Intraocular Injection Of Bevacizumab Research Articles

Role of bevacizumab intraocular injection in the management of neovascular glaucoma.

To assess the long-term effects of intraocular bevacizumab (Avastin) injections as an adjunctive drug to manage patients with neovascular glaucoma (NVG). A retrospective study was conducted consisting of 34 eyes with secondary NVG caused by proliferative diabetic retinopathy (n=25), ischemic central retinal vein occlusion (n=8), and retinal ischemia resulting from persistent detachment (n=1) were managed by intraocular injections of bevacizumab (1.25 mg/0.05 mL), in addition to other treatments. The main outcome measure was the change in the degree of iris neovascularization. Secondary outcomes included intraocular pressure and the number of additional interventions or antiglaucoma medications administered after injection. All patients were followed-up for at least 12mo. At the last follow-up, complete regression of rubeosis irides was detectable in 13 (38.2%) eyes and incomplete regression in 21 eyes (61.8%). The mean intraocular pressure was 45.32±7.185 mm Hg at baseline and significantly decreased to 26.15±5.679 mm Hg at the last follow-up visit (P=0.000005). Patients received an average of 4.97 injections. As additional treatments, 12 eyes (35%) received laser photocoagulation and 6 eyes (18%) underwent retinocryopexy. No further treatment was needed in 16 eyes (47.1%). Intravitreal bevacizumab injection can have a favorable effect in controlling intraocular pressure and pain control in patients with NVG because it decreases the angiogenesis and helps to augment the results of conventional procedures. The primary cause of retinal ischemia should be always targeted.

Short-Term Changes in Intraocular Pressure After Intravitreal Injection of Bevacizumab for the Treatment of Retinopathy of Prematurity.

PurposeTo evaluate short-term changes in intraocular pressure after intravitreal injection of bevacizumab for retinopathy of prematurity.Patients and methodsThis study was a prospective case-series. Consecutive infants underwent intravitreal injection with bevacizumab for type 1 retinopathy of prematurity at a university hospital. Intraocular pressure was measured with tonometer at baseline, at 1 min, and at 3, 10, 30 and 60 mins after injection.ResultsFive patients (four boys) were enrolled in this study. Mean (± standard deviation) intraocular pressure was 8.0 ± 2.4 mmHg (range: 6–11.5 mmHg) just before the intravitreal injection, and the pressures were 19.8 ± 2.8 mmHg (16.4–23.9 mmHg), 14.6 ± 4.4 mmHg (7.6–18.4 mmHg), 11.2 ± 4.2 mmHg (6.4–16.5 mmHg), 9.3 ± 3.5 mmHg (5.8–13.2 mmHg), and 8.2 ± 1.4 mmHg (6.9–10.0 mmHg) at 1 min, 3, 10, 30 and 60 mins after the injection, respectively. Mean intraocular pressure after 1 min was significantly higher than intraocular pressure before injection (p = 0.02). Pressures decreased between 1 min and 3 mins after intravitreal injection, although there was no statistically significant difference between the pressures at those time-points. Intraocular pressures after 3, 10, 30 and 60 mins were not significantly different from the pressure before injection.ConclusionIntraocular pressure elevation after intravitreal injection of bevacizumab for neonatal infants may be mild, so there may be a limited risk due to intraocular pressure after intraocular injection of bevacizumab for retinopathy of prematurity.

