The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology

Abstract

Vascular endothelial growth factor (VEGF) plays an important role in both physiologic and pathologic angiogenesis and contributes to increased permeability across both the blood-retinal and blood-brain barriers. After 2 decades of extensive research into the VEGF families and receptors, specific molecules have been targeted for drug development, and several medications have received US Food and Drug Administration approval. Bevacizumab, a full-length antibody against VEGF approved for the intravenous treatment of advanced carcinomas, has been used extensively in ophthalmology for exudative age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, retinopathy of prematurity, and other chorioretinal vascular disorders. Pegaptanib and ranibizumab have been developed specifically for intraocular use, whereas the soon-to-be-introduced aflibercept (VEGF Trap-Eye) is moving through clinical trials for both intraocular and systemic use. Although these drugs exhibit excellent safety profiles, ocular and systemic complications, particularly thromboembolic events, remain a concern in patients receiving therapy. Patients experiencing adverse events that may be related to VEGF suppression should be carefully evaluated by both the ophthalmologist and the medical physician to reassess the need for intraocular therapy and explore the feasibility of changing medications. For this review a search of PubMed from January 1, 1985 through April 15, 2011, was performed using the following terms (or combination of terms): vascular endothelial growth factors, VEGF, age-related macular degeneration, diabetic retinopathy, retina vein occlusions, retinopathy of prematurity, intravitreal injections, bevacizumab, ranibizumab, and VEGF Trap. Studies were limited to those published in English. Other articles were identified from bibliographies of retrieved articles and archives of the author.

Neuroprotective Effects of Cilostazol on Retinal Ganglion Cell Damage in Diabetic Rats

“…Indeed, current treatments for DR are mostly intended to block VEGF, by laser treatment and by anti-VEGF drugs (Stewart, 2012). However, VEGF is a survival factor for retinal neurons which are vulnerable to ischemic insult (Nishijima et al, 2007).…”

Subfoveal choroidal thickness changes after intravitreal bevacizumab therapy for central serous chorioretinopathy

“…Since 2005, it has been used in ophthalmology to treat various conditions, including neovascular age-related macular degeneration, diabetic macular edema, retinal vein occlusions, and neovascular glaucoma (26) . Variable outcomes have been reported on the use of bevacizumab in CSC (13,16) , and the mechanism of action of bevacizumab in CSC is unknown.…”

Early Experience with Diode Laser Combined with Systemic Steroid Therapy for Severe Stages of Retinopathy of Prematurity

“…Fundamental initiating process involved in retinal vascular development is angiogenesis which is regulated by growth factors, extracellular matrix components and complex of anti-and pro-inflammatory cytokines, among which IL-6, CRP, IL-17, IL-18, TNFα, TGF-β, BDNF, NT4, PDGF, IGF-I, EGF, FGF, PKC -protein kinase C-and HIF-1 α are recognized as key factors in the development of ROP. They have ability to modulate angiogenesis in ROP and are involved in dysregulation of this pathological phenomenon mainly through up-regulating VEGF messenger RNA synthesis, in response to tissue hypoxia or inflammation [2][3][4]. Additionally, it has been revealed that the so-called Fetal Inflammatory Response (FIRS) is the result of chorioamnionitis, antenatal intrauterine as well as Candida infections which are important agents in pathogenesis of prematurity complications such as sepsis, Periventricular Leukomalacia (PVL), Intraventricular Hemorrhage (IVH), Necrotizing Enterocolitis (NEC) or bronchopulmonary dysplasia [2,3,5,6].…”