Archives
Infections inflammation and corneal transplant can all
Infections, inflammation, and corneal transplant can all cause corneal neovascularization via upregulation of inflammatory cytokines, which attract myeloid isoprenaline receptor into the cornea. These myeloid cells establish a cycle of cytokine secretion and further myeloid cell recruitment in the cornea. There are significant alterations in multiple cytokines which increase the inflammatory status of cornea and lead to corneal neovascularization.230, 52 In human herpes simplex virus-1 (HSV-1) infection, the HSV-1 migrates from the initial infection site of cornea to the trigeminal ganglia, where it lies dormant. The virus replication cycle is reactivated upon stress and immunosuppression, during which the virus travels back to the corneal epithelial surfaces via the trigeminal nerve, which leads the elevation of VEGF-A and matrix metalloproteinase levels, and reduced the expression of antiangiogenic soluble VEGF receptor-1 (sFlt-1).139, 298 Matrix metalloproteinases are secreted by the neutrophils recruited through inflammatory cytokines, and they contribute to corneal neovascularization by degrading the remaining little amount of sFlt-1 produced.
Clinical assessment of corneal neovascularization
An essential requirement for evaluating the efficacy of any potential treatment for corneal neovascularization and performing clinical trials is the ability to grade and quantify corneal neovascularization before and after intervention (Fig. 2). Numerous modalities have been employed to evaluate corneal neovascularization. Historically, the most common method is to examine photographic images of corneas taken by slit lamp biomicroscopy,34, 65, 89, 90 but more advanced imaging techniques have been developed.169, 74, 82, 93
Biomicroscopic examination of corneal neovascularization is limited by inconsistent vessel delineation from frequently coexisting corneal opacification, poor standardization, and the inability to perform quantitative measurements (Fig. 2). Additionally, it is difficult to distinguish afferent from efferent vessels visually even with the aid of the patient's pulse.240, 58 Therefore, ancillary techniques were needed for the clinical characterization of corneal neovascularization. This was recognized by Bron and Easty, who in the 1970s used angiography to study corneal neovascularization in more than 250 patients. As acknowledged by these authors, relying solely on clinical assessment with biomicroscopic photography to estimate vessel leakage is unreliable; therefore, improved imaging techniques that make identification of small vessels more evident are essential.
Angiography using fluorescein or indocyanine green is an objective tool to measure corneal neovascularization.9, 148 Both techniques allow the characterization of corneal neovascularization (Fig. 2) based on the assessment of both morphological parameters (such as diameter, length tortuosity, area, and so forth) and functional parameters (such as flow and time to leakage) that are indicators of vessel maturity and disease activity.9, 238, 261, 264 With angiography, the anatomy of the marginal corneal and limbal vascular arcades can be elucidated, which is important for assessing the progression of corneal neovascularization and limbal disorders. Angiography, even in the presence of exudate and scarring, allows precise detection of the afferent stems of the vessel, which is helpful for guiding surgical treatment of corneal neovascularization.261, 264 Therefore, angiography provides an objective evaluation of corneal neovascularization to plan surgical treatment and monitor treatment responses. In addition, digital subtraction analysis of corneal angiograms depicts and characterizes clinically invisible corneal lymphatic new vessels. The in vivo depiction of corneal lymphatic vessels is of great importance as peristalsis has been shown that lymphatic, rather than hematic, corneal new vessels are the primary mediators of immunological graft rejection in vascularized corneas.117, 79