Ranibizumab for the treatment of degenerative ocular conditions

Clinical Ophthalmology, Jun 2014

Ranibizumab for the treatment of degenerative ocular conditions Magdalini Triantafylla,1 Horace F Massa,2 Doukas Dardabounis,1 Zisis Gatzioufas,2 Vassilios Kozobolis,1 Konstantinos Ioannakis,1 Irfan Perente,1,3 Georgios D Panos1,21Department of Ophthalmology, University General Hospital of Alexandroupolis, School of Medicine, University of Thrace, Alexandroupolis, Greece; 2Department of Ophthalmology, Geneva University Hospitals, Faculty of Medicine, University of Geneva, Switzerland; 3Beyoglou Eye Research and Teaching Hospital, Istanbul University, Istanbul, TurkeyAbstract: Degenerative ocular conditions, such as age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, and myopic degeneration, have become a major public health problem and a leading cause of blindness in developed countries. Anti-vascular endothelial growth factor (VEGF) drugs seem to be an effective and safe treatment for these conditions. Ranibizumab, a humanized monoclonal antibody antigen-binding fragment, which inhibits all biologically active isoforms of VEGF-A, is still the gold standard treatment for the majority of these pathological entities. In this review, we present the results of the most important clinical trials concerning the efficacy and safety of ranibizumab for the treatment of degenerative ocular conditions.Keywords: age-related macular degeneration, diabetic macular edema, retinal vein occlusion, anti-VEGF, safety, efficacy, quality of life

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Ranibizumab for the treatment of degenerative ocular conditions

Clinical Ophthalmology Ranibizumab for the treatment of degenerative ocular conditions Magdalini Triantafylla 2 Horace F Massa 1 Doukas Dardabounis 2 Zisis Gatzioufas 1 v assilios Kozobolis 2 Konstantinos ioannakis 2 irfan Perente 0 2 Georgios D Panos 1 2 0 Beyoglou eye Research and Teaching Hospital, istanbul University , istanbul , Turkey 1 Department of Ophthalmology, Geneva University Hospitals, Faculty of Medicine, University of Geneva , Switzerland 2 Department of Ophthalmology, University General Hospital of Alexandroupolis, School of Medicine, University of Thrace , Alexandroupolis , Greece Degenerative ocular conditions, such as age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, and myopic degeneration, have become a major public health problem and a leading cause of blindness in developed countries. Anti-vascular endothelial growth factor (VEGF) drugs seem to be an effective and safe treatment for these conditions. Ranibizumab, a humanized monoclonal antibody antigen-binding fragment, which inhibits all biologically active isoforms of VEGF-A, is still the gold standard treatment for the majority of these pathological entities. In this review, we present the results of the most important clinical trials concerning the efficacy and safety of ranibizumab for the treatment of degenerative ocular conditions. - Introduction to degenerative ocular conditions and their management Age-related macular degeneration The disease was first described by Holloway and Verhoeff in 1929 and has grown to be an important public health problem ever since, with various resources trying to demonstrate the mechanisms being evolved.1–3 As the population ages, the percentage of patients suffering from age-related macular degeneration (AMD) increases rapidly, new therapeutic options are constantly under development, and research focuses on understanding the mechanisms related to the disease and the role of human genetics and environmental risk factors.4 AMD is a multifactorial disease characterized by progressive degeneration of photoreceptors and the retinal pigment epithelium (RPE) in the macular region of the retina, resulting in irreversible central vision loss. It is the leading cause of irreversible vision loss in individuals over 65 years in developed countries.5 In the US alone, over 10 million individuals have AMD, regardless of type. These numbers are projected to increase by 50% over the next 10 years.6 AMD is classified into two types: non-neovascular (dry AMD) and neovascular (wet AMD), with the neovascular form of AMD responsible for the most severe and rapid visual loss, although it is less common, affecting only 10% of AMD patients; it is characterized by choroidal neovascularization (CNV) development. CNV consists of immature new pathological blood vessels growing from the choroid towards the retina, which can leak or exude fluid, causing damage to the retinal layers by separating its structures and resulting in loss of vision. Finally, this disturbance in the architecture of the eye – especially in the fovea – results in scarring, causing permanent loss of vision. Clinical Ophthalmology 2014:8 1187–1198 1187 © 2014 Triantafyl a et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The ful terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php AMD is influenced by genetics as well as environmental factors, such as diet and smoking, which are the most consistent non-genetic risk factors.7,8 Furthermore, hypertension and hyperlipidemia have been associated with AMD as well, and contribute in up to 75% of AMD cases.9–11 Vascular endothelial growth factor-A (VEGF-A) plays a critical role in the pathogenesis of neovascular AMD through its effects on angiogenesis and vascular permeability. Elevated levels of VEGF-A have been found in CNV membranes from patients with AMD.12,13 Ranibizumab targets all VEGF-A isoforms. Thus, this neovascular AMD treatment demonstrates stabilization and even improvement in vision for many patients. Polypoidal choroidal vasculopathy Polypoidal choroidal vasculopathy (PCV) was first identified as a distinct form of wet AMD in 1990 by Yannuzzi et al14 who reported a series of patients with polypoidal, subretinal vascular lesions that cause serous and/or hemrsseep l.yon orrhagic detachment of the RPE and exudative macular .vdo lsue degeneration. Thus, it was described to be an abnormality tt/sphwww rrsopenoaF toyfpteheofcChoNroVi.d1a5–l18vasculature and now represents a separate / : (...truncated)


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Magdalini Triantafylla, Horace F Massa, Doukas Dardabounis, Zisis Gatzioufas, Vassilios Kozobolis, Konstantinos Ioannakis, Irfan Perente, Georgios D Panos. Ranibizumab for the treatment of degenerative ocular conditions, Clinical Ophthalmology, 2014, pp. 1187-1198, DOI: 10.2147/OPTH.S40350