in a dose-dependent manner, and α-smooth muscle actin, matrix metalloproteinase-9, and vimentin expression levels showed dose-dependent changes in a B3 cell line. Microscopic observation of porcine capsular bag revealed changes in cellular morphology and a decline in cell density compared to the control after 2 mg/mL treatment. The central aspect of posterior capsule showed delayed confluence, and the factors related to EMT revealed similar expression patterns to those identified in the cell line. Based on these results, bevacizumab modulates the proliferation

Effect of Hemifacial Spasm on Intraocular Pressure Measurement.

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Cicik, Erdogan; Yildirim, Rengin; Arici, Ceyhun; Dikkaya, Funda; Arslan, Osman Sevki

2018-01-01

To evaluate the effect of hemifacial spasm (HFS) on intraocular pressure (IOP) measurement. Twenty-four consecutive patients with HFS and 25 age- and gender-matched randomly selected eyes of healthy volunteers underwent corneal pachymetry and IOP measurements using Goldmann applanation tonometer (GAT) and noncontact tonometer (NCT). IOP measurements were performed before (during HFS) and 2 weeks after Botox injections in HFS patients and in healthy volunteers without Botox injections. There was no statistical difference between involved eye side and uninvolved eye side of HFS patients in measured central corneal thickness. Similarly, no difference was found between involved eye side of HFS patients and controls. There were no statistically significant differences comparing IOP values before treatment and levels measured at 2 weeks of Botox injections, either with GAT ( p = 0.33, 0.11) or NCT ( p = 0.80, 0.43) devices in the involved eyes and uninvolved eyes of patients with HFS, respectively. There were also no significant differences in these parameters (GAT ( p = 0.63) and NCT ( p = 0.54)) in controls. Contractions in facial muscles may not lead to significant increase in IOP in HFS patients. This result may help clinical decision making in the treatment of glaucoma patients with HFS. This trial is registered with NCT03390803.

Bevacizumab plus FOLFIRI or FOLFOX in chemotherapy-refractory patients with metastatic colorectal cancer: a retrospective study

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Portales Fabienne

2009-09-01

Full Text Available Abstract Background The anti-VEGF antibody bevacizumab associated with an irinotecan or oxaliplatin-based chemotherapy was proved to be superior to the chemotherapy alone in first or second line treatment of metastatic colorectal cancer (mCRC. However, it was reported to have no efficacy in 3rd or later-line, alone or with 5FU. The aim of this study was to evaluate the activity of bevacizumab combined with FOLFIRI or FOLFOX in mCRC who have failed prior chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin. Methods Thirty one consecutive patients treated between May 2005 and October 2006 were included in this retrospective study. All of them have progressed under a chemotherapy with fluoropyrimidine plus irinotecan and/or oxaliplatin and received bevacizumab (5 mg/kg in combination with FOLFIRI or simplified FOLFOX4 every 14 days. Results Ten patients (32.2% had an objective response (1 CR, 9 PR and 12 (38.8% were stabilized. The response and disease control rates were 45.4% and 100% when bevacizumab was administered in 2nd or 3rd line and 25% and 55% in 4th or later line respectively (p = 0.024 and p = 0.008. Among the patients who had previously received the same chemotherapy than that associated with bevacizumab (n = 28 the overall response rate was 35.7% and 39.3% were stabilized. Median progression free survival (PFS and overall survival (OS were of 9.7 and 18.4 months respectively. Except a patient who presented a hypertension associated reversible posterior leukoencephalopathy syndrome, tolerance of bevacizumab was acceptable. A rectal bleeding occurred in one patient, an epistaxis in five. Grade 1/2 hypertension occurred in five patients. Conclusion This study suggests that bevacizumab combined with FOLFOX or FOLFIRI may have the possibility to be active in chemorefractory and selected mCRC patients who did not receive it previously.

The effects of repeated Ozurdex injections on ocular hypertension

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Bahadorani S

2018-04-01

Full Text Available Sepehr Bahadorani,1 Chelsey Krambeer,2 Kendall Wannamaker,1 Wayne Tie,1 Michael Jansen,1 Jason Espitia,2 Jeong-Hyeon Sohn,1 Michael A Singer2 1Department of Ophthalmology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; 2Medical Center Ophthalmology Associates, San Antonio, TX, USA Purpose: The purpose of this study was to correlate the degree of ocular hypertension with the number of Ozurdex injections.Methods: Intraocular pressure (IOP fluctuations for a total of 183 injections were studied over a period of at least 12 months. The main indications for treatment were uveitis, diabetic macular edema, and retinal vein occlusion.Results: Results of the study demonstrate that repeated Ozurdex injections do not increase the frequency of IOP spikes beyond 30 mmHg. For lower IOPs, however, a positive correlation exists. Furthermore, patients with primary open angle glaucoma and uveitis had the highest IOP response to repeated injections. On average, patients with an IOP of ≥28.6 mmHg received pressure lowering medications, after which their IOP reached a stable level (16.7 mmHg without the need for additional interventions.Conclusion: The data support the conclusion that multiple Ozurdex injections does not increase the frequency of IOP spikes beyond 30 mmHg, but patients still must be closely monitored if they have a history of primary open angle glaucoma. Keywords: Ozurdex, dexamethasone, glaucoma, intraocular pressure, ocular hypertension

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.

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. 

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......-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.......AIM: Treatment of multiresistant epithelial ovarian cancer (EOC) is palliative and patients who have become resistant after multiple lines of chemotherapy often have an unmet need for further and less toxic treatment. Anti-angiogenic therapy has attracted considerable attention in the treatment...

Intraocular inflammation in autoimmune diseases.

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Pras, Eran; Neumann, Ron; Zandman-Goddard, Gisele; Levy, Yair; Assia, Ehud I; Shoenfeld, Yehuda; Langevitz, Pnina

2004-12-01

The uveal tract represents the vascular organ of the eye. In addition to providing most of the blood supply to the intraocular structures, it acts as a conduit for immune cells, particularly lymphocytes, to enter the eye. Consequently, the uveal tract is represented in many intraocular inflammatory processes. Uveitis is probably a misnomer unless antigens within the uvea are the direct targets of the inflammatory process. A better term of the condition is "intraocular inflammation" (IOI). To review the presence of IOI in autoimmune diseases, the immunopathogenic mechanisms leading to disease, and treatment. We reviewed the English medical literature by using MEDLINE (1984-2003) employing the terms "uveitis," "intraocular inflammation," and "autoimmune diseases." An underlying autoimmune disease was identified in up to 40% of patients with IOI, and included spondyloarthropathies, Behcets disease, sarcoidosis, juvenile chronic arthritis, Vogt-Koyanagi-Harada syndrome (an inflammatory syndrome including uveitis with dermatologic and neurologic manifestations), immune recovery syndrome, and uveitis with tubulointerstitial disease. The immunopathogenesis of IOI involves enhanced T-cell response. Recently, guidelines for the use of immunosuppressive drugs for inflammatory eye disease were established and include: corticosteroids, azathioprine, methotrexate, mycophenolate mofetil, cyclosporine, tacrolimus, cyclophosphamide, and chlorambucil. New therapies with limited experience include the tumor necrosis factor alpha inhibitors, interferon alfa, monoclonal antibodies against lymphocyte surface antigens, intravenous immunoglobulin (IVIG), and the intraocular delivery of immunosuppressive agents. An underlying autoimmune disease was identified in up to 40% of patients with IOI. Immunosuppressive drugs, biologic agents, and IVIG are employed for the treatment of IOI in autoimmune diseases.

Intraocular Implants for the Treatment of Autoimmune Uveitis

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Darren J. Lee

2015-07-01

Full Text Available Uveitis is the third leading cause of blindness in developed countries. Currently, the most widely used treatment of non-infectious uveitis is corticosteroids. Posterior uveitis and macular edema can be treated with intraocular injection of corticosteroids, however, this is problematic in chronic cases because of the need for repeat injections. Another option is systemic immunosuppressive therapies that have their own undesirable side effects. These systemic therapies result in a widespread suppression of the entire immune system, leaving the patient susceptible to infection. Therefore, an effective localized treatment option is preferred. With the recent advances in bioengineering, biodegradable polymers that allow for a slow sustained-release of a medication. These advances have culminated in drug delivery implants that are food and drug administration (FDA approved for the treatment of non-infectious uveitis. In this review, we discuss the types of ocular implants available and some of the polymers used, implants used for the treatment of non-infectious uveitis, and bioengineered alternatives that are on the horizon.

The Effect of Altitude on Intraocular Pressure in Vitrectomized Eyes with Sulfur Hexafluoride Tamponade by the Friedenwald Method: Rabbit Animal Model

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Jans Fromow-Guerra

2016-01-01

Full Text Available The aim of this study is to assess the change in intraocular pressure after a road trip, in eyes with different levels of filling with gas tamponade. Five rabbit eyes were subject to pars plana vitrectomy and gas tamponade (filling percentage: 25%, 50%, and 100% of nonexpansile SF6, 100% saline solution, and 100% room air. A sixth eye was injected with 0.35 cc of undiluted SF6 without vitrectomy. Guided by global positioning system, they were driven to the highest point of the highway connecting Mexico City with Puebla city and back, stopping every 300 m to assess intraocular pressure. The rabbit’s scleral rigidity and estimation for human eyes were done by using the Friedenwald nomogram. Maximum altitude was 3209 m (Δ949 m. There were significant differences in intraocular pressure on the rabbit eyes filled with SF6 at 100%, 50%, 25%, and 100% room air. Per every 100 m of altitude rise, the intraocular pressure increased by 1.53, 1.0046, 0.971, and 0.97 mmHg, respectively. Using the human Friedenwald rigidity coefficient, the human eye estimate for intraocular pressure change was 2.1, 1.8, 1.4, and 1.1 mmHg per every 100 m of attitude rise. Altitude changes have a significant impact on intraocular pressure. The final effect depends on the percentage of vitreous cavity fill and scleral rigidity.

Cost-effectiveness analysis of additional bevacizumab to pemetrexed plus cisplatin for malignant pleural mesothelioma based on the MAPS trial.

Science.gov (United States)

Zhan, Mei; Zheng, Hanrui; Xu, Ting; Yang, Yu; Li, Qiu

2017-08-01

Malignant pleural mesothelioma (MPM) is a rare malignancy, and pemetrexed/cisplatin (PC) is the gold standard first-line regime. This study evaluated the cost-effectiveness of the addition of bevacizumab to PC (with maintenance bevacizumab) for unresectable MPM based on a phase III trial that showed a survival benefit compared with chemotherapy alone. To estimate the incremental cost-effectiveness ratio (ICER) of the incorporation of bevacizumab, a Markov model based on the MAPS trial, including the disease states of progression-free survival, progressive disease and death, was used. Total costs were calculated from a Chinese payer perspective, and health outcomes were converted into quality-adjusted life year (QALY). Model robustness was explored in sensitivity analyses. The addition of bevacizumab to PC was estimated to increase the cost by $81446.69, with a gain of 0.112 QALYs, resulting in an ICER of $727202.589 per QALY. In both one-way sensitivity and probabilistic sensitivity analyses, the ICER exceeded the commonly accepted willingness-to-pay threshold of 3 times the gross domestic product per capita of China ($23970.00 per QALY). The cost of bevacizumab had the most important impact on the ICER. The combination of bevacizumab with PC chemotherapy is not a cost-effective treatment option for MPM in China. Given its positive clinical value and extremely low incidence of MPM, an appropriate price discount, assistance programs and medical insurance should be considered to make bevacizumab more affordable for this rare patient population. Copyright © 2017 Elsevier B.V. All rights reserved.

Predictive Biomarkers for Bevacizumab in Anti-tumor Therapy

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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.

Applying quantitative adiposity feature analysis models to predict benefit of bevacizumab-based chemotherapy in ovarian cancer patients

Science.gov (United States)

Wang, Yunzhi; Qiu, Yuchen; Thai, Theresa; More, Kathleen; Ding, Kai; Liu, Hong; Zheng, Bin

2016-03-01

How to rationally identify epithelial ovarian cancer (EOC) patients who will benefit from bevacizumab or other antiangiogenic therapies is a critical issue in EOC treatments. The motivation of this study is to quantitatively measure adiposity features from CT images and investigate the feasibility of predicting potential benefit of EOC patients with or without receiving bevacizumab-based chemotherapy treatment using multivariate statistical models built based on quantitative adiposity image features. A dataset involving CT images from 59 advanced EOC patients were included. Among them, 32 patients received maintenance bevacizumab after primary chemotherapy and the remaining 27 patients did not. We developed a computer-aided detection (CAD) scheme to automatically segment subcutaneous fat areas (VFA) and visceral fat areas (SFA) and then extracted 7 adiposity-related quantitative features. Three multivariate data analysis models (linear regression, logistic regression and Cox proportional hazards regression) were performed respectively to investigate the potential association between the model-generated prediction results and the patients' progression-free survival (PFS) and overall survival (OS). The results show that using all 3 statistical models, a statistically significant association was detected between the model-generated results and both of the two clinical outcomes in the group of patients receiving maintenance bevacizumab (p<0.01), while there were no significant association for both PFS and OS in the group of patients without receiving maintenance bevacizumab. Therefore, this study demonstrated the feasibility of using quantitative adiposity-related CT image features based statistical prediction models to generate a new clinical marker and predict the clinical outcome of EOC patients receiving maintenance bevacizumab-based chemotherapy.

An Overview of Fotemustine in High-Grade Gliomas: From Single Agent to Association with Bevacizumab

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Giuseppe Lombardi

2014-01-01

Full Text Available Fotemustine is a third-generation nitrosourea showing efficacy in various types of tumors such as melanoma and glioma. We reviewed the most important studies on fotemustine treatment in glioma patients analyzing its pharmacological profile and its activity and safety. Fotemustine was used as single agent or in association with new targeted drugs such as bevacizumab; fotemustine was used both as first-line chemotherapy before temozolomide era and in refractory-temozolomide patients during temozolomide era. Finally, analyzing and comparing the activity and safety of fotemustine alone or in combination with bevacizumab versus other nitrosoureas such as lomustine, we may suggest that the combination treatment with bevacizumab and fotemustine may be active and tolerable in patients with high grade gliomas.

21 CFR 886.3600 - Intraocular lens.

Science.gov (United States)

2010-04-01

... DEVICES OPHTHALMIC DEVICES Prosthetic Devices § 886.3600 Intraocular lens. (a) Identification. An intraocular lens is a device made of materials such as glass or plastic intended to be implanted to replace the natural lens of an eye. (b) Classification. Class III. (c) Date PMA or notice of completion of a...

21 CFR 886.4275 - Intraocular fluid.

Science.gov (United States)

2010-04-01

... DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4275 Intraocular fluid. (a) Identification. An intraocular fluid is a device consisting of a nongaseous fluid intended to be introduced into the eye to aid... section 515 of the act is required before this device may be commercially distributed. See § 886.3. ...

A Case Report of Intraocular Metastasis Treated with Radiotherapy

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Kim, Ok Bae; Byun, Sang Jun; Kim, Kwang Soo; Kim, Jin Hee [Keimyung University School of Medicine, Daegu (Korea, Republic of); Lee, Ho Jun [Daegu Catholic University School of Medicine, Daegu (Korea, Republic of)

2009-09-15

Intraocular metastasis is the most common malignancy of the eye. The frequency of intraocular metastasis in all the patients dying of cancer is about 12% and ocular metastases will be detected more frequently in the future because the patients with malignant tumor are now living longer. Intraocular metastasis can cause a serious clinical problem such as blindness. The early recognition and treatment of intraocular metastasis are very important clinical oncologic issues to maintain vision and to maximize the quality of life. However, significance of intraocular metastasis is still under-evaluated for practicing oncologists. External beam radiotherapy is a safe, effective palliative treatment in terms of preserving both the vision and the eye globe.

Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer

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Yang, R.F.; Yu, B.; Zhang, R.Q.; Wang, X.H.; Li, C.; Wang, P.; Zhang, Y.; Han, B.; Gao, X.X.; Zhang, L. [Taian City Central Hospital, Taian, Shandong (China); Jiang, Z.M., E-mail: dmyh2436@126.com [Qianfoshan Hospital of Shandong Province, Shandong University, Ji’nan, Shandong (China)

2018-02-01

Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinibWBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (Po0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (Po0.05). Although bevacizumabgefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC. (author)

Bevacizumab improves survival for patients with advanced cervical cancer

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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

21 CFR 886.4270 - Intraocular gas.

Science.gov (United States)

2010-04-01

... DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4270 Intraocular gas. (a) Identification. An intraocular gas is a device consisting of a gaseous fluid intended to be introduced into the eye to place pressure... required. As of May 28, 1976, an approval under section 515 of the act is required before this device may...

[Retrospective analysis of 24 recurrent glioblastoma after chemoradiation and treated with nitrosoureas or irinotecan and bevacizumab].

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Vauleon, Elodie; Mesbah, Habiba; Gedouin, Daniel; Lecouillard, Isabelle; Louvel, Guillaume; Hamlat, Abderrahmane; Riffaud, Laurent; Carsin, Béatrice; Quillien, Véronique; Audrain, Odile; Lesimple, Thierry

2012-02-01

Despite progress in the initial management of glioblastoma (GB), the vast majority of patients will experience recurrence within 2-3 years. The medical treatment of these recurrences is being modified by the use of antiangiogenic therapies. Twenty-four patients, who relapsed from GB after chemoradiation followed by adjuvant temozolomide in Rennes, were treated by conventional chemotherapy (nitrosourea) or by the combination of irinotecan and bevacizumab. In this retrospective analysis, overall survival from diagnosis of recurrence was significantly longer in patients treated with the combination of bevacizumab and irinotecan than with nitrosourea (5 months versus 11.5 months). The combination of irinotecan and bevacizumab appeared to provide clinical benefit to patients with recurrent GB.

Effects of tramadol and acepromazine on intraocular pressure and pupil diameter in young healthy cats

OpenAIRE

Schroder, Deise Cristine; Monteiro, Bianca Garay; Pytlak, Deborah Braga; Souza, Mayara Carvalho de; Mendonça, Adriane Jorge; Ribeiro, Alexandre Pinto

2018-01-01

ABSTRACT: This study aimed to investigate the effects of the systemic administration of acepromazine, tramadol and the association of both on intraocular pressure (IOP) and pupil diameter (PD) in young healthy cats. Cats were randomly allocated into three groups (n=10/each) and intramuscular acepromazine (AG), tramadol (TG) or acepromazine combined with tramadol (ATG) were injected. PD (electronic caliper) and IOP (applanation tonometry) were assessed before (baseline) and following 15, 30, 6...

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

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...... expression profiling of formalin-fixed paraffin-embedded tumor tissue was performed using RNA-sequencing.Results: By comparing pretreatment samples of responders with those of non-responders no significant difference was observed. In a paired comparison analysis of pre- and posttreatment samples of non...

Feasibility trial of letrozole in combination with bevacizumab in patients with metastatic breast cancer.

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Traina, Tiffany A; Rugo, Hope S; Caravelli, James F; Patil, Sujata; Yeh, Benjamin; Melisko, Michele E; Park, John W; Geneus, Stephanie; Paulson, Matthew; Grothusen, Jill; Seidman, Andrew D; Fornier, Monica; Lake, Diana; Dang, Chau; Robson, Mark; Theodoulou, Maria; Flombaum, Carlos D; Norton, Larry; Hudis, Clifford A; Dickler, Maura N

2010-02-01

Preclinical models suggest that the use of anti-vascular endothelial growth factor (anti-VEGF) therapy with antiestrogens may prevent or delay the development of endocrine therapy resistance. We therefore performed a feasibility study to evaluate the safety of letrozole plus bevacizumab in patients with hormone receptor-positive metastatic breast cancer (MBC). Patients with locally advanced breast cancer or MBC were treated with the aromatase inhibitor (AI) letrozole (2.5 mg orally daily) and the anti-VEGF antibody bevacizumab (15 mg/kg intravenously every 3 weeks). The primary end point was safety, defined by grade 4 toxicity using the National Cancer Institute Common Toxicity Criteria, version 3.0. Secondary end points included response rate, clinical benefit rate, and progression-free survival (PFS). Prior nonsteroidal AIs (NSAIs) were permitted in the absence of progressive disease. Forty-three patients were treated. After a median of 13 cycles (range, 1 to 71 cycles), select treatment-related toxicities included hypertension (58%; grades 2 and 3 in 19% and 26%), proteinuria (67%; grades 2 and 3 in 14% and 19%), headache (51%; grades 2 and 3 in 16% and 7%), fatigue (74%; grades 2 and 3 in 19% and 2%), and joint pain (63%; grades 2 and 3 in 19% and 0%). Eighty-four percent of patients had at least stable disease on an NSAI, confounding efficacy results. Partial responses were seen in 9% of patients and stable disease >or= 24 weeks was noted in 67%. Median PFS was 17.1 months. Combination letrozole and bevacizumab was feasible with expected bevacizumab-related events of hypertension, headache, and proteinuria. Phase III proof-of-efficacy trials of endocrine therapy plus bevacizumab are in progress (Cancer and Leukemia Group B 40503).

Intraocular Lens Dislocation after Cataract Surgery in Tambolaka, Southwest Sumba, Indonesia: A Case Report

OpenAIRE

Ratna Sitompul

2018-01-01

Intraocular lens (IOL) dislocation is a rare complication of cataract extraction requiring prompt surgery. This case report aims to raise awareness of such cases and the importance of post-surgery follow-up. A 58-year-old female patient was found with anterior IOL dislocation a week after phacoemulsification surgery in her right eye. Visual acuity of the right eye was 1/60 with ciliary injection and IOL dislocation to the anterior chamber of the right eye. The patient underwent surgery of the...

Prediction of novel target genes and pathways involved in bevacizumab-resistant colorectal cancer

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Makondi, Precious Takondwa; Lee, Chia-Hwa; Huang, Chien-Yu; Chu, Chi-Ming; Chang, Yu-Jia

2018-01-01

Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic colorectal cancer (mCRC) therapy; however, its treatment efficacy is hampered by therapeutic resistance. Therefore, understanding the mechanisms underlying bevacizumab resistance is crucial to increasing the therapeutic efficacy of bevacizumab. The Gene Expression Omnibus (GEO) database (dataset, GSE86525) was used to identify the key genes and pathways involved in bevacizumab-resistant mCRC. The GEO2R web tool was used to identify differentially expressed genes (DEGs). Functional and pathway enrichment analyses of the DEGs were performed using the Database for Annotation, Visualization, and Integrated Discovery(DAVID). Protein–protein interaction (PPI) networks were established using the Search Tool for the Retrieval of Interacting Genes/Proteins database(STRING) and visualized using Cytoscape software. A total of 124 DEGs were obtained, 57 of which upregulated and 67 were downregulated. PPI network analysis showed that seven upregulated genes and nine downregulated genes exhibited high PPI degrees. In the functional enrichment, the DEGs were mainly enriched in negative regulation of phosphate metabolic process and positive regulation of cell cycle process gene ontologies (GOs); the enriched pathways were the phosphoinositide 3-kinase-serine/threonine kinase signaling pathway, bladder cancer, and microRNAs in cancer. Cyclin-dependent kinase inhibitor 1A(CDKN1A), toll-like receptor 4 (TLR4), CD19 molecule (CD19), breast cancer 1, early onset (BRCA1), platelet-derived growth factor subunit A (PDGFA), and matrix metallopeptidase 1 (MMP1) were the DEGs involved in the pathways and the PPIs. The clinical validation of the DEGs in mCRC (TNM clinical stages 3 and 4) revealed that high PDGFA expression levels were associated with poor overall survival, whereas high BRCA1 and MMP1 expression levels were associated with favorable progress free survival(PFS). The identified genes and pathways

Prediction of novel target genes and pathways involved in bevacizumab-resistant colorectal cancer.

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Precious Takondwa Makondi

Full Text Available Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic colorectal cancer (mCRC therapy; however, its treatment efficacy is hampered by therapeutic resistance. Therefore, understanding the mechanisms underlying bevacizumab resistance is crucial to increasing the therapeutic efficacy of bevacizumab. The Gene Expression Omnibus (GEO database (dataset, GSE86525 was used to identify the key genes and pathways involved in bevacizumab-resistant mCRC. The GEO2R web tool was used to identify differentially expressed genes (DEGs. Functional and pathway enrichment analyses of the DEGs were performed using the Database for Annotation, Visualization, and Integrated Discovery(DAVID. Protein-protein interaction (PPI networks were established using the Search Tool for the Retrieval of Interacting Genes/Proteins database(STRING and visualized using Cytoscape software. A total of 124 DEGs were obtained, 57 of which upregulated and 67 were downregulated. PPI network analysis showed that seven upregulated genes and nine downregulated genes exhibited high PPI degrees. In the functional enrichment, the DEGs were mainly enriched in negative regulation of phosphate metabolic process and positive regulation of cell cycle process gene ontologies (GOs; the enriched pathways were the phosphoinositide 3-kinase-serine/threonine kinase signaling pathway, bladder cancer, and microRNAs in cancer. Cyclin-dependent kinase inhibitor 1A(CDKN1A, toll-like receptor 4 (TLR4, CD19 molecule (CD19, breast cancer 1, early onset (BRCA1, platelet-derived growth factor subunit A (PDGFA, and matrix metallopeptidase 1 (MMP1 were the DEGs involved in the pathways and the PPIs. The clinical validation of the DEGs in mCRC (TNM clinical stages 3 and 4 revealed that high PDGFA expression levels were associated with poor overall survival, whereas high BRCA1 and MMP1 expression levels were associated with favorable progress free survival(PFS. The identified genes and pathways

Docetaxel-carboplatin in combination with erlotinib and/or bevacizumab in patients with non-small cell lung cancer

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Boutsikou E

2013-03-01

Full Text Available Eftimia Boutsikou,1 Theodoros Kontakiotis,1 Paul Zarogoulidis,1 Kaid Darwiche,2 Ellada Eleptheriadou,1 Konstantinos Porpodis,1 Grammati Galaktidou,3 Leonidas Sakkas,4 Wolfgang Hohenforst-Schmidt,5 Kosmas Tsakiridis,6 Theodoros Karaiskos,7 Konstantinos Zarogoulidis11Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Greece; 2University Pulmonary Department-Interventional Unit, Ruhrland Klinic, University of Duisburg-Essen, Essen, Germany; 3Theagenio Anticancer Institute Research Laboratory, 4Department of Pathology, G Papanikolaou Hospital, Thessaloniki, Greece; 5II Medical Clinic, Hospital Coburg, University of Wuerzburg, Coburg, Germany; 6Cardiothoracic Surgery Department, Saint Luke Private Hospital, Panorama, 7Cardiothoracic Surgery Department, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, GreeceBackground: Bevacizumab and erlotinib have been demonstrated to prolong overall survival in patients with non-squamous non-small cell lung cancer (NSCLC. We designed a four-arm Phase III trial to evaluate the efficacy and toxicity of the combination of docetaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with NSCLC.Methods: A total of 229 patients with stage IIIb/IV non-squamous NSCLC were treated with two cycles of carboplatin (area under the concentration-time curve 5.5 and docetaxel 100 mg/m2 as chemotherapy. After completion of two treatment cycles, patients were evaluated for response and divided into four groups: 61/229 continued with four more cycles of chemotherapy (control group, 52/229 received chemotherapy plus erlotinib 150 mg daily, 56/229 received chemotherapy plus bevacizumab 7.5 mg/kg, and 60/229 were treated with the combination of chemotherapy, erlotinib, and bevacizumab until disease progression. The primary endpoint was overall survival.Results: Over 4 years of follow-up, there was no statistically

Piggyback intraocular lens implantation to correct pseudophakic refractive error after segmental multifocal intraocular lens implantation.

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Venter, Jan A; Oberholster, Andre; Schallhorn, Steven C; Pelouskova, Martina

2014-04-01

To evaluate refractive and visual outcomes of secondary piggyback intraocular lens implantation in patients diagnosed as having residual ametropia following segmental multifocal lens implantation. Data of 80 pseudophakic eyes with ametropia that underwent Sulcoflex aspheric 653L intraocular lens implantation (Rayner Intraocular Lenses Ltd., East Sussex, United Kingdom) to correct residual refractive error were analyzed. All eyes previously had in-the-bag zonal refractive multifocal intraocular lens implantation (Lentis Mplus MF30, models LS-312 and LS-313; Oculentis GmbH, Berlin, Germany) and required residual refractive error correction. Outcome measurements included uncorrected distance visual acuity, corrected distance visual acuity, uncorrected near visual acuity, distance-corrected near visual acuity, manifest refraction, and complications. One-year data are presented in this study. The mean spherical equivalent ranged from -1.75 to +3.25 diopters (D) preoperatively (mean: +0.58 ± 1.15 D) and reduced to -1.25 to +0.50 D (mean: -0.14 ± 0.28 D; P < .01). Postoperatively, 93.8% of eyes were within ±0.50 D and 98.8% were within ±1.00 D of emmetropia. The mean uncorrected distance visual acuity improved significantly from 0.28 ± 0.16 to 0.01 ± 0.10 logMAR and 78.8% of eyes achieved 6/6 (Snellen 20/20) or better postoperatively. The mean uncorrected near visual acuity changed from 0.43 ± 0.28 to 0.19 ± 0.15 logMAR. There was no significant change in corrected distance visual acuity or distance-corrected near visual acuity. No serious intraoperative or postoperative complications requiring secondary intraocular lens removal occurred. Sulcoflex lenses proved to be a predictable and safe option for correcting residual refractive error in patients diagnosed as having pseudophakia. Copyright 2014, SLACK Incorporated.

A common humoral background of intraocular and arterial blood pressure dysregulation.

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Skrzypecki, Janusz; Grabska-Liberek, Iwona; Przybek, Joanna; Ufnal, Marcin

2018-03-01

It has been postulated that intraocular pressure, an important glaucoma risk factor, correlates positively with arterial blood pressure (blood pressure). However, results of experimental and clinical studies are often contradictory. It is hypothesized that, in some hypertensive patients, disturbances in intraocular pressure regulation may depend on biological effects of blood borne hormones underlying a particular type of hypertension, rather than on blood pressure level itself. This review compares the effects of hormones on blood pressure and intraocular pressure, in order to identify a hormonal profile of hypertensive patients with an increased risk of intraocular pressure surge. The PUBMED database was searched to identify pre-clinical and clinical studies investigating the role of angiotensin II, vasopressin, adrenaline, noradrenaline, prostaglandins, and gaseous transmitters in the regulation of blood pressure and intraocular pressure. Studies included in the review suggest that intraocular and blood pressures often follow a different pattern of response to the same hormone. For example, vasopressin increases blood pressure, but decreases intraocular pressure. In contrast, high level of nitric oxide decreases blood pressure, but increases intraocular pressure. Arterial hypertension is associated with altered levels of blood borne hormones. Contradicting results of studies on the relationship between arterial hypertension and intraocular pressure might be partially explained by diverse effects of hormones on arterial and intraocular pressures. Further studies are needed to evaluate if hormonal profiling may help to identify glaucoma-prone patients.

Bevacizumab with metronomic chemotherapy of low-dose oral cyclophosphamide in recurrent cervical cancer: Four cases

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Rose Isono-Nakata

2018-05-01

Full Text Available Standard chemotherapy for women with advanced or recurrent cervical cancer involves a combination of paclitaxel, platinum, and bevacizumab. However, for patients who experience anaphylaxis in response to paclitaxel or platinum, have permanent peripheral neuropathy, or develop early recurrence or progressive disease during first-line chemotherapy, the development of a non-taxane non-platinum regimen is mandatory. Clinical trials using anti-angiogenic treatment demonstrated favorable outcomes in cases of highly vascularized cervical cancer. Metronomic chemotherapy has been considered an anti-angiogenic treatment, although its use in combination with bevacizumab has not been studied in cervical cancer. We treated four patients with recurrent cervical cancer with 50 mg of oral cyclophosphamide daily and 15 mg/kg of intravenous bevacizumab every 3 weeks (CFA-BEV. One patient experienced disease progression after 4 months, whereas the other three patients continued the regimen until their last follow-up at 13, 14, and 15 months, respectively. One patient suffered from grade 3 neutropenia; however, no grade 2 or higher non-hematological toxicities were observed. These cases demonstrate the use of CFA-BEV with minimal toxicity and expected anti-cancer activity and indicate that this regimen should be considered for second-line chemotherapy in advanced recurrent cervical cancer. Keywords: Cervical cancer, Metronomic chemotherapy, Bevacizumab

Greater efficacy of chemotherapy plus bevacizumab compared to chemo- and targeted therapy alone on non-small cell lung cancer patients with brain metastasis.

