Corneal Neovascularisation

Corneal neovascularisation is the growth of new blood and lymphatic vessels into the avascular cornea, driven by hypoxia, inflammation and an imbalance between pro angiogenic factors (vascular endothelial growth factor, fibroblast growth factor, interleukin-1) and anti-angiogenic factors (pigment epithelium derived factor, endostatin).

• Causes: contact lens overwear (hypoxia), infectious keratitis (herpetic stromal keratitis, bacterial, fungal), chemical and thermal burns, limbal stem cell deficiency, trachoma, graft rejection, ocular cicatricial pemphigoid, Stevens-Johnson syndrome, atopic and vernal disease, rosacea, and corneal degenerations.
• Types: superficial (arising from limbal arcades, branched, ends in an arcade) and deep stromal (straight, from the ciliary vessels, can be ghost vessels, empty).
• Consequences: reduced vision, lipid keratopathy, stromal scarring, oedema, and loss of immune privilege, raising the risk of graft rejection (high risk graft bed: vessels in 2 or more quadrants).

• Redness, photophobia, reduced vision, contact lens intolerance.
• Vessels extending 1 mm or more beyond the limbus, in one or more quadrants, with stromal haze, lipid deposition, oedema or scarring.
• Associated features of the underlying cause (infiltrate, ulcer, limbal ischaemia, pannus).

• Slit lamp: depth, extent, quadrants, calibre, activity, associated lipid. Fluorescein or indocyanine green angiography of the anterior segment for vessel mapping and activity.
• Anterior segment OCT angiography where available; corneal photography for monitoring (area of neovascularisation).
• Identify cause: culture and PCR for infection, ocular surface assessment, contact lens review.

• Treat the cause: stop or modify contact lenses (higher oxygen permeability silicone hydrogel, reduced wear), treat infection, control inflammation, reconstruct the ocular surface.
• Topical corticosteroids reduce active inflammatory neovascularisation: prednisolone acetate 1 percent four times daily or loteprednol 0.5 percent four times daily for 2 to 4 weeks, then taper; watch pressure and infection.
• Anti-VEGF therapy: topical bevacizumab 1 percent (10 mg/mL) four times daily for 2 to 4 weeks, or subconjunctival bevacizumab 2.5 mg (0.1 mL of 25 mg/mL) every 4 weeks, or ranibizumab. Regression of 30 to 50 percent of the vessel area; effect is partial and recurrence common after stopping. Avoid in thin or melting corneas and in epithelial defects.
• Occlusion of mature vessels: fine needle diathermy, argon laser photocoagulation (green or yellow, 100 to 200 micrometres, 0.1 to 0.2 seconds, 200 to 400 mW), and photodynamic therapy with verteporfin 6 mg/m2 intravenous followed by laser at 15 minutes.
• Pre-keratoplasty therapy: subconjunctival bevacizumab 1 to 2 weeks before surgery, systemic immunosuppression, and tissue matching in high risk grafts.
• Topical ciclosporin 0.05 percent twice daily as a steroid sparing agent.
• Follow every 2 to 4 weeks until stable. Lipid keratopathy may require keratoplasty.