Testing Intravitreal Toxicity of Bevacizumab (Avastin)

Ophthalmic Surgery, Lasers, and Imaging, 2012

BACKGROUND AND OBJECTIVE: To evaluate a minimally invasive injector for intravitreal and subconjunctival administration of medications.

Eye, 2009

Introduction The aim of this study was to report the incidence and management of acute endophthalmitis after intravitreal injection of Avastin (bevacizumab), and visual acuity outcomes of three eyes of three patients who developed acute endophthalmitis following intravitreal injection of Avastin. Methods This clinical retrospective, non-comparative study included 3022 intravitreal injections of 1.25 mg bevacizumab consecutively performed for 1822 eyes with exudative age-related macular degeneration and other retinal diseases. Of 3022 injections, 1200 were reinjections. After clinical appearance of post-injection endophthalmitis, immediate intervention was performed, including injection of intravitreal antibiotics and early pars plana vitrectomy. Results Three eyes of three patients with acute postoperative endophthalmitis were identified in the first week following intravitreal injections of 1.25 mg bevacizumab. Among of these patients, two cases were culture-positive and one case was culture-negative. Compared with presenting visual acuities, all of three patients improved at the end of follow-up time. The overall incidence rate of post-injection culture-proven endophthalmitis was 0.066%. Discussion Acute culture-proven endophthalmitis is still a potential complication of intravitreal bevacizumab injection (approximately 0.066%) despite using maximal sterile techniques. Acute post-injection endophthalmitis following intravitreal bevacizumab occurs rapidly and can result in severe loss of vision. Prompt recognition and treatment are key in maximizing outcomes in patients who developed endophthalmitis after intravitreal injection of bevacizumab.

Acta Ophthalmologica Scandinavica, 2007

Purpose: This study aimed to assess the pharmacodynamic profile of intravitreal bevacizumab in relation to best corrected visual acuity (BCVA), foveal thickness, and other aspects of macular morphology after intravitreal injection of bevacizumab in eyes with subretinal choroidal neovascularization (CNV). Methods: A retrospective observational, uncontrolled case series including 26 eyes in 25 patients followed for up to 6 months after intravitreal injection of bevacizumab 1 mg repeated as deemed necessary after monthly assessments by biomicroscopy, optical coherence tomography, colour fundus photography, fluorescein angiography and BCVA determination. At follow-up, cases were classified by morphological treatment response (reduction or elimination of pathological neovascular leakage, retinal thickening or serous retinal detachment) or absence of response (deterioration or lack of improvement). Primary disease entities included age-related macular degeneration (22 eyes, four of which had evidence of retinal angiomatous proliferation), idiopathic peripapillary neovascularization (one eye), and angioid streaks (three eyes in two patients). Results: One month after the first injection, apparent morphological improvement was observed in 24 ⁄ 26 eyes and mean BCVA had improved by 3.1 ± 7.8 letters (p ¼ 0.05). Of these 24 responders, which included all primary diagnoses, 11 (46%) demonstrated BCVA improvement of ‡ 5 letters. The two nonresponders (7.7%) had lost > 3 lines of vision at 2 months follow-up. Overall, 18 eyes completed 6 months follow-up, with a mean BCVA improvement of 0.5 ± 12.7 letters, and 22 eyes completed 3 months follow-up, with a mean BCVA improvement of 2.0 ± 11.0 letters. Two months after the first injection, 11 (46%) of the 24 responders demonstrated signs of recurrent CNV activity, defined as decreased BCVA and ⁄ or increased retinal thickness and ⁄ or fluorescein angiographic CNV leakage. No serious drug-related adverse events were observed during the course of the study. Conclusions: Overall mean BCVA remained stable throughout the study. Morphological signs of reduced CNV activity were seen in the majority of eyes at 2-4 weeks after intravitreal bevacizumab injection. Half the responders showed signs of renewed CNV activity at 2 months after their first injection. All firstinjection responders were also second-injection responders.

Bioengineering, 2022

Ocular drug delivery remains the focus of much modern research. Primary routes of administration include the surface, the intravitreal space, the subretinal space, and the subconjunctival space, each with its own series of unique challenges, limitations, and advantages. Each of these approaches requires careful consideration of the local anatomy, physical barriers, and key cells as well as the interface between the anatomy and the drug or drug system being delivered. While least invasive, the topical route poses a challenge with the many physical barriers that prevent drug penetration into the eye; while injection into the intravitreal, subretinal, and subconjunctival spaces are direct and targeted but limited due to the many internal clearance mechanisms and potential for damage to the eye. Polymeric-based, sustained-release drug delivery systems have been identified as a potential solution to many of these challenges; however, the design and successful implementation of a sustaine...

Expert Opinion on Emerging Drugs, 2006

Age-related macular degeneration (AMD) is a leading cause of blindness that until recently had no recognised drug treatment. In wet AMD, choroidal neovascularisation (CNV) causes a profound loss of central vision. CNV is a complex process in which tissue ischaemia and/or inflammation is thought to trigger production of angiogenic signal molecules. The release of VEGF appears to be particularly important. Verteporfin photodynamic therapy was the first drug therapy to be licensed for the treatment of some types of wet AMD. Other treatments directly targeting VEGF or other aspects of angiogenesis, such as pegaptanib, ranibizumab and anecortave acetate, have either recently been licensed or are in the advanced stages of development. These and other promising treatment options such as combination strategies are reviewed.