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Tang, Ning; Guo, Jun; Zhang, Qianqian; Wang, Yali; Wang, Zhehai

2016-01-19

Control of non-small-cell lung cancer (NSCLC) with brain metastasis is clinically challenging. This study retrospectively evaluated the efficacy of different adjuvant therapies for 776 cases of advanced NSCLCs with brain metastasis who treated with chemotherapy, chemotherapy plus bevacizumab, tyrosine kinase inhibitor (TKI) alone, or supportive care. The median progression-free survival (mPFS) and median overall survival (mOS) of patients treated with chemotherapy plus bevacizumab were 8.5 and 10.5 months, respectively, which were better than those of patients treated with other three therapies(P chemotherapy plus bevacizumab but was significantly better than that of other therapies. Moreover, for patients with EGFR wild-type NSCLC, the mPFS and mOS after chemotherapy plus bevacizumab were greater than those with other two therapies (P Chemotherapy plus bevacizumab was more effective for NSCLC patients with brain metastasis. Further studies will investigate the benefit of TKI alone for patients with EGFR-mutated. For patients with EGFR wild-type, chemotherapy plus bevacizumab did improve PFS and OS. Furthermore, regimens including pemetrexed led to a greater RR.

Systemic administration of bevacizumab prolongs survival in an in vivo model of platinum pre-treated ovarian cancer

Science.gov (United States)

REIN, DANIEL T.; VOLKMER, ANNE KATHRIN; VOLKMER, JENS; BEYER, INES M.; JANNI, WOLFGANG; FLEISCH, MARKUS C.; WELTER, ANNE KATHRIN; BAUERSCHLAG, DIRK; SCHÖNDORF, THOMAS; BREIDENBACH, MARTINA

2012-01-01

Ovarian cancer patients often suffer from malignant ascites and pleural effusion. Apart from worsening the outcome, this condition frequently impairs the quality of life in patients who are already distressed by ovarian cancer. This study investigated whether single intraperitoneal administration of the anti-VEGF antibody bevacizumab is capable of reducing the ascites-related body surface and prolonging survival. The study was performed in an orthotopic murine model of peritoneal disseminated platin-resistant ovarian cancer. Mice were treated with bevacizumab and/or paclitaxel or buffer (control). Reduction of body surface and increased survival rates were assessed as therapeutic success. Survival of mice in all treatment groups was significantly enhanced when compared to the non-treatment control group. The combination of paclitaxel plus bevacizumab significantly improved body surface as well as overall survival in comparison to a treatment with only one of the drugs. Treatment of malignant effusion with a single dose of bevacizumab as an intraperitoneal application, with or without cytostatic co-medication, may be a powerful alternative to systemic treatment. PMID:22740945

Intravitreal ranibizumab and bevacizumab for the treatment of nonsubfoveal choroidal neovascularization in age-related macular degeneration Ranibizumab e bevacizumab intravítreo no tratamento da neovascularização de coróide extrafoveal da degeneração macular relacionada à idade

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Aaron Brock Roller

2009-10-01

Full Text Available PURPOSE: To investigate the efficacy of vascular endothelial growth factor-specific (VEGF monoclonal antibodies in the treatment of choroidal neovascularization secondary to age-related macular degeneration (AMD that does not extend beneath the foveal center (nonsubfoveal CNV. METHODS: The study design was a retrospective chart review of consecutive patients over a two-month period under active treatment with bevacizumab and/or ranibizumab for neovascular AMD. Patients with neovascularization within the macula that did not extend beneath the center of the foveal avascular zone, along with at least one large drusen (>125 µ or many intermediate size (63-124 µ drusen were included. Best corrected Snellen visual acuity and optical coherence tomography (OCT analysis of the central macular thickness was recorded for each visit. Serial injections of bevacizumab and/or ranibizumab were administered until there was resolution of subretinal fluid clinically or by OCT. Data over the entire follow-up period were analyzed for overall visual acuity and OCT changes. All patients had follow-up since diagnosis of at least 6 months (mean=9.6 months. RESULTS: Of the thirteen included patients, eleven had reduction of retinal thickening in the area involved by the CNV. The remaining two patients did not have OCT data available but had no fluid or activity on clinical examination at last follow-up. One patient (8% lost one line of vision; one (8% remained stable, and eleven (84% gained one or more lines of visual acuity. Three patients (23% gained three or more lines. The average treatment outcome for all patients was a gain of 1.7 ± 1.3 lines of Snellen acuity. Both therapeutic agents were effective, with an average gain of 1.6 ± 0.6 lines for patients treated with bevacizumab, 1.5 ± 1.9 lines gained for patients treated with ranibizumab and 2.5 ± 0.7 lines gained in the two patients who received both agents over the course of their treatment. CONCLUSIONS

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

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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.

21 CFR 886.4300 - Intraocular lens guide.

Science.gov (United States)

2010-04-01

...) MEDICAL DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4300 Intraocular lens guide. (a) Identification. An intraocular lens guide is a device intended to be inserted into the eye during surgery to direct... lenses, the device is exempt from the premarket notification procedures in subpart E of part 807 of this...

DESIGN OF THE MULTIORDER INTRAOCULAR LENSES

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V. G. Kolobrodov

2015-01-01

Full Text Available Intraocular lenses (IOLs are used to replace the natural crystalline lens of the eye. Just few basic designs of IOLs are used clinically. Multiorder diffractive lenses (MODL which operate simultaneously in several diffractive orders were proposed to decrease the chromatic aberration. Properties analysis of MODL showed a possibility to use them to develop new designs of IOLs. The purpose of this paper was to develop a new method of designing of multiorder intraocular lenses with decreased chromatic aberration. The theoretical research of the lens properties was carried out. The diffraction efficiency dependence with the change of wavelength was studied. A computer simulation of MODL in a schematic model of the human eye was carried out. It is found the capability of the multiorder diffractive lenses to focus polychromatic light into a segment on the optical axis with high diffraction efficiency. At each point of the segment is present each component of the spectral range, which will build a color image in combination. The paper describes the new design method of intraocular lenses with reduced chromaticism and with endless adaptation. An optical system of an eye with an intraocular lens that provides sharp vision of objects located at a distance of 700 mm to infinity is modeled.

Lente intra-ocular multifocal difrativa apodizada: resultados Diffractive apodized multifocal intraocular lens: results

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Virgilio Centurion

2007-12-01

Full Text Available OBJETIVO: Mostrar os resultados visuais e refracionais com lente intra-ocular multifocal difrativa apodizada. MÉTODOS: Estudo de 100 olhos de 50 pacientes com catarata, submetidos à facoemulsificação com implante bilateral de lente intra-ocular (LIO multifocal difrativa apodizada. Foi avaliada a acuidade visual binocular sem e com correção para longe e perto, a previsibilidade refracional e a freqüência de uso de óculos. RESULTADOS: A acuidade visual sem correção para longe foi de e " 20/30 em 97,56% dos olhos operados e e" J2 em 100%, sendo que 82% dos pacientes nunca usam óculos e 16% usam de forma esporádica. CONCLUSÃO: A LIO multifocal difrativa apodizada mostrou ser uma opção previsível, reproduzível e segura na correção dos vícios de refração para longe e perto durante a cirurgia da catarata, permitindo elevado índice de independência ao uso de óculos.OBJECTIVE: To show visual and refraction results using multifocal diffractive apodized intraocular lens. METHODS: The study of 100 eyes of 50 patients with cataract, submitted to phacoemulsification with bilateral implant of multifocal diffractive apodized intraocular lens (IOL. Binocular visual acuity was evaluated with and without correction for near and distance, and refraction previsibility and frequency of wearing glasses. RESULTS: Visual acuity without correction for distance was e" 20/30 in 97.56% of eyes operated on and e" J2 in 100%, of these 82% of patients never wear glasses and 16% wear glasses sporadically. CONCLUSION: Multifocal diffractive apodized IOL proved to be a foreseeable option, reproducible and safe in the correction of refraction errors for distance and near during cataract surgery, enabling a high rate of independence from the use of glasses.

Perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01).

Science.gov (United States)

Suenaga, Mitsukuni; Fujimoto, Yoshiya; Matsusaka, Satoshi; Shinozaki, Eiji; Akiyoshi, Takashi; Nagayama, Satoshi; Fukunaga, Yosuke; Oya, Masatoshi; Ueno, Masashi; Mizunuma, Nobuyuki; Yamaguchi, Toshiharu

2015-01-01

Perioperative chemotherapy combined with surgery for liver metastases is considered an active strategy in metastatic colorectal cancer (CRC). However, its impact on initially unresectable, previously untreated advanced CRC, regardless of concurrent metastases, remains to be clarified. A Phase II study was conducted to evaluate the safety and efficacy of perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced CRC. Patients with previously untreated advanced colon or rectal cancer initially diagnosed as unresectable advanced CRC (TNM stage IIIb, IIIc, or IV) but potentially resectable after neoadjuvant chemotherapy (NAC) were studied. Preoperatively, patients received six cycles of NAC (five cycles of neoadjuvant FOLFOX4 plus bevacizumab followed by one cycle of FOLFOX4 alone). The interval between the last dose of bevacizumab and surgery was at least 5 weeks. Six cycles of adjuvant FOLFOX4 plus bevacizumab were given after surgery. The completion rate of NAC and feasibility of curative surgery were the primary endpoints. An interim analysis was performed at the end of NAC in the 12th patient to assess the completion rate of NAC. The median follow-up time was 56 months. The characteristics of the patients were as follows: sex, eight males and four females; tumor location, sigmoid colon in three, ascending colon in one, and rectum (above the peritoneal reflection) in eight; stage, III in eight and IV in four (liver or lymph nodes). All patients completed six cycles of NAC. There were no treatment-related severe adverse events or deaths. An objective response to NAC was achieved in nine patients (75%), and no disease progression was observed. Eleven patients underwent curative tumor resection, including metastatic lesions. In December 2012, this Phase II study was terminated because of slow registration. Perioperative FOLFOX4 plus bevacizumab is well tolerated and has a promising response rate leading to curative surgery, which offers a survival

Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma.

Science.gov (United States)

Shah, Manish A; Ramanathan, Ramesh K; Ilson, David H; Levnor, Alissa; D'Adamo, David; O'Reilly, Eileen; Tse, Archie; Trocola, Robin; Schwartz, Lawrence; Capanu, Marinela; Schwartz, Gary K; Kelsen, David P

2006-11-20

Bevacizumab improves survival in several solid tumor malignancies when combined with chemotherapy. We evaluated the efficacy and safety of the addition of bevacizumab to chemotherapy in the treatment of gastric and gastroesophageal junction (GEJ) adenocarcinoma. Forty-seven patients with metastatic or unresectable gastric/GEJ adenocarcinoma were treated with bevacizumab 15 mg/kg on day 1, irinotecan 65 mg/m2, and cisplatin 30 mg/m2 on days 1 and 8, every 21 days. The primary end point was to demonstrate a 50% improvement in time to progression over historical values. Secondary end points included safety, response, and survival. Patient characteristics were as follows: median age 59 years (range, 25 to 75); Karnofsky performance status 90% (70% to 100%); male:female, 34:13; and gastric/GEJ, 24:23. With a median follow-up of 12.2 months, median time to progression was 8.3 months (95% CI, 5.5 to 9.9 months). In 34 patients with measurable disease, the overall response rate was 65% (95% CI, 46% to 80%). Median survival was 12.3 months (95% CI, 11.3 to 17.2 months). We observed no increase in chemotherapy related toxicity. Possible bevacizumab-related toxicity included a 28% incidence of grade 3 hypertension, two patients with a gastric perforation and one patient with a near perforation (6%), and one patient with a myocardial infarction (2%). Grade 3 to 4 thromboembolic events occurred in 25% of patients. Although the primary tumor was unresected in 40 patients, we observed only one patient with a significant upper gastrointestinal bleed. Bevacizumab can be safely given with chemotherapy even with primary gastric and GEJ tumors in place. The response rate, time to disease progression (TTP), and overall survival are encouraging, with TTP improved over historical controls by 75%. Further development of bevacizumab in gastric and GEJ cancers is warranted.

Restriction spectrum imaging of bevacizumab-related necrosis in a patient with GBM

Directory of Open Access Journals (Sweden)

Nikdokht eFarid

2013-09-01

Full Text Available Importance:With the increasing use of antiangiogenic agents in the treatment of high grade gliomas, we are becoming increasingly aware of distinctive imaging findings seen in a subset of patients treated with these agents. Of particular interest is the development of regions of marked and persistent restricted diffusion. We describe a case with histopathologic validation, confirming that this region of restricted diffusion represents necrosis and not viable tumor. Observations:We present a case report of a 52-year-old man with GBM treated with temozolomide, radiation, and concurrent bevacizumab following gross total resection. The patient underwent sequential MRI's which included restriction-spectrum imaging (RSI, an advanced diffusion-weighted imaging (DWI technique, and MR perfusion. Following surgery, the patient developed an area of restricted diffusion on RSI which became larger and more confluent over the next several months. Marked signal intensity on RSI and very low cerebral blood volume (CBV on MR perfusion led us to favor bevacizumab-related necrosis over recurrent tumor. Subsequent histopathologic evaluation confirmed coagulative necrosis.Conclusions and Relevance:Our report increases the number of pathologically-proven cases of bevacizumab-related necrosis in the literature from three to four. Furthermore, our case demonstrates this phenomenon on RSI, which has been shown to have good sensitivity to restricted diffusion.

ELLIPSE Study: a Phase 1 study evaluating the tolerance of bevacizumab nasal spray in the treatment of epistaxis in hereditary hemorrhagic telangiectasia.

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Dupuis-Girod, Sophie; Ambrun, Alexis; Decullier, Evelyne; Samson, Géraldine; Roux, Adeline; Fargeton, Anne-Emmanuelle; Rioufol, Catherine; Schwiertz, Verane; Disant, François; Chapuis, François; Donazzolo, Yves; Paintaud, Gilles; Edery, Patrick; Faure, Frederic

2014-01-01

Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited genetic vascular disorder in which epistaxis is the most frequent manifestation, responsible for high morbidity. Management of this symptom has no standard, and local treatments are often aggressive. Their efficacy is variable and has not been proven. Anti-angiogenic drugs, such as bevacizumab, are a new treatment strategy. Its systemic administration in patients with HHT improves liver damage-related symptoms and epistaxis. To limit the systemic adverse effects of bevacizumab and to ease administration, a local administration seems suitable. To evaluate the tolerance of increasing doses of bevacizumab administered as a nasal spray in patients with HHT-related epistaxis. Secondary objectives were to study the bioavailability and efficacy of bevacizumab against epistaxis when given as a nasal spray. Phase 1, randomized, double-blind, placebo-controlled, monocentric study performed sequentially (dose escalation) on 5 groups of 8 patients. Each group was made up of 6 verum and 2 placebos. Five increasing doses of bevacizumab nasal spray (25 mg/mL) were evaluated: 12.5, 25, 50, 75 and 100 mg. A total of 40 patients were included between October 2011 and October 2012. Bevacizumab nasal spray was well tolerated in all patients and the drug was not detected in their serum. No dose limiting toxicity was observed. No efficacy was observed at any dose in this study. Based on these results, bevacizumab nasal spray is a safe treatment of epistaxis in HHT. However, a randomized Phase 2 study is needed to determine its efficacy. ClinicalTrials.gov Identifier #NCT01507480.

Relation between intraocular pressure and size of transverse sinuses

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Kantarci, Mecit; Onbas, Omer; Alper, Fatih; Okur, Adnan [Atatuerk University, Department of Radiology, Medical Faculty, Erzurum (Turkey); Dane, Senol; Gumustekin, Kenan [Atatuerk University, Department of Physiology, Medical Faculty, Erzurum (Turkey); Aslankurt, Murat [Atatuerk University, Department of Ophtalmatology, Medical Faculty, Erzurum (Turkey); Yazici, Ahmet Taylan [Beyoglu Goez Egitim ve Arastirma Hastanesi, Istanbul (Turkey)

2005-01-01

There are asymmetries in the sizes of transverse sinus and intraocular pressure. The purpose of this study was to investigate possible relationships between the asymmetry of transverse sinuses in TOF MR venography and intraocular pressures of right and left eyes. In this study, subjects were 63 male and 42 female medical school students, aged 18-21 years (mean{+-}SD; 19.72{+-}0.67 years). Subjects with neurological and ophthalmologic disease, particularly dural sinus thrombosis, myopia, trauma and glaucoma, were excluded the study. Subjects were divided into five groups according to the magnitudes of the right- and left-transverse sinuses in MR venography results. There is a functional relation between intraocular pressures of the right and left eyes and asymmetry of the transverse sinus. If the transverse sinus on one side is larger and its venous drainage is greater, the intraocular pressure of the eye on this side is lower. It can be speculated that the transverse sinus size may be associated with pathogenesis of diseases with increased intraocular pressure such as glaucoma. We aim to determine the relation between the size and drainage of transverse sinuses in TOF MR venography and intraocular pressure in patients with open-angle glaucoma in our next study. (orig.)

Relation between intraocular pressure and size of transverse sinuses

International Nuclear Information System (INIS)

Kantarci, Mecit; Onbas, Omer; Alper, Fatih; Okur, Adnan; Dane, Senol; Gumustekin, Kenan; Aslankurt, Murat; Yazici, Ahmet Taylan

2005-01-01

There are asymmetries in the sizes of transverse sinus and intraocular pressure. The purpose of this study was to investigate possible relationships between the asymmetry of transverse sinuses in TOF MR venography and intraocular pressures of right and left eyes. In this study, subjects were 63 male and 42 female medical school students, aged 18-21 years (mean±SD; 19.72±0.67 years). Subjects with neurological and ophthalmologic disease, particularly dural sinus thrombosis, myopia, trauma and glaucoma, were excluded the study. Subjects were divided into five groups according to the magnitudes of the right- and left-transverse sinuses in MR venography results. There is a functional relation between intraocular pressures of the right and left eyes and asymmetry of the transverse sinus. If the transverse sinus on one side is larger and its venous drainage is greater, the intraocular pressure of the eye on this side is lower. It can be speculated that the transverse sinus size may be associated with pathogenesis of diseases with increased intraocular pressure such as glaucoma. We aim to determine the relation between the size and drainage of transverse sinuses in TOF MR venography and intraocular pressure in patients with open-angle glaucoma in our next study. (orig.)

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...... from febrile neutropenia whereas non-hematological toxicity was manageable. CONCLUSIONS: Only the Bev-Tem arm met the pre-specified level of activity of interest. Our results did not indicate any benefit from Bev-Iri in first-line therapy as opposed to Bev-Tem in terms of response and PFS....

Edge Contrast of the FLAIR Hyperintense Region Predicts Survival in Patients with High-Grade Gliomas following Treatment with Bevacizumab.

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Bahrami, N; Piccioni, D; Karunamuni, R; Chang, Y-H; White, N; Delfanti, R; Seibert, T M; Hattangadi-Gluth, J A; Dale, A; Farid, N; McDonald, C R

2018-04-05

Treatment with bevacizumab is standard of care for recurrent high-grade gliomas; however, monitoring response to treatment following bevacizumab remains a challenge. The purpose of this study was to determine whether quantifying the sharpness of the fluid-attenuated inversion recovery hyperintense border using a measure derived from texture analysis-edge contrast-improves the evaluation of response to bevacizumab in patients with high-grade gliomas. MRIs were evaluated in 33 patients with high-grade gliomas before and after the initiation of bevacizumab. Volumes of interest within the FLAIR hyperintense region were segmented. Edge contrast magnitude for each VOI was extracted using gradients of the 3D FLAIR images. Cox proportional hazards models were generated to determine the relationship between edge contrast and progression-free survival/overall survival using age and the extent of surgical resection as covariates. After bevacizumab, lower edge contrast of the FLAIR hyperintense region was associated with poorer progression-free survival ( P = .009) and overall survival ( P = .022) among patients with high-grade gliomas. Kaplan-Meier curves revealed that edge contrast cutoff significantly stratified patients for both progression-free survival (log-rank χ 2 = 8.3, P = .003) and overall survival (log-rank χ 2 = 5.5, P = .019). Texture analysis using edge contrast of the FLAIR hyperintense region may be an important predictive indicator in patients with high-grade gliomas following treatment with bevacizumab. Specifically, low FLAIR edge contrast may partially reflect areas of early tumor infiltration. This study adds to a growing body of literature proposing that quantifying features may be important for determining outcomes in patients with high-grade gliomas. © 2018 by American Journal of Neuroradiology.

A systematic review of bevacizumab efficacy in breast cancer

DEFF Research Database (Denmark)

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

2014-01-01

demonstrated an OS benefit. In the neoadjuvant setting 23 phase II and III trials were identified. All studies found increased pCR/tpCR but no benefit in terms of OS could be demonstrated. The only study conducted in the adjuvant setting failed to show any survival benefit of bevacizumab. CONCLUSION: Despite...

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

leaking on FA, whereas only one of five bevacizumab-injected eyes exhibited leakage. On histological examination, all 11 eyes contained CNV membranes of similar size, regardless of treatment. The number of vascular endothelial cells was significantly reduced (p = 0.03) in CNV membranes from eyes that had...... was identified immunohistochemically in the inner limiting membrane (ILM) and to a lesser degree in the remaining retina. Strong staining was also detected in both retinal blood vessels and entire CNV membranes with no cellular predisposition. Vascular endothelial growth factor expression was found in the CNV...... membranes, in the ILM, in the ganglion cell layer, in Müller cells throughout the neuroretina and in retinal blood vessels. CONCLUSIONS: Bevacizumab significantly reduced the proliferation of vascular endothelial cells in CNV membranes and showed a strong trend towards a reduction of leakage from...

Effect of Bevacizumab Nasal Spray on Epistaxis Duration in Hereditary Hemorrhagic Telangectasia: A Randomized Clinical Trial.

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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

Impact of Primary Tumor Location on First-line Bevacizumab or Cetuximab in Metastatic Colorectal Cancer.

Science.gov (United States)

Snyder, Matthew; Bottiglieri, Sal; Almhanna, Khaldoun

2018-01-01

Colorectal cancer is one of the most common malignancies in the United States, with a large proportion of patients presenting with metastatic disease or developing a recurrence. Systemic chemotherapy is the mainstay of therapy in this setting. There is a clear benefit in the addition of bevacizumab or cetuximab (for rat sarcoma [RAS] wild type tumors) to oxaliplatin- and irinotecan-based regimens which can be considered for first-line therapy. However, many significant questions remain as to which agent reflects best practice. Our review aimed to elucidate the benefit of adding bevacizumab and cetuximab to initial therapy for metastatic colorectal cancer based on primary tumor location and a variety of other disease- and patient-related factors, addressing the paucity of evidence that currently exists in this area and contributing to current literature and clinical practices. The primary endpoints of the study were first Progression-Free Survival (PFS) and Overall Survival (OS). Secondary endpoints included best response to first- and second-line therapies, Treatment- Related Adverse Events (TRAEs), second PFS, cost of therapy, and an assessment of other patient- and disease-related factors affecting PFS and OS. While there were trends towards improved OS in patients with left-sided primary tumors (n=57) compared to those with right-sided disease (n=23), there were no significant differences between the two groups in either primary endpoint. While no differences were found for patients with left- or right- sided tumors stratified by add-on agent, these analyses were limited by the small number of patients receiving cetuximab with first-line therapy (n=4). However, the bevacizumab cohort (n=76) was sizable enough to provide ample data and produce clinically relevant results. Add-on therapy with bevacizumab in our study achieved impressive survival outcomes in both left-sided (median first PFS = 13 months, 95% CI 11-15 months; median OS = 37 months, 95% CI 21

Association of Primary Tumor Site With Mortality in Patients Receiving Bevacizumab and Cetuximab for Metastatic Colorectal Cancer.

Science.gov (United States)

Aljehani, Mayada A; Morgan, John W; Guthrie, Laurel A; Jabo, Brice; Ramadan, Majed; Bahjri, Khaled; Lum, Sharon S; Selleck, Matthew; Reeves, Mark E; Garberoglio, Carlos; Senthil, Maheswari

2018-01-01

Biologic therapy (BT) (eg, bevacizumab or cetuximab) is increasingly used to treat metastatic colorectal cancer (mCRC). Recent investigations have suggested that right- or left-sided primary tumor origin affects survival and response to BT. To evaluate the association of tumor origin with mortality in a diverse population-based data set of patients receiving systemic chemotherapy (SC) and bevacizumab or cetuximab for mCRC. This population-based nonconcurrent cohort study of statewide California Cancer Registry data included all patients aged 40 to 85 years diagnosed with mCRC and treated with SC only or SC plus bevacizumab or cetuximab from January 1, 2004, through December 31, 2014. Patients were stratified by tumor origin in the left vs right sides. Treatment with SC or SC plus bevacizumab or cetuximab. Mortality hazards by tumor origin (right vs left sides) were assessed for patients receiving SC alone or SC plus bevacizumab or cetuximab. Subgroup analysis for patients with wild-type KRAS tumors was also performed. A total of 11 905 patients with mCRC (6713 men [56.4%] and 5192 women [43.6%]; mean [SD] age, 60.0 [10.9] years) were eligible for the study. Among these, 4632 patients received SC and BT. Compared with SC alone, SC plus bevacizumab reduced mortality among patients with right- and left-sided mCRC, whereas SC plus cetuximab reduced mortality only among patients with left-sided tumors and was associated with significantly higher mortality for right-sided tumors (hazard ratio [HR], 1.31; 95% CI, 1.14-1.51; P < .001). Among patients treated with SC plus BT, right-sided tumor origin was associated with higher mortality among patients receiving bevacizumab (HR, 1.31; 95% CI, 1.25-1.36; P < .001) and cetuximab (HR, 1.88; 95% CI, 1.68-2.12; P < .001) BT, compared with left-sided tumor origin. In patients with wild-type KRAS tumors (n = 668), cetuximab was associated with reduced mortality among only patients with left-sided mCRC compared

Addition of bevacizumab to first-line chemotherapy in advanced colorectal cancer: a systematic review and meta-analysis, with emphasis on chemotherapy subgroups

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Macedo Ligia

2012-03-01

Full Text Available Abstract Background Bevacizumab has an important role in first-line treatment of metastatic colorectal cancer. However, clinical trials studying its effect have involved distinct chemotherapy regimens with divergent results. The aim of this meta-analysis is to gather current data and evaluate not only the efficacy of bevacizumab, but also the impact of divergent backbone regimens. Methods A wide search of randomized clinical trials using bevacizumab in first-line metastatic colorectal cancer was performed in Embase, MEDLINE, LILACS and Cochrane databases. Meeting presentations and abstracts were also investigated. The resulting data were examined and included in the meta-analysis according to the type of regimen. Results Six trials, totaling 3060 patients, were analyzed. There was an advantage to using bevacizumab for overall survival (OS and progression-free survival (PFS (HR = 0.84; CI: 0.77-0.91; P Conclusions Bevacizumab has efficacy in first-line treatment of advanced colorectal cancer, but the current data are insufficient to support efficacy in all regimens, especially infusional fluorouracil regimens, like FOLFIRI and FOLFOX.

A cost-benefit analysis of bevacizumab in combination with paclitaxel in the first-line treatment of patients with metastatic breast cancer.

Science.gov (United States)

Montero, Alberto J; Avancha, Kiran; Glück, Stefan; Lopes, Gilberto

2012-04-01

Bevacizumab in combination with chemotherapy increases progression-free survival (PFS), but not overall survival when compared to chemotherapy alone in the treatment of metastatic breast cancer (MBC). Recently in November, 2011 the Food and drug administration revoked approval of bevacizumab in combination with paclitaxel for the treatment of MBC. The European Medicines Agency, in contrast, maintained its approval of bevacizumab in MBC. While neither agency considers health economics in their decision-making process, one of the greatest challenges in oncology practice today is to reconcile hard-won small incremental clinical benefits with exponentially rising costs. To inform policy-makers in the US, this study aimed to assess the cost-effectiveness of bevacizumab/paclitaxel in MBC, from a payer perspective. We created a decision analytical model using efficacy and adverse events data from the ECOG 2100 trial. Health utilities were derived from available literature. Costs were obtained from the Center for Medicare Services Drug Payment Table and Physician Fee Schedule and are represented in 2010 US dollars. Quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER) were calculated. Sensitivity analyses were performed. Bevacizumab added 0.49 years of PFS and 0.135 QALY with an incremental cost of $100,300, and therefore a cost of $204,000 per year of PFS gained and an ICER of $745,000 per QALY. The main drivers of the model were drug acquisition cost, PFS, and health utility values. Using a threshold of $150,000/QALY, drug price would have to be reduced by nearly 80% or alternatively PFS increased by 10 months to make bevacizumab cost-effective. The results of the model were robust in sensitivity analyses. Bevacizumab plus paclitaxel is not cost-effective in treating MBC. Value-based pricing and the development of biomarkers to improve patient selection are needed to better define the role of the drug in this population.

Development and evaluation of bevacizumab-modified pegylated cationic liposomes using cellular and in vivo models of human pancreatic cancer

Science.gov (United States)

Kuesters, Geoffrey M.

Targeting the tumor vascular supply in a homogenous manner is a difficult task to achieve with the use of pegylated cationic liposomes (PCLs) alone. Our formulation consisting of bevacizumab conjugated to the distal end of PEG on PCLs was thus developed in an effort to eliminate some of this heterogeneity as well as to increase tumor targeting overall. This study focuses on pancreatic cancer, which has the poorest five-year survival rate of all cancers because of its late diagnosis. The addition of bevacizumab will target tumor areas because it binds to VEGF which is secreted by tumors in high levels. In vitro, we showed that pancreatic cancer cells (Capan-1, HPAF-II and PANC-1) all secrete VEGF into media at different levels, with Capan-1 producing the most and HPAF-II producing the least. A murine endothelial cell line, MS1-VEGF, produces and secretes the most VEGF. A human microvascular endothelial cell line (HMEC-1) was grown in two different conditions, with and without VEGF in the media. Modifying PCLs with bevacizumab enhanced the binding and uptake of PCLs by some pancreatic and endothelial cells in vitro, particularly the cells that had or secreted the most significant amount of VEGF in the media. This translated into enhanced tumor targeting in a biodistribution study using a Capan-1 subcutaneous pancreatic tumor model. This also showed enhanced blood retention compared to the unmodified PCLs while it diminished uptake by the spleen and increased uptake by the kidney. To test the therapeutic benefit of this enhanced uptake and targeting, an anti-angiogenic agent, 2-methoxyestradiol was incorporated into the formulation with 20% incorporation efficiency. Both the unmodified and modified drug-loaded PCLs were the least efficacious against Capan-1, moderately effective against HPAF-II, PANC-1, MS1-VEGF and HMEC-1 grown without VEGF in the media and most efficacious against HMEC-1 grown with VEGF which had the most VEGF present in the media. Multiple in vivo

Acute Retention of Urine Following Intraocular Surgery | Nwosu ...

African Journals Online (AJOL)

Hyperosmolar agents and carbonic anhydrase inhibitors are used to lower the intraocular pressure and thus minimize the chances of vitreous loss during intraocular surgery. However, these agents could precipitate urinary retention. This is a report on two elderly men who had perioperative acute urinary retention following ...

Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival

International Nuclear Information System (INIS)

Paiva, Tadeu Ferreira Jr.; Jesus, Victor Hugo Fonseca de; Marques, Raul Amorim; Costa, Alexandre André Balieiro Anastácio da; Macedo, Mariana Petaccia de; Peresi, Patricia Maria; Damascena, Aline; Rossi, Benedito Mauro; Begnami, Maria Dirlei; Lima, Vladmir Cláudio Cordeiro de

2015-01-01

The development of targeted therapies has undoubtedly broadened therapeutic options for patients with colorectal cancer (CRC). The use of bevacizumab to reduce angiogenesis has been associated with improved clinical outcomes. However, an urgent need for prognostic/predictive biomarkers for anti-angiogenic therapies still exists. Clinical data of 105 CRC patients treated with bevacizumab in conjunction with chemotherapy were analyzed. The expression of vascular endothelial growth factor (VEGF) receptors, NOTCH1 receptor and its ligand DLL4 were determined by immunohistochemistry. Tumor samples were arranged on a tissue microarray. The association between protein expression and clinicopathological characteristics and outcomes was determined. Bevacizumab was administered as a first-line of treatment in 70.5 % of our cases. The median progression-free survival (PFS) was 10.2 months. The median overall survival (OS) of the total cohort was 24.4 months. Bevacizumab, as the first-line of treatment, and the presence of liver metastasis were independently associated with objective response rate. Membrane VEGFR1 and VEGFR3 expressions were associated with the presence of lung metastasis; interestingly, VEGFR3 was associated with less liver metastasis. NOTCH1 expression was associated with lymph node metastasis. There was a trend toward association between improved PFS and lower NOTCH1 expression (p = 0.06). Improved OS was significantly associated with lower NOTCH1 expression (p = 0.01). In a multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status, liver metastasis, histological grade, and NOTCH1 expression were independently associated with OS. Our findings illustrated the expression profile of angiogenesis-related proteins and their association with clinicopathological characteristics and outcomes. NOTCH1 expression is a detrimental prognostic factor in metastatic CRC patients treated with chemotherapy plus bevacizumab. The online version of

Prognostic Value of CD109+ Circulating Endothelial Cells in Recurrent Glioblastomas Treated with Bevacizumab and Irinotecan

Science.gov (United States)

Cuppini, Lucia; Calleri, Angelica; Bruzzone, Maria Grazia; Prodi, Elena; Anghileri, Elena; Pellegatta, Serena; Mancuso, Patrizia; Porrati, Paola; Di Stefano, Anna Luisa; Ceroni, Mauro; Bertolini, Francesco; Finocchiaro, Gaetano; Eoli, Marica

2013-01-01

Background Recent data suggest that circulating endothelial and progenitor cells (CECs and CEPs, respectively) may have predictive potential in cancer patients treated with bevacizumab, the antibody recognizing vascular endothelial growth factor (VEGF). Here we report on CECs and CEPs investigated in 68 patients affected by recurrent glioblastoma (rGBM) treated with bevacizumab and irinotecan and two Independent Datasets of rGBM patients respectively treated with bevacizumab alone (n=32, independent dataset A: IDA) and classical antiblastic chemotherapy (n=14, independent dataset B: IDB). Methods rGBM patients with KPS ≥50 were treated until progression, as defined by MRI with RANO criteria. CECs expressing CD109, a marker of tumor endothelial cells, as well as other CEC and CEP subtypes, were investigated by six-color flow cytometry. Results A baseline count of CD109+ CEC higher than 41.1/ml (1st quartile) was associated with increased progression free survival (PFS; 20 versus 9 weeks, P=0.008) and overall survival (OS; 32 versus 23 weeks, P=0.03). Longer PFS (25 versus 8 weeks, P=0.02) and OS (27 versus 17 weeks, P=0.03) were also confirmed in IDA with CD109+ CECs higher than 41.1/ml but not in IDB. Patients treated with bevacizumab with or without irinotecan that were free from MRI progression after two months of treatment had significant decrease of CD109+ CECs: median PFS was 19 weeks; median OS 29 weeks. The presence of two non-contiguous lesions (distant disease) at baseline was an independent predictor of shorter PFS and OS (P<0.001). Conclusions Data encourage further studies on the predictive potential of CD109+ CECs in GBM patients treated with bevacizumab. PMID:24069296

Effect of bevacizumab combined with boron neutron capture therapy on local tumor response and lung metastasis

Science.gov (United States)

MASUNAGA, SHIN-ICHIRO; SAKURAI, YOSHINORI; TANO, KEIZO; TANAKA, HIROKI; SUZUKI, MINORU; KONDO, NATSUKO; NARABAYASHI, MASARU; WATANABE, TSUBASA; NAKAGAWA, YOSUKE; MARUHASHI, AKIRA; ONO, KOJI

2014-01-01

The aim of the present study was to evaluate the effect of bevacizumab on local tumor response and lung metastatic potential during boron neutron capture therapy (BNCT) and in particular, the response of intratumor quiescent (Q) cells. B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously administered bromodeoxyuridine (BrdU) to label all proliferating (P) tumor cells. The tumors were irradiated with thermal neutron beams following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)], with or without the administration of bevacizumab. This was further combined with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH, 40°C for 60 min). Immediately following the irradiation, cells from certain tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q cells and the total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days following irradiation, lung metastases were enumerated. Three days following bevacizumab administration, the sensitivity of the total tumor cell population following BPA-BNCT had increased more than that following BSH-BNCT. The combination with MTH, but not with nicotinamide, further enhanced total tumor cell population sensitivity. Regardless of the presence of a 10B-carrier, MTH enhanced the sensitivity of the Q cell population. Regardless of irradiation, the administration of bevacizumab, as well as nicotinamide treatment, demonstrated certain potential in reducing the number of lung metastases especially in BPA-BNCT compared with BSH-BNCT. Thus, the current study revealed that BNCT combined with bevacizumab has the potential to sensitize total tumor cells and cause a reduction in the number of lung metastases to a similar level as nicotinamide. PMID:24944637

Design and preliminary assessment of 99mTc-labeled ultrasmall superparamagnetic iron oxide-conjugated bevacizumab for single photon emission computed tomography/magnetic resonance imaging of hepatocellular carcinoma

International Nuclear Information System (INIS)

Yanzhao Zhao; Hui Tan; Bing Wu; Pengcheng Hu; Pengyue Wu; Yushen Gu; Dengfeng Cheng; Hongcheng Shi; Qi Yao; Chunfu Zhang

2014-01-01

Hepatocellular carcinoma (HCC) has a very high incidence and mortality. Early diagnosis and timely treatments are therefore required to improve the quality of life and survival rate of HCC patients. Here, we developed a vascular endothelial growth factor (VEGF)-based multimodality imaging agent for single photon emission computed tomography (SPECT), computed tomography (CT) and magnetic resonance imaging (MRI) and used it to assess HCC mice and explore the combinative value of CT/MRI-based morphological imaging and SPECT functional imaging. HCC targeting with 125 I-labeled bevacizumab monoclonal antibody (mAb) was examined using SPECT/CT in HepG2 tumor-bearing mice after intravenous mAb injection. Based on this, an integrated, bimodal, VEGF-targeted, ultrasmall superparamagnetic iron oxide (USPIO)-conjugated 99m Tc-labeled bevacizumab mAb was synthesized to increase tumor penetration and accumulations. The in vivo pharmacokinetics and HepG2 tumor targeting were explored through in vivo planar imaging and SPECT/CT using a mouse model of HepG2 liver cancer. The specificity of the radiolabeled nanoparticles for HepG2 HCC was verified using in vitro immunohistochemistry and Prussian blue staining. With diethylenetriamine pentaacetic acid as a bifunctional chelating agent, USPIO-bevacizumab achieved a 99m Tc labeling efficiency of >90 %. The in vivo imaging results also exhibited the targeting of USPIO on HepG2 HCC. The specificity of these results was confirmed using in vitro immunohistochemistry and Prussian blue staining. Our preliminary findings showed the potential of USPIO as an imaging agent for the SPECT/MRI of HepG2 HCC. (author)

Refractive and Biometric Outcomes in Patients with Retinopathy of Prematurity Treated with Intravitreal Injection of Ranibizumab as Compared with Bevacizumab: A Clinical Study of Correction at Three Years of Age.

Science.gov (United States)

Chen, Yen-Chih; Chen, San-Ni; Yang, Benjamin Chi-Lan; Lee, Kun-Hsien; Chuang, Chih-Chun; Cheng, Chieh-Yin

2018-01-01

To compare refractive and biometric outcomes in patients with type 1 retinopathy of prematurity (ROP) treated with intravitreal injection of ranibizumab (IVR) versus bevacizumab (IVB), at a corrected age of 3 years. A retrospective case series compared cycloplegic refractive statuses and biometric statuses in patients who received either IVR or IVB for type 1 ROP, from April 2011 to April 2014. A total of 62 eyes (33 patients) with type 1 ROP were evaluated (26 eyes in 13 IVR patients and 36 eyes in 20 IVB patients). There were no differences in birth statuses including gestational age and birth body weight between the two groups. The prevalence of refractive error greater than 1 D was higher in the IVB group ( p = 0.03), and there was a higher prevalence of high myopia (biometric finding showed that IVB patients had shallower anterior chamber depth ( p = 0.01). Both IVR and IVB showed low refractive errors, even followed at the corrected age of 3 years. No difference was noted between the two groups in refractive statuses. However, IVB was associated with shallower anterior chamber and higher prevalence of refractive error at the corrected age of 3 years. This trial is registered with NCT03334513.

Protective Effect of Combined Caffeic Acid Phenethyl Ester and Bevacizumab Against Hydrogen Peroxide-Induced Oxidative Stress in Human RPE Cells.

Science.gov (United States)

Dinc, Erdem; Ayaz, Lokman; Kurt, Akif Hakan

2017-12-01

This study aimed to evaluate the protective effects of caffeic acid phenethyl ester (CAPE) and combined CAPE-bevacizumab against oxidative stress induced by hydrogen peroxide (H 2 O 2 ) in human retinal pigment epithelium. ARPE-19 cells were pretreated with 5, 10, and 30 μM CAPE alone and in combination with bevacizumab for 3 h, then exposed to H 2 O 2 for 16 h. Cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Vascular endothelial growth factor (VEGF) protein levels in the medium were measured using a human VEGF ELISA kit. Total antioxidant status (TAS) and total oxidant status (TOS) were measured in ARPE-19 cells using the test kit from Rel Assay. Expression levels of VEGF, Bax, Bcl-2, cytochrome c, apoptotic protease activating factor-1 (apaf-1), and caspase-3 were determined using reverse transcription polymerase chain reaction. Pretreatment of ARPE-19 cells with 30 μM CAPE and combined CAPE-bevacizumab reduced H 2 O 2 mediated cell death. H 2 O 2 -induced oxidative stress increased TOS and VEGF production, which was significantly inhibited by CAPE and the CAPE-bevacizumab combination. VEGF, Bax, cytochrome c, apaf-1, and caspase-3 gene expressions were significantly decreased in cells pretreated with 5, 10, and 30 μM CAPE and combined CAPE-bevacizumab compared to the H 2 O 2 group. In addition, Bcl-2 expression was significantly increased in both the CAPE and CAPE-bevacizumab combination groups compared to the H 2 O 2 group. CAPE has a protective effect on ARPE-19 cells against oxidative stress, and VEGF protein level and expression can be decreased by incubation with different concentrations of CAPE. These results demonstrate that CAPE suppresses the mitochondria-mediated apoptosis in ARPE-19 cells under oxidative stress. In addition, the use of CAPE in combination with bevacizumab has an additive effect.

An Association between Bevacizumab and Recurrent Posterior Reversible Encephalopathy Syndrome in a Patient Presenting with Deep Vein Thrombosis: A Case Report and Review of the Literature

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Mark Lazarus

2012-01-01

Full Text Available Background. The posterior reversible encephalopathy syndrome (PRES is a syndrome characterized by hypertension, headache, seizures, and visual disturbances. Causes of PRES include preeclampsia/eclampsia, hypertension, and recently bevacizumab, a monoclonal antibody vascular endothelial growth factor (VEGF inhibitor. There is no information to date about PRES recurrence in patients taking bevacizumab or descriptions of deep vein thrombosis (DVT in the setting of PRES. We reviewed data on a patient receiving bevacizumab who presented with a DVT and PRES and later developed recurrent PRES. Case. A 72-year-old man with metastatic pulmonary adenocarcinoma received maintenance bevacizumab following six cycles of carboplatin and paclitaxel. Following his eighth dose of bevacizumab, he developed a DVT as well as PRES. He made a rapid recovery and was discharged from the hospital but went on to develop PRES recurrence nine days following his original episode. Conclusion. Several mechanisms exist whereby exposure to bevacizumab could be related to the development of both DVT and PRES by inducing global endothelial dysfunction. Recurrent PRES may result from bevacizumab’s prolonged half-life (11–50 days and suboptimal blood pressure control. In the setting of bevacizumab, PRES surveillance may play a similar role in preeclampsia screening as both diseases share similar antiangiogenic signaling pathways.

Intraocular osseous metaplasia. A clinico-pathological study

OpenAIRE

Vemuganti Geeta; Honavar Santosh; Jalali Subhadra

2002-01-01

Purpose: To evaluate the clinico-pathologic features of intraocular osseous metaplasia. Methods: Pathology specimens of enucleated eyes submitted to the ophthalmic pathology service at a tertiary eye-care referral center between January 1995 and June 1999 were studied for intraocular osseous metaplasia. Specific histopathologic features noted in specimens with osseous metaplasia were the presence of retinal detachment, gliosis, retinal pigment epithelial hyperplasia, drusen, epiretinal membra...

Preliminary study of a new intraocular method in the diagnosis and treatment of Propionibacterium acnes endophthalmitis following cataract extraction.

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Owens, S L; Lam, S; Tessler, H H; Deutsch, T A

1993-04-01

Late endophthalmitis, due to Propionibacterium acnes, developed in three patients following uncomplicated extracapsular cataract extraction and posterior chamber intraocular lens (PC-IOL) insertion. Cultures from the capsular bag yielded P. acnes in all three. With topical anesthesia and through an anterior chamber paracentesis, culture specimens were taken from and clindamycin irrigated into the capsular bag. Filtered 100% oxygen was introduced into the anterior chamber in two; the third also received an injection of gentamicin and dexamethasone into the capsular bag. After treatment, two patients received oral antibiotics; one received hyperbaric oxygen therapy. Visual acuity was improved and inflammation reduced in all three. However, after treatment, ocular toxic effects due to clindamycin were suspected in one. This approach offers several clear advantages, including topical anesthesia, outpatient management, elimination of the need for vitrectomy, and retention of the intraocular lens (IOL).

Resultados da troca de lente intra-ocular de hidrogel opacificada

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Salera Cristina Moreira

2004-01-01

Full Text Available OBJETIVO: Avaliar os resultados da explantação e substituição das lentes intra-oculares (LIO de hidrogel opacificadas. MÉTODOS: Foram analisados retrospectivamente os prontuários de 12 pacientes (15 olhos submetidos à explantação e substituição das lentes intra-oculares de hidrogel opacificadas. RESULTADOS: A opacificação das lentes intra-oculares de hidrogel causou perdas de linhas de visão em 13 olhos (86,7%. A troca das lentes intra-oculares opacificadas promoveu o ganho de linhas de visão em 11 olhos (73,3%. As complicações peroperatórias ocorreram em três olhos (20% e foram as seguintes: perda de óleo de silicone, ruptura total de zônula com perda do saco capsular e ruptura parcial de zônula. Durante a explantação das lentes intra-oculares foi necessária a realização de incisões relaxantes na borda da capsulorrexe anterior em três olhos (20% e em dois olhos (13,3% os hápticos foram cortados sendo retirada somente a zona óptica das lentes intra-oculares. CONCLUSÃO: A cirurgia para explantação e substituição das lentes intra-oculares opacificadas mostrou-se eficaz naqueles pacientes com perdas de linhas de visão (p > 0,05.

Bevacizumab with or after chemotherapy for platinum-resistant recurrent ovarian cancer

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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 ...

Importance of intraocular pressure in glaucoma

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Joos, Karen M.

1999-06-01

Glaucoma results in permanent vision loss and affects the peripheral vision initially. It is presented in 22.5 million people worldwide and is the 3rd cause of blindness. Present tonometers are not ideal for intraocular pressure measurements in all eyes. Of concern, PRK and LASIK may result in lower intraocular pressure readings. A challenges now exists for the development of a tonometer which can easily compensate for corneas with many parameters to avoid a future increase in normal-tension glaucoma or glaucoma which is advanced.

Reducing intratumour acute hypoxia through bevacizumab treatment, referring to the response of quiescent tumour cells and metastatic potential

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Masunaga, S; Liu, Y; Tanaka, H; Sakurai, Y; Suzuki, M; Kondo, N; Maruhashi, A; Ono, K

2011-01-01

Objectives The aim was to evaluate the influence of bevacizumab on intratumour oxygenation status and lung metastasis following radiotherapy, with specific reference to the response of quiescent (Q) cell populations within irradiated tumours. Methods B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-ray irradiation following treatment with the acute hypoxia-releasing agent nicotinamide or local mild temperature hyperthermia (MTH) with or without the administration of bevacizumab under aerobic conditions or totally hypoxic conditions, achieved by clamping the proximal end of the tumours. Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In the other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation. Results 3 days after bevacizumab administration, acute hypoxia-rich total cell population in the tumour showed a remarkably enhanced radiosensitivity to γ-rays, and the hypoxic fraction (HF) was reduced, even after MTH treatment. However, the hypoxic fraction was not reduced after nicotinamide treatment. With or without γ-ray irradiation, bevacizumab administration showed some potential to reduce the number of lung metastases as well as nicotinamide treatment. Conclusion Bevacizumab has the potential to reduce perfusion-limited acute hypoxia and some potential to cause a decrease in the number of lung metastases as well as nicotinamide. PMID:21586505

Solid intraocular xanthogranuloma in three Miniature Schnauzer dogs.

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Zarfoss, Mitzi K; Dubielzig, Richard R

2007-01-01

Macrophages that contain abundant intracytoplasmic lipid are called 'foam cells'. In four canine globes submitted to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW), foam cells formed a solid intraocular mass. The purpose of this study was to describe the histopathologic findings in these cases. The electronic COPLOW database (1993-2006) was searched for the diagnosis of 'foam cell tumor'. Clinical history, gross pathology and histopathology (5-micron sections, hematoxylin and eosin and Alcian blue periodic acid Schiff) were reviewed in all cases. Cases were included if the globe was grossly filled by a solid mass and if all intraocular structures were effaced by lipid-laden foam cell macrophages admixed with birefringent, Alcian blue-positive crystals oriented in stellate patterns. All three patients (four globes) satisfying the selection criteria were Miniature Schnauzers. In all cases the clinical history included diabetes mellitus, hyperlipidemia and chronic bilateral uveitis that was interpreted to be lens-induced. All globes were enucleated because of glaucoma. The term solid intraocular xanthogranuloma was used to describe these cases because the intraocular contents were effaced by a solid mass of foam cells and birefringent crystals. The cases in this report suggest that diabetic Miniature Schnauzers with hyperlipidemia are at risk for lipid and macrophage-rich uveitis, which may in some cases form a solid inflammatory intraocular mass, precipitate glaucoma, and lead to enucleation.

Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab

DEFF Research Database (Denmark)

Eefsen, Rikke Løvendahl; Engelholm, Lars Henning; Willemoe, Gro L.

2016-01-01

with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy......The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing...... treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p chemotherapy-treated patients (p = 0.006/p = 0.002). Tumour cell...

Impact of Serum Apolipoprotein A-I on Prognosis and Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer: a Propensity Score-Matched Analysis

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Qi Quan

2017-04-01

Full Text Available PURPOSE: We aimed to investigate the role of apolipoprotein A-I (ApoA-I as a predictor of prognosis and treatment efficacy of bevacizumab in patients with metastatic colorectal cancer (mCRC treated with first-line chemotherapy with or without bevacizumab. METHODS: We conducted a retrospective study on consecutive patients who were diagnosed with mCRC at Sun Yat-sen University Cancer Center. According to their pretreatment ApoA-I level, patients were divided into low– and high–ApoA-I groups. Propensity score-matched method was performed to balance baseline characteristics between two groups. Based on whether they accepted bevacizumab as a first-line therapy, patients were further divided into the chemo + bevacizumab group and the chemo group. Overall survival (OS and progression-free survival (PFS were assessed with Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: The optimal cutoff value for the ApoA-I level was determined to be 1.105 g/l. In the propensity-matched cohort of 508 patients, low ApoA-I was significantly associated with inferior OS (P < .001 and PFS (P < .001 than high ApoA-I. Multivariate analysis showed that ApoA-I level was an independent prognostic maker of OS (P < .001 and PFS (P = .001. PFS (P < .001 in either the high– or low–ApoA-I groups could be extended significantly after the administration of bevacizumab, and patients with a high ApoA-I level also had a better OS in the chemo + bevacizumab group than the chemo group (P = .049. CONCLUSIONS: Patients with a low ApoA-I level have poor prognoses, and they did not display an OS benefit from bevacizumab.

The Longitudinal Transcriptional Response to Neoadjuvant Chemotherapy with and without Bevacizumab in Breast Cancer.

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Silwal-Pandit, Laxmi; Nord, Silje; von der Lippe Gythfeldt, Hedda; Møller, Elen K; Fleischer, Thomas; Rødland, Einar; Krohn, Marit; Borgen, Elin; Garred, Øystein; Olsen, Tone; Vu, Phuong; Skjerven, Helle; Fangberget, Anne; Holmen, Marit M; Schlitchting, Ellen; Wille, Elisabeth; Nordberg Stokke, Mette; Moen Vollan, Hans Kristian; Kristensen, Vessela; Langerød, Anita; Lundgren, Steinar; Wist, Erik; Naume, Bjørn; Lingjærde, Ole Christian; Børresen-Dale, Anne-Lise; Engebraaten, Olav

2017-08-15

Purpose: Chemotherapy-induced alterations to gene expression are due to transcriptional reprogramming of tumor cells or subclonal adaptations to treatment. The effect on whole-transcriptome mRNA expression was investigated in a randomized phase II clinical trial to assess the effect of neoadjuvant chemotherapy with the addition of bevacizumab. Experimental Design: Tumor biopsies and whole-transcriptome mRNA profiles were obtained at three fixed time points with 66 patients in each arm. Altogether, 358 specimens from 132 patients were available, representing the transcriptional state before treatment start, at 12 weeks and after treatment (25 weeks). Pathologic complete response (pCR) in breast and axillary nodes was the primary endpoint. Results: pCR was observed in 15 patients (23%) receiving bevacizumab and chemotherapy and 8 patients (12%) receiving only chemotherapy. In the estrogen receptor-positive patients, 11 of 54 (20%) treated with bevacizumab and chemotherapy achieved pCR, while only 3 of 57 (5%) treated with chemotherapy reached pCR. In patients with estrogen receptor-positive tumors treated with combination therapy, an elevated immune activity was associated with good response. Proliferation was reduced after treatment in both treatment arms and most pronounced in the combination therapy arm, where the reduction in proliferation accelerated during treatment. Transcriptional alterations during therapy were subtype specific, and the effect of adding bevacizumab was most evident for luminal-B tumors. Conclusions: Clinical response and gene expression response differed between patients receiving combination therapy and chemotherapy alone. The results may guide identification of patients likely to benefit from antiangiogenic therapy. Clin Cancer Res; 23(16); 4662-70. ©2017 AACR . ©2017 American Association for Cancer Research.

Evaluation of subconjunctival injection of triamcinolone acetonide in patients with macular edema secondary to uveitis

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Yu Chen

2016-05-01

Full Text Available AIM:To evaluate the clinical effect of subconjunctival injection of triamcinolone acetonide in patients with macular edema secondary to uveitis. METHODS:Sixty-eight patients(82 eyeswith macular edema secondary to uveitis selected in our hospital from October 2014 to October 2015 were assigned into control group and experimental group according to random number table method, with 34 cases(41 eyesin each group. Patients in the control group were treated by intraocular injection of triamcinolone acetonide, and patients in the experimental group were given subconjunctival injection of triamcinolone acetonide. Clinical effect, central macular thickness and adverse reactions in the two groups were compared. RESULTS:There was no significant difference on the central macular thickness and best corrected visual acuity between the two groups before treatment(P>0.05. Central macular thickness in the experimental group after treatment(214.26±65.54 μmwas significantly lower than that in the control group after treatment(256.47±84.52 μm,PPPPCONCLUSION:Subconjunctival injection of triamcinolone acetonide exerts obvious effect in uveitis patients with macular edema, effectively improves visual acuity, alleviates macular edema and reduces the incidence of intraocular pressure increasing, conjunctival hemorrhage and other adverse reactions, which is safe and effective, thus has potential application.

Bevacizumab Inhibits Breast Cancer-Induced Osteolysis, Surrounding Soft Tissue Metastasis, and Angiogenesis in Rats as Visualized by VCT and MRI

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Tobias Bäuerle

2008-05-01

Full Text Available The aim of this study was to evaluate the effect of an antiangiogenic treatment with the vascular endothelial growth factor antibody bevacizumab in an experimental model of breast cancer bone metastasis and to monitor osteolysis, soft tissue tumor, and angiogenesis in bone metastasis noninvasively by volumetric computed tomography (VCT and magnetic resonance imaging (MRI. After inoculation of MDA-MB-231 human breast cancer cells into nude rats, bone metastasis was monitored with contrast-enhanced VCT and MRI from day 30 to day 70 after tumor cell inoculation, respectively. Thereby, animals of the treatment group (10 mg/kg bevacizumab IV weekly, n = 15 were compared with sham-treated animals (n = 17. Treatment with bevacizumab resulted in a significant difference versus control in osteolytic as well as soft tissue lesion sizes (days 50 to 70 and 40 to 70 after tumor cell inoculation, respectively; P < .05. This observation was paralleled with significantly reduced vascularization in the treatment group as shown by reduced increase in relative signal intensity in dynamic contrast-enhanced MRI from days 40 to 70 (P < .05. Contrast-enhanced VCT and histology confirmed decreased angiogenesis as well as new bone formation after application of bevacizumab. In conclusion, bevacizumab significantly inhibited osteolysis, surrounding soft tissue tumor growth, and angiogenesis in an experimental model of breast cancer bone metastasis as visualized by VCT and MRI.

Microvessel density and endothelial cell proliferation levels in colorectal liver metastases from patients given neo-adjuvant cytotoxic chemotherapy and bevacizumab.

Science.gov (United States)

Eefsen, Rikke Løvendahl; Engelholm, Lars; Willemoe, Gro L; Van den Eynden, Gert G; Laerum, Ole Didrik; Christensen, Ib Jarle; Rolff, Hans Christian; Høyer-Hansen, Gunilla; Osterlind, Kell; Vainer, Ben; Illemann, Martin

2016-04-01

The treatment of patients with colorectal liver metastasis has improved significantly and first line therapy is often combined chemotherapy and bevacizumab, although it is unknown who responds to this regimen. Colorectal liver metastases grow in different histological growth patterns showing differences in angiogenesis. To identify possible response markers, histological markers of angiogenesis were assessed. Patients who underwent resection of colorectal liver metastasis at Rigshospitalet, Copenhagen, Denmark from 2007 to 2011 were included (n = 254) including untreated and patients treated with chemotherapy or chemotherapy plus bevacizumab. The resected liver metastases were characterised with respect to growth pattern, endothelial and tumour cell proliferation as well as microvessel density and tumour regression. Tumour regression grade of liver metastases differed significantly between untreated/chemotherapy treated patients in comparison to chemotherapy plus bevacizumab treated patients (both p chemotherapy-treated patients (p = 0.006/p = 0.002). Tumour cell proliferation assessed by Ki67 expression correlated to a shorter recurrence free survival in the total patient cohort. In conclusion, liver metastases from patients treated with neo-adjuvant chemotherapy and bevacizumab had significantly lower microvessel densities and tumour regression grades when compared to liver metastases from untreated or chemotherapy treated patients. This may indicate that bevacizumab treatment results in altered vascular biology and tumour viability, with possible tumour reducing effect. © 2015 UICC.

Bevacizumab plus chemotherapy as third- or later-line therapy in patients with heavily treated metastatic colorectal cancer

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Yang Q

2015-09-01

Full Text Available Qiong Yang,1–4,* Chenxi Yin,1,3,4,* Fangxin Liao,1,3,4 Yuanyuan Huang,1,3,4 Wenzhuo He,1,3,4 Chang Jiang,1,3,4 Guifang Guo,1,3,4 Bei Zhang,1,3,4 Liangping Xia1,3,41VIP Region, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 2Department of Oncology, Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, People’s Republic of China; 3State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 4Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workBackground: Currently available third- or later-line therapy for metastatic colorectal cancer (mCRC is limited in its efficacy, with a weak survival benefit in patients who progressed after two or more lines of standard therapy. Our retrospective study aimed to explore the value of bevacizumab plus chemotherapy in this setting.Methods: Patients with mCRC who received fluoropyrimidine, oxaliplatin, and irinotecan as first- and second-line chemotherapy were selected for inclusion. Treatment consisted of bevacizumab plus chemotherapy. Chemotherapy consisted mainly of oxaliplatin, irinotecan, and fluoropyrimidine.Results: Between February 2010 and December 2012, 35 consecutive patients with mCRC were treated with bevacizumab plus chemotherapy as a third- or later-line treatment. No complete responses, seven partial responses (20%, 22 stable disease responses (62.9%, and six progressive disease responses (17.1% were obtained, producing an objective response rate of 20% and a disease control rate of 82.9%. With a median follow-up of 11.3 months (range: 0.7–48.0 months, the median progression-free survival was 5.98 months (95% confidence interval: 4.76–7.2 months, and the median overall survival was 14.77 months (95% confidence interval: 11.45–18.1 months. In the univariate analysis

The Increase of Intra-Abdominal Pressure Can Affect Intraocular Pressure

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Ilhan Ece

2015-01-01

Full Text Available Objective. This study aims to explore the usage of intraocular pressure measurements as the early indicator of the increase in intra-abdominal pressure. Methods. In this prospective study, 40 patients undergoing elective surgery were included. Patients were divided into four groups of 10 patients. The control group (Group C was not subjected to laparoscopic intervention. Laparoscopic surgery was, respectively, performed with an intra-abdominal pressure of 9, 12, and 15 mmHg in Groups L (low, M (medium, and H (high pressure. Intraocular pressure was measured binocularly in each patient at three different times (before, during, and end of surgery using a contact tonometer. Results. Patients’ gender, age, body mass index (BMI, American Society of Anesthesiology (ASA class, and operative times were not different among the groups. No complications occurred with either the surgery or measurement of intraocular pressure. Intubation was associated with a severe rise in IOP (P<0.05. An increase in intraocular pressure was seen in groups M and H (P<0.05. Conclusion. Intraocular pressure was increased in the groups with an intra-abdominal pressure of 12 mmHg or more. Measuring the intraocular pressure might be a useful method to estimate the intra-abdominal pressure. This trial is registered with NCT02319213.

Safety and efficacy of first-line bevacizumab combination therapy in Chinese population with advanced non-squamous NSCLC: data of subgroup analyses from MO19390 (SAiL) study.

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Zhou, C C; Bai, C X; Guan, Z Z; Jiang, G L; Shi, Y K; Wang, M Z; Wu, Y L; Zhang, Y P; Zhu, Y Z

2014-05-01

Bevacizumab is a monoclonal antibody with high antitumor activity against malignant diseases. Previous studies have demonstrated the efficacy of first-line bevacizumab combination therapy in advanced, non-squamous non-small cell lung cancer (NS-NSCLC). SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a subgroup analysis of Chinese patients enrolled in SAiL. Chemo-naive Chinese patients with locally advanced, metastatic or recurrent NSCLC were randomized to receive Bev 15 mg/kg every 3 weeks plus carboplatin + paclitaxel for maximum of six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety. Secondary endpoints included time to progression and overall survival. The Chinese intent-to-treat (ITT) population consists of 198 Chinese patients, among whom 107 (54 %) were non-smokers and 90 (45.5 %) were female. The median cycle of bevacizumab administration was 10 and median duration of bevacizumab treatment was 29.5 weeks. Only eight cases of severe adverse events were observed in the study, which were deemed to be related to bevacizumab. The incidence of AEs over grade 3 in Chinese ITT patients was generally low (SAiL study. No new safety signals were reported.

Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab

International Nuclear Information System (INIS)

Bukowski, Ronald M

2010-01-01

The biology and pathogenesis of clear cell carcinoma of the kidney has been extensively investgated, and the role of von Hipple-Landau gene inactivation and tumor associated angiogenesis is now recognized. Development of vascular endothelial growth factor inhibitors and phase 3 clinical trials utilizing this class of agents has produced a new treatment paradigm for patients with metastatic renal cell carcinoma (RCC). One of the active regimens identified is the combination of bevacizumab and interferon-α. Recently published reports provided evidence of the clinical and biologic activity of this therapy. The current manuscript reviews the background and rationale for the activity of bevacizumab in RCC, and results from recent clinical trials with this agent alone or in combination with targeted agents or cytokines. The role of this therapy in contrast to other targeted agents is reviewed, and the potential utility as well as questions raised by recent studies are discussed

Resultados de implante de lente intraocular en niños Results of intraocular lens implantation in children

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Nashelly I. Mejía Cruz

2007-12-01

Full Text Available En este estudio se describen los resultados obtenidos del implante de lente intraocular en niños, quienes acudieron al servicio de Oftalmología Pediátrica de Instituto Cubano de oftalmología “Ramón Pando Ferrer” con el diagnóstico de catarata de diversas etiologías, en período comprendido entre abril del 2002 al 2005 cuyo seguimiento fue durante un año. En nuestro universo de estudio se determinan algunos parámetros como la edad del paciente, etiología de las cataratas, agudeza visual, defecto refractivo preoperatorio y posoperatorio. Se identificó el poder dióptrico del lente intraocular más frecuente, la presencia de complicaciones durante la cirugía y después de esta. Se evaluaron finalmente, los pacientes que requerían de tratamiento adicional como la capsulotomía con láser o membranectomía quirúrgica. El implante del lente intraocular a temprana edad se relacionó con buenos resultados quirúrgicos: mejoría de la agudeza visual corregida, presentándose el astigmatismo como el error refractivo más frecuente. La complicación transoperatorio y postoperatoria más frecuente fue la membrana inflamatoria, mientras que la complicación posoperatoria más frecuente fue la opacidad de la cápsula posterior.This paper described the results of the intraocular lens implantation performed in children, who had been seen at the Pediatric Ophthalmologic Service of " Ramon Pando Ferrer " Cuban Institute of Ophthalmology and had been diagnosed as having cataract of various etiologies, from April 2002 to April 2005. They were all followed-up for a year. Some parameters like the patient’s age, the etiology of cataract, visual acuity, pre-operative and post-operative refractive defect were considered in our study. The dioptric power of the most common intraocular lens and the most frequent complications during and after surgery were identified. The patients requiring additional treatment such as laser capsulotomy and surgical

Efficacy, safety, and biomarkers of single-agent bevacizumab therapy in patients with advanced hepatocellular carcinoma.

Science.gov (United States)

Boige, Valérie; Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

2012-01-01

Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. The 16W-DCR was 42% (95% confidence interval, 27%-57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3-4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04). Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation.

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....

Identification of serum angiopoietin-2 as a biomarker for clinical outcome of colorectal cancer patients treated with bevacizumab-containing therapy.

