Strategies for Management of Corneal Neovascularisation

Overview

The cornea is the transparent window of the eye, which allows light to enter into the eye and also contributes to the focusing of the light rays. One of the major factors responsible for its transparency is the lack of blood vessels. However, following inflammation new blood vessels (corneal vascularisation \[CVas\]) grow into the cornea affecting its transparency and impairing vision. CVas leads to further damage in the form of scarring,oedema,fat deposition and is a major cause of corneal graft rejection. In 2000 with ethical approval (OY129801) the investigators developed and published a clinical technique called Fine Needle Diathermy occlusion of corneal vessels (FND). This has proven very successful for occluding established vessels and is practiced in many centers across the world. Recently it has been demonstrated that by inhibiting a chemical stimulant of vessel formation called vascular endothelial growth factor(VEGF) active new vessel growth in the retina can be suppressed. The approach is also being used for corneal new vessels. Bevacizumab (Avastin) is a chemical inhibitor of VEGF and is used extensively to treat retinal new vessels in macular degeneration. Avastin has been shown to be effective and safe in treating corneal new vessels. The investigators propose to evaluate the efficacy and safety of FND alone and FND combined with Avastin in treatment of CVas.

Corneal neovascularisation is a very common problem affecting both sexes at all ages and induced by differing underlying causes. It is considered to be the single most important risk factor for graft rejection. The process of angiogenesis, i.e. the formation of new blood vessels, is similar in any part of the body. Hence principles adopted to alleviate new blood vessels in one area can be applied to blood vessels in other areas using similar drugs. Over the past 8 years a component necessary for angiogenesis, i.e Vascular endothelial growth factor (VEGF) has been targeted to induce regression of blood vessels in patients with cancer with an intravenous dosage of an anti-VEGF. More recently, anti-VEGF therapies have targeted eye related neovascularisation, especially in the treatment of age related macular degeneration. This role has been expanded to include all other structures in the eye affected by angiogenesis such as neovascular glaucoma(Iris) and diabetic retinopathy(Retina). Over the past few years attention has been drawn to the use of antiVEGF therapies to the surface of the eye. Many reports in international peer reviewed literature have commented on the use of anti VEGF therapy in the form of drops or injections on the surface of the eye, subconjunctivally and within the cornea. They have found drops and injections are safe, although injections appear to act more favourably. Avastin has been investigated for treating corneal new vessels and was proved to be both safe and effective. Fine needle diathermy (FND) is a routine method for occluding corneal vessels that was developed in our department in 2000 and is used worldwide. It has been established that this technique is suitable for active and mature vessels. However, the consequent transient tissue injury and inflammation can trigger further new vessel formation. Avastin is effective in occlusion of the active vessels only.It does not affect the established mature vessels. Hence if FND is combined with Avastin it is expected and hypothesized that a more efficient and lasting occlusion of vessels will be obtained. In this study, the investigators aim to investigate the combined action of Avastin and fine needle diathermy in occlusion of corneal vessels. The actual incidence of corneal neovascularisation in the UK is unknown but American studies suggest up to 1.4 million people are affected with sight threatening complications on annual basis. These blood vessels arise from a multitude of causes, including viral infections, corneal injuries, chronic inflammation and as a result of corneal transplantation. Conventional therapies at the present time include surgical occlusion of the blood vessels with a diathermy or laser or chronic use of steroids. The latter option is a associated with potential sight threatening complications such as glaucoma. This study will generate data to inform further controlled studies towards establishing Avastin and fine needle diathermy as the treatment of choice for corneal new vessels.