Age-related macular degeneration (AMD) is intimately associated with visual impairment, considered as the leading cause of vision loss in elderly people.(1–3) Indeed, it is reported that 9% of all cases of blindness are related to the progression of this disease.(4) AMD frequency accompanies the advancing age and is known to be a progressive and degenerative disease in the macula.(1, 5) It is estimated that around 200 million people are affected with AMD worldwide, and with the phenomenon of aging in the entire world, the prevalence of this disease may increase in a near future.(3–6) Allied with the increased life expectancy, there are other risk factors identified such as environmental factors, obesity, atherosclerosis, smoking, genetic background, metabolic and functional factors.(2, 7)
AMD can be divided into early, intermediate, and late stages. The early and intermediate stages are mainly asymptomatic and represent about 90% of cases.(6–8) Late AMD is classified into two main types, which are non-vascular or dry (atrophic) AMD and neovascular (wet or exudative) AMD, and is the main cause of AMD visual impairment.(2, 4, 5, 8) AMD diagnosis and grading are based on color fundus examination in people ages 50 years and older.(9) There are some differences to be aware of between both main types of AMD, where non-advanced AMD is characterized by typical focal drusen with a whitish-yellow localized between retinal pigment epithelium and bruch membrane (BrMb). On the other hand, wet AMD is known to present neovascularization within the macula.(10)
AMD pathogenesis is not fully understood yet but some studies are starting to elucidate the underlying process behind the appearance of this disease.(8, 10, 11) Both non-vascular and neovascular AMD are related to a dysfunction and/or death of all constituents of the photoreceptor/retinal pigment epithelium (RPE)/BrMb/choriocapillaris (CC) complex, as they are working in combination. The development of each type of AMD seems to be associated with the location where initiating events start to disenroll.(11) Non-vascular AMD development is characterized, in the beginning, by a formation of large confluent drusen and hyperpigmentation, which can be underlined by RPE dysfunction, carrying a risk for the appearance of geographic atrophy.(11, 12) On the other hand, neovascular AMD is associated with an initial loss of choroidal vasculature, which will affect the photoreceptor/RPE/BrMb/CC complex and, appears to be underlined by a reduction in blood supply, induced by stenosis of large vessels. An inflammatory environment establishes with an accumulation of proinflammatory cytokines, promoting the progression of AMD.(11, 13) RPE remains intact however, due to the stenosis observed in large vessels, it becomes hypoxic and starts to release angiogenic substances, including vascular endothelial growth factor (VEGF), stimulating the formation of new vessels from CC, denominated as choroidal neovascularization.(11)
Taking into account the underlying process behind the development of neovascular AMD, its current pharmacological treatment is characterized by intravitreal administrations of molecules specifically targeted to VEGF.(4, 14) Additionally, the drugs currently accepted by the regulatory authorities, for the treatment of this condition are, for example, pegaptanib, ranibizumab, aflibercept, and brolucizumab.(4, 8) Also, it has been reported the off-label use of bevacizumab in the treatment of neovascular AMD, which is a drug commonly used in oncology, and more specifically, in the treatment of metastatic colorectal cancer, breast and lung cancers.(2, 4, 14) Indeed, some authors have shown a positive influence of intravitreal administrations of bevacizumab in cases of neovascular AMD, allied with a lower cost for the community in comparison with other drugs currently used, for example, ranibizumab.(2, 14, 15) Therefore, given the rise in bevacizumab use in neovascular AMD, it would be interesting to evaluate, more specifically, its long-term influence on the development and progression of this disease. In this sense, this study aims to evaluate the use of bevacizumab in the treatment of neovascular AMD, through the analysis of its efficacy, safety, and efficiency profiles from data present in clinical studies made, with special emphasis in long-term results.