Bevacizumab for the Treatment of Macular Edema

Background: anti-vascular endothelial growth factor (anti-VEGF) has been suggested for the treatment of macular edema. In this study we are assessing the efficacy of one type of anti-vascular endothelial growth factor which is Bevacizumab (Avastin) in the reduction of macular thickness. Patients and Methods: from the period of February 2012 to February 2015, we have gathered the data of 54 patients (39=males, 15 =females) suffering from macular edema who received variable number of intraocular injections of Bevacizumab to be included in a retrospective study. One eye from each patient was chosen randomly and then we observe their follow-up Optical Coherence Tomography (OCT) for any changes in the thickness of the macula. Results: after receiving a single Bevacizumab injection, 16 patients (29.6%) did not show any improvement while 22 (40.7%) patients show an improvement that was less than 50 microns of reduction in magnitude, 5 patients (9.2%) showed an improvement that was greater than 50 microns in reduction of macular thickness and the remaining 11 patients (20.3%) had a reduction of macular thickness that was greater than 100 microns. Conclusion: despite being used originally for metastatic colon cancer, Bevacizumab (Avastin) can be used in the treatment of diabetic macular edema.

Reduced vision caused by choroid osteoma

The authors present a case of choroidal osteoma diagnosed in a 25-year-old female patient. A well-defined and slightly elevated yellow lesion located in the posterior pole of the right eye was suspected to be a tumor. Confirmation of diagnosis was obtained with A and B ecography. The patient had low vision and macular edema, which improved after intraocular injection of bevacizumab .

Bevacizumab treatment of macular edema in CRVO and BRVO: long-term follow-up. (BERVOLT study: Bevacizumab for RVO long-term follow-up).

To assess the efficacy and safety of intraocular injections of bevacizumab in patients with macular edema (ME) following branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). Retrospective, non-comparative case series. Patients ≥18years of age with ME secondary to BRVO or CRVO who received a minimum of one intravitreal injection of bevacizumab with a follow-up >3months were included. Primary endpoints were mean change in best corrected visual acuity (BCVA) from baseline to 12 and 24months, and mean change in central macular thickness (CMT) after 3 injections. Secondary endpoints were mean change in BCVA and CMT from baseline to end of follow-up, number of injections, and ocular adverse events. Eighty-seven eyes with BRVO and 65 eyes with CRVO were included. Mean follow-up time was 24.4 and 26.1months in the BRVO and CRVO groups, respectively. The mean change in BCVA was 0.25 LogMAR in the BRVO group and -0.118 LogMAR in the CRVO group. Visual acuity outcomes in the CRVO group were poorer, especially in patients with low baseline BCVA.

Efficacy and visual prognostic factors of intravitreal bevacizumab as needed for macular edema secondary to central retinal vein occlusion.

PurposeOur aim was to investigate the efficacy and prognostic factors of intraocular injections of bevacizumab as needed in patients with macular edema secondary to central retinal vein occlusion (CRVO).MethodsThis is a retrospective study including 28 eyes of 27 consecutive patients with macular edema due to CRVO and followed for at least 6 months. The mean age of the patients was 66.3 years. The patients underwent an intravitreal injection of bevacizumab (1.25 mg) at the initial visit. Retreatments were performed when macular edema was persistent or worsened (as-needed regimen). The primary outcome measure was the mean change in best-corrected visual acuity (BCVA). The change in central retinal thickness (CRT) was evaluated as the secondary outcome. Finally, the factors useful for predicting BCVA outcome were determined.ResultsThe mean number of injections was 1.8 over a period of 6 months. The mean BCVA (logarithm of minimum angle of resolution) was significantly improved at 1 (−0.097), 3 (−0.14), and 6 months (−0.25) after the initial injection (P<0.05, <0.01, and <0.001, respectively). The mean CRT was also improved significantly at 1 (−250.4), 3 (−150.0), and 6 months (−187.2) (P<0.001 each). Earlier treatment and better improvement in BCVA at 1 month after the initial treatment were the prognostic factors significantly associated with better visual outcomes at 6 months (P=0.047 and 0.029, respectively).ConclusionIntravitreal injection of bevacizumab as needed significantly improved visual acuity and macular edema in CRVO patients. Time before the treatment and early response to the treatment were important factors for the visual outcome.

Thrombotic microangiopathy in a patient with adult-onset Still's disease.