Science.gov (United States)

Goede, V; Coutelle, O; Neuneier, J; Reinacher-Schick, A; Schnell, R; Koslowsky, T C; Weihrauch, M R; Cremer, B; Kashkar, H; Odenthal, M; Augustin, H G; Schmiegel, W; Hallek, M; Hacker, U T

2010-10-26

The combination of chemotherapy with the vascular endothelial growth factor (VEGF) antibody bevacizumab is a standard of care in advanced colorectal cancer (CRC). However, biomarkers predicting outcome of bevacizumab-containing treatment are lacking. As angiopoietin-2 (Ang-2) is a key regulator of vascular remodelling in concert with VEGF, we investigated its role as a biomarker in metastatic CRC. Serum Ang-2 levels were measured in 33 healthy volunteers and 90 patients with CRC. Of these, 34 had metastatic disease and received bevacizumab-containing therapy. To determine the tissue of origin of Ang-2, quantitative real-time PCR was performed on microdissected cryosections of human CRC and in a murine xenograft model of CRC using species-specific amplification. Ang-2 originated from the stromal compartment of CRC tissues. Serum Ang-2 levels were significantly elevated in patients with metastatic CRC compared with healthy controls. Amongst patients receiving bevacizumab-containing treatment, low pre-therapeutic serum Ang-2 levels were associated with a significant better response rate (82 vs 31%; Panti-angiogenic treatment.

A pilot study to determine the timing and effect of bevacizumab on vascular normalization of metastatic brain tumors in breast cancer

International Nuclear Information System (INIS)

Chen, Bang-Bin; Lu, Yen-Shen; Lin, Ching-Hung; Chen, Wei-Wu; Wu, Pei-Fang; Hsu, Chao-Yu; Yu, Chih-Wei; Wei, Shwu-Yuan; Cheng, Ann-Lii; Shih, Tiffany Ting-Fang

2016-01-01

To determine the appropriate time of concomitant chemotherapy administration after antiangiogenic treatment, we investigated the timing and effect of bevacizumab administration on vascular normalization of metastatic brain tumors in breast cancer patients. Eight patients who participated in a phase II trial for breast cancer-induced refractory brain metastases were enrolled and subjected to 4 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations that evaluated Peak, Slope, iAUC 60 , and Ktrans before and after treatment. The treatment comprised bevacizumab on Day 1, etoposide on Days 2–4, and cisplatin on Day 2 in a 21-day cycle for a maximum of 6 cycles. DCE-MRI was performed before treatment and at 1 h, 24 h, and 21 days after bevacizumab administration. Values of the 4 DCE-MRI parameters reduced after bevacizumab administration. Compared with baseline values, the mean reductions at 1 and 24 h were −12.8 and −24.7 % for Peak, −46.6 and −65.8 % for Slope, −27.9 and −55.5 % for iAUC 60 , and −46.6 and −63.9 % for Ktrans, respectively (all P < .05). The differences in the 1 and 24 h mean reductions were significant (all P < .05) for all the parameters. The generalized estimating equation linear regression analyses of the 4 DCE-MRI parameters revealed that vascular normalization peaked 24 h after bevacizumab administration. Bevacizumab induced vascular normalization of brain metastases in humans at 1 and 24 h after administration, and the effect was significantly higher at 24 h than at 1 h. ClinicalTrials.gov, identifier NCT01281696, registered prospectively on December 24, 2010

The effect of intraocular gas and fluid volumes on intraocular pressure.

Science.gov (United States)

Simone, J N; Whitacre, M M

1990-02-01

Large increases in the intraocular pressure (IOP) of postoperative gas-containing eyes may require the removal of gas or fluid to reduce the IOP to the normal range. Application of the ideal gas law to Friedenwald's equation provides a mathematical model of the relationship between IOP, intraocular gas and fluid volumes, and the coefficient of scleral rigidity. This mathematic model shows that removal of a given volume of gas or fluid produces an identical decrease in IOP and that the more gas an eye contains, the greater the volume reduction necessary to reduce the pressure. Application of the model shows that the effective coefficient of scleral rigidity is low (mean K, 0.0021) in eyes with elevated IOP that have undergone vitrectomy and retinal cryopexy and very low (mean K, 0.0013) in eyes with elevated IOP that have undergone placement of a scleral buckle and band. By using the appropriate mean coefficient of rigidity, the volume of material to be aspirated to produce a given decrease in IOP can be predicted with clinically useful accuracy.

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

International Nuclear Information System (INIS)

Nyflot, Matthew J.; Kruser, Tim J.; Traynor, Anne M.; Khuntia, Deepak; Yang, David T.; Hartig, Gregory K.; McCulloch, Timothy M.; Wiederholt, Peggy A.; Gentry, Lindell R.; Hoang, Tien; Jeraj, Robert

2015-01-01

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 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 [ 18 F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [ 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 demonstrates

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

Bevacizumab as a treatment option for radiation-induced cerebral necrosis

Energy Technology Data Exchange (ETDEWEB)

Matuschek, Christiane; Boelke, Edwin; Budach, Wilfried [Univ. Hospital Duesseldorf (Germany). Dept. of Radiation Oncology; Nawatny, Jens [Univ. Hospital Duesseldorf (Germany). Dept. of Radiology; Hoffmann, Thomas K. [Duisburg-Essen Univ., Essen (Germany). Dept. of Otorhinolaryngology; Peiper, Matthias; Orth, Klaus [Hospital Essen-Sued, Essen (Germany). Dept. of Surgery; Gerber, Peter Arne [Univ. Hospital Duesseldorf (Germany). Dept. of Dermatology; Rusnak, Ethelyn [State Univ. of New York, Buffalo, NY (United States). Dept. of Anesthesiology; Lammering, Guido [Univ. Hospital Duesseldorf (Germany). Dept. of Radiation Oncology; MAASTRO Clinic, Maastricht (Netherlands). Radiation Oncology

2011-02-15

Radiation necrosis of normal CNS tissue represents one of the main risk factors of brain irradiation, occurring more frequently and earlier at higher total doses and higher doses per fraction. At present, it is believed that the necrosis results due to increasing capillary permeability caused by cytokine release leading to extracellular edema. This process is sustained by endothelial dysfunction, tissue hypoxia, and subsequent necrosis. Consequently, blocking the vascular endothelial growth factor (VEGF) at an early stage could be an option to reduce the development of radiation necrosis by decreasing the vascular permeability. This might help to reverse the pathological mechanisms, improve the symptoms and prevent further progression. A patient with radiation-induced necrosis was treated with an anti-VEGF antibody (bevacizumab), in whom neurologic signs and symptoms improved in accordance with a decrease in T1-weighted fluid-attenuated inversion recovery signals. Our case report together with the current literature suggests bevacizumab as a treatment option for patients with symptoms and radiological signs of cerebral necrosis induced by radiotherapy. (orig.)

Bevacizumab as a treatment option for radiation-induced cerebral necrosis

International Nuclear Information System (INIS)

Matuschek, Christiane; Boelke, Edwin; Budach, Wilfried; Nawatny, Jens; Hoffmann, Thomas K.; Peiper, Matthias; Orth, Klaus; Gerber, Peter Arne; Rusnak, Ethelyn; Lammering, Guido; MAASTRO Clinic, Maastricht

2011-01-01

Radiation necrosis of normal CNS tissue represents one of the main risk factors of brain irradiation, occurring more frequently and earlier at higher total doses and higher doses per fraction. At present, it is believed that the necrosis results due to increasing capillary permeability caused by cytokine release leading to extracellular edema. This process is sustained by endothelial dysfunction, tissue hypoxia, and subsequent necrosis. Consequently, blocking the vascular endothelial growth factor (VEGF) at an early stage could be an option to reduce the development of radiation necrosis by decreasing the vascular permeability. This might help to reverse the pathological mechanisms, improve the symptoms and prevent further progression. A patient with radiation-induced necrosis was treated with an anti-VEGF antibody (bevacizumab), in whom neurologic signs and symptoms improved in accordance with a decrease in T1-weighted fluid-attenuated inversion recovery signals. Our case report together with the current literature suggests bevacizumab as a treatment option for patients with symptoms and radiological signs of cerebral necrosis induced by radiotherapy. (orig.)

Intraocular Inflammation Associated with Ocular Toxoplasmosis : Relationships at Initial Examination

NARCIS (Netherlands)

Dodds, Emilio M.; Holland, Gary N.; Stanford, Miles R.; Yu, Fei; Siu, Willie O.; Shah, Kayur H.; Loon, Ninette Ten Dam-Van; Muccioli, Cristina; Hovakimyan, Anna; Barisani-Asenbauer, Talin

2008-01-01

PURPOSE: To describe characteristics of intraocular inflammation in eyes with active ocular toxoplasmosis and to identify relationships between signs of inflammation, complications (including elevated intraocular pressure [IOP]), other disease features, and host characteristics. DESIGN: Multicenter,

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,

Toric Intraocular Lens Outcomes in Patients With Glaucoma.

Science.gov (United States)

Brown, Reay H; Zhong, Le; Bozeman, Caroline W; Lynch, Mary G

2015-06-01

To report the outcomes of toric intraocular lens implantation in patients with glaucoma and corneal astigmatism. One hundred twenty-six eyes of 87 patients with glaucoma and corneal astigmatism that underwent cataract surgery with an AcrySof toric intraocular lens (Alcon Laboratories, Inc., Fort Worth, TX) implant were selected for this single-center, retrospective case series. Corrected distance visual acuity, intraocular pressure, and refractive astigmatism were measured in each eye preoperatively and postoperatively. Uncorrected distance visual acuity and toric alignment were measured postoperatively. The uncorrected distance visual acuity was 0.04 ± 0.08 logMAR (20/22 Snellen) for all eyes. Ninety-eight percent of all eyes achieved an uncorrected distance visual acuity of 20/40 or better, with 76% achieving 20/25 or better and 47% achieving 20/20. The corrected distance visual acuity for all eyes was 0.01 ± 0.03 logMAR (20/20.5 Snellen) postoperatively. The refractive cylinder improved from 1.47 ± 1.10 diopters preoperatively to 0.31 ± 0.37 diopters postoperatively. The residual refractive cylinder was 1.00 diopter or less in 97% of eyes, 0.75 diopters or less in 90% of eyes, and 0.50 diopters or less in 83% of eyes. Mean misalignment was 4.4° ± 5.1°. Intraocular pressure decreased by a mean of 2.3 ± 3.3 mm Hg following the surgery. Toric intraocular lenses can reliably reduce astigmatism and improve uncorrected vision in eyes with cataract and glaucoma. Copyright 2015, SLACK Incorporated.

Accidental injections of dexamethasone intravitreal implant (Ozurdex) into the crystalline lens.

Science.gov (United States)

Coca-Robinot, Javier; Casco-Silva, Bruno; Armadá-Maresca, Felix; García-Martínez, Jesús

2014-01-01

To describe the side effects and management after inadvertent injection of a dexamethasone implant (Ozurdex) into the crystalline lens. Two case reports. Two patients with macular edema due to unilateral retinal vein occlusion were scheduled for an intravitreal injection of Ozurdex. During the procedure, the implant was accidentally injected into the crystalline lens. Both patients developed cataracts during the course of several weeks and in both there was an intraocular pressure (IOP) increase, which required treatment with topical hypotensives. Macular edema improved only slightly. Cataract surgery with uneventful removal of the implant was performed 3 (case 1) and 6 months (case 2) after the injection. After inadvertent injection of Ozurdex into the crystalline lens, cataract surgery with removal of the implant should be performed as soon as possible in order to avoid IOP increase and so that the underlying condition may be treated adequately.

Injection frequency and anatomic outcomes 1 year following conversion to aflibercept in patients with neovascular age-related macular degeneration.

Science.gov (United States)

Messenger, Wyatt B; Campbell, J Peter; Faridi, Ambar; Shippey, Loton; Bailey, Steven T; Lauer, Andreas K; Flaxel, Christina J; Hwang, Thomas S

2014-09-01

To evaluate the clinical, anatomic and functional effects of conversion to aflibercept following ranibizumab and/or bevacizumab in patients with neovascular age-related macular degeneration (AMD). A retrospective review of patients with neovascular AMD treated with intravitreal ranibizumab and/or bevacizumab who were switched to aflibercept was performed. The primary outcome was change in injection frequency in the year following the change. Secondary outcomes included change in central macular thickness (CMT) at 6 months and 1 year, presence of intraretinal and subretinal fluid at 6 months and visual acuity at 1 year. A total of 109 eyes with neovascular AMD were switched to aflibercept and met inclusion criteria. Overall, aflibercept injection frequency was unchanged with patients receiving 7.4 antivascular endothelial growth factor (VEGF) injections the year prior to conversion compared with 7.2 aflibercept injections in the year following (p=0.47). However, the change to aflibercept was associated with improvement in CMT from 324 to 295 μm (p=0.0001) at 6 months and 299 μm (p=0.0047) at 1 year. There was no effect on visual acuity at 1 year. In a subgroup analysis, patients who had received ≥10 anti-VEGF injections in the year prior had fewer injections (11.1 to 8.4, p<0.0001) and clinic visits (13.9 to 9.6, p<0.0001) as well as a significant decrease in CMT (-35 μm, p=0.02). In our population, switching to aflibercept therapy was not associated with a change in injection frequency nor improved visual acuity, but was associated with improved CMT at 6 months and 1 year. In patients who received at least 10 anti-VEGF injections in the year prior, transitioning to aflibercept was associated with a reduced injection frequency and CMT, suggesting potential cost savings in this population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effect of plasma colloid osmotic pressure on intraocular pressure during haemodialysis

OpenAIRE

Tokuyama, T.; Ikeda, T.; Sato, K.

1998-01-01

BACKGROUND—In a previous case report, it was shown that an increase in plasma colloid osmotic pressure induced by the removal of fluid during haemodialysis was instrumental in decreasing intraocular pressure. The relation between changes in intraocular pressure, plasma osmolarity, plasma colloid osmotic pressure, and body weight before and after haemodialysis is evaluated.
METHODS—Intraocular pressure, plasma osmolarity, plasma colloid osmotic pressure, and body weight were evaluated before a...

Therapeutic significance of a D-dimer cut-off level of >3 μg/ml in colorectal cancer patients treated with standard chemotherapy plus bevacizumab

International Nuclear Information System (INIS)

Mochizuki, Satoshi; Yoshino, Takayuki; Kojima, Takashi

2010-01-01

The risk of venous thromboembolism has been reported to increase when receiving bevacizumab. Many cancer patients are reported to have elevated D-dimer levels. It is not clear what D-dimer level might indicate an increased risk of venous thromboembolism in the colorectal cancer patients treated with bevacizumab-containing chemotherapy. The D-dimer levels and any event concurrent with an elevated D-dimer level were evaluated in patients receiving bevacizumab. The D-dimer cut-off level was determined using the receiver-operating characteristic analysis. The selection criteria were as follows: histologically proven metastatic and unresectable colorectal adenocarcinoma; no prior chemotherapy containing bevacizumab; D-dimer test performed repetitively on the baseline and during bevacizumab administration; no venous thromboembolism identified at the baseline; and enhanced computed tomographic scan performed every 2 months. Sixty-nine patients were included. The chemotherapy regimens with bevacizumab included the regimen of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX), the regimen of 5-fluorouracil, leucovorin and irinotecan (FOLFIRI), and leucovorin-modulated 5-fluorouracil. The median baseline D-dimer level was 1.2 μg/ml. The appropriate D-dimer cut-off level was 3 μg/ml with the negative predictive value of 98% and relative risk of 6.9. Twenty-one of 69 patients showed elevated D-dimer levels of >3 μg/ml, with 11 patients for unknown reasons, 6 with tumor progression, 3 with venous thromboembolism and 1 with sepsis. In the remaining 48 patients whose D-dimer levels were ≤3 μg/ml, only one patient developed a venous thromboembolism. A D-dimer cut-off level of 3 μg/ml might be a useful indicator level to exclude venous thromboembolism or show an increased risk for venous thromboembolism in colorectal cancer patients treated with bevacizumab-containing chemotherapy. (author)

Combination of paclitaxel and bevacizumab in heavily pre-treated non-small-cell lung cancer (NSCLC) patients: a case series study on 15 patients.

Science.gov (United States)

Le Moulec, Sylvestre; Hadoux, Julien; Gontier, Eric; Chargari, Cyrus; Helissey, Carole; Lamand, Virginie; Tanz, Rachid; Farace, Françoise; Vedrine, Lionel; Bonardel, Gérald; Soria, Jean-Charles; Besse, Benjamin

2013-12-01

The combination of paclitaxel and bevacizumab was EMA-approved as first-line therapy in metastatic breast cancer. Moreover, in vitro studies showed a potential antiangiogenic synergistic effect of paclitaxel and bevacizumab. Between November 2008 and March 2010, this case series study included 15 patients with metastatic non squamous-cell lung carcinoma (NSCLC). Those were bevacizumab eligible and received the same regimen used in metastatic breast cancer with weekly paclitaxel (80 mg/m(2), days 1, 8 and 15) and bevacizumab (10 mg/kg at days 1 and 15) after at least one prior line of chemotherapy. Efficacy was evaluated by CT-scan and PET-FDG every two months. Circulating endothelial progenitor cells (CEP) and circulating endothelial cells (CEC) levels were explored in a subset of patients. Median age 56 (36-75), female: 47%, never smokers: 27%, adenocarcinoma: 100%, PS 0-1: 87% and PS 3: 13%. All patients were treated with a first-line platinum-based doublet with or without bevacizumab and 70% of them with erlotinib in the second-line. No major toxicity was observed. Partial response (PR) rate was 44% (31-63%) using RECIST criteria on CT-scan, and 65% (29-88%) with PET FDG. PS improved in 33% of the cases. Median progression free survival was 4.6 months. An increase of CEC and CEP was observed in patients with NSCLC treated with paclitaxel and bevacizumab. In this retrospective series, our results suggest efficacy signal in pre-treated metastatic NSCLC and warrant further assessment in a randomized clinical trial.

Severe pigment dispersion after iris-claw phakic intraocular lens implantation.

Science.gov (United States)

Galvis, Virgilio; Carreño, Néstor I; Tello, Alejandro; Laiton, Andrea N

2017-12-01

A 23-year-old female patient presented 3 months after the implantation of an Artisan® phakic intraocular lens with a severe depigmentation of the iris and peripheral anterior synechiae. Explantation of the intraocular lens and goniosynechialysis were performed. Eleven months after the explantation appearance of the iris significantly improved. There was no loss of lines of corrected distance visual acuity. Severe pigment dispersion after the implantation of an Artisan® phakic intraocular lens may happen and may require explantation of the lens. Iris depigmentation may improve with time.

Severe pigment dispersion after iris-claw phakic intraocular lens implantation

Directory of Open Access Journals (Sweden)

Virgilio Galvis

2017-01-01

Full Text Available A 23-year-old female patient presented 3 months after the implantation of an Artisan® phakic intraocular lens with a severe depigmentation of the iris and peripheral anterior synechiae. Explantation of the intraocular lens and goniosynechialysis were performed. Eleven months after the explantation appearance of the iris significantly improved. There was no loss of lines of corrected distance visual acuity. Severe pigment dispersion after the implantation of an Artisan® phakic intraocular lens may happen and may require explantation of the lens. Iris depigmentation may improve with time.

The effects of repeated Ozurdex injections on ocular hypertension.

Science.gov (United States)

Bahadorani, Sepehr; Krambeer, Chelsey; Wannamaker, Kendall; Tie, Wayne; Jansen, Michael; Espitia, Jason; Sohn, Jeong-Hyeon; Singer, Michael A

2018-01-01

The purpose of this study was to correlate the degree of ocular hypertension with the number of Ozurdex injections. Intraocular pressure (IOP) fluctuations for a total of 183 injections were studied over a period of at least 12 months. The main indications for treatment were uveitis, diabetic macular edema, and retinal vein occlusion. Results of the study demonstrate that repeated Ozurdex injections do not increase the frequency of IOP spikes beyond 30 mmHg. For lower IOPs, however, a positive correlation exists. Furthermore, patients with primary open angle glaucoma and uveitis had the highest IOP response to repeated injections. On average, patients with an IOP of ≥28.6 mmHg received pressure lowering medications, after which their IOP reached a stable level (16.7 mmHg) without the need for additional interventions. The data support the conclusion that multiple Ozurdex injections does not increase the frequency of IOP spikes beyond 30 mmHg, but patients still must be closely monitored if they have a history of primary open angle glaucoma.

Fundus autofluorescence patterns in primary intraocular lymphoma.

Science.gov (United States)

Casady, Megan; Faia, Lisa; Nazemzadeh, Maryam; Nussenblatt, Robert; Chan, Chi-Chao; Sen, H Nida

2014-02-01

To evaluate fundus autofluorescence (FAF) patterns in patients with primary intraocular (vitreoretinal) lymphoma. Records of all patients with primary intraocular lymphoma who underwent FAF imaging at the National Eye Institute were reviewed. Fundus autofluorescence patterns were evaluated with respect to clinical disease status and the findings on fluorescein angiography and spectral-domain optical coherence tomography. There were 18 eyes (10 patients) with primary intraocular lymphoma that underwent FAF imaging. Abnormal autofluorescence in the form of granular hyperautofluorescence and hypoautofluorescence was seen in 11 eyes (61%), and blockage by mass lesion was seen in 2 eyes (11%). All eyes with granular pattern on FAF had active primary intraocular lymphoma at the time of imaging, but there were 5 eyes with unremarkable FAF, which were found to have active lymphoma. The most common pattern on fluorescein angiography was hypofluorescent round spots with a "leopard spot" appearance (43%). These hypofluorescent spots on fluorescein angiography correlated with hyperautofluorescent spots on FAF in 5 eyes (36%) (inversion of FAF). Nodular hyperreflective spots at the level of retinal pigment epithelium on optical coherence tomography were noted in 43% of eyes. The hyperautofluorescent spots on FAF correlated with nodular hyperreflective spots on optical coherence tomography in 6 eyes (43%). Granularity on FAF was associated with active lymphoma in majority of the cases. An inversion of FAF (hyperautofluorescent spots on FAF corresponding to hypofluorescent spots on fluorescein angiography) was observed in less than half of the eyes.

Aderência in vitro do Staphylococcus epidermidis e da Pseudomonas alcaligenes em lentes intra-oculares In vitro adherence of Staphylococcus epidermidis and Pseudomonas alcaligenes to intraocular lenses

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Patrícia Ioschpe Gus

2006-06-01

Full Text Available OBJETIVO: Quantificar e comparar a aderência in vitro das bactérias Staphylococcus epidermidis e Pseudomonas alcaligenes em diferentes tipos de lentes intra-oculares (LIOs. MÉTODOS: Quatorze lentes intra-oculares foram usadas no experimento. Quatro de polimetilmetacrilato (PMMA, quatro de silicone, quatro de hidrogel e duas de acrílico. Oito lentes intra-oculares foram colocadas em oito tubos de ensaio contendo 4 ml de suspensão de Pseudomonas alcaligenes, e seis lentes intra-oculares foram colocadas em seis tubos de ensaio contendo 4 ml de suspensão de Staphylococcus epidermidis. A concentração do caldo utilizada para o teste de aderência foi de 10(8 unidades formadoras de colônias por mililitro (CFU/mL que corresponde a 0,5 na escala de McFarland. As lentes foram incubadas a 37° por duas horas. Após, foram removidas dos caldos e enxaguadas em água destilada estéril por duas vezes. As lentes foram cultivadas em placas de ágar-sangue a 35-37° e evaliadas a cada 24h por um período de 72h. Nas amostras que tiveram crescimento bacteriano, foram contadas as colônias utilizando os métodos convencionais de laboratório. Todos os ensaios foram executados em duplicata. RESULTADOS: A aderência do Staphylococcus epidermidis nas lentes de PMMA foi menor se comparada com as de silicone e de hidrogel. A aderência daPseudomonas alcaligenes nas lentes de hidrogel foi menor se comparada com as de silicone, PMMA e acrílico. CONCLUSÃO: Os resultados sugerem que a aderência do Staphylococcus epidermidis e da Pseudomonas alcaligenes nas lentes intra-oculares é influenciada pelo tipo de material da lente e pela espécie do microorganismo. A aderência bacteriana pode ter papel importante na patogenicidade da endoftalmite pós-cirurgia de catarata.PURPOSE: To quantify and compare the in vitro adherence of Staphylococcus epidermidis and Pseudomonas alcaligenes to different intraocular lenses (IOLs. METHODS: Fourteen intraocular lenses were

Adjuvant capecitabine plus bevacizumab versus capecitabine alone in patients with colorectal cancer (QUASAR 2): an open-label, randomised phase 3 trial.

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Kerr, Rachel S; Love, Sharon; Segelov, Eva; Johnstone, Elaine; Falcon, Beverly; Hewett, Peter; Weaver, Andrew; Church, David; Scudder, Claire; Pearson, Sarah; Julier, Patrick; Pezzella, Francesco; Tomlinson, Ian; Domingo, Enric; Kerr, David J

2016-11-01

Antiangiogenic agents have established efficacy in the treatment of metastatic colorectal cancer. We investigated whether bevacizumab could improve disease-free survival in the adjuvant setting after resection of the primary tumour. For the open-label, randomised, controlled QUASAR 2 trial, which was done at 170 hospitals in seven countries, we recruited patients aged 18 years or older with WHO performance status scores of 0 or 1 who had undergone potentially curative surgery for histologically proven stage III or high-risk stage II colorectal cancer. Patients were randomly assigned (1:1) to receive eight 3-week cycles of oral capecitabine alone (1250 mg/m 2 twice daily for 14 days followed by a break for 7 days) or the same regimen of oral capecitabine plus 16 cycles of 7·5 mg/kg bevacizumab by intravenous infusion over 90 min on day 1 of each cycle. Randomisation was done by a computer-generated schedule with use of minimisation with a random element stratified by age, disease stage, tumour site, and country. The study was open label and no-one was masked to treatment assignment. The primary endpoint was 3-year disease-free survival, assessed in the intention-to-treat population. Toxic effects were assessed in patients who received at least one dose of randomised treatment. This trial is registered with the ISRCTN registry, number ISRCTN45133151. Between April 25, 2005, and Oct 12, 2010, 1952 eligible patients were enrolled, of whom 1941 had assessable data (968 in the capecitabine alone group and 973 in the capecitabine and bevacizumab group). Median follow-up was 4·92 years (IQR 4·00-5·16). Disease-free survival at 3 years did not differ between the groups (75·4%, 95% CI 72·5-78·0 in the capecitabine and bevacizumab group vs 78·4%, 75·7-80·9 in the capecitabine alone group; hazard ratio 1·06, 95% CI 0·89-1·25, p=0·54). The most common grade 3-4 adverse events were hand-foot syndrome (201 [21%] of 963 in the capecitabine alone group vs 257 [27%] of

Visual outcome with the Oculentis Mplus intraocular lens

OpenAIRE

Si-Yuan Liu; Xu Yang

2017-01-01

AIM: To evaluate the visual outcome of Oculentis Mplus intraocular lens(IOL).METHODS: Totally 20 eyes in 20 patients received phacoemulsification and Oculentis Mplus intraocular lens implantation were as test group, and 20 eyes(Aspira-aA IOL)were as control group. The following postoperative examinations were performed after operation for 3mo: uncorrected visual acuity of distance and near, refractive results, UBM examination, the rate of wearing spectacles and the complications. RESULTS: At ...

Towards customized intraocular lenses

NARCIS (Netherlands)

de Jong, Tim

2017-01-01

In the eye there are two refractive components that make light focus on the retina and let you see: the cornea and the lens. When a eye develops cataract the lens becomes caractarous and is removed and replaced with a synthetic intraocular lens during a cataract surgery procedure. Although there was

Comparison of intravitreal bevacizumab treatment between phakic and pseudophakic neovascular age-related macular degeneration.

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Ozkaya, Abdullah; Alkin, Zeynep; Perente, Irfan; Yuksel, Kemal; Baz, Okkes; Alagoz, Cengiz; Yazici, Ahmet Taylan; Demirok, Ahmet

2014-01-01

Before the era of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment, only prevention for visual loss might have been achieved in a limited number of neovascular age-related macular generation (nAMD) patients with different treatment options. To compare the efficacy of intravitreal bevacizumab (IVB) for the treatment of nAMD between phakic and pseudophakic eyes. The newly diagnosed nAMD patients were included in this retrospective study. The patients were divided into the phakic and pseudophakic groups. Initially, the patients received three consecutive, monthly, IVB injections, and then the treatment was continued on an as-needed regimen. The patients were examined monthly, and the data at the baseline, at 3, 6, 9, and 12 months and at the last follow-up were evaluated. The changes in the visual acuity (VA), central retinal thickness (CRT) and the number of injections were compared between the two groups. The study included 62 eyes of 62 patients (39 phakic, and 23 pseudophakic patients). The mean follow-up time was 19.7 and 17.2 months in the phakic and pseudophakic groups, respectively (p=0.06). The mean Log MAR VA at the baseline, 12 months and the last follow-up was 0.82, 0.72 and 0.75 in the phakic group and 0.77, 0.67, and 0.68 in the pseudophakic group, respectively. The change in the mean BCVA from the baseline to 12 months and at the last follow-up was not statistically different between the two groups (p=0.9 and p=0.7, respectively). The mean injection number at 12 months was 4.5 and 4.9 in the phakic and pseudophakic group, respectively (p=0.2). The beneficial effect of IVB is equal in both the phakic and pseudophakic group of nAMD patients. The functional and anatomical outcomes of the treatment and the number of injections were similar in the two groups. © NEPjOPH.

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

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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.

Tachyphylaxis after intravitreal bevacizumab for exudative age-related macular degeneration.

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Forooghian, Farzin; Cukras, Catherine; Meyerle, Catherine B; Chew, Emily Y; Wong, Wai T

2009-06-01

To describe tachyphylaxis to intravitreal bevacizumab (IVB) in patients with exudative age-related macular degeneration (AMD). We retrospectively reviewed the records of 59 consecutive patients treated with IVB at the National Eye Institute over a 14-month period and identified cases demonstrating loss of treatment efficacy as revealed by spectral domain optical coherence tomography. We defined tachyphylaxis as a loss of therapeutic response to IVB 28 +/- 7 days after administration in an eye that had previously demonstrated a therapeutic response in the same time interval. Five patients (six eyes) were identified as developing tachyphylaxis after repeated treatment with IVB. High-dose IVB (2.50 mg) did not restore therapeutic response in these patients. Bilateral tachyphylaxis to IVB was seen after an episode of unilateral postinjection anterior uveitis. After the first treatment of IVB, the median time taken to develop tachyphylaxis was 100 weeks (range: 31-128 weeks), and the median number of IVB treatments to the development of tachyphylaxis was 8 treatments (range: 5-10 treatments). Tachyphylaxis can occur after long-term intravitreal use of bevacizumab in patients with AMD. The precise mechanism of tachyphylaxis is unclear, but both local and/or systemic factors may be involved.

Genetic modification of neurons to express bevacizumab for local anti-angiogenesis treatment of glioblastoma.

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Hicks, Martin J; Funato, Kosuke; Wang, Lan; Aronowitz, Eric; Dyke, Jonathan P; Ballon, Douglas J; Havlicek, David F; Frenk, Esther Z; De, Bishnu P; Chiuchiolo, Maria J; Sondhi, Dolan; Hackett, Neil R; Kaminsky, Stephen M; Tabar, Viviane; Crystal, Ronald G

2015-01-01

The median survival of glioblastoma multiforme (GBM) is approximately 1 year. Following surgical removal, systemic therapies are limited by the blood-brain barrier. To circumvent this, we developed a method to modify neurons with the genetic sequence for therapeutic monoclonal antibodies using adeno-associated virus (AAV) gene transfer vectors, directing persistent, local expression in the tumor milieu. The human U87MG GBM cell line or patient-derived early passage GBM cells were administered to the striatum of NOD/SCID immunodeficient mice. AAVrh.10BevMab, an AAVrh.10-based vector coding for bevacizumab (Avastin), an anti-human vascular endothelial growth factor (VEGF) monoclonal antibody, was delivered to the area of the GBM xenograft. Localized expression of bevacizumab was demonstrated by quantitative PCR, ELISA and western blotting. Immunohistochemistry showed that bevacizumab was expressed in neurons. Concurrent administration of AAVrh.10BevMab with the U87MG tumor reduced tumor blood vessel density and tumor volume, and increased survival. Administration of AAVrh.10BevMab 1 week after U87MG xenograft reduced growth and increased survival. Studies with patient-derived early passage GBM primary cells showed a reduction in primary tumor burden with an increased survival. These data support the strategy of AAV-mediated central nervous system gene therapy to treat GBM, overcoming the blood-brain barrier through local, persistent delivery of an anti-angiogenesis monoclonal antibody.

