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

2. 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

3. 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

4. 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 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

5. 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

6. 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