Since there are many disorders that can present with thrombotic microangiopathy (TMA), establishing a correct diagnosis is important to offer the most appropriate therapy. A 26-year-old woman was transferred to our hospital with fragmentation hemolytic anemia, thrombocytopenia, and acute kidney failure. History revealed that she was recently diagnosed with adult-onset Still's disease (AOSD) and received intraocular injections of bevacizumab to treat acute retinal artery occlusion. At our hospital, she underwent extensive investigations and was treated with high-dose steroids, hemodialysis, and therapeutic plasma exchange. For recurrent disease, she received a single dose of eculizumab. The patient's ADAMTS13 activity was normal and she had evidence of complement activation. Genetic testing identified a benign polymorphism in the C3 gene. Pathophysiology of TMA in AOSD is briefly discussed and an overview of the literature is presented. Work-up of a new fragmentation hemolytic anemia and thrombocytopenia should include careful review of past history, including medications, as well as relevant laboratory investigations with aim to establish a correct diagnosis. Occasionally, the correct diagnosis is not the obvious one and there could be multiple contributors to the pathogenesis. Establishing diagnosis is important for counseling patient on disease prognosis and to guide treatment.

M-charts as a tool for quantifying metamorphopsia in age-related macular degeneration treated with the bevacizumab injections

BackgroundThis article is aimed to assess quantitatively metamorphopsia using M-charts in patients suffering from wet age-related macular degeneration (AMD) treated with the intravitreal bevacizumab injections and to compare the results with traditional Amsler grid and ocular coherence tomography (OCT).MethodsThirty-six patients diagnosed with wet AMD were examined one day before and one month after the intraocular injection of bevacizumab. Horizontal and vertical metamorphopsia scores using M-charts, distance visual acuity, Amsler test and OCT were performed at each visit. Additionally, 23 healthy subjects were examined as a control group.Results The rate of metamorphopsia detection was 89% with M-charts and 69% with Amsler test. The horizontal metamorphopsia score improved in 22 patients, the vertical metamorphopsia score improved in 16 patients, the Amsler grid results improved in 6 patients, visual acuity improved in 17 patients. There was no correlation between the degree of metamorphopsia and the visual acuity or the central retinal thickness (CRT). The specificity of both the M-charts and Amsler grid was 100%.ConclusionsThe rate of metamorphopsia detection in wet AMD patients was better with M-charts than with Amsler grid. M-charts may be used in the assessment of efficacy of treatment with intravitreal bevacizumab injections as another outcome measure, moreover they can be used even at home for the self-assessment. M-charts provide additional information concerning the visual function, independent of the visual acuity, CRT and morphological changes in OCT.

Benefit from Bevacizumab for Macular Edema in Central Retinal Vein Occlusion: Twelve-Month Results of a Prospective, Randomized Study

To evaluate the efficacy of intraocular injections with bevacizumab over 12 months in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). A prospective study including a randomized 6-month, sham injection-controlled, double-masked clinical trial followed by a 6-month open-label extension. Sixty patients with ME secondary to CRVO. At baseline, patients were randomized 1:1 to receive intraocular injections of bevacizumab or sham injections every 6 weeks for 6 months. From month 6, all patients received intraocular injections of bevacizumab every 6 weeks for 6 months. The primary outcome measure was the proportion of patients gaining at least 15 letters at 12 months. Secondary outcome measures included mean change from baseline best-corrected visual acuity (BCVA), change in foveal thickness, and development of neovascular glaucoma. At the end of follow-up, 18 of 30 patients (60.0%) in the bevacizumab/bevacizumab (bz/bz) group had gained ≥ 15 letters compared with 10 of 30 patients (33.3%) in the sham/bevacizumab (sh/bz) group (P < 0.05). The BCVA improved by 16.0 letters at 12 months in the bz/bz group compared with 4.6 letters in the sh/bz group (P < 0.05). In an unplanned retrospective analysis, patients aged >70 years had a significantly worse outcome when receiving delayed treatment, losing 1.4 letters (95% confidence interval [CI], -9.7 to 8.4) in the sh/bz group compared with a gain of 20.1 letters (95% CI, 13.9-26.3) in the bz/bz group in patients aged <70 years (P < 0.003). The mean decrease in central retinal thickness (CRT) was 435 μm in the bz/bz group compared with 404 μm in the sh/bz group (P = not significant). No patients developed iris rubeosis during the 6-month open-label extension period. There were no events of endophthalmitis, retinal tear, or retinal detachment during the 12-month treatment period. No serious nonocular adverse events were reported. Intraocular injections of bevacizumab given every 6 weeks for 12 months improve visual acuity (VA) and reduce ME significantly. Patients receiving delayed treatment have a limited visual improvement. Proprietary or commercial disclosure may be found after the references.