Effect of aspherical and yellow tinted intraocular lens on blue-on-yellow perimetry

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Rodrigo França de Espíndola

2012-10-01

Full Text Available PURPOSE: To investigate the possible effect of aspherical or yellow tinted intraocular lens (IOL on contrast sensitivity and blue-on-yellow perimetry. METHODS: This prospective randomized bilateral double-masked clinical study included 52 patients with visually significant bilateral cataracts divided in two groups; 25 patients (50 eyes received aspherical intraocular lens in one eye and spherical intraocular lens in the fellow eye; and 27 patients (54 eyes received ultraviolet and blue light filter (yellow tinted IOL implantation in one eye and acrylic ultraviolet filter IOL in the fellow eye. The primary outcome measures were contrast sensitivity and blue-on-yellow perimetry values (mean deviation [MD] and pattern standard deviation [PSD] investigated two years after surgery. The results were compared intra-individually. RESULTS: There was a statistically significant between-group (aspherical and spherical intraocular lens difference in contrast sensitivity under photopic conditions at 12 cycles per degree and under mesopic conditions at all spatial frequencies. There were no between-group significant differences (yellow tinted and clear intraocular lens under photopic or mesopic conditions. There was no statistically significant difference between all intraocular lens in MD or PSD. CONCLUSION: Contrast sensitivity was better under mesopic conditions with aspherical intraocular lens. Blue-on-yellow perimetry did not appear to be affected by aspherical or yellow tinted intraocular lens. Further studies with a larger sample should be carried out to confirm or not that hypotheses.

A Case of Appendiceal Adenocarcinoma with Clinical Benefit from FOLFOX and Bevacizumab

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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.

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

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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.

Societal savings in patients with advanced non-squamous non-small-cell lung cancer receiving bevacizumab-based versus non-bevacizumab-based treatments in France, Germany, Italy, and Spain

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Lister J

2012-10-01

Full Text Available Johanna Lister,1 Sanja Stanisic,1 Klaus Kaier,2 Christian Hagist,2 Dmitry Gultyaev,1 Stefan Walzer31Analytica LA-SER International Inc, Lörrach, Germany; 2Research Centre for Generational Contracts, University of Freiburg, Freiburg, Germany; 3F Hoffmann-La Roche Ltd, Pharmaceuticals Division, Basel, SwitzerlandBackground: The purpose of this study was to investigate the savings accrued using bevacizumab-based treatment for non-small-cell lung cancer from the societal perspective, taking only public costs into account, in France, Germany, Italy, and Spain.Methods: Societal costs were estimated by collecting and analyzing labor costs, carer costs, sickness benefits, disability benefits, and home care benefits. Cost inputs were derived from publicly available databases or from the published literature. Expert opinion was only used if no other source was available. Efficacy data from two randomized clinical trials were used. The time horizon in the health economic model was lifetime. Efficacy and costs were discounted by 3.5%. All main model parameters were tested in deterministic and probabilistic sensitivity analyses.Results: Mean incremental savings to society per patient ranged from €2277 in Italy to €4461 in Germany. The results were most sensitive to the change in proportion of patients working full-time and the proportion of patients who were able to return to work.Conclusion: This analysis shows that bevacizumab-based treatment in non-small-cell lung cancer is associated with more savings to society compared to standard chemotherapy in terms of increased productivity and decreased social benefits paid to patients who are able to work in France, Germany, Italy, and Spain.Keywords: non-small-cell lung cancer, bevacizumab, chemotherapy, economic model, France, Germany, Italy, Spain

Advantages of high b-value diffusion-weighted imaging to diagnose pseudo-responses in patients with recurrent glioma after bevacizumab treatment

International Nuclear Information System (INIS)

Yamasaki, Fumiyuki; Kurisu, Kaoru; Aoki, Tomokazu; Yamanaka, Masami; Kajiwara, Yoshinori; Watanabe, Yosuke; Takayasu, Takeshi; Akiyama, Yuji; Sugiyama, Kazuhiko

2012-01-01

Background: The diagnosis of pseudo-responses after bevacizumab treatment is difficult. Because diffusion-weighted imaging (DWI) is associated with cell density, it may facilitate the differentiation between true- and pseudo-responses. Furthermore, as high b-value DWI is even more sensitive to diffusion, it has been reported to be diagnostically useful in various clinical settings. Materials and methods: Between September 2008 and May 2011, 10 patients (5 males, 5 females; age range 6–65 years) with recurrent glioma were treated with bevacizumab. All underwent pre- and post-treatment MRI including T2- or FLAIR imaging, post-gadolinium contrast T1-weighted imaging, and DWI with b-1000 and b-4000. Response rates were evaluated by MacDonald- and by response assessment in neuro-oncology working group (RANO) criteria. We also assessed the response rate by calculating the size of high intensity areas using high b-value diffusion-weighted criteria. Prognostic factors were evaluated using Kaplan–Meier survival curves (log-rank test). Results: It was easier to identify pseudo-responses with RANO- than MacDonald criteria, however the reduction of edema by bevacizumab rendered the early diagnosis of tumor progression difficult by RANO criteria. In some patients with recurrent glioma treated with bevacizumab, high b-value diffusion-weighted criteria did, while MacDonald- and RANO criteria did not identify pseudo-responses at an early point after the start of therapy. Discussion and conclusion: High b-value DWI reflects cell density more accurately than regular b-value DWI. Our findings suggest that in patients with recurrent glioma, high b-value diffusion-weighted criteria are useful for the differentiation between pseudo- and true responses to treatment with bevacizumab

Advantages of high b-value diffusion-weighted imaging to diagnose pseudo-responses in patients with recurrent glioma after bevacizumab treatment.

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Yamasaki, Fumiyuki; Kurisu, Kaoru; Aoki, Tomokazu; Yamanaka, Masami; Kajiwara, Yoshinori; Watanabe, Yosuke; Takayasu, Takeshi; Akiyama, Yuji; Sugiyama, Kazuhiko

2012-10-01

The diagnosis of pseudo-responses after bevacizumab treatment is difficult. Because diffusion-weighted imaging (DWI) is associated with cell density, it may facilitate the differentiation between true- and pseudo-responses. Furthermore, as high b-value DWI is even more sensitive to diffusion, it has been reported to be diagnostically useful in various clinical settings. Between September 2008 and May 2011, 10 patients (5 males, 5 females; age range 6-65 years) with recurrent glioma were treated with bevacizumab. All underwent pre- and post-treatment MRI including T2- or FLAIR imaging, post-gadolinium contrast T1-weighted imaging, and DWI with b-1000 and b-4000. Response rates were evaluated by MacDonald- and by response assessment in neuro-oncology working group (RANO) criteria. We also assessed the response rate by calculating the size of high intensity areas using high b-value diffusion-weighted criteria. Prognostic factors were evaluated using Kaplan-Meier survival curves (log-rank test). It was easier to identify pseudo-responses with RANO- than MacDonald criteria, however the reduction of edema by bevacizumab rendered the early diagnosis of tumor progression difficult by RANO criteria. In some patients with recurrent glioma treated with bevacizumab, high b-value diffusion-weighted criteria did, while MacDonald- and RANO criteria did not identify pseudo-responses at an early point after the start of therapy. High b-value DWI reflects cell density more accurately than regular b-value DWI. Our findings suggest that in patients with recurrent glioma, high b-value diffusion-weighted criteria are useful for the differentiation between pseudo- and true responses to treatment with bevacizumab. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Blindness following cosmetic injections of the face.

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Lazzeri, Davide; Agostini, Tommaso; Figus, Michele; Nardi, Marco; Pantaloni, Marcello; Lazzeri, Stefano

2012-04-01

Complications following facial cosmetic injections have recently heightened awareness of the possibility of iatrogenic blindness. The authors conducted a systematic review of the available literature to provide the best evidence for the prevention and treatment of this serious eye injury. The authors included in the study only the cases in which blindness was a direct consequence of a cosmetic injection procedure of the face. Twenty-nine articles describing 32 patients were identified. In 15 patients, blindness occurred after injections of adipose tissue; in the other 17, it followed injections of various materials, including corticosteroids, paraffin, silicone oil, bovine collagen, polymethylmethacrylate, hyaluronic acid, and calcium hydroxyapatite. Some precautions may minimize the risk of embolization of filler into the ophthalmic artery following facial cosmetic injections. Intravascular placement of the needle or cannula should be demonstrated by aspiration before injection and should be further prevented by application of local vasoconstrictor. Needles, syringes, and cannulas of small size should be preferred to larger ones and be replaced with blunt flexible needles and microcannulas when possible. Low-pressure injections with the release of the least amount of substance possible should be considered safer than bolus injections. The total volume of filler injected during the entire treatment session should be limited, and injections into pretraumatized tissues should be avoided. Actually, no safe, feasible, and reliable treatment exists for iatrogenic retinal embolism. Nonetheless, therapy should theoretically be directed to lowering intraocular pressure to dislodge the embolus into more peripheral vessels of the retinal circulation, increasing retinal perfusion and oxygen delivery to hypoxic tissues. Risk, V.

Mean intraocular pressure in hypertensive adults

International Nuclear Information System (INIS)

Irum, S.; Malik, A.M.; Saeed, M.

2015-01-01

To determine the mean Intraocular Pressure (IOP) in already diagnosed adult hypertensive patients with different grades of hypertension. Study Design: Cross-sectional descriptive study. Place and Duration of Study: Combined Military Hospital, Lahore, from March 2012 to Aug 2012. Patients and Methods: A total of 178 already diagnosed hypertensive patients were selected. A detailed history of ocular or systemic diseases was taken. Intraocular pressure was measured with help of Goldmann applanation tonometer. Three consecutive readings of IOP of each eye were taken at 30 minutes interval and mean calculated. Blood pressure was recorded in seated position from right upper arm, by mercury sphygmomanometer. Blood pressure measurements were determined by taking the mean value of three systolic and diastolic readings. Results: The results of intraocular pressure (IOP) between various grades of hypertension were determined. There was an increase in mean IOP with rise in blood pressure. The subjects with grade I hypertension showed a mean IOP of 13.95 ± 3.74 mmHg, while grade II and grade III hypertensive subjects had mean IOPs as 18.10 ± 3.32 and 20.21 ± 2.52 mmHg respectively. Conclusion: A higher value of mean IOP was found with increase in systolic and diastolic blood pressures. (author)

Pigment dispersion syndrome associated with intraocular lens implantation: a new surgical technique.

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Canut Jordana, M Isabel; Pérez Formigó, Daniel; Abreu González, Rodrigo; Nadal Reus, Jeroni

2010-11-11

We report the case of a myopic patient who, after intraocular lens transplant in the posterior chamber, suffered elevated intraocular pressure due to pigment dispersion, with recurrent episodes of blurred vision. The patient was treated with a new surgical technique that can avoid potential iridolenticular contact. Complete ophthalmologic examination and optical coherence tomography (OCT) of the anterior segment were performed. Contact between the pigmentary epithelium and the iris with an intraocular lens was revealed by utrasound biomicroscopy and OCT. In this case, Nd:YAG laser iridotomy and laser iridoplasty were not effective for iridolenticular separation and control of the pigment dispersion. We propose a new technique: stitches on the surface of the iris to obtain good iridolenticular separation and good intraocular pressure control. Stitches on the iris surface should be considered as optional therapy in pigmentary glaucoma secondary to intraocular lens implantation. This surgical technique can avoid potential iridolenticular contacts more definitively.

Efficacy and safety of intravitreal bevacizumab in eyes with neovascular glaucoma undergoing Ahmed glaucoma valve implantation: 2-year follow-up.

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Arcieri, Enyr S; Paula, Jayter S; Jorge, Rodrigo; Barella, Kleyton A; Arcieri, Rafael S; Secches, Danilo J; Costa, Vital P

2015-02-01

To evaluate the efficacy and safety of intravitreal bevacizumab (IVB) in eyes with neovascular glaucoma (NVG) undergoing Ahmed glaucoma valve (AGV) implantation. This was a multicentre, prospective, randomized clinical trial that enrolled 40 patients with uncontrolled neovascular glaucoma that had undergone panretinal photocoagulation and required glaucoma drainage device implantation. Patients were randomized to receive IVB (1.25 mg) or not during Ahmed valve implant surgery. Injections were administered intra-operatively, and 4 and 8 weeks after surgery. After a mean follow-up of 2.25 ± 0.67 years (range 1.5-3 years), both groups showed a significant decrease in IOP (p glaucoma undergoing Ahmed glaucoma valve implantation. There is a trend to slightly lower IOPs and number of medications with IVB use during AGV implantation for neovascular glaucoma. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Vincristine, Irinotecan, and Bevacizumab in Relapsed Wilms Tumor With Diffuse Anaplasia.

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Schiavetti, Amalia; Varrasso, Giulia; Collini, Paola; Clerico, Anna

2018-05-01

The prognosis of relapsed Wilms tumor (WT) with diffuse anaplasia is dismal, therefore, novel therapeutic strategies need to be explored. We reported on 2 consecutive cases with relapsed anaplastic WT who presented a partial response after 2 courses of vincristine, irinotecan, and bevacizumab association. This regimen may have a role in the treatment of patients with anaplastic advanced WT.

Intraocular methotrexate in the treatment of uveitis and uveitic cystoid macular edema.

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Taylor, Simon R J; Habot-Wilner, Zohar; Pacheco, Patricio; Lightman, Sue L

2009-04-01

A pilot study to evaluate the use of intravitreal methotrexate (MTX) for the treatment of uveitis and uveitic cystoid macular edema (CME). Prospective, consecutive, interventional case series. Fifteen eyes of 15 patients with a unilateral exacerbation of noninfectious intermediate, posterior uveitis, or panuveitis and/or CME such that visual acuity (VA) was 20/40 or worse, together with a history of increased intraocular pressure (IOP) in response to corticosteroid administration. Intravitreal injection of 400 microg in 0.1 ml MTX. The primary outcome measure was VA (using the Early Treatment Diabetic Retinopathy Study chart). Other outcome measures included ocular inflammation scores, time to relapse, levels of systemic corticosteroid and immunosuppressive therapy, and ocular coherence tomography. Potential complications of intravitreal MTX injection, including cataract progression, vitreous hemorrhage, retinal detachment, and corneal epitheliopathy, were assessed. VA improved at all time points and was statistically significant at the 3- and 6-month follow-up examinations. The mean visual improvement was 4 lines at 3 months and 4.5 lines at 6 months, with no statistical difference between the best VA obtained after MTX injection and after previous corticosteroid treatment, including intravitreal triamcinolone acetate injection. Five patients relapsed after a median of 4 months; a similar improvement was seen after re-injection. Ocular inflammation scores improved at all time points, and systemic immunosuppressive medication was reduced in 3 of 7 patients taking this at the start of the trial. In patients with uveitis and uveitic CME, intravitreal MTX can improve VA and reduce CME and, in some patients, allows the reduction of immunosuppressive therapy. Relapse occurs at a median of 4 months in some patients, but reinjection has similar efficacy.

Traumatic chorioretinal folds treated with intra-vitreal triamcinolone injection

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Kook Young Kim

2013-01-01

Full Text Available A 34-year-old male visited the hospital due to decreased visual acuity in the left eye following an injury from a car accident. In the left eye, best-corrected visual acuity (BCVA was hand motion and intraocular pressure (IOP was 8 mmHg. Choroidal vasodilation and chorioretinal folds were observed by spectral domain-optical coherence tomography (SD-OCT. Topical and systemic steroid treatments did not improve the chorioretinal folds. Twelve months after the injury, intra-vitreal triamcinolone (4 mg/0.1 ml was injected. Six months after intra-vitreal triamcinolone injection, BCVA in the left eye had improved to 20/100. Fundus examination showed improvement in retinal vascular tortuosity and SD-OCT revealed improvements in choroidal vasodilation and chorioretinal folds. Intra-vitreal triamcinolone injection (IVTI was effective against traumatic chorioretinal folds with no recurrence based on objective observation by fundus photography and SD-OCT.

Topical versus subconjunctival anti-vascular endothelial growth factor therapy (Bevacizumab, Ranibizumab and Aflibercept for treatment of corneal neovascularization

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Tariq Al-Debasi

2017-04-01

Anti-VEGF agents (Bevacizumab, Ranibizumab and Aflibercept seem to have a higher efficiency and efficacy for corneal NV treatment. Both subconjunctival therapy and topical therapy of bevacizumab prohibit corneal NV, while early treatment with subconjunctival administration of ranibizumab may successfully reduce corneal NV. Therefore, establishment of safe doses is highly important before these drugs can be involved in the clinical setting. Further investigations and studies are highly warranted to adjust the dose and route of administration for the antibodies directed against VEGF to be the key therapeutic agents in the corneal NV treatment.

Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan

DEFF Research Database (Denmark)

Hasselbalch, Benedikte; Eriksen, Jesper Grau; Broholm, Helle

2010-01-01

, hypoxia and mediators of the epidermal growth factor receptor (EGFR) pathway were investigated. Tumor tissue was obtained from a previous phase II study, treating recurrent primary glioblastoma multiforme (GBM) patients with the EGFR inhibitor cetuximab in combination with bevacizumab and irinotecan....... Of the 37 patients with available tumor tissue, 29 were evaluable for response. We concurrently performed immunohistochemical stainings on tumor tissue from 21 GBM patients treated with bevacizumab and irinotecan. We found a tendency of correlation between the hypoxia-related markers, indicating...

Anti-vascular endothelial growth factors for choroidal neovascularization secondary to choroidal osteoma: Long-term results

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T Lekha

2015-01-01

Full Text Available Choroidal osteoma is an uncommon benign osseous intraocular tumor typically seen unilaterally in young women. Visual loss can occur due to choroidal neovascularization (CNV complicating osteoma. We report a rare case of bilateral choroidal osteoma with secondary CNV in a young male and the long-term results following anti-vascular endothelial growth factor (VEGF therapy. A 30-year-old male with history of defective vision in both eyes since several years and recent worsening in the right eye (RE since 2 months was found to have bilateral macular osteoma with CNV in the RE based on clinical evaluation, fluorescein angiography, optical coherence tomography, and ultrasonography. Intravitreal injection of ranibizumab at monthly intervals for three doses resulted in resolution of CNV and remained stable for 5 years. Recurrent CNV detected 6 years later responded to an injection of intravitreal bevacizumab and has remained stable till date. Anti-VEGF therapy stabilized the secondary CNV in our patient for 7 years with satisfactory structural and functional outcome, demonstrating the long-term efficacy of this modality of treatment.

Intraocular pressure variations during zygomatic fracture reduction and fixation: a clinical study.

LENUS (Irish Health Repository)

Murray, Dylan J

2012-02-03

BACKGROUND: The reduction of midface fractures has been associated with the rare but devastating complication of blindness. An increase in intraocular pressure is important in the mechanism of blindness in this setting. In this study, the authors assessed the intraocular pressure in patients who underwent zygomatic fracture reduction (with or without fixation). METHODS: Using applanation tonometry, 29 patients underwent intraocular pressure measurements before, during, and after fracture fixation. The contralateral pressures were measured and used as the control. RESULTS: There were 29 patients with a mean age of 35 years, and the mean time to surgery was 5 days. Preoperatively, all patients had normal intraocular pressures and normal visual acuity. All patients underwent a Gillies lift and 18 patients required open reduction and fixation of the frontozygomatic suture (n = 4) or the infraorbital margin (n = 2), and the remainder (n = 12) required fixation of both points. There was no statistically significant increase in the intraocular pressures following the reduction of uncomplicated zygomatic fractures. Statistically significant pressure reductions were noted immediately after reduction and fixation. CONCLUSIONS: The surgical reduction of uncomplicated zygomatic fractures has no adverse effect on the intraocular pressure. It is the authors\\' opinion that adjunctive measures to reduce the pressures are unnecessary.

Topical tissue plasminogen activator appears ineffective for the clearance of intraocular fibrin.

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Zwaan, J; Latimer, W B

1998-06-01

To determine the efficacy of topical tissue plasminogen activator (tPA) for the resolution of postoperative or inflammatory intraocular fibrinous exudates. Each treatment consisted of drops of 1 mg/ml tPA given 9 times 5 minutes apart. Records were reviewed and the results at 24 and 48 hours were recorded. Sixty-two patients had a total of 94 treatments. Fibrin exudates following intraocular surgery in 34 patients were treated 44 times. In 6 patients there was a positive result. Fibrin associated with intraocular infection was treated in 9 patients. None showed clear improvement. Nineteen patients had a total of 34 treatments for poorly controlled intraocular pressure (IOP) after glaucoma surgery. Five patients showed adequate control of the IOP, 12 did not change, and 2 had a questionable improvement. Eleven patients had adequate IOP control after additional treatment. Seven required suture lysis, 2 ab interno bleb revision, and 2 YAG capsulotomy or iridotomy to reduce the IOP to an acceptable level. Within the limits of this retrospective study and taking into account that fibrin may resolve spontaneously, it appears that topical tPA drops are not effective for the liquefaction of intraocular fibrin after surgery or in association with intraocular inflammation. They did not improve IOP control after glaucoma surgery.

Pigment dispersion syndrome associated with intraocular lens implantation: a new surgical technique

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M Isabel Canut Jordana

2010-11-01

Full Text Available M Isabel Canut Jordana1, Daniel Pérez Formigó1, Rodrigo Abreu González2, Jeroni Nadal Reus11Barraquer Ophthalmology Centre, Barcelona, Spain; 2University Hospital of La Candelaria, Tenerife, SpainAims: We report the case of a myopic patient who, after intraocular lens transplant in the posterior chamber, suffered elevated intraocular pressure due to pigment dispersion, with recurrent episodes of blurred vision. The patient was treated with a new surgical technique that can avoid potential iridolenticular contact.Methods: Complete ophthalmologic examination and optical coherence tomography (OCT of the anterior segment were performed.Results: Contact between the pigmentary epithelium and the iris with an intraocular lens was revealed by utrasound biomicroscopy and OCT. In this case, Nd:YAG laser iridotomy and laser iridoplasty were not effective for iridolenticular separation and control of the pigment dispersion. We propose a new technique: stitches on the surface of the iris to obtain good iridolenticular separation and good intraocular pressure control.Conclusion: Stitches on the iris surface should be considered as optional therapy in pigmentary glaucoma secondary to intraocular lens implantation. This surgical technique can avoid potential iridolenticular contacts more definitively.Keywords: pigmentary glaucoma, intraocular lens, optical coherence tomography, laser

Advanced pigment dispersion glaucoma secondary to phakic intraocular collamer lens implant

Directory of Open Access Journals (Sweden)

Clara Ye

2018-06-01

Full Text Available Purpose: We report a case of pigment dispersion glaucoma secondary to uncomplicated phakic intraocular collamer lens (ICL (Visian ICL™, Staar Inc., Monrovia, CA implant that resulted in advanced visual field loss. Observations: A 50-year-old man presented for routine follow-up status post bilateral phakic intraocular collamer lens (ICL placement 8 years earlier. He was incidentally found to have a decline in visual acuity from an anterior subcapsular cataract and elevated intraocular pressure (IOP in the left eye. There were signs of pigment dispersion and no evidence of angle closure. Diffuse optic nerve thinning was consistent with advanced glaucomatous visual field defects. Pigment dispersion was also present in the patient's right eye, but without elevated IOP or visual field defects. The patient was treated with topical glaucoma medications and the phakic ICL in the left eye was removed concurrently with cataract surgery to prevent further visual field loss. Conclusions and importance: Pigment dispersion glaucoma is a serious adverse outcome after phakic ICL implantation and regular post-operative monitoring may prevent advanced visual field loss. Keywords: Phakic intraocular lens, Intraocular collamer lens, Pigment dispersion, Glaucoma

Phase II Trial of Preoperative Radiation With Concurrent Capecitabine, Oxaliplatin, and Bevacizumab Followed by Surgery and Postoperative 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX), and Bevacizumab in Patients With Locally Advanced Rectal Cancer: 5-Year Clinical Outcomes ECOG-ACRIN Cancer Research Group E3204.

Science.gov (United States)

Landry, Jerome C; Feng, Yang; Prabhu, Roshan S; Cohen, Steven J; Staley, Charles A; Whittington, Richard; Sigurdson, Elin Ruth; Nimeiri, Halla; Verma, Udit; Benson, Al Bowen

2015-06-01

The 5-year oncologic outcomes from the trial regimen were excellent. However, the neoadjuvant and surgical toxicity of this regimen was significant and was the primary reason for the low compliance with adjuvant systemic therapy.Due to the lack of an improvement in the pathologic complete response rate, the substantial associated toxicity, and the negative phase III trials of adjuvant bevacizumab in colon cancer, this regimen will not be pursued for further study. The addition of bevacizumab to chemotherapy improves overall survival for metastatic colorectal cancer. We initiated a phase II trial to evaluate preoperative capecitabine, oxaliplatin, and bevacizumab with radiation therapy (RT) followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab for locally advanced rectal cancer. The purpose of this report is to describe the 5-year oncologic outcomes of this regimen. In a phase II Simon two-stage design study, we evaluated preoperative treatment with capecitabine (825 mg/m(2) b.i.d. Monday-Friday), oxaliplatin (50 mg/m(2) weekly), bevacizumab (5 mg/kg on days 1, 15, and 29), and RT (50.4 Gy). Surgery was performed by 8 weeks after RT. Beginning 8-12 weeks after surgery, patients received FOLFOX plus bevacizumab (5 mg/kg) every 2 weeks for 12 cycles (oxaliplatin stopped after 9 cycles). The primary endpoint was a pathologic complete response (path-CR) rate of 30%. Fifty-seven patients with resectable T3/T4 rectal adenocarcinoma were enrolled between 2006 and 2010. Of 57 enrolled patients, 53 were eligible and included in the analysis. Forty-eight (91%) patients completed preoperative therapy, all of whom underwent curative surgical resection. Nine patients (17%) achieved path-CR. There were 29 worst grade 3 events, 8 worst grade 4 events, and 2 patient deaths, 1 of which was attributed to study therapy. Twenty-six patients (54%) began adjuvant chemotherapy. After a median follow-up period of 41 months, the 5-year

Safety and efficacy of first-line bevacizumab with chemotherapy in Asian patients with advanced nonsquamous NSCLC: results from the phase IV MO19390 (SAiL) study.

Science.gov (United States)

Tsai, Chun-Ming; Au, Joseph Siu-kie; Chang, Gee-Chen; Cheng, Ashley Chi-kin; Zhou, Caicun; Wu, Yi-long

2011-06-01

First-line treatment with bevacizumab combined with chemotherapy has been shown to improve outcomes in patients with advanced, nonsquamous non-small cell lung cancer (NSNSCLC) in phase III clinical trials. SAiL (MO19390), an open-label, multicenter, single-arm study, evaluated the safety and efficacy of first-line bevacizumab-based treatment in clinical practice. This report presents the results of a preplanned subanalysis of Asian patients enrolled in SAiL. Patients with untreated, locally advanced, metastatic or recurrent NSNSCLC received bevacizumab 7.5 or 15 mg/kg every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Eligibility criteria for SAiL permitted enrolment of a broad patient population. The primary end point was safety; secondary end points included time to disease progression and overall survival. The Asian intent-to-treat population comprised 314 of the 2212 patients enrolled in the SAiL trial. In the Asian subanalysis, patients received a median of nine cycles of bevacizumab, and the median follow-up was 16.4 months. The incidence of clinically significant adverse events (grade ≥3) of special interest was relatively low in this population (15.6% overall); proteinuria (7.6%), hypertension (4.8%), and bleeding (2.5%) were the most common. A total of five adverse events related to bevacizumab were reported as grade 5. Disease control rate was 94.1%, median time to disease progression was 8.3 months, and median overall survival was 18.9 months. The safety and efficacy of first-line bevacizumab-based treatment in Asian patients with advanced NSNSCLC is consistent with that demonstrated in phase III studies and in the overall SAiL population. There were no new safety signals.

Assessment of intraocular foreign bodies by helical-CT multiplanar imaging

International Nuclear Information System (INIS)

Papadopoulos, A.; Fotinos, A.; Maniatis, V.; Kavadias, S.; Michaelides, A.; Avouri, M.; Kalamara, C.; Stringaris, K.

2001-01-01

The aim of this study was to examine the effectiveness of helical CT in the assessment of intraocular foreign bodies, evaluating two protocols with different collimation. We performed helical-CT studies in 30 patients. Fifteen patients were examined with 1.5-mm collimation and the other 15 patients with 3.0-mm collimation. All other imaging parameters were identical in both protocols. Multiplanar images were reconstructed. The examinations were reviewed for presence, localization and size of intraocular foreign bodies. We compare our results with the surgical data. We estimate the required examination time. In the first group (collimation 1.5 mm) an intraorbital foreign body was detected in 8 of 15 patients. In 3 of 8 patients an intraocular foreign body (all were metallic) was detected. In the second group (collimation 3.0 mm) an intraorbital foreign body was detected in 9 of 15 patients. In 8 of 9 patients an intraocular foreign body (all were metallic) was detected. Our results were confirmed by surgery in all cases. Examination time was 36 s in the first group and 18 s in the second group. Computed tomography should be considered the imaging modality of choice in the assessment of metallic intraocular foreign bodies and 3.0-mm collimation is optional, because of reduced examination time and radiation exposure. (orig.)

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

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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

Safety and maximum tolerated dose of superselective intraarterial cerebral infusion of bevacizumab after osmotic blood-brain barrier disruption for recurrent malignant glioma. Clinical article.

Science.gov (United States)

Boockvar, John A; Tsiouris, Apostolos J; Hofstetter, Christoph P; Kovanlikaya, Ilhami; Fralin, Sherese; Kesavabhotla, Kartik; Seedial, Stephen M; Pannullo, Susan C; Schwartz, Theodore H; Stieg, Philip; Zimmerman, Robert D; Knopman, Jared; Scheff, Ronald J; Christos, Paul; Vallabhajosula, Shankar; Riina, Howard A

2011-03-01

The authors assessed the safety and maximum tolerated dose of superselective intraarterial cerebral infusion (SIACI) of bevacizumab after osmotic disruption of the blood-brain barrier (BBB) with mannitol in patients with recurrent malignant glioma. A total of 30 patients with recurrent malignant glioma were included in the current study. The authors report no dose-limiting toxicity from a single dose of SIACI of bevacizumab up to 15 mg/kg after osmotic BBB disruption with mannitol. Two groups of patients were studied; those without prior bevacizumab exposure (naïve patients; Group I) and those who had received previous intravenous bevacizumab (exposed patients; Group II). Radiographic changes demonstrated on MR imaging were assessed at 1 month postprocedure. In Group I patients, MR imaging at 1 month showed a median reduction in the area of tumor enhancement of 34.7%, a median reduction in the volume of tumor enhancement of 46.9%, a median MR perfusion (MRP) reduction of 32.14%, and a T2-weighted/FLAIR signal decrease in 9 (47.4%) of 19 patients. In Group II patients, MR imaging at 1 month showed a median reduction in the area of tumor enhancement of 15.2%, a median volume reduction of 8.3%, a median MRP reduction of 25.5%, and a T2-weighted FLAIR decrease in 0 (0%) of 11 patients. The authors conclude that SIACI of mannitol followed by bevacizumab (up to 15 mg/kg) for recurrent malignant glioma is safe and well tolerated. Magnetic resonance imaging shows that SIACI treatment with bevacizumab can lead to reduction in tumor area, volume, perfusion, and T2-weighted/FLAIR signal.

A novel clinical sign in intraocular tuberculosis: Active chorioretinitis within chorioretinal atrophy

OpenAIRE

Avinash Pathengay; Bhavik Panchal; Himadri Choudhury; Soumyava Basu; Nidhi Relhan; Harry W. Flynn, Jr.

2017-01-01

Purpose: To report a novel clinical sign in patients with intraocular tuberculosis. The current study is an observational consecutive case series of patients diagnosed with intraocular tuberculosis managed at a tertiary eye care centre from June 1, 2012 to December 31, 2015. Observations: The diagnosis of intraocular tuberculosis was made in 6 patients based on ocular features suggestive of tuberculosis along with a positive tuberculin skin testing and chest X-ray consistent with tuberculo...

Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial.

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Bear, Harry D; Tang, Gong; Rastogi, Priya; Geyer, Charles E; Liu, Qing; Robidoux, André; Baez-Diaz, Luis; Brufsky, Adam M; Mehta, Rita S; Fehrenbacher, Louis; Young, James A; Senecal, Francis M; Gaur, Rakesh; Margolese, Richard G; Adams, Paul T; Gross, Howard M; Costantino, Joseph P; Paik, Soonmyung; Swain, Sandra M; Mamounas, Eleftherios P; Wolmark, Norman

2015-09-01

NSABP B-40 was a 3 × 2 factorial trial testing whether adding capecitabine or gemcitabine to docetaxel followed by doxorubicin plus cyclophosphamide neoadjuvant chemotherapy would improve outcomes in women with operable, HER2-negative breast cancer and whether adding neoadjuvant plus adjuvant bevacizumab to neoadjuvant chemotherapy regimens would also improve outcomes. As reported previously, addition of neoadjuvant bevacizumab increased the proportion of patients achieving a pathological complete response, which was the primary endpoint. We present secondary patient outcomes, including disease-free survival, a specified endpoint by protocol, and data for distant recurrence-free interval, and overall survival, which were not prespecified endpoints but were collected prospectively. In this randomised controlled trial (NSABP B-40), we enrolled women aged 18 years or older, with operable, HER2-non-amplified invasive adenocarcinoma of the breast, 2 cm or greater in diameter by palpation, clinical stage T1c-3, cN0, cN1, or cN2a, without metastatic disease and diagnosed by core needle biopsy. Patients received one of three docetaxel-based neoadjuvant regimens for four cycles: docetaxel alone (100 mg/m(2)) with addition of capecitabine (825 mg/m(2) oral twice daily days 1-14, 75 mg/m(2) docetaxel) or with addition of gemcitabine (1000 mg/m(2) days 1 and 8 intravenously, 75 mg/m(2) docetaxel), all followed by neoadjuvant doxorubicin and cyclophosphamide (60 mg/m(2) and 600 mg/m(2) intravenously) every 3 weeks for four cycles. Those randomly assigned to bevacizumab groups were to receive bevacizumab (15 mg/kg, every 3 weeks for six cycles) with neoadjuvant chemotherapy and postoperatively for ten doses. Randomisation was done (1:1:1:1:1:1) via a biased-coin minimisation procedure to balance the characteristics with respect to clinical nodal status, clinical tumour size, hormone receptor status, and age. Intent-to-treat analyses were done for disease-free survival and

Phase III Prospective Randomized Comparison Trial of Depot Octreotide Plus Interferon Alfa-2b Versus Depot Octreotide Plus Bevacizumab in Patients With Advanced Carcinoid Tumors: SWOG S0518.

