Current treatment options for corneal neovascularization inc

Current treatment options for corneal neovascularization include topical application of steroids220, 25, 35, 43 or surgical interventions: laser ablation,14, 203, 234, 48 photodynamic therapy (PDT),4, 93 and fine-needle diathermy.221, 238, 240, 261 Targeting proangiogenic molecules with topical or subconjunctival use of vascular endothelial growth factor (VEGF) inhibitors such as bevacizumab has been reported. Despite some degree of success, the current treatment options are restricted by adverse effects.23, 143, 145, 175, 236, 279 Gene-based therapy might be able to circumvent these shortcomings and improve the duration of therapeutic effect. The unique anatomical and immune characteristics of the cornea along with the relative ease of access make it an ideal candidate for gene-based therapy; however, gene-based therapies for corneal neovascularization are still largely at the preclinical stage.160, 244, 289, 308, 97 Herein, we provide a comprehensive review on therapeutic target Imiquimod hydrochloride and potential vectors available to treat corneal neovascularization.
Pathophysiology of corneal angiogenesis Clinically, corneal neovascularization is subdivided into 3 groups based on the pattern of angiogenic invasion: 1) superficial neovascularization, new vessels that invade just below the corneal epithelium into the stroma; this is commonly seen in stromal keratitis; 2) vascular pannus involves both the extension of vessels and fibrous tissues onto the peripheral cornea and is mainly seen in ocular surface disorders; and 3) interstitial and deep neovascularization consists of lamina of new vessels in stroma as seen in herpetic and luetic interstitial keratitis. Deep neovascularization is a specific interstitial neovascularization in which there is angiogenesis between the stroma and Descemet membrane.54, 68 The progression of corneal neovascularization is broadly divided into 3 phases: a latent prevascular phase, an active neovascularization phase, and lastly a maturation phase (Fig. 1). Upon exposure to a stimulus such as injury or hypoxia, the corneal epithelium, leukocytes, pericorneal blood vessels, and extracellular matrix release angiogenic growth factors that bind to receptors on the vascular endothelial cells of pericorneal vessels. These vessels dilate, their permeability increases, and leukocytes migrate into the surrounding corneal stroma, resulting in inflammatory edema and opacification. Subsequently, these endothelial cells are “activated,” characterized by decreased cell junction integrity and degradation of the endothelial lamina.136, 172, 245 Matrix metalloproteinases released by endothelial cells and migrating leukocytes degrade the surrounding extracellular matrix, paving the way for invasion and proliferation of vascular endothelial cells. This is followed by the endothelial cell migration toward the angiogenic stimulus source. The endothelial migration and proliferation from parent vascular structures is facilitated by altered expression of adhesive proteins, such as integrins and selectins, and cytoskeletal reorganization. Finally, the formation of vascular lumen and anastomosis ensues as supporting pericytes are recruited, marking the maturation of vessels do not require the stimulus of proangiogenic factors for survival.
Cause of corneal neovascularization A wide range of clinical conditions can cause corneal neovascularization. Most of these conditions induce corneal neovascularization via 3 broad pathological mechanisms: hypoxia, inflammation, and limbal barrier dysfunction. Hypoxia, one of the pathological mechanisms that drives corneal neovascularization, is commonly seen in contact lens use. Contact lens use is the leading cause of corneal neovascularization in the USA, and 20% of contact lens users suffer from corneal neovascularization. Contact lenses reduce by 8%–14% of the oxygen delivered to the cornea, and this hypoxic condition leads to the downregulation of antiangiogenic factors (e.g., pigment epithelium–derived factor [PEDF]) and an upregulation of angiogenic factors (principally VEGF, mediated by hypoxia-inducible factor 1-alpha), initiating the neovascularization process to deliver oxygen to the hypoxic cornea.168, 230