**2. Pathophysiology**

Angiogenesis is a complex processs. First, inflammatory mediators trigger vasodilation and increase vascular permeability of limbal and conjunctival vasculature. Vascular endothelial growth factor (VEGF) is one of the most important regulators of corneal angiogenesis. It is produced primarily by macrophages, T cells, and smooth muscle cells in ocular surface.

A second important regulator of corneal neovascularization is basic fibroblast growth factor (bFGF) and the third important signal is platelet aggregation factor (PAF). Others include insulin like growth factor, integrins, transforming growth factor, tumor necrosis factor and matrix metalloproteinase.

Corneal neovascularization can be prevented by various anti angiogenic factors that have been identified in the cornea. Angiostatin, a proteolytic fragment of plasminogen prevents neovascularization and also induces regression of existing vessels. This has been identified in chronic contact lens user where it suppresses the angiogenic stimuli of hypoxia. Second antiangiogenic factor is endostatin which is a proteolytic fragment of collagen XVIII inhibits bFGF and VEGF stimulated corneal neovascularization. Third naturally occurring antiangiogenic factor is pigment epithelium derived growth factor (PEDF) which is a serine protease inhibitor and inhibits bFGF stimulated corneal neovascularization.

Corneal neovascularization most frequently results from corneal oxygen deprivation, or hypoxia. In response to this hypoxia, the body attempts to provide necessary nutrients and oxygen to the deprived corneal tissues by the creation of new blood vessels. During the early stages, this abnormal growth of blood vessels may produce no signs at all, or it may

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Transport humoral and cellular elements of immunological defence and raw material

Corneal neovascularization is one of the main risk factor for immune rejection after corneal transplantation. Healthy cornea is devoid of blood vessels and is said to be immune privileged. When corneal grafts are placed into an avascular recipient corneal bed (*low risk keratoplasty*) the two year survival rate approaches 90% under cover of

The survival rates of corneal grafts placed over vascularized recipient beds (*high risk keratoplasty*) decrease significantly. Even in low risk setting, mild angiogenesis develops after keratoplasty and increase risk of immune graft rejection. For this reason aggressive treatment of neovascularization may be necessary prior to corneal transplant surgery to

Various antiangiogenic agents may be used in management of post keratoplasty graft

Corticosteroids and systemic immunosuppression remain an important aspect in prevention of post keratoplasty graft rejection. Corticosteroids inhibit macrophages that release growth

 Contact lens intolerance Decreased vision

Repair and regeneration

Eliminates toxic substances

Sensitization to other antigen

Graft rejection in keratoplasty

It can also lead to blindness

ensure lower risk of graft rejection.

Vascular endothelial growth factor inhibitor

Angiostatic steroids

 MMP inhibitor COX-2 inhibitor Antioxidants

Protein kinase c inhibitor

Dietary derived inhibitor

Intrastromal/subepithelial bleeding

**4.3 Complications**  Corneal edema Corneal opacity

Lipid keratopathy

**5. Management** 

steroids.

rejection:

**4.1 Advantages of neovascularization** 

Carry antibiotic and drugs to site of infection

**4.2 Disadvantages of neovascularization**  Interfere with corneal transparency Graft rejection and failure in keratoplasty

cause a variety of symptoms, including eye pain and excessive tearing, light sensitivity, redness, intolerance to contact lenses, and decreased vision.