Science.gov (United States)

Yao, James C; Guthrie, Katherine A; Moran, Cesar; Strosberg, Jonathan R; Kulke, Matthew H; Chan, Jennifer A; LoConte, Noelle; McWilliams, Robert R; Wolin, Edward M; Mattar, Bassam; McDonough, Shannon; Chen, Helen; Blanke, Charles D; Hochster, Howard S

2017-05-20

Purpose Treatment options for neuroendocrine tumors (NETs) remain limited. This trial assessed the progression-free survival (PFS) of bevacizumab or interferon alfa-2b (IFN-α-2b) added to octreotide among patients with advanced NETs. Patients and Methods Southwest Oncology Group (SWOG) S0518, a phase III study conducted in a US cooperative group system, enrolled patients with advanced grades 1 and 2 NETs with progressive disease or other poor prognostic features. Patients were randomly assigned to treatment with octreotide LAR 20 mg every 21 days with either bevacizumab 15 mg/kg every 21 days or 5 million units of IFN-α-2b three times per week. The primary end point was centrally assessed PFS. This trial is registered with ClinicalTrials.gov as NCT00569127. Results A total of 427 patients was enrolled, of whom 214 were allocated to bevacizumab and 213 to IFN-α-2b. The median PFS by central review was 16.6 months (95% CI, 12.9 to 19.6 months) in the bevacizumab arm and was 15.4 months (95% CI, 9.6 to 18.6 months) in the IFN arm (hazard ratio [HR], 0.93; 95% CI, 0.73 to 1.18; P = .55). By site review, the median PFS times were 15.4 months (95% CI, 12.6 to 17.2 months) for bevacizumab and 10.6 months (95% CI, 8.5 to 14.4 months) for interferon (HR, 0.90; 95% CI, 0.72 to 1.12; P = .33). Time to treatment failure was longer with bevacizumab than with IFN (HR, 0.72; 95% CI, 0.58 to 0.89; P = .003). Confirmed radiologic response rates were 12% (95% CI, 8% to 18%) for bevacizumab and 4% (95% CI, 2% to 8%) for IFN. Common adverse events with bevacizumab and octreotide included hypertension (32%), proteinuria (9%), and fatigue (7%); with IFN and octreotide, they included fatigue (27%), neutropenia (12%), and nausea (6%). Conclusion No significant differences in PFS were observed between the bevacizumab and IFN arms, which suggests that these agents have similar antitumor activity among patients with advanced NETs.

First-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer : analysis of the Italian patients enrolled in the SAiL study.

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Bearz, Alessandra; Passalacqua, Rodolfo; Alabiso, Oscar; Cinieri, Saverio; Gridelli, Cesare; Cravesana, Claudia; Crinò, Lucio

2012-11-01

First-line bevacizumab-based therapy has been shown to improve outcomes in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). The recent international phase IV SAiL study (a Study of Avastin [bevacizumab] in combination with platinum-containing chemotherapy in patients with advanced or recurrent non-squamous cell Lung cancer) evaluated the safety and efficacy of bevacizumab combined with standard chemotherapy regimens in routine clinical practice. Here we report the results of a subanalysis of baseline characteristics and efficacy data for Italian patients enrolled in SAiL. In the SAiL study, patients with untreated locally advanced, metastatic or recurrent non-squamous NSCLC received bevacizumab (7.5 or 15 mg/kg) every 3 weeks plus chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. Efficacy was assessed in terms of time to disease progression (TTP) and overall survival (OS). The Italian intent-to-treat population comprised 215 patients from a SAiL population of 2212 patients. At baseline, Italian patients tended to have less advanced disease than the overall population. Thus, the proportion of patients at enrollment with tumour stage IIIb and IV was 23.7 and 76.3 %, respectively, for the Italian population versus 19.7 and 80.3 % for the whole SAiL population. In addition, a higher proportion of Italian patients had an Eastern Cooperative Oncology Group performance status of 0 (72.6 vs. 37.2 %) and the prevalence of co-morbid conditions was lower in Italian patients (59.5 % of Italian patients reported a co-morbid condition and 60.0 % were receiving non-oncological treatment compared with 73.3 and 73.4 %, respectively, of SAiL patients overall). The mean exposures to bevacizumab and to chemotherapy were comparable between the Italian patient group and overall patient population, although cisplatin doublets were more commonly employed in Italian patients whereas carboplatin doublets were more

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 postoperative complications (ileus, small bowel obstruction, and infection). With a median follow-up of 34 months, 1 patient developed distant metastasis, and no patient had local recurrence or died. The 3-year disease-free survival was 94%. Conclusions: The combination of preoperative radiation therapy with concurrent capecitabine, bevacizumab, and erlotinib was well tolerated. The pathologic complete response rate appears promising and may warrant further investigation.

Comparison of a new refractive multifocal intraocular lens with an inferior segmental near add and a diffractive multifocal intraocular lens.

Science.gov (United States)

Alio, Jorge L; Plaza-Puche, Ana B; Javaloy, Jaime; Ayala, María José; Moreno, Luis J; Piñero, David P

2012-03-01

To compare the visual acuity outcomes and ocular optical performance of eyes implanted with a multifocal refractive intraocular lens (IOL) with an inferior segmental near add or a diffractive multifocal IOL. Prospective, comparative, nonrandomized, consecutive case series. Eighty-three consecutive eyes of 45 patients (age range, 36-82 years) with cataract were divided into 2 groups: group A, 45 eyes implanted with Lentis Mplus LS-312 (Oculentis GmbH, Berlin, Germany); group B, 38 eyes implanted with diffractive IOL Acri.Lisa 366D (Zeiss, Oberkochen, Germany). All patients underwent phacoemulsification followed by IOL implantation in the capsular bag. Distance corrected, intermediate, and near with the distance correction visual acuity outcomes and contrast sensitivity, intraocular aberrations, and defocus curve were evaluated postoperatively during a 3-month follow-up. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected near visual acuity (UNVA), corrected distance near and intermediate visual acuity (CDNVA), contrast sensitivity, intraocular aberrations, and defocus curve. A significant improvement in UDVA, CDVA, and UNVA was observed in both groups after surgery (P ≤ 0.04). Significantly better values of UNVA (P<0.01) and CDNVA (P<0.04) were found in group B. In the defocus curve, significantly better visual acuities were present in eyes in group A for intermediate vision levels of defocus (P ≤ 0.04). Significantly higher amounts of postoperative intraocular primary coma and spherical aberrations were found in group A (P<0.01). In addition, significantly better values were observed in photopic contrast sensitivity for high spatial frequencies in group A (P ≤ 0.04). The Lentis Mplus LS-312 and Acri.Lisa 366D IOLs are able to successfully restore visual function after cataract surgery. The Lentis Mplus LS-312 provided better intermediate vision and contrast sensitivity outcomes than the Acri.Lisa 366D. However, the

A Case of High-Grade Neuroendocrine Carcinoma That Improved with Bevacizumab plus Modified FOLFOX6 as the Fourth-Line Chemotherapy

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Satoshi Takeuchi

2011-05-01

Full Text Available High-grade neuroendocrine carcinoma differs from usual neuroendocrine carcinoma, and its prognosis is dismal. In this case report, a case of high-grade neuroendocrine carcinoma that improved with bevacizumab plus modified FOLFOX6 as the fourth-line chemotherapy is presented. A 29-year-old male with a huge liver tumor was diagnosed with high-grade neuroendocrine carcinoma originating from the liver. Multiple liver and bone metastases were found one month after surgery. He was treated with three chemotherapy regimens used for the management of small-cell lung cancer with extensive disease. However, none of them could be maintained because of tumor progression. He was then treated with bevacizumab plus modified FOLFOX6 as the fourth-line regimen. Dramatic tumor shrinkage was obtained, and a partial response was achieved. This case suggests that high-grade neuroendocrine carcinoma can be treated with bevacizumab in combination with cytotoxic chemotherapy.

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.

[Evaluation of accuracy of measuring intraocular pressure by handheld non-contact applanation tonometer].

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Chen, X; Peng, D; Zhou, W; Zhong, Y

1995-06-01

To evaluate the accuracy of measuring intraocular pressure by handheld non-contact applanation tonometer. 58 patients' (113 eyes) intraocular pressure were measured by Keeler, non-contact tonometer and R 900 Goldmann applanation tonometer and the results of measurement of intraocular pressure by the two kinds of tonometers were compared. The mean intraocular pressure measured by non-contact is 16.31 +/- 5.59 mmHg and 17.49 +/- 6.13 mmHg (1 mmHg = 0.1333 kPa) by Goldmann applanation tonometer, respectively. There was no statistical significance to be found (P > 0.05) between the two methods. By linear correlation and regression analysis, a positive correlation was found between the two methods (r = 0.8942, b = 0.8154). The handheld non-contact tonometer has the same accuracy and reliability of measurement of intraocular pressure comparing with Goldmann applanation tonometer, and it can be used in glaucoma clinic and screening.

Retropupillary iris claw intraocular lens implantation in aphakia for dislocated intraocular lens.

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Faria, Mun Yueh; Ferreira, Nuno Pinto; Pinto, Joana Medeiros; Sousa, David Cordeiro; Leal, Ines; Neto, Eliana; Marques-Neves, Carlos

2016-01-01

Nowadays, dislocated intraocular lenses (IOLs) and inadequate capsular support are becoming a challenge for every ophthalmic surgeon. Explantation of dislocated IOL and iris claw IOL (ICIOL) are the techniques that have been used in our ophthalmic department. The aim of this study is to report our technique for retropupillar ICIOL. This study is a retrospective case series. A total of 105 eyes with dislocated IOL from the patients at the Department of Ophthalmology in Santa Maria Hospital, a tertiary reference hospital in Lisbon, Portugal, from January 2012 until January 2016, had been analyzed. Of these 105 eyes, 66 eyes had dislocated one-piece IOL and 39 eyes had dislocated three-piece IOL. The latter underwent iris suture of the same IOL and were excluded from this study. The remaining 66 eyes with dislocated one-piece IOL underwent pars plana vitrectomy, that is, explantation of dislocated IOL through corneal incision and an implantation of retropupillary ICIOL. Operative data and postoperative outcomes included best corrected visual acuity, IOL position, intraocular pressure, pigment dispersion, clinical signs of endothelial cell loss, and anterior chamber depth. The mean follow-up was 23 months (range: 6-48 months). The mean preoperative best corrected visual acuity was 1.260±0.771 logMAR, and postoperative best corrected visual acuity was 0.352±0.400 logMAR units. Mean vision gain was 0.909 logMar units. The patients had the following complications: 1) retinal detachment was found in one patient, 2) corneal edema was found in three patients, 3) high intraocular pressure was observed in twelve patients, 4) subluxation of the IOL was observed in one patient, and 5) macular edema was found in three eyes. The results demonstrate that retropupillary ICIOL is an easy and effective method for the correction of aphakia in patients not receiving capsule support. The safety of this procedure must be interpreted in the context of a surgery usually indicated in

Predictors of Visual Response to Intravitreal Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration

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Kai Fang

2013-01-01

Full Text Available Purpose. To identify the predictors of visual response to the bevacizumab treatment of neovascular age-related macular degeneration (AMD. Design. A cohort study within the Neovascular AMD Treatment Trial Using Bevacizumab (NATTB. Methods. This was a multicenter trial including 144 participants from the NATTB study. Visual outcomes measured by change in visual acuity (VA score, proportion gaining ≥15 letters, and change in central retinal thickness (CRT were compared among groups according to the baseline, demographic, and ocular characteristics and genotypes. Results. Mean change in the VA score was 9.2 ± 2.3 SD letters with a total of 46 participants (31.9% gaining ≥15 letters. Change in median CRT was −81.5 μm. Younger age, lower baseline VA score, shorter duration of neovascular AMD, and TT genotype in rs10490924 were significantly associated with greater VA score improvement (P=0.028, P<0.001, P=0.02, and P=0.039, resp.. Lower baseline VA score and TT genotype in rs10490924 were significantly associated with a higher likelihood of gaining ≥15 letters (P=0.028, and P=0.021, resp.. Conclusions. Baseline VA and genotype of rs10490924 were both important predictors for visual response to bevacizumab at 6 months. This trial is registered with the Registration no. NCT01306591.

Differential histopathologic parameters in colorectal cancer liver metastases resected after triplets plus bevacizumab or cetuximab: a pooled analysis of five prospective trials.

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Cremolini, Chiara; Milione, Massimo; Marmorino, Federica; Morano, Federica; Zucchelli, Gemma; Mennitto, Alessia; Prisciandaro, Michele; Lonardi, Sara; Pellegrinelli, Alessio; Rossini, Daniele; Bergamo, Francesca; Aprile, Giuseppe; Urbani, Lucio; Morelli, Luca; Schirripa, Marta; Cardellino, Giovanni Gerardo; Fassan, Matteo; Fontanini, Gabriella; de Braud, Filippo; Mazzaferro, Vincenzo; Falcone, Alfredo; Pietrantonio, Filippo

2018-04-01

Many factors, including histopathologic parameters, seem to influence the prognosis of patients undergoing resection of colorectal cancer liver metastases (CRCLM), although their relative weight is unclear. Histopathologic growth patterns (HGPs) of CRCLM may affect sensitivity to antiangiogenics. We aimed at evaluating differences in histopathologic parameters of response according to the use of bevacizumab or cetuximab as first-line targeted agents, and at exploring the prognostic and predictive role of HGPs. We performed a comprehensive histopathologic characterisation of CRCLM from 159 patients who underwent secondary resection, after receiving triplets FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) or COI (capecitabine, oxaliplatin, and irinotecan) plus bevacizumab (N = 103) vs cetuximab (N = 56) in five first-line no-profit clinical trials. Both major histopathologic response (tumour regression grade TRG1-2, 32 vs 14%, p = 0.013) and infarct-like necrosis (80 vs 64%, p = 0.035) were significantly higher in the bevacizumab than in the cetuximab group. Achieving major response positively affected relapse-free survival (RFS) (p = 0.012) and overall survival (OS) (p = 0.045), also in multivariable models (RFS, p = 0.008; OS, p = 0.033). In the desmoplastic HGP (N = 28), a higher percentage of major response was reported (57 vs 17% in pushing and 22% in replacement HGP, p < 0.001) and an unsignificant advantage from cetuximab vs bevacizumab was evident in RFS (p = 0.116). In the pushing HGP (N = 66), a significant benefit from bevacizumab vs cetuximab (p = 0.017) was observed. No difference was described in the replacement HGP (N = 65, p = 0.615). The histopathologic response is the only independent determinant of survival in patients resected after triplets plus a biologic. When associated with triplet chemotherapy, bevacizumab induces a higher histopathologic response rate than

Sutureless, Glueless, Scleral Fixation of Single-Piece and Toric Intraocular Lens: A Novel Technique

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Aditya Kelkar

2015-07-01

Full Text Available Sutureless, glueless, scleral fixation of an intraocular lens is a known technique of fixing a lens in the scleral pockets. However, this technique is applied to single-piece and toric lenses instead of 3-piece lenses, allowing the advantage of the use of premium lenses in patients with poor capsular support. Favourable results without complications of pigment dispersion, iris transillumination defects, dysphotopsia, elevated intraocular pressure, intraocular hemorrhage and cystoid macular edema with a well-centered, stable intraocular lens have been observed in the 3-month postoperative period in both cases.

Flurbiprofen and intraocular pressure.

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Gieser, D K; Hodapp, E; Goldberg, I; Kass, M A; Becker, B

1981-07-01

Systemic or topical administration of corticosteroids may produce a rise in intraocular pressure (IOP). Nonsteroidal anti-inflammatory drugs (NSAI drugs) are alternate therapy for ocular inflammatory disease. Flurbiprofen, a new NSAI drug, was tested in double-masked fashion to delineate its effect on IOP. Flurbiprofen did not alter IOP in known high corticosteroid responders nor did it block corticosteroid-induced ocular hypertension.

An open-label, two-stage, phase II study of bevacizumab and lapatinib in children with recurrent or refractory ependymoma: a collaborative ependymoma research network study (CERN).

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DeWire, Mariko; Fouladi, Maryam; Turner, David C; Wetmore, Cynthia; Hawkins, Cynthia; Jacobs, Carmen; Yuan, Ying; Liu, Diane; Goldman, Stewart; Fisher, Paul; Rytting, Michael; Bouffet, Eric; Khakoo, Yasmin; Hwang, Eugene I; Foreman, Nicholas; Stewart, Clinton F; Gilbert, Mark R; Gilbertson, Richard; Gajjar, Amar

2015-05-01

Co-expression of ERBB2 and ERBB4, reported in 75% of pediatric ependymomas, correlates with worse overall survival. Lapatinib, a selective ERBB1 and ERBB2 inhibitor has produced prolonged disease stabilization in patients with ependymoma in a phase I study. Bevacizumab exposure in ependymoma xenografts leads to ablation of tumor self-renewing cells, arresting growth. Thus, we conducted an open-label, phase II study of bevacizumab and lapatinib in children with recurrent ependymomas. Patients ≤ 21 years of age with recurrent ependymoma received lapatinib orally twice daily (900 mg/m(2)/dose to the first 10 patients, and then 700 mg/m(2)/dose) and bevacizumab 10 mg/kg intravenously on days 1 and 15 of a 28-day course. Lapatinib serum trough levels were analyzed prior to each course. Total and phosphorylated VEGFR2 expression was measured in peripheral blood mononuclear cells (PBMCs) before doses 1 and 2 of bevacizumab and 24-48 h following dose 2 of bevacizumab. Twenty-four patients with a median age of 10 years (range 2-21 years) were enrolled; 22 were eligible and 20 evaluable for response. Thirteen had anaplastic ependymoma. There were no objective responses; 4 patients had stable disease for ≥ 4 courses (range 4-14). Grade 3 toxicities included rash, elevated ALT, and diarrhea. Grade 4 toxicities included peri-tracheostomy hemorrhage (n = 1) and elevated creatinine phosphokinase (n = 1). The median lapatinib pre-dose trough concentration was 3.72 µM. Although the combination of bevacizumab and lapatinib was well tolerated in children with recurrent ependymoma, it proved ineffective.

Professor Peter Choyce: an early pioneer of intraocular lenses and corneal/refractive surgery.

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Pandey, Suresh K; Apple, David J

2005-06-01

Professor Peter Choyce, FRCS, DOMS, MS, was one of the pioneers of intraocular lens implant surgery. He developed an interest in artificial lens implantation following cataract surgery, a procedure that was widely criticized by the ophthalmic establishment in the UK, Europe, North America and other countries. Owing to the opposition to the intraocular lenses, Peter Choyce together with Sir Harold Ridley co-founded the International Intraocular Implant Club in 1966, which was responsible for the gradual acceptance of artificial lens implantation. Peter Choyce developed several models of intraocular lens, but did not patent the majority of them. The Choyce Mark IX, manufactured by Rayner Intraocular Lenses, became the first US Food and Drug Administration-approved intraocular lens in 1981. A review of Peter Choyce's record confirms a significant number of original innovations in the field of anterior segment surgery, including many procedures taken for granted today, but not associated with his name. These include early work on both kerato- and intraocular lens-refractive procedures, keratoprosthesis, pioneering paediatric implant procedures and others. Unfortunately his tenacious adherence to anterior chamber lens technology, while in general clinically sound, caused many to question his influence and hence he remained poorly understood even until after his death. He passed away on 8 August 2001 after a long fight with colon cancer. In this article, we provide evidence and elaborate Peter Choyce's accomplishments, which places him as one of the most innovative ophthalmologist in his surgical field in the twentieth century.

Assessing Biological Response to Bevacizumab Using 18F-Fluoromisonidazole PET/MR Imaging in a Patient with Recurrent Anaplastic Astrocytoma

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Ramon F. Barajas

2015-01-01

Full Text Available We present our initial experience in using single modality fluoromisonidazole (FMISO PET/MR imaging to noninvasively evaluate the biological effects induced by bevacizumab therapy in a patient treated for recurrent high grade glioma. In this index patient, bevacizumab therapy resulted in the development of nonenhancing tumor characterized by reduced diffusion and markedly decreased FMISO uptake in the setting of maintained CBF and CBV. These observations suggest that the dynamic biological interplay between tissue hypoxia and vascular normalization occurring within treated recurrent high grade glioma can be captured utilizing FMISO PET/MR imaging.

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

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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.

Experiencia con la lente intraocular RAYNER 620H Experience gained with the use of intraocular lens RAYNER 620 H

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Juan Raúl Hernández Silva

2008-06-01

Full Text Available Un importante eslabón en el progreso alcanzado en la cirugía de cataratas, está fundamentado en el desarrollo industrial paralelo que ha ocurrido durante los últimos años con la introducción de nuevos modelos de lentes intraoculares, como el Rayner 620 H; el perfeccionamiento del instrumental quirúrgico, sistemas de aspiración e irrigación bimanual y bisturí con la medida exacta para colocar el inyector de la lente intraocular. La lente intraocular Rayner 620H significó un gran paso para la facoemulsificación y el control de la opacidad de la cápsula posterior posoperatoria por el diseño peculiar de su óptica y hápticos, que permiten un implante seguro, fácil y una incisión mínima. Se realizó un estudio prospectivo y descriptivo, cuyo universo de estudio fueron 28 ojos con diagnóstico de cataratas a los cuales se les realizó facoemulsificación con implante de lente intraocular Rayner 620 H, en el Centro de Microcirugía Ocular del Instituto Cubano de oftalmología "Ramón Pando Ferrer" en el período comprendido entre junio de 2006 a febrero de 2007. El grupo de edades donde se encontró el de mayor número de pacientes fue en el de más de 60 años. En todos los casos hubo un aumento significativo de la agudeza visual sin corrección y con ella, del preoperatorio al posoperatorio. Hubo un aumento del cilindro queratométrico del preoperatorio al posoperatorio, pero este fue mínimo La pérdida de células endoteliales fue baja del preoperatorio al posoperatorio, respectivamente. No hubo ninguna complicación durante la cirugía ni después de esta. Evaluamos como satisfactoria la efectividad del lente intraocular Rayner 620 H, por el aumento de la agudeza visual del paciente, el bajo astigmatismo inducido, mejoría del campo visual por confrontación, mínima pérdida de células endoteliales, y ausencia de complicaciones y de deslumbramiento posoperatorio en los pacientes.An important link in the advances made by the

Intraocular pressure in very low birth weight preterm infants and its association with postconceptional age

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Rodrigo L. Lindenmeyer

2012-11-01

Full Text Available OBJECTIVE: To evaluate intraocular pressure in very low birth weight preterm infants and correlate it with postconceptional age. METHODS: The intraocular pressure in a prospective cohort of very low birth weight premature infants (defined as a birth weight <1,500 g and gestational age <32 weeks admitted to Hospital de Clínicas de Porto Alegre , Brazil was evaluated weekly. The evaluated outcome was the variation in the intraocular pressure following changes in the postconceptional age (defined as the gestational age at birth plus the age in weeks at the time of examination in the weeks following preterm birth. Mixed-effects models were used for the statistical analysis to determine the intraocular pressure variation according to postconceptional age, and means and 10th and 90th percentiles were calculated for the intraocular pressure values. RESULTS: Fifty preterm infants with a mean gestational age of 29.7 ± 1.6 weeks and a mean birth weight of 1,127.7 ± 222.7 g were evaluated. The mean intraocular pressure for the entire cohort considering both eyes was 14.9 ± 4.5 mmHg, and 13.5% of all recorded intraocular pressure values were greater than 20 mmHg. The analysis revealed a mean reduction in the intraocular pressure of 0.29 mmHg for each increase in postconceptional age (p = 0.047; 95% CI: -0.58 to -0.0035. The mean intraocular pressure (P10-P90 decreased from 16.3 mmHg (10.5222.16 at 26.3 weeks to 13.1 mmHg (7.28-18.92 at 37.6 weeks of postconceptional age. CONCLUSIONS: The mean intraocular pressure in very low birth weight preterm infants was 14.9 ± 4.5 mmHg. This value decreased 0.29 mmHg per week as the postconceptional age increased.

Intraocular manifestations of mycobacterium tuberculosis: A review of the literature

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Lauren A. Dalvin

2017-05-01

Full Text Available Mycobacterium tuberculosis: is most commonly associated with pulmonary infection. However, tuberculosis (TB can also affect the eye. TB can affect nearly any tissue in the eye, and a high index of suspicion is required for accurate diagnosis, as many of the intraocular manifestations of TB can mimic other, more common diseases. Correct diagnosis is critical because systemic anti-tuberculosis treatment may be required, and vision loss or even loss of the affected eye can occur without proper treatment. Thus, it is important for ophthalmologists and infectious disease specialists to work together to accurately diagnose and treat intraocular TB. This article reports the various known presentations of intraocular TB and reviews important elements of diagnosis and treatment. Keywords: Mycobacterium, Tuberculosis, Choroidal granuloma, Retinal vasculitis

Location of a Dexamethasone Implant at the Macula after Intravitreal Injection in a Silicone Oil-Filled Eye

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Cenap Mahmut Esenulku

2016-01-01

Full Text Available Here, we report a case with cystoid macular edema (CME due to central retinal vein occlusion (CRVO presented with a dexamethasone implant (Ozurdex trapped at the macula in her silicone oil- (SO- filled eye after injection. No additional complications such as intraocular pressure (IOP rise or retinal damage were observed. The CME was resolved during the follow-up period. At the last visit, 3 months following the injection, Ozurdex implant was found to be mostly dissolved without any additional ocular complications.

Comparison between intraocular pressure spikes with water loading and postural change.

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Chong, Calum Wk; Wang, Sarah B; Jain, Neeranjali S; Bank, Cassandra S; Singh, Ravjit; Bank, Allan; Francis, Ian C; Agar, Ashish

2016-12-01

To compare the agreement between peak intraocular pressures measured through the water drinking test and the supine test, in patients with primary open angle glaucoma. Consecutive, prospective, blinded. Twenty-one patients from the Glaucoma Unit, Prince of Wales Hospital, Sydney, Australia. For the supine test, intraocular pressure was recorded immediately after the patient had lain down and at 20 and 40 min. At the second evaluation, intraocular pressure was measured in each patient after drinking 10 mL/kg body weight of water for the water drinking test. Again, all patients had their intraocular pressure measured at 20 and 40 min (t = 20 and t = 40, respectively). Patients were excluded from the study if they had pre-existing cardiac, renal or pulmonary complications or had concurrent ocular disease or an anatomical abnormality (including angle recession, peripheral anterior synechiae and developmental anomalies of the angle) that may have influenced intraocular pressure. Bland-Altman analysis. Bland-Altman analysis indicated an overall excellent agreement in terms of mean difference between methods (1.0, -1.0 and -0.90 mmHg, at 0, 20 and 40 min, respectively). Further, with the exception of t = 40, all measured time points had 95% confidence intervals within 6.5 mmHg of their mean difference on the Bland-Altman plot. There was close agreement between the intraocular pressure values of the supine test and water drinking test. However, as the water drinking test may be uncomfortable and potentially hazardous, there is potential that the supine test may be a safer and more comfortable alternative. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

A Feasibility Study of Bevacizumab Plus Dose-Dense Doxorubicin–Cyclophosphamide (AC) Followed by Nanoparticle Albumin–Bound Paclitaxel in Early-Stage Breast Cancer

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McArthur, Heather L.; Rugo, Hope; Nulsen, Benjamin; Hawks, Laura; Grothusen, Jill; Melisko, Michelle; Moasser, Mark; Paulson, Matthew; Traina, Tiffany; Patil, Sujata; Zhou, Qin; Steingart, Richard; Dang, Chau; Morrow, Monica; Cordeiro, Peter; Fornier, Monica; Park, John; Seidman, Andrew; Lake, Diana; Gilewski, Theresa; Theodoulou, Maria; Modi, Shanu; D’Andrea, Gabriella; Sklarin, Nancy; Robson, Mark; Moynahan, Mary Ellen; Sugarman, Steven; Sealey, Jane E.; Laragh, John H.; Merali, Carmen; Norton, Larry; Hudis, Clifford A.; Dickler, Maura N.

2016-01-01

Purpose Bevacizumab confers benefits in metastatic breast cancer but may be more effective as adjuvant therapy. We evaluated the cardiac safety of bevacizumab plus dose-dense doxorubicin–cyclophosphamide (ddAC)→nanoparticle albumin−bound (nab)-paclitaxel in human epidermal growth factor receptor 2 normal early-stage breast cancer. Experimental Design Eighty patients with normal left ventricular ejection fraction (LVEF) were enrolled. Bevacizumab was administered for 1 year, concurrently with ddAC→nab-paclitaxel then as a single agent. LVEF was evaluated at months 0, 2, 6, 9, and 18. This regimen was considered safe if fewer than three cardiac events or fewer than two deaths from left ventricular dysfunction occurred. Correlative studies of cardiac troponin (cTn) and plasma renin activity (PRA) were conducted. Results The median age was 48 years (range, 27−75 years), and baseline LVEF was 68% (53%−82%). After 39 months’ median follow-up (5−45 months): median LVEF was 68% (53%−80%) at 2 months (n=78), 64% (51%−77%) at 6 months (n=66), 63% (48%−77%) at 9 months (n=61), and 66% (42%−76%) at 18 months (n=54). One patient developed symptomatic LV dysfunction at month 15. Common toxicities necessitating treatment discontinuation were hypertension (HTN, 4%), wound-healing complications (4%), and asymptomatic LVEF declines (4%). Neither cTn nor PRA predicted CHF or HTN, respectively. Conclusions Bevacizumab with ddAC→nab-paclitaxel had a low rate of cardiac events; cTn and PRA levels are not predictive of CHF or HTN, respectively. The efficacy of bevacizumab as adjuvant treatment will be established in several ongoing phase III trials. PMID:21350003

A new device to noninvasively estimate the intraocular pressure produced during ocular compression

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Korenfeld MS

2016-01-01

Full Text Available Michael S Korenfeld,1,2 David K Dueker3 1Comprehensive Eye Care, Ltd., 2Department of Ophthalmology and Visual Sciences, Washington University, Washington, MO, USA; 3Hamad Medical Corporation, Doha, Qatar Purpose: To describe a noninvasive instrument that estimates intraocular pressure during episodes of external globe compression and to demonstrate the accuracy and reliability of this device by comparing it to the intraocular pressures simultaneously and manometrically measured in cannulated eyes. Methods: A thin fluid-filled bladder was constructed from flexible and inelastic plastic sheeting and was connected to a pressure transducer with high pressure tubing. The output of the pressure transducer was sent to an amplifier and recorded. This device was validated by measuring induced pressure in the fluid-filled bladder while digital pressure was applied to one surface, and the other surface was placed directly against a human cadaver eye or in vivo pig eye. The human cadaver and in vivo pig eyes were each cannulated to provide a manometric intraocular pressure control. Results: The measurements obtained with the newly described device were within ~5% of simultaneously measured manometric intraocular pressures in both a human cadaver and in vivo pig eye model for a pressure range of ~15–100 mmHg. Conclusion: This novel noninvasive device is useful for estimating the intraocular pressure transients induced during any form of external globe compression; this is a clinical setting where no other devices can be used to estimate intraocular pressure. Keywords: glaucoma, intraocular pressure, tonometer, ocular compression

Bevacizumab for the treatment of nonsquamous non-small-cell lung cancer in Portugal: a retrospective, multicenter study

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Estevinho, Fernanda; Soares, Marta; Azevedo, Isabel; Queiroga, Henrique; Parente, Bárbara; Brito, Ulisses; Teixeira, Encarnação; Sotto-Mayor, Renato; Araújo, António

2012-01-01

Lung cancer is the leading cause of cancer-related mortality. In patients with nonsquamous non-small-cell lung cancer (NSCLC) stage IIIB/IV treatment with chemotherapy plus bevacizumab led to significant improvements in progression-free and median overall survival (OS). To report the experience of five Portuguese centers in treating patients with nonsquamous NSCLC in stage IIIB or IV with bevacizumab and chemotherapy regarding survival and toxicity outcomes. This was a retrospective, multicenter study on patients with nonsquamous stage IIIB/IV NSCLC treated with bevacizumab and chemotherapy from November 2007 to August 2010 through special use permits. We reviewed the medical records, registry of demographic characteristics, treatments provided, treatment responses, adverse events, and dates of death. Statistical analysis was performed with SPSS statistics software. Median OS and event-free survival (EFS) were calculated using the Kaplan–Meier method. From an eligible population of 41 patients, 37 participants were registered. Study participants were predominantly male (78.4%) with a median age of 53 years (29–75 years). In total, 83.8% patients had stage IV disease (TNM, 6th Ed.). The OS was 21.5 months (95% confidence interval [CI]: 12.6–30.5] and median EFS was 9.4 months (95% CI9: 7.1–11.7). Hematologic toxicity grade 3/4 occurred in 35.1% of patients, and nonhematologic toxicity in 24.3% patients. One fatal thromboembolic event was recorded (2.7%). The results of chemotherapy plus bevacizumab treatment for nonsquamous NSCLC obtained from the daily clinical practice of the centers involved in this study were similar to those of published clinical trials. Collaboration between the different Portuguese centers is crucial for this kind of study

Serial corneal endothelial cell loss with lathe-cut and injection-molded posterior chamber intraocular lenses.

