Consensus statement on indications for anti-angiogenic therapy in the management of corneal diseases associated with neovascularisation: outcome of an expert roundtable

Abstract

The cornea is the clear window at the front of the eye and is the eye's main refractive medium. Its transparency is essential for vision. Corneal neovascularisation is a common clinical problem with serious consequences for vision; it can compromise corneal transparency and plays a major role in corneal graft rejection by breaching corneal immune privilege. In this review, we formulate a consensus on the unmet medical needs in the management of corneal neovascularisation and outline a framework for the clinical research that is needed to identify suitable agents to meet these needs.

Sunitinib Inhibits Inflammatory Corneal Lymphangiogenesis

“…Thus, such a corneal neovascularization (NV) can occur in several pathologic conditions such as hypoxia, infections (e.g., Herpes Simplex Virus, Chlamydia trachomatis), trauma, or keratoplasty, leading to reduced visual acuity. 7 NV, in particular lymphangiogenesis, is also the major factor leading to cornea graft rejection occurring after keratoplasty. 8 The VEGF family members are generally considered as the main regulators of lymph/angiogenesis through the binding to their receptors, the VEGFRs.…”

“…Although bevacizumab was approved by Food and Drug Administration (FDA) for cancer and AMD treatment, 13 and several molecules including anti-VEGF antibodies and tyrosine kinase inhibitors have been demonstrated to efficiently inhibit corneal NV in mice models, [14][15][16] no treatment specifically targeting lymph/angiogenesis is available to treat corneal NV. 7 Corneal NV is currently treated with corticosteroids, which control inflammatory reaction and display antilymph/angiogenic properties, but their effects are limited and are associated to adverse effects. 7,17 In the present work, we evaluated the impact of sunitinib on corneal NV.…”

“…7 Corneal NV is currently treated with corticosteroids, which control inflammatory reaction and display antilymph/angiogenic properties, but their effects are limited and are associated to adverse effects. 7,17 In the present work, we evaluated the impact of sunitinib on corneal NV. Sunitinib is a multi-target tyrosine kinase inhibitor able to inhibit VEGFRs, platelet-derived growth factor receptor (PDGFR), c-kit and ret, and has already been approved by FDA for the treatment of metastasic renal cell carcinomas and gastro intestinal stromal tumors that are resistant to imatinib.…”

Emerging techniques to treat corneal neovascularisation

“…Most pathological processes of the cornea that lead to vascularisation can be assigned to one of the three main categories: hypoxic (mainly contact lens wear), inflammatory (eg, infectious keratitis or corneal graft rejection), and loss of limbal barrier function (limbal stem cell deficiency, for instance, due to aniridia). [21][22][23] Presence of aberrant vessels in turn increases corneal oedema and leads to lipid deposition, haemorrhage, and scarring, further compromising corneal transparency and visual acuity. 24 Neovascularisation also increases the rate of failure and rejection of corneal grafts.…”

“…Such studies are warranted to confirm safety and efficacy of these anti-VEGF treatment for corneal neovascularisation, with inhibition of corneal neovascularisation having been proposed as a clinically relevant endpoint. 23 The only antiangiogenic compound for corneal neovascular disease, which has reached a controlled clinical testing, is an antisense oligonucleotide, designed to inhibit the expression of insulin receptor substrate-1 (IRS-1). 85 IRSs are cytosolic adaptor proteins involved in the organisation of growth hormone and cytokine receptor signalling.…”