Application of antivascular endothelial growth factors in diseases of anterior segment of an eye

Y.A. Dyomin, P.V. Biletska


Proangiogenic growth factors, mainly VEGF (vascular endothelial growth factor) play a significant role in anterior segment diseases, characterized by neovascularization. Newly grown vessels in the cornea can lead to an impairment of its transparency and visual acuity. Under physiologic conditions the cornea has the unique feature of being avascular, actively maintained by expression of antiangiogenic and antilymphangiogenic factors. Under pathologic conditions, vessels invade the cornea form the limbal vascular plexus. Corneal neovascularization (NV) is a final pathway common to numerous ocular insults and disorders such as infection, inflammation, ischemia, degeneration, loss of the limbal stem cell barrier and trauma. An impaired visual acuity is not the only negative result of newly grown corneal vessels. Corneal NV leads to the loss of the immune privilege of the cornea. The result is a worsening of the prognosis of penetrating keratoplasty being a major cause for corneal graft rejection. On the other hand, various risk factors have been shown to be associated with an increased likelihood of corneal NV after penetrating keratoplasty. The classic treatment (steroids, non-steroid anti-inflammatory agents, laser photocoagulation, fine-needle diathermy, photodynamic therapy and restoration of the ocular surface with the use of conjunctival, limbal or amniotic membrane transplantation) is often ineffective, requiring multiple treatment sessions. Last few years the rapid progress in angiogenesis research has led to the development of several novel, specific antiangiogenic drugs for use in both oncology and ophthalmology. A major focus of the research into antiangiogenic therapy is vascular endothelial growth factor (VEGF), which is known to promote several steps in angiogenesis, including proteolytic activities, endothelial cell proliferation, endothelial cell migration and capillary tube formation. Neovascularization of the iris (rubeosis iris’s) and the anterior chamber angle are caused by ischemic retinopathies, usually leading to neovascular glaucoma with serious loss of vision. Neovascular glaucoma is a potentially devastating glaucoma, where delayed diagnosis or poor management can result in complete loss of vision or, quite possibly, loss of the globe itself.

Retinal ischemia is the most common and important mechanism in most cases that result in the anterior segment changes causing neovascular glaucoma. The disease management usually attempts to control the ocular ischemia, aiming at a regression of the iris rubeosis. Panretinal photocoagulation is the only routine treatment of choice. However, it often takes several weeks to induce neovascular regression. During this period, progressive angle closure and optic nerve damage may occur as a result of the elevated intra-ocular pressure. VEGF levels are indirectly reduced after panretinal photocoagulation in patients with ischemic retinal disorders. However, panretinal photocoagulation alone is not successful in halting iris 
neovascularization in every patient, especially those with severe and rapid neovascular progression. VEGF is an important regulator of pathological neovascularization of the iris in patients with neovascular glaucoma secondary to proliferative vasculopathies. A pterygium is characterized, amongst others, by fibrovascular proliferation and may have vision threatening consequences if left untreated. Many growth factors, amongst them VEGF, chemically stimulate angiogenesis and have been observed in fibroblastic and inflammatory pterygium cells. It has been suggested that not only an overexpression of VEGF, but also the absence of angiogenesis inhibitors plays a decisive role in the pathogenesis of pterygium. Several antiangiogenic drugs have evolved in the last decade, mainly used for the treatment of neovascularization in posterior pole.
Though bevacizumab is also widely used off-label, in topic form or as an intracameral injection, to treat anterior segment neovascularization with encouraging results.


corneal neovascularization, ocular anterior segment, rubeosis iris’s, neovascular glaucoma, pterygium, VEGF


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