*Retina Division, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland †Retina-Vitreous Associates Medical Group, Los Angeles, California ‡VitreoRetinal Surgery, PA, Minneapolis, Minnesota §Genentech, South San Francisco, California.
: To analyze cerebrovascular accidents (CVAs) pooled from large, randomized, controlled clinical trials of ranibizumab treatment for neovascular age-related macular degeneration.
: Events in five trials (FOCUS, MARINA, ANCHOR, PIER, and SAILOR) were analyzed using a standard safety monitoring process. Exact methods, stratified by study, were used to test for treatment differences based on odds ratios. A stepwise logistic regression model was fit to classify subjects' risk for CVA based on medical history. Treatment differences in CVA rates at 1 year or 2 years were evaluated within risk groups using stratified exact methods.
: Pooled 2-year CVA rates were <3%; odds ratios (95% confidence intervals) for CVA risk were 1.2 (0.4-4.4) for ranibizumab 0.3-mg versus control, 2.2 (0.8-7.1) for 0.5 mg versus control, and 1.5 (0.8-3.0) for 0.5-mg versus 0.3-mg ranibizumab. No substantial increased risk of CVA for 0.5 mg versus 0.3 mg was identified in pooled analyses or any of the individual trials. In pooled analyses, the difference between 0.5-mg ranibizumab and control was larger (7.7 [1.2-177]) among high-risk CVA patients.
: This analysis provided some evidence, although not definitive, of a potential increased risk of CVA with ranibizumab versus control or with 0.5-mg versus 0.3-mg ranibizumab. Continued monitoring for CVA within clinical trials seems warrented.
"Despite both studies incorporating patients with a prior history of cardiovascular disorders and concluding no significant difference in the incidence of such adverse events, their findings were deemed inconclusive due to their insufficient sample sizes [29, 30]. Alongside this, the safety concerns regarding this anti-VEGF agent have been augmented following studies noting that it may potentially increase the risk of stroke . "
[Show abstract][Hide abstract] ABSTRACT: Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly population worldwide and is defined as a chronic, progressive disorder characterized by changes occurring within the macula reflective of the ageing process. At present, the prevalence of AMD is currently rising and is estimated to increase by a third by 2020. Although our understanding of the several components underpinning the pathogenesis of this condition has increased significantly, the treatment options for this condition remain substantially limited. In this review, we outline the existing arsenal of therapies available for AMD and discuss the additional role of further novel therapies currently under investigation for this debilitating disease.
[Show abstract][Hide abstract] ABSTRACT: Ranibizumab (Lucentis®), an inhibitor of multiple vascular endothelial growth factor A isoforms, is approved for the intravitreal treatment of neovascular (wet) age-related macular degeneration (AMD). In clinical trials in patients with neovascular AMD, monthly or less frequent injections of ranibizumab were effective in the treatment of predominantly classic choroidal neovascularization (CNV) and minimally classic or occult CNV lesions. Ranibizumab has a well-established safety profile, and is associated with low rates of ocular and systemic serious adverse events. In head-to-head comparisons, the efficacy of monthly bevacizumab was equivalent to monthly ranibizumab at 1 and 2 years, individualized treatment with bevacizumab was equivalent to individualized treatment with ranibizumab at 1 and 2 years, and bimonthly aflibercept was noninferior to monthly ranibizumab at 1 year. These trials were not powered to detect between-treatment differences in safety.
[Show abstract][Hide abstract] ABSTRACT: Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. The retina at the macula thickens and this can cause gradual loss of central vision. Grid or focal laser photocoagulation is effective in treating DMO and has been used for several years, but vision is rarely improved. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) modalities has recently been proposed to try to improve vision in people with DMO. Anti-VEGF drugs are delivered by an injection in the vitreous cavity of the eye and need to be repeated for maintenance. We included 11 studies in this review comparing intravitreal antiangiogenic therapy with sham, laser photocoagulation or investigating its effect when added to photocoagulation. About one in five or seven more people gained a good amount of vision, i.e. 3 lines, using antiangiogenic therapy compared with laser, using seven to 10 intraocular injections in the first year, and two in the second year. Little is known about treatment needs beyond this term. Two related UK-based economic evaluations disagreed on whether ranibizumab was cost-effective compared with laser photocoagulation. The evaluation finding ranibizumab not cost-effective was revised while this review was being updated, leading the UK National Institute of Health and Clinical Excellence (NICE) to recommend ranibizumab for patients with visual impairment and more severe oedema on optical coherence tomography. Antiangiogenic treatment was well tolerated in these studies, but since all studies were short- or medium-term, we were unable to investigate long-term effects as well as risks.
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