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.
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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)
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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
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