European Journal of Ophthalmology, 2009

Purpose. To evaluate the use of preoperative intravitreal bevacizumab (IVB) injection in patients undergoing pars plana vitrectomy for complications of proliferative diabetic retinopathy (PDR). Methods. In this prospective surgeon-masked randomized clinical trial, 40 eyes of 40 diabetic patients who were candidates for vitrectomy were randomly assigned to receive 2.5 mg IVB 3-5 days before operation (injected group) or no injection before operation (noninjected group). A preoperative complexity score (CS) was recorded. Best-corrected visual acuity, number of endodiathermy applications, backflush needle applications, duration of surgery, and postoperative vitreous hemorrhage were recorded. results. Twenty-two patients with a CS of 6±0.95 in the injected group and 18 patients with a CS of 5.7±1.1 in the noninjected group (p=0.3) were studied. Postoperative visual acuities were significantly better than preoperative visual acuities. Preoperative and 3-month postoperative visual acuities were the same for both groups; however, in the last follow-up examinations (mean 7± 3.6 months) the injected group had better visual acuities than the noninjected group (1.1±0.4 and 1.4±0.3 logMAR, respectively, p=0.006). Mean surgical time was 62±57.3 minutes in the injected group vs 95.5±36 minutes in the noninjected group (p=0.03): endodiathermy applications 6.0±4.3 vs 11.0±5.8 (p=0.004), backflush cannula applications 11.0±7.2 vs 18.1±7.8 (p=0.004). In non-silicone-filled eyes, no patient in the injected group developed significant postoperative vitreous hemorrhage obscuring the fundus details, while 7 eyes of noninjected eyes had this complication (p=0.01). ConClusions. IVB injection before vitrectomy for PDR facilitates the surgery, and may decrease the rate of postoperative vitreous hemorrhage and improve the visual acuity results of the operation.

Frontiers in Pharmacology, 2018

Introduction: Uveitis is an eye disease characterized by inflammation of the uvea and an early and exhaustive diagnosis is essential for its treatment. The aim of our study is to assess the potential toxicity and anti-inflammatory efficacy of Bevacizumab in an experimental uveitis model by subcutaneously injecting lipopolysaccharide into Lewis rats and to clarify its mechanism. Material and Methods: Blood-aqueous barrier integrity was assessed 24 h after endotoxin-induced uveitis (EIU) by analyzing two parameters: cell count and protein concentration in aqueous humors. Histopathology of all eye structures was also studied. Enzyme-linked immunosorbent analyses of the aqueous humor samples were performed in order to calculate the diverse chemokine and cytokine protein levels and oxidative stress-related markers were also evaluated. Results: The aqueous humor's cellular content significantly increased in the group treated with only Bevacizumab, but it had no effect on retina histopathological grading. Nevertheless, the inflammation noted in ocular structures when administering Bevacizumab with endotoxin was mostly prevented since aqueous humor cell content considerably lowered, and concomitantly with a sharp drop in uveal, vitreous, and retina histopathological grading. The values of the multi-faceted cytokine IL-2 also significantly decreased (p < 0.05 vs. endotoxin group), and the protective IL-6 and IL-10 cytokines values rose with related anti-oxidant system recovery (p < 0.05 vs. endotoxin group). Concurrently, some related M1 macrophage chemokines substantially increased, e.g., GRO/KC, a chemokine that also displays any kind of protective role. Conclusion: All these results revealed that 24 h after being administered, Bevacizumab treatment in EIU significantly prevented inflammation in various eye structures and correct results in efficacy vs. toxicity balance were obtained.

Cochrane Database of Systematic Reviews, 2014

Background Neovascular age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly populations of industrialised countries. Bevacizumab (Avastin®) and ranibizumab (Lucentis®) are targeted biological drugs (a monoclonal antibody) that inhibit vascular endothelial growth factor, an angiogenic cytokine that promotes vascular leakage and growth, thereby preventing its pathological angiogenesis. Ranibizumab is approved for intravitreal use to treat neovascular AMD, while bevacizumab is approved for intravenous use as a cancer therapy. However, due to the biological similarity of the two drugs, bevacizumab is widely used off-label to treat neovascular AMD.

European Journal of Ophthalmology, 2007

Purpose To investigate the 6-month safety and clinical outcomes of intravitreal injections of bevacizumab administered to treat choroidal neovascularization secondary to age-related macular degeneration. Methods Twenty-seven patients underwent 1.25 mg intravitreal injections of bevacizumab at baseline. A similar intravitreal injection was administered to all eyes at 1 and 2 month follow-up visits. At baseline and at each follow-up visit (1, 2, 3, and 6 months), patients underwent best-corrected visual acuity (BCVA) measurement, fluorescein angiography, indocyanine green angiography, and optical coherence tomography. Laboratory testing, visual field analyses, and endothelial cell counts were performed at baseline and third and sixth months. Results At 3 months, the mean BCVA remained substantially stable at 20/100. Mean central retinal thickness (CRT) decreased from 373 to 279 μm (p&lt;0.01). Mean lesion greatest linear dimension (GLD) decreased from 4087 to 3782 microns (p&lt;0.01)....