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Kraff, M C; Sanders, D R; Lieberman, H L

1983-01-01

We compared endothelial cell loss of patients implanted with lathe-cut posterior chamber lenses and those implanted with injection-molded lenses over a three-year postoperative period. Results were based on more than 2,500 measurements of corneal endothelial density. Although the technique of cataract extraction (anterior chamber phacoemulsification, posterior chamber phacoemulsification, or planned extracapsular extraction) significantly affected cell loss (P less than .01), the type of implant (lathe-cut or injection-molded) did not. Significant continuing endothelial cell loss did not occur during the first three postoperative years with injection-molded lenses. There was, however, a statistically significant 7% to 15% additional cell loss after surgery over the first two to three postoperative years with lathe-cut implants. There have been no cases of corneal endothelial decompensation developing after implantation of injection-molded or lathe-cut lenses. Because a standard field clinical specular microscope was used in this study, cell counting errors cannot be ruled out as a cause of these findings.

Pigment dispersion and chronic intraocular pressure elevation after sulcus placement of 3-piece acrylic intraocular lens.

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Almond, M Camille; Wu, Michael C; Chen, Philip P

2009-12-01

A 55-year-old man had phacoemulsification and implantation of a 3-piece acrylic intraocular lens (IOL) (AcrySof MA60AC) in the right eye. One month postoperatively, the intraocular pressure (IOP) was 48 mm Hg and peripheral transillumination defects were noted in the iris circumferentially, with the IOL optic edge visible as a silhouette. Gonioscopy showed dense pigmentation of the trabecular meshwork in the right eye, but in the left eye, only mild trabecular meshwork pigment was seen, along with a concave peripheral iris insertion. At 21 months, the right eye required 3 medications for IOP control. While pigment dispersion has been widely reported after placement of 1-piece acrylic IOLs in the ciliary sulcus, we conclude that in susceptible individuals with a concave peripheral iris insertion, pigment dispersion can occur with sulcus placement of a 3-piece acrylic model despite its thinner optic and angulated haptics.

Posterior Segment Intraocular Foreign Body: Extraction Surgical Techniques, Timing, and Indications for Vitrectomy

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Dante A. Guevara-Villarreal

2016-01-01

Full Text Available Ocular penetrating injury with Intraocular Foreign Body (IOFB is a common form of ocular injury. Several techniques to remove IOFB have been reported by different authors. The aim of this publication is to review different timing and surgical techniques related to the extraction of IOFB. Material and Methods. A PubMed search on “Extraction of Intraocular Foreign Body,” “Timing for Surgery Intraocular Foreign Body,” and “Surgical Technique Intraocular Foreign Body” was made. Results. Potential advantages of immediate and delayed IOFB removal have been reported with different results. Several techniques to remove IOFB have been reported by different authors with good results. Conclusion. The most important factor at the time to perform IOFB extraction is the experience of the surgeon.

Bacillus cereus panophthalmitis associated with intraocular gas bubble.

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al-Hemidan, A; Byrne-Rhodes, K A; Tabbara, K F

1989-01-01

It has become increasingly apparent that Bacillus cereus can cause a severe and devastating form of endophthalmitis following penetrating trauma by a metallic object. B. cereus is an uncommon aetiological agent in non-clostridial gas-forming infections. The patient studied in this single case report showed evidence of intraocular gas mimicking gas gangrene infection. The physiology of non-clostridial bacteria producing gas from anaerobic metabolic conditions is reviewed. Further intraocular and systemic complications which may be avoided by accurate and early diagnosis and the use of recommended treatment with antibiotics such as clindamycin. Images PMID:2493262

Influence of macular pigment optical density spatial distribution on intraocular scatter.

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Putnam, Christopher M; Bland, Pauline J; Bassi, Carl J

This study evaluated the summed measures of macular pigment optical density (MPOD) spatial distribution and their effects on intraocular scatter using a commercially available device (C-Quant, Oculus, USA). A customized heterochromatic flicker photometer (cHFP) device was used to measure MPOD spatial distribution across the central 16° using a 1° stimulus. MPOD was calculated as a discrete measure and summed measures across the central 1°, 3.3°, 10° and 16° diameters. Intraocular scatter was determined as a mean of 5 trials in which reliability and repeatability measures were met using the C-Quant. MPOD spatial distribution maps were constructed and the effects of both discrete and summed values on intraocular scatter were examined. Spatial mapping identified mean values for discrete MPOD [0.32 (s.d.=0.08)], MPOD summed across central 1° [0.37 (s.d.=0.11)], MPOD summed across central 3.3° [0.85 (s.d.=0.20)], MPOD summed across central 10° [1.60 (s.d.=0.35)] and MPOD summed across central 16° [1.78 (s.d.=0.39)]. Mean intraocular scatter was 0.83 (s.d.=0.16) log units. While there were consistent trends for an inverse relationship between MPOD and scatter, these relationships were not statistically significant. Correlations between the highest and lowest quartiles of MPOD within the central 1° were near significance. While there was an overall trend of decreased intraocular forward scatter with increased MPOD consistent with selective short wavelength visible light attenuation, neither discrete nor summed values of MPOD significantly influence intraocular scatter as measured by the C-Quant device. Published by Elsevier España, S.L.U.

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

BACKGROUND: The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results...... 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....... This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN91273375. FINDINGS: Between Dec 18, 2006, and Feb 16, 2009, 1528 women were enrolled and randomly assigned to receive chemotherapy (n=764) or chemotherapy plus bevacizumab (n=764). Median follow-up at the end...

Bilateral spontaneous dislocation of posterior chamber intraocular lens in a patient with gyrate atrophy

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Michael Kinori

2012-01-01

Full Text Available We report a patient with gyrate atrophy, a rare metabolic disease, who had bilateral late spontaneous posterior dislocation of in-the-bag posterior chamber intraocular lens (PCIOL. He underwent pars plana vitrectomy, PCIOL retrieval and anterior chamber intraocular lens implantation in both eyes. This report may imply that patients with gyrate atrophy are at risk for spontaneous dislocation of intraocular lenses.

The Effect of Various Contact Lenses on Intraocular Pressure Measurement by Goldman Tonometer

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Monireh Mahjoob

2014-06-01

Full Text Available Background: Today, contact lenses have extensive usages. Contact lens places on cornea, so it may induce variation on cornea and these variations can influence the measurement of intraocular pressure (IOP by Goldman tonometer. The aim of this research was to study the effect of various contact lenses on measurement of intraocular pressure by Goldman tonometer. Materials and Methods: In this study, 80 subjects aged 18-25 were selected randomly among patients of Al-Zahra ophthalmology center. None of them has any eye pathological problems. Before wearing the lens, intraocular pressure was measured, and then patients were divided into two groups of soft and hard contact lenses. Soft and hard contact lenses were placed on the eye for two hours, and the intraocular pressure was measured again. Results: The mean of IOP before wearing contact lenses and two hours later was 15.96 mmHg and 13.93, s respectively. Paired test showed a significant difference between IOP before and after wearing contact lenses (p=0.001.There was no significant differences in mean of intraocular pressure decline before and after placing the contact lens in both soft and hard lenses. Conclusion: According to this study, the intraocular pressure decreases after wearing contact lenses (CL. This decline may be due to variation in properties of cornea after wearing CL that can also affect IOP measurement.

Clinical utilization of anti-vascular endothelial growth-factor agents and patient monitoring in retinal vein occlusion and diabetic macular edema

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Kiss S

2014-08-01

Full Text Available Szilárd Kiss,1 Ying Liu,2 Joseph Brown,3 Nancy M Holekamp,4,5 Arghavan Almony,6 Joanna Campbell,2 Jonathan W Kowalski2 1Weill Cornell Medical College, New York, NY; 2Allergan, Inc., Irvine, CA; 3IMS Health, Woodland Hills, CA; 4Pepose Vision Institute, Chesterfield, MO; 5Washington University School of Medicine, St Louis, MO; 6Carolina Eye Associates, Southern Pines, NC, USA Purpose: To examine the utilization of bevacizumab and ranibizumab and disease monitoring in patients with branch or central retinal vein occlusion (BRVO/CRVO or diabetic macular edema (DME in clinical practice.Patients and methods: This retrospective claims analysis included newly diagnosed patients with one or more bevacizumab or ranibizumab injections. Bevacizumab or ranibizumab utilization was assessed by year of first injection: 2008–2010 cohorts (12-month follow-up, January to June 2011 cohort (6-month follow-up. The main outcome measures were mean annual numbers of injections, ophthalmologist visits and optical coherence tomography examinations, and proportion of patients with additional laser or intravitreal triamcinolone (IVTA use.Results: A total of 885 BRVO, 611 CRVO, and 2,733 DME patients treated with bevacizumab were included, with too few ranibizumab-treated patients for meaningful analysis. Across the 2008, 2009, and 2010 cohorts, mean annual numbers of bevacizumab injections increased, but remained low (BRVO 2.5, 3.1, 3.3; CRVO 3.1, 3.1, 3.5; and DME 2.2, 2.5, 3.6, respectively; mean ophthalmologist visits ranged between 4.4 and 6.5, and mean optical coherence tomography examinations ranged between 3.1 and 3.9 across all conditions. A total of 42.0% of BRVO, 16.5% of CRVO, and 57.7% of DME patients received additional laser or IVTA therapy. The number of bevacizumab injections was positively associated with laser use in BRVO (3.3 versus 2.9, P<0.03, and with laser or IVTA use in DME (laser, 3.3 versus 2.7, P<0

The role of bevacizumab in targeted vascular endothelial growth factor therapy for epithelial ovarian cancer: an updated systematic review and meta-analysis

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Ruan GY

2018-01-01

Full Text Available Guanyu Ruan,1,* Lixiang Ye,2,* Guifen Liu,3 Jian An,3 Jalid Sehouli,4 Pengming Sun1,3 1Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, 2Fujian Center for Safety Evaluation of New Drugs, Fujian Medical University, 3Department of Gynecology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Gynecologic Oncology and Gynecology, Charité Campus Virchow-Klinikum, European Competence Center for Ovarian Cancer, University of Berlin, Berlin, Germany *These authors contributed equally to this work Abstract: The impact of bevacizumab (an anti-vascular endothelial growth factor therapy remains uncertain, which has been the focus of studies on the management of epithelial ovarian cancer (EOC. To investigate the efficacy of bevacizumab combinations with different regimens in the treatment of patients with EOC, a meta-analysis of Phase III randomized controlled trials was conducted. The databases searched included PubMed, Embase, ClinicalTrials.gov, Chinese Knowledge Infrastructure, as well as the Cochrane Central Register of Controlled Trials. After evaluation of quality, a meta-analysis of valid extracted data was performed using Review Manager (RevMan software. Five studies with 4,369 patients were included. Bevacizumab plus chemotherapy improved progression-free survival (hazard ratio [HR] =0.63; 95% confidence interval [CI], 0.51–0.77; P<0.01 and overall survival (HR =0.91; 95% CI, 0.84–0.99; P<0.05. Interestingly, in patients with a high risk of progression, the subgroups that received bevacizumab combined with different regimens of chemotherapy showed a significant improvement with paclitaxel plus carboplatin-based chemotherapy (HR =0.86; 95% CI, 0.77–0.95; P<0.01, but not with non-paclitaxel plus carboplatin-based chemotherapy (HR =0.91; 95% CI, 0

Magnetic resonance imaging diagnosis of intraocular lenses. Die kernspintomographische Diagnostik der Hinterkammerlinse

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Tosch, U. (Strahlenklinik und Poliklinik, Universitaetsklinik Rudolf Virchow, Berlin (Germany)); Bleckmann, H. (Strahlenklinik und Poliklinik, Universitaetsklinik Rudolf Virchow, Berlin (Germany)); Kaczmarek, U. (Strahlenklinik und Poliklinik, Universitaetsklinik Rudolf Virchow, Berlin (Germany))

1994-09-01

Intraocular lenses were investigated by MRI to obtain information about the quality of this method. In experimental studies, seven lenses of between 0 and 30 diopters were visualized. By MRI it was possible to differentiate the various diameters of lenses. It was not possible to discriminate the material of the intraocular lenses. After these first studies the eyes of two corpses and eight patients were investigated. Because of the resolution of MRI it was possible to tell the diopter of implanted lenses. However, by use of MRI in the regular position, a tilting or decentration of the intraocular lens was demonstrated. (orig.)

Electrochemical lysis at the stage of endoresection for large posterior intraocular tumors

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Yu. A. Belyy

2012-01-01

Full Text Available Purpose: to design the new combined technique of endoresection with intraoperative intraocular electrochemical lysis at the tumor destruction stage for large posterior intraocular tumors.Methods: 3 patients (3 eyes with large choroidal melanomas t3N0M0 (tumor thickness — 8-10 mm, base diameter — 13-15 mm, juxtapapillary localization. Mean age was 55.4 years old. Endoresection with intraoperational intraocular electrochemical lysis of the tumor was performed. Electrochemical lysis was performed with use of the technical unit ECU 300 (Soering, Germany and the original method of combined intratumoral positioning of two platinum electrodes: anode and cathode.Results: the tumor was removal completely in all 3 cases. the anatomical retinal reattachment was reached in all patients. Sclera was safe in all 3 cases. Visual acuity was not changed (NLP. At the place of the removal tumor a surgical choroidal coloboma without pigmentation all over scleral bed and periphery was shown in all cases in distant postoperative period (from 1.5 to 3 years. No local recurrences or metastasis were revealed in all patients.Conclusion: Further investigations in clinical group are necessarily to determinate the real possibilities of the combined method and the indications for endoresection with intraoperative intraocular electrochemical lysis for large intraocular tumors. 

A Polymorphism within the Vitamin D Transporter Gene Predicts Outcome in Metastatic Colorectal Cancer Patients Treated with FOLFIRI/Bevacizumab or FOLFIRI/Cetuximab.

Science.gov (United States)

Berger, Martin D; Stintzing, Sebastian; Heinemann, Volker; Cao, Shu; Yang, Dongyun; Sunakawa, Yu; Matsusaka, Satoshi; Ning, Yan; Okazaki, Satoshi; Miyamoto, Yuji; Suenaga, Mitsukuni; Schirripa, Marta; Hanna, Diana L; Soni, Shivani; Puccini, Alberto; Zhang, Wu; Cremolini, Chiara; Falcone, Alfredo; Loupakis, Fotios; Lenz, Heinz-Josef

2018-02-15

Purpose: Vitamin D exerts its inhibitory influence on colon cancer growth by inhibiting Wnt signaling and angiogenesis. We hypothesized that SNPs in genes involved in vitamin D transport, metabolism, and signaling are associated with outcome in metastatic colorectal cancer (mCRC) patients treated with first-line FOLFIRI and bevacizumab. Experimental Design: 522 mCRC patients enrolled in the FIRE-3 (discovery cohort) and TRIBE (validation set) trials treated with FOLFIRI/bevacizumab were included in this study. 278 patients receiving FOLFIRI and cetuximab (FIRE-3) served as a control cohort. Six SNPs in 6 genes ( GC, CYP24A1, CYP27B1, VDR, DKK1, CST5 ) were analyzed. Results: In the discovery cohort, AA carriers of the GC rs4588 SNP encoding for the vitamin D-binding protein, and treated with FOLFIRI/bevacizumab had a shorter overall survival (OS) than those harboring any C allele (15.9 vs. 25.1 months) in both univariable ( P = 0.001) and multivariable analyses ( P = 0.047). This association was confirmed in the validation cohort in multivariable analysis (OS 18.1 vs. 26.2 months, HR, 1.83; P = 0.037). Interestingly, AA carriers in the control set exhibited a longer OS (48.0 vs. 25.2 months, HR, 0.50; P = 0.021). This association was further confirmed in a second validation cohort comprising refractory mCRC patients treated with cetuximab ± irinotecan (PFS 8.7 vs. 3.7 months) in univariable ( P = 0.033) and multivariable analyses ( P = 0.046). Conclusions: GC rs4588 SNP might serve as a predictive marker in mCRC patients treated with FOLFIRI/bevacizumab or FOLFIRI/cetuximab. Whereas AA carriers derive a survival benefit with FOLFIRI/cetuximab, treatment with FOLFIRI/bevacizumab is associated with a worse outcome. Clin Cancer Res; 24(4); 784-93. ©2017 AACR . ©2017 American Association for Cancer Research.

Risk of adverse events with bevacizumab addition to therapy in advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials

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Lai XX

2016-04-01

Full Text Available Xi-Xi Lai, Ren-Ai Xu, Yu-Ping Li, Han Yang Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China Background: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor ligand, has shown survival benefits in the treatment of many types of malignant tumors, including non-small-cell lung cancer (NSCLC. We conducted this systematic review and meta-analysis to investigate the risk of the most clinically relevant adverse events related to bevacizumab in advanced NSCLC.Methods: Databases from PubMed, Web of Science, and Cochrane Library up to August 2015, were searched to identify relevant studies. We included prospective randomized controlled Phase II/III clinical trials that compared therapy with or without bevacizumab for advanced NSCLC. Summary relative risk (RR and 95% confidence intervals were calculated using random effects or fixed effects according to the heterogeneity among included trials.Results: A total of 3,745 patients from nine clinical trials were included in the meta-analysis. Summary RRs showed a statistically significant bevacizumab-associated increased risk in three of the adverse outcomes studied: proteinuria (RR =7.55, hypertension (RR =5.34, and hemorrhagic events (RR =2.61. No statistically significant differences were found for gastrointestinal perforation (P=0.60, arterial and venous thromboembolic events (P=0.35 and P=0.92, respectively, or fatal events (P=0.29.Conclusion: The addition of bevacizumab to therapy in advanced NSCLC did significantly increase the risk of proteinuria, hypertension, and hemorrhagic events but not arterial/venous thromboembolic events, gastrointestinal perforation, or fatal adverse events. Keywords: toxicities, angiogenesis inhibitors, non-small-cell lung carcinoma, meta-analysis, safety

The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients

DEFF Research Database (Denmark)

Poulsen, Hans Skovgaard; Urup, Thomas; Michaelsen, Signe Regner

2014-01-01

in newly diagnosed GBM patients have been performed during recent years to test the hypothesis that newly diagnosed GBM patients should be treated with standard multimodality treatment, in combination with bevacizumab, in order to prolong life and maintain or improve quality of life. The results...... treatment is therefore to prolong life, with a maintenance or improvement of quality of life. GBM is a highly vascular tumor and overexpresses the vascular endothelial growth factor A, which promotes angiogenesis. Preclinical data have suggested that anti-angiogenic treatment efficiently inhibits tumor...... growth. Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor A, and treatment has shown impressive response rates in recurrent GBM. In addition, it has been shown that response is correlated to prolonged survival and improved quality of life. Several investigations...

Phacoemulsification and intraocular lens implantation in patients with oculocutaneous albinism.

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Dávila, Pedro J; Ulloa-Padilla, Jan P; Izquierdo, Natalio J

2017-01-01

To evaluate the benefits of phacoemulsification and intraocular lens implantation in patients with oculocutaneous albinism (OCA). The charts of 195 patients with OCA who visited a local eye clinic were reviewed. All of these patients had genetic linkage analysis to establish OCA type. Frequencies and Paired t-test analysis were determined. Of the 195 patients, nine (4.6%) underwent clear cornea phacoemulsification with intraocular lens implantation. Seven of the nine patients with OCA had the Hermansky-Pudlak (HPS) type 1; two had OCA type 1. Pre-operative BCVA of all eyes ranged from 1.0 to 2.3 logMAR with a mean of 1.42 logMAR and a standard deviation of 0.41 logMAR. Post-operative BCVA of all eyes ranged from 1.0 to 1.30 logMAR with a mean of 1.04 logMAR and a standard deviation of 0.10 logMAR. BCVA improved after phacoemulsification surgery and intraocular lens implantation (p = 0.002). Pre-operative astigmatism of all eyes ranged from +0.50 to +5.75 with a mean of +2.25 and a standard deviation of +2.40. Post-operative astigmatism of all eyes ranged from +0.50 to +2.00 with a mean of +1.23 and a standard deviation of +0.42. Astigmatism improved after phacoemulsification surgery and intraocular lens implantation (p = 0.05). Nine patients with OCA who underwent phacoemulsification and intraocular lens implant experienced improved visual acuity and reduced astigmatism post-operatively. These results suggest cataract surgery may improve vision and refractive errors, and thus quality of life, in patients with albinism.

The value of [11C]-acetate PET and [18F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab

International Nuclear Information System (INIS)

Li, Shuren; Ubl, Philipp; Wadsak, Wolfgang; Mitterhauser, Markus; Rainer, Eva; Haug, Alexander; Hacker, Marcus; Peck-Radosavljevic, Markus; Pinter, Matthias; Wang, Hao; Nanoff, Christian; Kaczirek, Klaus

2017-01-01

This prospective study was to investigate the value of [ 11 C]-acetate PET and [ 18 F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab). Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [ 11 C]-acetate PET and [ 18 F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively. The patient-related sensitivity of [ 11 C]-acetate PET, [ 18 F]-FDG PET, and combined [ 11 C]-acetate and [ 18 F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [ 11 C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC. Our study suggests that combining [ 18 F]-FDG with [ 11 C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information. (orig.)

The value of [11C]-acetate PET and [18F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab.

Science.gov (United States)

Li, Shuren; Peck-Radosavljevic, Markus; Ubl, Philipp; Wadsak, Wolfgang; Mitterhauser, Markus; Rainer, Eva; Pinter, Matthias; Wang, Hao; Nanoff, Christian; Kaczirek, Klaus; Haug, Alexander; Hacker, Marcus

2017-09-01

This prospective study was to investigate the value of [ 11 C]-acetate PET and [ 18 F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab). Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [ 11 C]-acetate PET and [ 18 F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively. The patient-related sensitivity of [ 11 C]-acetate PET, [ 18 F]-FDG PET, and combined [ 11 C]-acetate and [ 18 F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [ 11 C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC. Our study suggests that combining [ 18 F]-FDG with [ 11 C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information.

X-ray diffraction enhanced imaging study of intraocular tumors in human beings

International Nuclear Information System (INIS)

Tan Gao; Wang Huaqiao; Chen Yu; Yuan Qing; Li Gang; Zhu Peiping; Zhang Xiaodan; Zhong Xiufeng; Tang Jintian

2010-01-01

Diffraction enhanced imaging (DEI) with edge enhancement is suitable for the observation of weakly absorbing objects. The potential ability of the DEI was explored for displaying the microanatomy and pathology of human eyeball in this work. The images of surgical specimens from malignant intraocular tumor of hospitalized patients were taken using the hard X-rays from the topography station of Beamline 4W1A at Beijing Synchrotron Radiation Facility (BSRF). The obtained radiographic images were analyzed in correlation with those of pathology. The results show that the anatomic and pathologic details of intraocular tumors in human beings can be observed clearly by DEI for the first time, with good visualization of the microscopic details of eyeball ring such as sclera, choroid and other details of intraocular organelles. And the best resolution of DEI images reaches up to the magnitude of several tens of μm. The results suggest that it is capable of exhibiting clearly the details of intraocular tumor using DEI method. (authors)

Effects of tramadol and acepromazine on intraocular pressure and pupil diameter in young healthy cats

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Deise Cristine Schroder

2018-03-01

Full Text Available ABSTRACT: This study aimed to investigate the effects of the systemic administration of acepromazine, tramadol and the association of both on intraocular pressure (IOP and pupil diameter (PD in young healthy cats. Cats were randomly allocated into three groups (n=10/each and intramuscular acepromazine (AG, tramadol (TG or acepromazine combined with tramadol (ATG were injected. PD (electronic caliper and IOP (applanation tonometry were assessed before (baseline and following 15, 30, 60, and 120 minutes of treatments. It was verified that in AG, PD decreased significantly from time point 30 to 120 (P=0.002, but such reduction did not differ significantly from baseline (P=0.89. In TG, PD increased significantly from the first 15 minutes, until the last time point of evaluation (P0.05. It can be concluded that tramadol alone or in association with acepromazine produced significant mydriasis for up to 120 minutes, without changing IOP values in normal cats. Results of this study suggested that tramadol alone or in association with acepromazine caused significant mydriasis and did not change IOP values in normal cats. Therefore, it may be considered a satisfactory pre-anesthetic combination for ophthalmic surgery in cats. However, further studies are warranted on the use of such protocols in cats with ophthalmic diseases undergoing ocular or intraocular surgery.

[Changes in intraocular pressure depending on posture].

Science.gov (United States)

Barac, Ramona; Pop, Monica; Tătaru, C; Gheorghe, A; Bădescu, Silvia; Stanciu, Maria; Burcea, M

2014-01-01

Glaucoma is an important eye disease that, left untreated, causes irreversible blindness by affecting optic nerve threads. Decreasing intraocular pressure and maintaining it at a low level throughout the day is one of the objectives of antiglaucoma therapy. This is a prospective study conducted on a sample of 80 patients who presented at "Emergency Eye Hospital" Bucharest between 1st of December 2013 30th of July 2014. Patients were divided into two groups: 40 patients with glaucoma and 40 patients without glaucoma (control group). THE OBJECTIVE OF THE STUDY: To determine changes in intraocular pressure that may occur depending on body posture and the correlations between changes in intraocular pressure and glaucoma, obesity, hypertension. These IOP changes may be important in the progression of glaucoma regarding that one third of our time is spent on supine position during night. RESULTS AND CONCLUZIONS: IOP varies from sitting down to supine position. IOP increases in supine in most patients (with or without glaucoma) with an average of 1.25 mmHg. The increase among patients with glaucoma is higher (1.67 mmHg) compared to those without glaucoma (0.82 mmHg). In patients with hypertension and glaucoma, IOP increased with 2.62 mmHg. In patients with hypertension and obesity IOP increased with 2.5 mmHg.

Near-infrared transillumination photography of intraocular tumours.

Science.gov (United States)

Krohn, Jørgen; Ulltang, Erlend; Kjersem, Bård

2013-10-01

To present a technique for near-infrared transillumination imaging of intraocular tumours based on the modifications of a conventional digital slit lamp camera system. The Haag-Streit Photo-Slit Lamp BX 900 (Haag-Streit AG) was used for transillumination photography by gently pressing the tip of the background illumination cable against the surface of the patient's eye. Thus the light from the flash unit was transmitted into the eye, leading to improved illumination and image resolution. The modification for near-infrared photography was done by replacing the original camera with a Canon EOS 30D (Canon Inc) converted by Advanced Camera Services Ltd. In this camera, the infrared blocking filter was exchanged for a 720 nm long-pass filter, so that the near-infrared part of the spectrum was recorded by the sensor. The technique was applied in eight patients: three with anterior choroidal melanoma, three with ciliary body melanoma and two with ocular pigment alterations. The good diagnostic quality of the photographs made it possible to evaluate the exact location and extent of the lesions in relation to pigmented intraocular landmarks such as the ora serrata and ciliary body. The photographic procedure did not lead to any complications. We recommend near-infrared transillumination photography as a supplementary diagnostic tool for the evaluation and documentation of anteriorly located intraocular tumours.

Intraocular pressure measurement: Goldmann Applanation Tonometer vs non contact airpuff tonometer.

Science.gov (United States)

Shah, Masood Alam; Bin Saleem, Khalid; Mehmood, Talat

2012-01-01

An accurate assessment of Intraocular pressure (IOP) is vital in establishing diagnosis of Glaucoma and decision making regarding various treatment modalities available. The purpose of this study is to compare Goldmann Applanation Tonometer (GAT) with Air puff tonometer. Cross-sectional comparative study conducted. 73 eyes from 73 patients were included in this study and intraocular pressure (IOP) was measured by GAT and PT100 at Sheikh Khalifa Bin Zayed Hospital, Muzaffarabad, Benazir Shaheed Teaching Hospital, Abbottabad. Mean age of the patients was 53.17 +/- 13.80 years. Mean IOP measurements showed significant differences in measurements performed by the two tonometers (p contact air-puff tonometer, the Goldmann applanation tonometer is a reliable and consistent technique for measurement of intraocular pressure.

Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study.

Science.gov (United States)

Crinò, Lucio; Dansin, Eric; Garrido, Pilar; Griesinger, Frank; Laskin, Janessa; Pavlakis, Nick; Stroiakovski, Daniel; Thatcher, Nick; Tsai, Chun-Ming; Wu, Yi-long; Zhou, Caicun

2010-08-01

Results of two phase 3 trials have shown first-line bevacizumab in combination with chemotherapy improves clinical outcomes in patients with advanced or recurrent non-squamous non-small-cell lung cancer (NSCLC). The SAiL (MO19390) study was undertaken to assess the safety and efficacy of first-line bevacizumab combined with standard chemotherapy regimens in clinical practice. Between August, 2006, and June, 2008, patients with untreated locally advanced, metastatic, or recurrent non-squamous NSCLC were recruited to this open-label, single group, phase 4 study from centres in 40 countries. Eligible patients had histologically or cytologically documented inoperable, locally advanced, metastatic, or recurrent disease (stage IIIB-IV); an Eastern Cooperative Oncology Group performance status of 0-2; and adequate haematological, hepatic, and renal function. Patients received bevacizumab (7.5 or 15 mg/kg every 3 weeks) plus standard chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety; analysis was by intention to treat (ITT). This study is registered with ClinicalTrials.gov, number NCT00451906. At the final data cutoff (July 24, 2009), an ITT population of 2212 patients was assessed. The incidence of clinically significant (grade > or = 3) adverse events of special interest was generally low; thromboembolism occurred in 172 (8%) patients, hypertension in 125 (6%), bleeding in 80 (4%), proteinuria in 67 (3%), and pulmonary haemorrhage in 15 (1%). 57 (3%) patients died because of these adverse events, with thromboembolism (26 patients, 1%) and bleeding (17, 1%) as the most common causes. The most common grade 3 or higher serious adverse events deemed by investigators to be associated with bevacizumab were pulmonary embolism (28 patients; 1%) and epistaxis, neutropenia, febrile neutropenia, and deep vein thrombosis (all of which occurred in 13 patients [1%]). Bevacizumab was temporarily

Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture

Science.gov (United States)

Malik, Deepika; Tarek, Mohamed; Caceres del Carpio, Javier; Ramirez, Claudio; Boyer, David; Kenney, M Cristina; Kuppermann, Baruch D

2014-01-01

Purpose To compare the safety profiles of antivascular endothelial growth factor (VEGF) drugs ranibizumab, bevacizumab, aflibercept and ziv-aflibercept on retinal pigment epithelium cells in culture. Methods Human retinal pigment epithelium cells (ARPE-19) were exposed for 24 h to four anti-VEGF drugs at 1/2×, 1×, 2× and 10× clinical concentrations. Cell viability and mitochondrial membrane potential assay were performed to evaluate early apoptotic changes and rate of overall cell death. Results Cell viability decreased at 10× concentrations in bevacizumab (82.38%, p=0.0001), aflibercept (82.68%, p=0.0002) and ziv-aflibercept (77.25%, p<0.0001), but not at lower concentrations. However, no changes were seen in cell viability in ranibizumab-treated cells at all concentrations including 10×. Mitochondrial membrane potential was slightly decreased in 10× ranibizumab-treated cells (89.61%, p=0.0006) and 2× and 10× aflibercept-treated cells (88.76%, 81.46%; p<0.01, respectively). A larger reduction in mitochondrial membrane potential was seen at 1×, 2× and 10× concentrations of bevacizumab (86.53%, 74.38%, 66.67%; p<0.01) and ziv-aflibercept (73.50%, 64.83% and 49.65% p<0.01) suggestive of early apoptosis at lower doses, including the clinical doses. Conclusions At clinical doses, neither ranibizumab nor aflibercept produced evidence of mitochondrial toxicity or cell death. However, bevacizumab and ziv-aflibercept showed mild mitochondrial toxicity at clinically relevant doses. PMID:24836865

Ocular onchocerciasis in the Yanomami communities from Brazilian Amazon: effects on intraocular pressure.