Bevacizumab for Macular Edema in Central Retinal Vein Occlusion: A Prospective, Randomized, Double-Masked Clinical Study

To evaluate the efficacy of intraocular injections with bevacizumab in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). Prospective, randomized, sham injection-controlled, double-masked clinical trial. Sixty patients with ME secondary to CRVO. At baseline, patients were randomized 1:1 to receive intraocular injections of bevacizumab or sham injections every 6 weeks for 6 months. The primary outcome measure was the proportion of patients gaining at least 15 letters at 6 months. Secondary outcome measures included mean change from baseline best-corrected visual acuity (BCVA), foveal thickness, and neovascular glaucoma. At the end of follow-up, 18 of 30 patients (60.0%) in the study group had gained ≥15 letters compared with 6 of 30 patients (20.0%) in the control group (P=0.003). The BCVA improved by 14.1 letters at 24 weeks compared with a decrease of 2.0 letters in the control group (P < 0.003). The mean decrease in central retinal thickness (CRT) was significantly greater in the study group (426 μm) than in the control group (102 μm) at all time points up to week 24 (P < 0.001). No residual edema, defined as CRT <300 μm at 24 weeks, was found in 26 of 30 patients (86.7%) in the treatment group compared with 6 of 30 patients (20%) in the control group (P < 0.001). In the sham group, 5 of 30 patients (16.7%) had developed iris rubeosis at week 24. No patients in the study group had rubeosis at week 24 (P=0.052). There were no events of endophthalmitis, retinal tear, or retinal detachment during the 24-week treatment period. No serious non-ocular adverse events were reported. Intraocular injections of bevacizumab given every 6 weeks for 6 months improve visual acuity (VA) and reduce ME significantly compared with sham. Proprietary or commercial disclosure may be found after the references.

Safe Preparation and Administration of Intravitreal Bevacizumab Injections

Three clusters of endophthalmitis after intraocular injection of bevacizumab underscore the importance of sterile compounding by pharmacists.

Adverse events associated with intraocular injections of bevacizumab in eyes with neovascular glaucoma

Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), has been reported to cause rapid regression of anterior segment neovascularization in eyes with neovascular glaucoma when administered intraocularly. Several studies have reported the safety profile of intravitreal injections of bevacizumab in patients with various retinal pathologies. We investigated the occurrence of adverse events associated with intraocular bevacizumab injections in patients with neovascular glaucoma. We retrospectively reviewed the charts of 84 eyes of 70 patients with neovascular glaucoma that received intraocular bevacizumab injections to treat anterior segment neovascularization for the first time at Kanazawa University Hospital. The mean age of the patients was 63.5 ± 13.3years (± standard deviation; range, 31-85years). The underlying retinal diseases were proliferative diabetic retinopathy in 58 eyes (69%), central retinal vein occlusion in 17 eyes (20%), ocular ischemic syndrome in four eyes (5%), central retinal artery occlusion in three eyes (4%), branch retinal vein occlusion in one eye (1%), and radiation retinopathy in one eye (1%). The total number of intraocular injections of bevacizumab was 116 (1.4 ± 0.8 injections/eye, range, one to five injections/eye). Most were intravitreal injections (1.25mg/0.05ml; 115 injections, 99%). No cases had marked inflammation, lens injuries, marked vitreous hemorrhage, retinal detachment, or endophthalmitis. However, two eyes (2%) of two cases (3%) developed central retinal artery occlusion 3 or 4days after bevacizumab injection. Both were among four eyes (i.e., 50%) with ocular ischemic syndrome. One of them had received an intracameral injection of bevacizumab (0.75mg/0.03ml) before the adverse event. No cases experienced systemic side-effects including myocardial infarction and cerebrovascular accidents within 3months after bevacizumab injection. Central retinal artery occlusion may be a relatively common complication following intraocular injection of anti-VEGF agents in patients with neovascular glaucoma, particularly when it was associated with ocular ischemic syndrome. Since visual prognosis of central retinal artery occlusions is usually poor, intraocular injection of anti-VEGF agents should be performed with thoughtful consideration of the risks and benefits of the treatment, and with a strict follow-up examination, especially in high-risk patients.

Anti–Vascular Endothelial Growth Factor Therapy in Glaucoma Filtration Surgery

To examine evidence supporting the use of vascular endothelial growth factor (VEGF) inhibition in controlling wound healing after glaucoma filtration surgery in primary open-angle glaucoma, to identify the optimum method of administration, and to clarify the potential position of anti-VEGF monoclonal antibodies in comparison with 5-fluorouracil and mitomycin C. Perspective based on an overview of evidence from current peer-reviewed literature. Analysis of evidence from animal studies, in vitro studies, human studies, and from the use of anti-VEGF monoclonal antibodies in systemic disease. There is evidence that glaucoma patients have elevated levels of VEGF in the aqueous before filtration surgery, that this increases in animals after filtration surgery, and that both can be suppressed in animals by intraocular injection of bevacizumab. VEGF not only has a role in angiogenesis, but also has a direct action on fibroblast activity that may be modified directly at the time of filtration surgery. There is evidence for a role for VEGF in wound healing after glaucoma filtration surgery. The optimum route of administration and dosing regimen of anti-VEGF antibodies and their positioning in comparison with 5-fluorouracil and mitomycin C are uncertain. There is some evidence that subconjunctival injection may produce sustained intraocular tissue levels. There is also evidence that bevacizumab may act in synergy with 5-fluorouracil. Although there are no direct comparative studies, it seems unlikely that bevacizumab alone will be as effective as mitomycin C, although bleb morphologic features may be better.

Effect of an intravitreal injection of bevacizumab on the expression of VEGF and CD34 in the retina of diabetic rats

To evaluate the efficacy of intravitreal injection of bevacizumab as a preventive intervention of vascular endothelial cell proliferation in the retina of diabetic rats. Fifty-four streptozotocin-induced diabetic Wistar rats were injected intravitreally with 3 µL (25 mg/mL) of bevacizumab into left eyes and 3 µL of saline into the right eyes. Immunohistochemistry and enzyme-linked immunosorbent assays for CD34 and VEGF were used to assess retinal angiogenesis, and transmission electron microscopy was used to evaluate the ultrastructure of retinal capillaries. Retinal expression of VEGF was inhibited 1 week and 1 month after injection (P < 0.01, paired t-test), and the expression of CD34 was not obviously inhibited until 2 months after injection (P < 0.05, paired t-test). Using multiple comparisons between the left eyes of bevacizumab-treated rats, the VEGF expression before injection was higher than at 1 week or 1 month after injection (P < 0.05, Dunnett's t-test), and similar to 2 months after injection (P > 0.05, Dunnett's t-test). The amount of VEGF expression was higher 2 months after injection than 1 week or 1 month after injection, and also higher 1 week after injection compared with 1 month after injection (P < 0.05, Student-Newman-Keuls test). CD34 expression decreased more significantly 2 months after injection compared with before injection, 1 week or 1 month after injection (P < 0.05, Dunnett's t-test). A single intraocular injection of bevacizumab may be beneficial as a therapy for preventing retinal vascular endothelial cell growth in the eyes of diabetic rats.

