Using Aflibercept Injection to Treat Blood Vessel Growth Over the Cornea

Corneal neovascularization is a sight threatening condition and is also a well recognized
risk factor for corneal graft failure. Current standard of care to prevent graft rejection
includes use of topical steroids and immunosuppressants. These do not address corneal
neovascularization. The cornea is kept in its avascular state by a complex interaction of
signal proteins and host receptors, with a vital role played by the soluble VEGF-receptor 1.
In any condition of chronic corneal inflammation or hypoxia, the balance may tip in favour
of pro-angiogenic factors, and neovascularization will ensue. Early and limited studies have
examined the effect of subconjunctival or intracorneal administration of monoclonal
antibodies to VEGF (bevacizumab, ranibizumab) in combating corneal neovascularization. Most
report subtotal or temporary regression. The development of aflibercept (also known as VEGF
Trap-Eye) offers new hope of more effectively combating the problem. In this study, research
will be conducted to investigate and assess safety of subconjunctival aflibercept injection
in patients with corneal neovascularization undergoing corneal transplantation.

This is a phase 1, prospective, randomized, open label clinical trial that will enroll 10
corneal transplant patients with corneal neovascularization in one or more quadrants
crossing more than 0.5 mm over the limbus at the time of corneal transplantation.

Inclusion Criteria:

A patient must meet the following criteria to be eligible for inclusion in the study:

1. Candidates for corneal transplantation (only one eye per patient would be enrolled)

2. Patients with corneal neovascularization in one or more quadrants crossing more than
1.0 mm over the limbus at time of enrollment in the study

3. Willing and able to comply with clinic visits and study-related procedures

4. Provide signed informed consent

5. Age 18 or over

Exclusion Criteria:

A patient who meets any of the following criteria will be excluded from the study:

1. Patients receiving antiangiogenic anti-VEGF medication either systemically or
intravitreally for other pathology or have received these drugs within 3 months of
study enrollment

2. Patients with active corneal infection requiring additional treatment modalities

3. Patients receiving coumadin with INR >2.0, other anti-thrombotic agents (e.g.,
aspirin, Plavix) permitted at discretion of investigator

4. History of cerebrovascular accident or myocardial infarction within 6 months prior to
study enrollment

5. Uncontrolled blood pressure- defined as SBP>160 mmHg or DBP >95mmHg while patient is
sitting

6. Pregnant or breast-feeding women

7. Sexually active men* or women of childbearing potential** who are unwilling to
practice adequate contraception during the study (adequate contraceptive measures
include stable use of oral contraceptives or other prescription pharmaceutical
contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device
[IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam,
or jelly, or diaphragm plus contraceptive sponge, foam, or jelly) *Contraception is
not required for men with documented vasectomy. **Postmenopausal women must be
amenorrheic for at least 12 months in order not to be considered of child bearing
potential. Pregnancy testing and contraception are not required for women with
documented hysterectomy or tubal ligation.