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Herzog-Neto, Guilherme; Jaegger, Karen; Nascimento, Erika S do; Marchon-Silva, Verônica; Banic, Dalma M; Maia-Herzog, Marilza

2014-01-01

To determine the influence of onchocercal eye disease on the intraocular pressure of the Yanomami Tribe Aratha-ú of Roraima State, Brazil, considered endemic for onchocerciasis, a total of 86 patients were submitted to an ophthalmologic exam that included external examination, slit lamp examination, intraocular pressure measurement, and a fundus ophthalmoscope examination. A high prevalence of onchocerciasis-related eye lesions was encountered in 68.6% of the patients. Punctate keratitis and microfilariae in the anterior chamber were found in ∼28%. The mean of intraocular eye pressure found was 10.47 mm of Hg.

Sensitivity of the corneal-plane refractive compensation to change in power and axial position of an intraocular lens

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W. F. Harris

2009-12-01

Full Text Available If an intraocular lens is displaced or if its power is changed what are the consequences for the refractive compensation of the eye?  Gaussian optics is used to obtain explicit formulae for the sensitivityof the corneal-plane refractive compensation (also called the refraction, refractive state, etc to change in power and axial displacement of a thin intraocular lens implanted in a simple eye.  In particular, for a pseudophakic Gullstrand simplified eye with intraocular lens placed 5 mm behind the cornea the sensitivity to errors in the power of the intraocular lens is about  71 . 0 − 71 for an intraocular lens of power   for an intraocular lens of power 20 D, that is, the refractive compensation decreases by about 0.71 dioptres per dioptre increase in the power of the intraocular lens.  More generally the sensitivity is approximately  ( m   0037 . 0 63 . 0 F − − 0.63 ( 003 . 0 63 . 0 − − (0.0037mF where FI is the power of the intraocular lens.  Also for Gullstrand’s simplified eye the sensitivity of refractive compensation to axial displacement of the intraocular lens is approximately linear in FI about  (64D FI, in fact.  That is, for each dioptre of the power of the intraocular lens the refractive compensation increases by about 0.064 dioptres per millimetre of axial displacement towards the retina. 

Vitrectorhexis and lens aspiration with posterior chamber intraocular lens implantation in spherophakia.

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Al-Haddad, Christiane; Khatib, Lama

2012-07-01

We describe a technique that uses the vitrector to perform successful lens aspiration and posterior chamber intraocular lens (IOL) implantation in children with spherophakia and anterior lens subluxation. After an anterior chamber maintainer is placed, the ocutome is introduced through a limbal incision to perform a circular vitrectorhexis to avoid excessive manipulation of the unstable lens followed by gentle cortex aspiration. A foldable IOL is injected into the sulcus (3-piece IOL) or bag (1-piece IOL) if the capsule is sufficiently stable. Through a pars plana incision, the ocutome is then used to perform a posterior capsulotomy to prevent late posterior capsule opacification. In our patient, sulcus IOL placement was more stable than in-the-bag placement. Neither author has a financial or proprietary interest in any material or method mentioned. Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Intraocular gnathostomiasis: report of a case and review of literature.

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Pillai, Gopal S; Kumar, Anil; Radhakrishnan, Natasha; Maniyelil, Jayasree; Shafi, Tufela; Dinesh, Kavitha R; Karim, Shamsul

2012-04-01

Intraocular gnathostomiasis is a rare parasitic infection caused by the third-stage larvae of spiruroid nematode Gnanthostoma spp. seen mostly in tropical and subtropical regions. It is a food-borne zoonosis caused by ingestion of raw or undercooked freshwater fish, amphibians, reptiles, birds, and mammals, all of which are known to harbor advanced third-stage larvae of Gnanthostoma spp. To date, 74 cases of intraocular gnathostomiasis have been reported from 12 different countries. Only four countries have reported more than 10 cases each, and India shares the rare distinction of being one of them, with 14 cases. Surprisingly, not a single case of cutaneous gnanthostomiasis has ever been reported from India. We present one such case of intraocular gnathostomiasis in a 41-year-old male who presented with an actively motile worm attached to the iris, and we review the pertinent literature of all such cases reported from India.

Safety assessment of a new single-use small-incision injector for intraocular lens implantation.

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Satanovsky, Alexandra; Ben-Eliahu, Shmuel; Apple, David J; Kleinmann, Guy

2011-07-01

To evaluate the safety of a new injector, the Raysert R-INJ-04/18, for implantation of the C-flex intraocular lens (IOL). Ophthalmology Department, Kaplan Medical Center, Rehovot, Israel. Experimental study. Sixty IOLs were subdivided into 2 equally sized groups. Group A IOLs were injected using the established R-INJ-04 injector, and those in Group B were injected with the new injector. The IOLs were injected into a Petri dish. Subsequently, all IOLs and injectors were evaluated macroscopically and microscopically and then photographed under light microscopy (LM). Two IOLs in each group were randomly chosen and sent for evaluation by scanning electron microscopy (SEM) and energy dispersive analysis of x-ray. All remaining IOLs were sent for power and modulation transfer function (MTF) analysis. All Group B IOLs were successfully injected without evident signs of scratching, cracks, or deposits on LM and SEM examination. In Group A, findings were confined to a singular incidence of a small deposit detected on the periphery of the posterior optical surface of the IOL, with corresponding findings detected on the injector nozzle. No signs of scratching, cracks, or deposits were found in the rest of the IOLs or injectors. The power and MTF analyses were within the normal range for all IOLs. The new 1.8 mm external diameter soft-tipped injector for 2.4 to 2.2 mm incisions was shown to be safe for the implantation of the C-flex 21.0 diopter IOL. Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Tumour vasculature immaturity, oxidative damage and systemic inflammation stratify survival of colorectal cancer patients on bevacizumab treatment

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Martin, Petra; Biniecka, Monika; Ó'Meachair, Shane; Maguire, Aoife; Tosetto, Miriam; Nolan, Blathnaid; Hyland, John; Sheahan, Kieran; O'Donoghue, Diarmuid; Mulcahy, Hugh; Fennelly, David; O'Sullivan, Jacintha

2018-01-01

Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA. This study identified that specific markers of angiogenesis, inflammation and oxidative damage stratify survival of patients on this anti-angiogenic treatment. Biomarkers of immature tumour vasculature (% IMM, p=0.026, n=80), high levels of oxidative damage in the tumour epithelium (intensity of 8-oxo-dG in nuclear and cytoplasmic compartments, p=0.042 and 0.038 respectively, n=75) and lower systemic pro-inflammatory cytokines (IL6 and IL8, p=0.053 and 0.049 respectively, n=61) significantly stratify with median overall survival (OS). In summary, screening for a panel of biomarkers for high levels of immature tumour vasculature, high levels of oxidative DNA damage and low levels of systemic pro-inflammatory cytokines may be beneficial in predicting enhanced survival outcome following bevacizumab treatment for mCRC. PMID:29535825

Sutureless Intrascleral Fixated Intraocular Lens Implantation.

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Karadag, Remzi; Celik, Haci Ugur; Bayramlar, Huseyin; Rapuano, Christopher J

2016-08-01

To review sutureless intrascleral intraocular lens (IOL) fixation methods. Review of published literature. Sutureless intrascleral IOL fixation methods are newer and have been developed to eliminate the suture-related complications of sutured scleral fixation methods such as suture-induced inflammation or infection and IOL dislocation or subluxation due to suture degradation or suture breakage. Sutureless intrascleral fixation methods aim for intrascleral haptic fixation to achieve stability of the IOL. Various methods of sutureless scleral fixation have been described. Using a needle, a blade, or a trochar, sclerostomies are created in all techniques for intraocular access. Some surgeons prefer to create scleral tunnels, whereas others use scleral flaps for scleral fixation of haptics. The stability of IOLs is attained by the scar tissue formed around the haptics. Short-term results of these new methods are acceptable; studies including more cases with longer follow-up are needed to determine their long-term success. [J Cataract Refract Surg. 2016;32(9):586-597.]. Copyright 2016, SLACK Incorporated.

The effects of anti-VEGF drugs on the retinal pigment epithelium and inner segment after intravitreal injection in the monkeys

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Nan Su

2016-06-01

Full Text Available AIM: To compare the effects on the retina inner segment and retinal pigment epithelium(RPEof intravitreally injecting bevacizumab, ranibizumab and aflibercept into monkey eyes.METHODS: Fourteen healthy cynomolgus monkeys(Macaca fascicularis, aged 3-8y,10 males,4 femaleswere raised at the Covance Laboratories under standard conditions. The 14 monkeys were grouped into 4 groups. Three of the groups with 4 monkeys each were injected intravitreally with one of the drugs, either bevacizumab, ranibizumab or aflibercept, while the 4th group with 2 monkeys served as a negative control. On 1d and 7d of injection, 2 monkeys from each drug treatment group were sacrificed under general anaesthesia and the 4 eyes were enucleated. All the enucleated eyes were fixed in formalin, embedded in paraffin wax, cut into 4.0 μm sections and deparaffinized according to standard procedures. Image-Pro Plus was used for all the photos to measure the content of vascular endothelial growth factor(VEGFin the inner segment and RPE. The ANOVA test from JMP10.0 statistical program was used to evaluate the results.RESULTS: Retinal sections were checked for their anti-VEGF immune reactivity. The untreated control samples had the highest level of VEGF in the RPE and inner segment. All of these three drugs can reduce the level of VEGF in the RPE and inner segment, but Avastin seems to be more effective than Eylea in this regard. Lucentis treatment at 1d seems to be more effective than Eylea at VEGF 1d. But at 7d, both Lucentis and Eylea have the same effect on reducing VEGF expression level in the RPE and inner segment.CONCLUSION: All of these three drugs can reduce the level of VEGF in the RPE and inner segment.

Microscopic and spectroscopic investigation of an explanted opacified intraocular lens

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Simon, V., E-mail: viosimon@phys.ubbcluj.ro [Babeş-Bolyai University, Faculty of Physics and Interdisciplinary Research Institute on Bio-Nano-Sciences, 400084 Cluj-Napoca (Romania); Radu, T.; Vulpoi, A. [Babeş-Bolyai University, Faculty of Physics and Interdisciplinary Research Institute on Bio-Nano-Sciences, 400084 Cluj-Napoca (Romania); Rosca, C. [Optilens Clinic of Ophthalmology, 400604 Cluj-Napoca (Romania); Eniu, D. [Iuliu Haţieganu University of Medicine and Pharmacy, Department of Molecular Sciences, 400349 Cluj-Napoca (Romania)

2015-01-15

Highlights: • Changes on intraocular lens (IOL) surface after implantation. • Partial opacification of IOL central area. • Elemental composition on IOL surface prior to and after implantation. • First XPS depth profiling examination of the opacifying deposits. • Cell-mediated hydroxyapatite structuring. - Abstract: The investigated polymethylmethacrylate intraocular lens explanted an year after implantation presented a fine granularity consisting of ring-like grains of about 15 μm in diameter. In order to evidence the changes occurred on intraocular lens relative to morphology, elemental composition and atomic environments, microscopic and spectroscopic analyses were carried out using scanning electron microscopy (SEM), Fourier transform infrared (FTIR), energy-dispersive X-ray (EDS), and X-ray photoelectron (XPS) spectroscopies. The results revealed that the grains contain hydroxyapatite mineral phase. A protein layer covers the lens both in opacified and transparent zones. The amide II band is like in basal epithelial cells. The shape and size of the grains, and the XPS depth profiling results indicate the possibility of a cell-mediated process involving lens epithelial cells which fagocitated apoptotic epithelial cells, and in which the debris derived from cell necrosis were calcified. To the best of our knowledge, this is the first investigation on explanted intraocular lenses using XPS depth profiling in order to examine the inside of the opacifying deposits.

Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis

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Botrel, Tobias Engel Ayer; Clark, Luciana Gontijo de Oliveira; Paladini, Luciano; Clark, Otávio Augusto C.

2016-01-01

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined with different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin. This systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus chemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC). Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were overall survival and progression-free survival. Data extracted from the studies were combined by using hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI). The final analysis included 9 trials comprising 3,914 patients. Patients who received the combined treatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003) with heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher overall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse events and severe toxicities (grade ≥ 3), the group receiving the combined therapy had higher rates of hypertension (RR = 3.56 95 % CI: 2.58 to 4.92; p < 0.00001), proteinuria (RR = 1.89; 95 % CI: 1.26 to 2.84; p = 0.002), gastrointestinal perforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to 1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003). The combination of chemotherapy with bevacizumab increased the response rate, progression-free survival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free survival (PFS) and overall survival (OS) were comparatively higher

Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma.

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Shah, Manish A; Jhawer, Minaxi; Ilson, David H; Lefkowitz, Robert A; Robinson, Edric; Capanu, Marinela; Kelsen, David P

2011-03-01

To evaluate the safety and efficacy of a modified administration schedule of docetaxel, cisplatin, and fluorouracil (mDCF) with bevacizumab in patients with advanced gastroesophageal malignancies. Previously untreated patients with metastatic gastroesophageal adenocarcinoma received bevacizumab 10 mg/kg, docetaxel 40 mg/m², fluorouracil 400 mg/m², leucovorin 400 mg/m² on day 1, fluorouracil 1,000 mg/m²/d × 2 days intravenous continuous infusion beginning on day 1, and cisplatin 40 mg/m² on day 3. The primary objective was to improve 6-month progression-free survival (PFS) from 43% (historical DCF control) to 63% with the addition of bevacizumab. The target accrual was 44 patients to have 10% type I and II error rates. In total, 44 eligible patients with cancer were enrolled from October 2006 to October 2008: 22 gastric, 20 gastroesophageal junction (GEJ), and two esophagus. In 39 patients with measurable disease, the confirmed response rate was 67% (95% CI, 50% to 81%). Six-month PFS was 79% (95% CI, 63% to 88%), and median PFS was 12 months (95% CI, 8.8 to 18.2 months). With 26-month follow-up, median overall survival (OS) was 16.8 months (95% CI, 12.1 to 26.1 months), and 2-year survival was 37%. Treatment-related grade 3 to 4 toxicity was as follows: neutropenia without fever (50%), fatigue (25%), venous thromboembolism (39%), and nausea, vomiting, mucositis, neuropathy, and febrile neutropenia less than 10% each. In subset analysis, diffuse gastric cancer had significantly worse PFS and OS, and the response rate in proximal/GEJ tumors was 85% (95% CI, 62% to 97%). mDCF with bevacizumab appears tolerable and has notable patient outcomes in patients with advanced gastroesophageal adenocarcinoma. Six-month PFS was 79%, surpassing our predefined efficacy end point, and median and 2-year OS were 16.8 months and 37%, respectively.

Outcomes and Complications of Scleral-Fixated Intraocular Lens Combined with Ahmed Tube Surgery

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Nikhel Sachdev

2018-01-01

Full Text Available Background. To evaluate the outcome and complications of transscleral suture-fixated posterior chamber intraocular lens (PCIOL implantation combined with Ahmed glaucoma valve (AGV surgery in Asian eyes. Design. This was a retrospective study that included 22 eyes from 22 participants. The surgeries were performed at Singapore’s National University Hospital. Participants underwent an Ahmed tube surgery, together with transscleral suture-fixated posterior chamber intraocular lens. Main Outcome Measures. Complete success was defined as 6 ≤ intraocular pressure (IOP ≤ 21 mmHg without medications at the last follow-up visit, with no reoperation required and no progression to no perception of light (NPL. Results. At the last follow-up, there was a significant reduction in mean IOP (22.4 ± 6.5 mmHg versus 13.9 ± 3.9 mmHg; p<0.001 and mean number of intraocular pressure-lowering medications (2.45 ± 1.30 versus 0.05 ± 0.21; p<0.001. There was no significant change in visual acuity [1.43 ± 1.21 (LogMAR versus 1.09 ± 1.31 (p=0.204]. Sixteen eyes (72.7% achieved complete success. The 3 commonest complications were bullous keratopathy, choroidal detachment, and displacement of intraocular lens. Conclusion and Relevance. This technique showed good success for intraocular pressure control and vision preservation. Postoperative complications were relatively common although most were self-limiting. Patients at increased risk of trabeculectomy failure may be suitable for this procedure.

Intraocular foreign-body hazard during vitrectomy.

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Bovino, J A; Marcus, D F

1982-03-01

We noted two instances of forceps-induced fragmentation of the bar used for scleral plug storage during vitreous surgery. The silicone bar material was adherent to the plug in both cases. Because this represents a significant intraocular foreign body hazard, the scleral plug should be carefully inspected before insertion.

A case of recurrent metastasis in the supraclavicular and axillary lymph nodes and vertebrae following irradiation and paclitaxel plus bevacizumab administration

International Nuclear Information System (INIS)

Nishiyama, Yasuyuki; Nishimura, Reiki; Ohsako, Tomofumi; Tashima, Rumiko; Nakano, Masahiro; Fujisue, Mamiko

2013-01-01

A 48-year-old woman with invasive ductal carcinoma of the left breast underwent breast-conserving surgery and axillary dissection; 19 months after surgery, she developed local recurrence. Subsequently, she underwent mastectomy and received endocrine therapy and chemotherapy. At 47 years of age, she developed pleural metastasis, which directly invaded the vertebrae as well as the right supraclavicular and right axillary lymph nodes. In addition, liver metastasis was observed. To avoid acute transverse myelopathy, the patient received radiation therapy to the vertebrae and the right supraclavicular and right axillary lymph nodes followed by paclitaxel plus bevacizumab administration. After 2 courses of paclitaxel plus bevacizumab, we observed a remarkable shrinkage of the vertebral tumor, and skin necrosis was observed in the right supraclavicular and right axillary region; in contrast, the liver metastasis had increased in size. After discontinuation of the combination therapy, the patient died of blood loss from the axillary skin defect. This wound healing complication might have arisen because of the synergistic effects of paclitaxel plus bevacizumab and irradiation. (author)

Two-step technique for posterior optic buttonholing of intraocular lens.

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Agarwal, Tushar; Jhanji, Vishal; Singh, Digvijay; Khokhar, Sudarshan

2014-04-01

This study aims to describe a two-step surgical technique for placement of a posterior chamber intraocular lens (IOL) in cases with crystalline lens subluxation resulting from non-progressive zonular dialysis. The first stage entails a phacoemulsification with creation of a 4-mm posterior capsular opening using an automated vitrector. The second stage performed 6 weeks later includes an anterior vitrectomy and injection of a foldable three-piece IOL in the sulcus. The haptics of IOL are positioned in the sulcus while the optic is pushed behind the posterior capsular opening therefore "buttonholing" the IOL. Seven eyes of seven patients with posttraumatic zonular dialysis were operated using this technique. Follow-up of all cases revealed a well-centered IOL with good postoperative visual acuity (20/20 to 20/80). Our two-stage surgical technique precludes the insertion of capsular tension ring in cases with non-progressive zonular dialysis. The technique is recommended in the presence of less than or equal to 6 clock hours of zonular dialysis with preexisting posterior capsular tear or herniation of vitreous in the anterior chamber.

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...... was not statistically significant. Mean macular thickness decreased significantly from baseline to all follow-up examinations (P Macular thickness improved significantly at all time...

Subretinal Hemorrhage after Photodynamic Therapy for Juxtapapillary Retinal Capillary Hemangioma

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Takayuki Baba

2011-04-01

Full Text Available A 75-year-old Japanese woman presented with a juxtapapillary retinal capillary hemangioma (RCH in her left eye. Twelve months after the initial examination, the size of the hemangioma had increased and the exudation from the RCH involved the macula. Her best-corrected visual acuity (BCVA had decreased from 0.8 to 0.3. A total of five intravitreal injections of bevacizumab (IVB; 1.25 mg was given but the RCH did not respond. A photodynamic therapy (PDT was done using multiple laser spots to avoid damaging the optic nerve head. After the first PDT, the subfoveal fluid was reduced but not completely gone. One week after the second PDT, a massive subretinal hemorrhage developed. The subretinal hemorrhage was successfully displaced by injecting intraocular sulfur hexafluoride (SF6 gas. At the 3-year follow-up examination, no subretinal hemorrhage or fluid was observed at the macula and the BCVA remained at 0.05. Our case was resistant to the combination of anti-vascular endothelial growth factor (VEGF and PDT and had a rare massive subretinal hemorrhage. A further collection of RCH cases treated with anti-VEGF and PDT that would justify this treatment is necessary.

Intravitreal injection of Ranibizumab combined with laser for diabetic macular edema

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Yan-Xia Huang

2018-04-01

Full Text Available AIM: To investigate the therapeutic effect of intravitreal injection of Ranibizumab combined with laser for diabetic macular edema(DME. METHODS: Totally 60 cases(60 eyesof DME patients treated in ophthalmology department of our hospital from June 2014 to June 2016 were selected and divided into the observation group and the control group. The control group were treated with laser therapy, and the observation group received intravitreal injection of ranibizumab on the basis of the treatment of the control group. Comparison between two groups on the best corrected visual acuity before operation and at 1wk, 1, 3, 6mo after operation was taken. The non-contact tonometer was used to measure intraocular pressure before and after treatment. The optical coherence tomography(OCTwas conducted to assess preoperative and postoperative central macular thickness(CMT.The postoperative complications of two groups were recorded subsequently. RESULTS: The two groups' postoperative visual acuity was significantly improved, data of the observation group at 1, 3mo after operation was sharply higher than that of the control group, there was statistical significance(PP>0.05. After 1wk of treatment, the two groups' intraocular pressure increased, with statistical significance(PP>0.05. The postoperative CMT of two groups significantly decreased, data of the observation group at 1, 3mo after treatment was evidently lower than that of the control group, there was statistical significance(PP>0.05. In the observation group, 5 cases(5 eyesrecurred within 6mo, the recurrence rate was 17%. In the control group, 10 cases(10 eyesrelapsed, the recurrence rate was 33%, the difference was statistically significant(PCONCLUSION: Compared with laser therapy alone, intravitreal injection of ranibizumab combined with laser therapy has a significant and safe short-term treatment effective for DME patients with a fast visual acuity recovery.

Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study.

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Herbst, Roy S; Redman, Mary W; Kim, Edward S; Semrad, Thomas J; Bazhenova, Lyudmila; Masters, Gregory; Oettel, Kurt; Guaglianone, Perry; Reynolds, Christopher; Karnad, Anand; Arnold, Susanne M; Varella-Garcia, Marileila; Moon, James; Mack, Philip C; Blanke, Charles D; Hirsch, Fred R; Kelly, Karen; Gandara, David R

2018-01-01

EGFR antibodies have shown promise in patients with advanced non-small-cell lung cancer (NSCLC), particularly with squamous cell histology. We hypothesised that EGFR copy number by fluorescence in-situ hybridisation (FISH) can identify patients most likely to benefit from these drugs combined with chemotherapy and we aimed to explore the activity of cetuximab with chemotherapy in patients with advanced NSCLC who are EGFR FISH-positive. We did this open-label, phase 3 study (SWOG S0819) at 277 sites in the USA and Mexico. We randomly assigned (1:1) eligible patients with treatment-naive stage IV NSCLC to receive paclitaxel (200 mg/m 2 ; every 21 days) plus carboplatin (area under the curve of 6 by modified Calvert formula; every 21 days) or carboplatin plus paclitaxel and bevacizumab (15 mg/kg; every 21 days), either with cetuximab (250 mg/m 2 weekly after loading dose; cetuximab group) or without (control group), stratified by bevacizumab treatment, smoking status, and M-substage using a dynamic-balancing algorithm. Co-primary endpoints were progression-free survival in patients with EGFR FISH-positive cancer and overall survival in the entire study population. We analysed clinical outcomes with the intention-to-treat principle and analysis of safety outcomes included patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (number NCT00946712). Between Aug 13, 2009, and May 30, 2014, we randomly assigned 1313 patients to the control group (n=657; 277 with bevacizumab and 380 without bevacizumab in the intention-to-treat population) or the cetuximab group (n=656; 283 with bevacizumab and 373 without bevacizumab in the intention-to-treat population). EGFR FISH was assessable in 976 patients and 400 patients (41%) were EGFR FISH-positive. The median follow-up for patients last known to be alive was 35·2 months (IQR 22·9-39·9). After 194 progression-free survival events in the cetuximab group and 198 in the control

Orthotopic glioblastoma stem-like cell xenograft model in mice to evaluate intra-arterial delivery of bevacizumab: from bedside to bench.

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Burkhardt, Jan-Karl; Hofstetter, Christoph P; Santillan, Alejandro; Shin, Benjamin J; Foley, Conor P; Ballon, Douglas J; Pierre Gobin, Y; Boockvar, John A

2012-11-01

Bevacizumab (BV), a humanized monocolonal antibody directed against vascular endothelial growth factor (VEGF), is a standard intravenous (IV) treatment for recurrent glioblastoma multiforme (GBM), that has been introduced recently as an intra-arterial (IA) treatment modality in humans. Since preclinical models have not been reported, we sought to develop a tumor stem cell (TSC) xenograft model to investigate IA BV delivery in vivo. Firefly luciferase transduced patient TSC were injected into the cortex of 35 nude mice. Tumor growth was monitored weekly using bioluminescence imaging. Mice were treated with either intraperitoneal (IP) or IA BV, with or without blood-brain barrier disruption (BBBD), or with IP saline injection (controls). Tumor tissue was analyzed using immunohistochemistry and western blot techniques. Tumor formation occurred in 31 of 35 (89%) mice with a significant signal increase over time (p=0.018). Post mortem histology revealed an infiltrative growth of TSC xenografts in a similar pattern compared to the primary human GBM. Tumor tissue analyzed at 24 hours after treatment revealed that IA BV treatment with BBBD led to a significantly higher intratumoral BV concentration compared to IA BV alone, IP BV or controls (pmouse model that allows us to study IA chemotherapy. However, further studies are needed to analyze the treatment effects after IA BV to assess tumor progression and overall animal survival. Copyright © 2012 Elsevier Ltd. All rights reserved.

Bilateral Acute Angle-closure after Intraocular Surgery.

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Hoskens, Kirsten; Pinto, Luis Abegão; Vandewalle, Evelien; Verdonk, Nancy; Stalmans, Ingeborg

2014-01-01

We report the case of a 75-year-old woman who developed an acute bilateral angle-closure associated with choroidal effusion a day after an uneventful cataract surgery. The same patient had undergone a similarly uneventful cataract surgery two weeks before, under the same protocol, with no postoperative complication in the other eye. Medical treatment, including the use of oral sulfamide-related drugs (acetazolamide), topical beta-blockers and steroids led to a gradual decrease in intraocular pressure (IOP) and choroidal effusion. Despite initial reports suggesting a link between sulfamide-exposure and these rare forms of angle-closure, our report would suggest a more complex pathophysiology behind this intriguing phenomenon. How to cite this article: Hoskens K, Pinto LA, Vandewalle E, Verdonk N, Stalmans I. Bilateral Acute Angle-closure after Intraocular Surgery. J Curr Glaucoma Pract 2014;8(3):113-114.

The value of [{sup 11}C]-acetate PET and [{sup 18}F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab

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Li, Shuren; Ubl, Philipp; Wadsak, Wolfgang; Mitterhauser, Markus; Rainer, Eva; Haug, Alexander; Hacker, Marcus [Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Vienna (Austria); Peck-Radosavljevic, Markus; Pinter, Matthias [Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Vienna (Austria); Wang, Hao [Chinese Academy of Medical Sciences, Peking Union Medical College, Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing (China); Nanoff, Christian [Medical University of Vienna, Institute of Pharmacology, Vienna (Austria); Kaczirek, Klaus [Medical University of Vienna, Department of Surgery, Vienna (Austria)

2017-09-15

This prospective study was to investigate the value of [{sup 11}C]-acetate PET and [{sup 18}F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab). Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [{sup 11}C]-acetate PET and [{sup 18}F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively. The patient-related sensitivity of [{sup 11}C]-acetate PET, [{sup 18}F]-FDG PET, and combined [{sup 11}C]-acetate and [{sup 18}F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [{sup 11}C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC. Our study suggests that combining [{sup 18}F]-FDG with [{sup 11}C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information. (orig.)

Changes of intraocular pressure in different trimesters of pregnancy among Syrian refugees in Turkey: A cross-sectional study.

Science.gov (United States)

Tolunay, Harun Egemen; Özcan, Sait Coşkun; Şükür, Yavuz Emre; Özarslan Özcan, Deniz; Adıbelli, Fatih Mehmet; Hilali, Neşe Gül

2016-06-01

To evaluate the physiologic changes in intraocular pressure associated with pregnancy in healthy Syrian refugee women in Turkey. In this cross-sectional study, intraocular pressures were measured using a Goldmann tonometer in 235 patients in the first, second, and third trimester of pregnancy and puerperium among Syrian refugees in Turkey. Mean intraocular pressures values of the right eye were 15.5±2.5 mmHg, 14.4±1.4 mmHg, 13.9±1.6 and 14.7±1.9 mmHg in the three trimesters and puerperium, respectively. Mean intraocular pressures values of the left eye were 15.3±1.6 mmHg, 14.3±1.4 mmHg, 13.9±1.6 and 15.3±2.2 mmHg in the three trimesters and puerperium, respectively. The mean intraocular pressures values measured from both eyes were significantly higher in first trimester and puerperal period than in the third trimester (p<0.001). Changes in the intraocular pressure in pregnancy are common and temporary. This study shows the baseline changes in the intraocular pressure during pregnancy in healthy women. Therefore, we cannot extrapolate the results to the whole eye. A decrease in intraocular pressures was shown in healthy pregnant women.

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...

INTRAOCULAR TRANSMISSIBLE VENEREAL TUMOR IN A DOG TUMOR VENÉREO TRANSMISSÍVEL INTRA-OCULAR EM CÃO

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Geórgia Nadalini Rodrigues

2001-02-01

Full Text Available Canine transmissible venereal tumor (TVT is a round cell neoplasm occurring on the external genital mucosa of male and female dogs. Transmission is by cell implantation during coitus, licking, or other interaction between an affected dog and a susceptible host. Metastasis of the tumor rarely occurs. This report describes an unusual presentation of TVT with intraocular involvement and inguinal lymph nodes metastasis. The subject was a six-year-old, intact, male, Brazilian Terrier dog with a history of abnormal masses in the right eye, penis and several subcutaneous nodules in the inguinal area. Histopathological examination of the eye specimens as well as cytologic examination of penile mass and subcutaneous nodules revealed similar findings. The examination revealed round cells containing a large nuclei with prominent, central located nucleoli and a pale cytoplasm containing few small, clear round vacuoles. Histologically, the subcutaneous nodules in the inguinal area were lymph nodes. The diagnosis of TVT with intraocular involvement and lymph nodes metastasis was based on clinical, cytologic and histopathologic findings.Tumor venéreo transmissível (TVT é uma neoplasia de células redondas que acomete a mucosa genital externa de cães, machos e fêmeas. A transmissão decorre da implantação de células tumorais durante o coito, brigas ou interações entre animais portadores e susceptíveis. Existem relatos referindo-se a localizações atípicas do TVT, mas metástases raramente ocorrem. O presente relato descreve um caso incomum de TVT, com acometimento intra-ocular e metástases nos linfonodos ingüinais, num cão Terrier Brasileiro, com seis anos de idade. O animal apresentava massas anormais de tecido no olho direito, extremidade do pênis e aumento de volume de linfonodos da região ingüinal. A histopatologia do globo ocular e as citologias da massa peniana e dos nódulos subcutâneos evidenciaram aspectos citológicos semelhantes

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

MO19390 (SAiL): bleeding events in a phase IV study of first-line bevacizumab with chemotherapy in patients with advanced non-squamous NSCLC.

Science.gov (United States)

Dansin, Eric; Cinieri, Saverio; Garrido, Pilar; Griesinger, Frank; Isla, Dolores; Koehler, Manfred; Kohlhaeufl, Martin

2012-06-01

The clinical benefit and safety profile associated with first-line bevacizumab with doublet chemotherapy in patients with advanced non-squamous non-small cell lung cancer (NSCLC) was established in two large phase III studies, E4599 and AVAiL. SAiL, a single-arm phase IV study, was conducted to evaluate bevacizumab with a range of first-line chemotherapy regimens in a routine oncology practice setting. This analysis of the SAiL data was undertaken to specifically evaluate bleeding adverse events (AEs) in this study, and to explore potential associations between bleeding and baseline patient and disease characteristics. In total, 2212 patients were evaluated. Bleeding AEs (any grade) occurred in 38.2% of patients (grade ≥ 3 bleeding AEs: 3.6%). Grade ≥ 3 pulmonary hemorrhage and central nervous system bleeding events were observed in 0.7% and 0.1% of patients, respectively. The incidence of grade ≥ 3 bleeding AEs was comparable across patient subgroups defined by central tumor location, tumor cavitation, histology, concomitant anticoagulation therapy and age. The majority (88.6%) of bleeding events resolved or improved, 10.2% persisted and 1.3% led to death; 10.2% of bleeding events required bevacizumab interruption or discontinuation. This analysis from the SAiL trial reaffirms a comparable incidence of clinically significant bleeding associated with first-line bevacizumab and chemotherapy as previous phase III studies in NSCLC patients despite less stringent first-line selection criteria. Grade ≥ 3 bleeding appears to be comparable when analyzed for patient and tumor characteristics, including tumor cavitation and concomitant anticoagulation therapy. Most bleeding events resolved or improved, and interruption/discontinuation of bevacizumab was infrequent in a standard oncology practice setting. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.