VASCULAR EVENTS IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION TREATED WITH INTRAOCULAR BEVACIZUMAB

The purpose of this study was to determine the incidence of vascular events in patients treated with intraocular injections of bevacizumab. The subjects were 769 persons (mean age, 79.9 years; range, 47-97 years) from the Barnes Retina Institute in St. Louis. Patients received at least one intraocular injection of bevacizumab for the treatment of neovascular age-related macular degeneration. The study endpoints included myocardial infarction, cerebrovascular accident, thromboembolic disease, new hypertension, bleeding, and death. There were events in 74 patients (9.6%; 95% confidence interval, 7.5-11.7%) over a mean follow-up of 13.2 months (range, 1-23 months). Among other events, 15 patients (2.0%; 95% confidence interval, 1-3%) had a nonlethal myocardial infarction, 27 patients (3.5%; 95% confidence interval, 2.2-4.8%) had an episode of new or increased blood pressure, and 19 patients (2.5%; 95% confidence interval, 1.4-3.6%) died. There was no correlation between the number of bevacizumab injections and incidence of any event. Intraocular bevacizumab may be safe for intraocular use from a systemic standpoint.

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

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 therefore cannot be considered careless, imprudent or unprofessional. We submit that an ophthalmologist who omits to inform a patient of the availability of Avastin for this form of treatment may be found to be negligent. Protocols developed by the South African Vitreoretinal Society and endorsed by the Ophthalmological Society of South Africa for administering Avastin and other intra-ocular medication intravitreally should be strictly adhered to.

Intraocular injection of bevacizumab for rubeosis capsulare in a pseudophakic eye

Intraocular injection of bevacizumab for rubeosis capsulare in a pseudophakic eye

Intraocular injections of bevacizumab in rare indications – two cases

Intravitreal anti-VEGF injections are currently the most effective treatment option for neovascular age-related macular degeneration. The anti-VEGF treatment of other, more common ocular diseases, such as diabetic retinopathy and vascular occlusions with neovascularization and retinal edema, is currently described in numerous studies and cases. Rare neovascular ocular diseases, such as Eales disease, presumed ocular histoplasmosis syndrome (POHS), retinopathy of prematurity, and idiopathic telangiectasia, may be future areas for anti-VEGF therapy. In our case report we describe intravitreal bevacizumab (Avastin) therapy for central serous chorioretinopathy and for pseudoxanthoma elasticum with angioid streaks and choroidal neovascularization. In both cases the intravitreal injection resulted in morphological and functional rehabilitation.

Ranibizumab Combined With Low-Dose Sorafenib for Exudative Age-Related Macular Degeneration

Ranibizumab Combined With Low-Dose Sorafenib for Exudative Age-Related Macular Degeneration

Intraocular Avastin (Bevacizumab) for Neovascularisation of the Iris and Neovascular Glaucoma

The aim of this study was to determine the effectiveness of intraocular injections of bevacizumab for neovascularisation of the iris and neovascular glaucoma. Three patients with neovascularisation of the iris due to various causes were recruited. Patients were treated with intraocular bevacizumab. Neovascularisation of the iris was noted to have completely regressed as early as 3 days after the injection and in all the patients (100%) within 8 days after injection. They were followed up for at least 1 month with no clinical evidence of recurrence. Visual acuity remained stable or improved, and the intraocular pressure was controlled in all the 3 patients' eyes. Vitreous haemorrhage also cleared. No signs of inflammation or complications were observed. Intraocular injection of bevacizumab is effective and safe for patients with neovascularisation of the iris and neovascular glaucoma with or without vitreous haemorrhage.