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Anti-vascular Endothelial Growth Factor Pharmacotherapy in the Treatment of Subretinal Choroidal Neovascularization

Published Online: June 21st 2012 US Ophthalmic Review, 2012;5(2):107–10 DOI: http://doi.org/10.17925/USOR.2012.05.02.107
Authors: Yoreh Barak, Mark A Ihnen, Shlomit Schaal
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Abstract:
Overview

Vascular endothelial growth factor (VEGF) plays a pivotal role in stimulating the growth of pathologic subretinal choroidal neovascularization (CNV). The increased production of VEGF and subsequent CNV formation can occur in degenerative, inflammatory, and vascular diseases of the retina and choroid, often leading to severe visual impairment. Anti-VEGF agents which are readily available today are much better, more potent, and longer acting in comparison with previous treatment modalities, and therefore have dramatically improved the prognosis of patients with CNV. There are four intravitreal anti-VEGF pharmacotherapies proven by large prospective, multicenter, randomized trials to be effective in the treatment of age-related macular degeneration (AMD)-related CNV: pegaptanib (Macugen®, Eyetech Pharmaceuticals, Palm Beach Gardens, FL), ranibizumab (Lucentis®, Genentech, Inc., South San Francisco, CA), bevacizumab (Avastin®, Genentech, Inc., South San Francisco, CA), and VEGF Trap-Eye (Eylea® Regeneron, Tarrytown, NY). However, there are still many challenges and unanswered questions regarding the optimal anti-VEGF pharmacotherapy agent, the best clinical treatment regimen, the most effective dosage, the optimal injection frequency, and the duration of treatment. The heavy burden of frequent injections on the elderly patient population and physicians begs for a simpler way of drug administration or development of more potent compounds.

Keywords

Vascular endothelial growth factor, subretinal choroidal neovascularization, age-related macular degeneration, pegaptanib, ranibizumab, bevacizumab, VEGF Trap-Eye

Article:

Intravitreal anti-vascular endothelial growth factor (VEGF) pharmacotherapy, introduced in 2004,1 has evolved over the last decade to revolutionize the treatment of patients suffering from subretinal choroidal neovascularization (CNV). Anti-VEGF agents, which are readily available today, are much better, more potent, and longer acting in comparison with previous treatment modalities, and therefore have dramatically improved the prognosis of patients with CNV.

Patients losing vision secondary to CNV, such as patients suffering from exudative age-related macular degeneration (AMD), can now expect stabilization and even improvement of their visual acuity, as opposed to the slow and certain visual deterioration that was the rule before the anti-VEGF era.2–6

Vascular Endothelial Growth Factor
VEGF is a diffusible cytokine that promotes angiogenesis and increases vascular permeability. It is a product of a gene family that plays an important role in normal development and angiogenesis.7 The influence of VEGF in retinal diseases is profound. This dimeric glycoprotein of approximately 40 kDa is upregulated in response to hypoxia. It plays a pivotal role in stimulating abnormal growth of pathological new blood vessels in the adult retina and choroid. VEGF is also a potent inducer of vascular permeability and leakage that can lead to retinal edema and thickening.8,9

There is mounting evidence that increased VEGF expression is associated with pathologic CNV.7 CNV, a form of abnormal blood vessel growth which emerges from choroidal vessels, penetrates Bruch’s membrane and grows below the retinal pigment epithelium (RPE) space and into the subretinal space.10 Figure 1 shows the different stages of growth of a subretinal choroidal membrane in response to VEGF stimulation. The increased production of VEGF and subsequent CNV formation can occur in degenerative, inflammatory, neoplastic, traumatic, hereditary, and idiopathic diseases of the retina and choroid. The most commonly encountered conditions associated with CNV are AMD and pathologic myopia. AMD is the leading cause of irreversible vision loss among the elderly population in the Western world.11

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Disclosure

The authors have no conflicts of interest to declare.

Correspondence

Shlomit Schaal, MD, PhD, 301 E Muhammad Ali Boulevard, Louisville, KY 40202, US. E: s.schaal@louisville.edu

Received

2011-10-29T00:00:00

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