Bevacizumab and corneal patology Marijana Bilen Babić Department of Ophthalmology, Clinical Hospital Center Rijeka, Croatia Maja Merlak No Financial Interest

Corneal neovascular disorders Purpose review of the current literature on anti-vascular endothelial growth factor (anti -VEGF) bevacizumab therapy for corneal neovascular disorders cornea is unique avascular, immunoprivileged connective tissue that acts as transparent mechanical barrier and the anterior eye refractive surface corneal neoangiogenesis affects about 1.4 million people a year corneal neovascularizations (NV) are caused by chronic corneal ischemia with pathological ingrowths of perylimbal plexus blood vessels into the cornea NV cause scarring of the cornea, compromising visual acuity and may lead to inflammation and edema pathological conditions that cause corneal neoangiogenesis are chemical burns, ischemia, infections, degeneration, trauma and immune processes

Setting/Venue corneal neovascularization occurs because of pro-angiogenic and antiangiogenic factors disequilibrium VEGF-A is the main regulator of angiogenesis the former treatment of corneal NV does not target the molecular mediators of angiogenesis bevacizumab recognizes all VEGF isoforms studies have demonstrated partial reduction of neovascularization through: topical subconjunctival BEVACIZUMAB APPLICATION intrastromal

Methods Topical bevacizumab application: bevacizumab can be used neovascular corneal disorders in: corneal inflammatory diseases (ocular pemphigoid, graft vs. host) infections traumatic/iatrogenic causes pterygium Topical bevacizumab application: topical 1% (10mg/ml) bevacizumab 4x/day topical (5 mg/ml) bevacizumab for 0.5-12 months (5x/day) 1% topical bevacizumab for 2-4x/day for 3 weeks Subconjunctival bevacizumab application: 2.5 mg/0.1 ml bevacizumab-decrease of NV for 3 months 3 injections of 2.5 mg/0.1 ml bevacizumab-36% recent NV reduction Intrastromal bevacizumab application: 1-2 subconjunctival+intrastromal injections (1.25 mg/0.05 mL) at 1-month intervals deep intrastromal (2.5 mg/1 mL) bevacizumab after deep anterior keratoplasty 31-gauge needle intrastromal 0.01 ml (25 mg/ml) bevacizumab in every affected quadrant

Results bevacizumab is apparently effective only against proliferating new blood vessels subconjunctival bevacizumab application is better for focal, deep and peripheral NV topical bevacizumab apliccation is better for diffuse superficial NV excluding factors for bevacizumab use: pregnancy uncontrolled blood pressure history of heart attack and cerebrovascular accident topical use side effects: corneal epithelial defects and thinning side effects of subconjunctival and intracorneal use are rare in a murine model of corneal transplantation, the reduction of NV was stronger in subconjunctival application and can reduce the rate of rejection with 33% survival of the transplant

Conclusion anti-VEGF agents have created enormous hope for the treatment of corneal neovascularization treatment of corneal NV with anti-VEGF antibody is only symptomatic treatment that does not treat cause of the disorder treatment of corneal NV with anti-VEGF antibody has limits and depends on the size of the scar, durability and range of neovascularization anti-VEGF agents are especially effective when administered early (< 2 weeks in neoangiogenesis) controlled prospective studies are needed to establish long-term safety, efficacy and minimum effective and maximum security concentration of the drug to treat neovascularisation of anterior eye segment