Subconjunctival Aflibercept (EYLEA®) for the Treatment of Corneal Neovascularization
Subconjunctival Aflibercept (EYLEA®) for the Treatment of Corneal Neovascularization
The goal of this current study is to prospectively evaluate the influence of a single
 subconjunctival aflibercept injection on the regression of corneal neovascularization. Twenty
 patients with corneal neovascularization who are candidates for anti VEGF treatment (by the
 discretion of a corneal specialist) will be included in this study. The patients will be
 treated with a single subconjunctival injection of 0.08 ml aflibercept (25 mg/ml) in a single
 quarter of the conjunctiva, near the limbus in a proximity to the area of pathological
 neovascularization. Regression of neovascularization will be documented.
An interruption of the equilibrium between proangiogenic and antiangiogenic factors in the
 usually nonvascularized cornea causes new corneal vessels to sprout, interfering with the
 corneal clarity that is essential for maintaining normal vision. Treating the neovascularized
 and often scarred cornea remains highly challenging because the loss of immunologic privilege
 in the avascular cornea makes it a poor candidate for corneal transplantation.

 Vascular endothelial growth factor (VEGF) is a key cytokine in the development of both normal
 blood vessels and vessels in tumors and other tissues undergoing abnormal angiogenesis. In
 the cornea, VEGF is one of several known mediators of neovascularization. In recent years,
 anti-VEGF compounds have been extensively investigated for use in the prevention and
 treatment of neovascularization in many tissues, including the cornea. Experimental models
 and clinical studies have reported promising results for such anti-VEGF compounds as
 bevacizumab (Avastin®) and ranibizumab (Lucentis®). Aflibercept is a VEGF-Trap molecule. It
 has the highest affinity of all VEGF blockers studied to date. Aflibercept has been approved
 in the United States and Europe for the treatment of macular degeneration under the trade
 name Eylea® and the treatment of metastatic colorectal cancer under the trade name Zaltrap®.
 It has been found to offer a more prolonged and potentially more potent anti-VEGF effect in
 wet age-related macular degeneration than both bevacizumab and ranibizumab. Aflibercept's
 safety has been proven for this indication.

 A preliminary study in a rat model recently conducted by our group demonstrated that
 subconjunctival (SC) injection and topical administration of aflibercept efficiently
 prevented corneal neovascularization compared to bevacizumab. The aim of this present study
 is to determine aflibercept's efficacy in the treatment of corneal neovascularization in
 humans.

 Goal:

 To prospectively evaluate the influence of a single subconjunctival aflibercept injection on
 the regression of corneal neovascularization.

 Design and Clinical Follow-up:

 A prospective study, including patients with various corneal pathologies complicated by
 corneal neovascularization.

 Twenty patients with corneal neovascularization who are candidates for anti VEGF treatment
 (by the discretion of a corneal specialist) will be included in this study. The patients will
 be treated with a single subconjunctival injection of 0.08 ml aflibercept (25 mg/ml) in a
 single quarter of the conjunctiva, near the limbus in a proximity to the area of pathological
 neovascularization.

 During follow-up period, previous medical and ophthalmic history will be documented. On the
 first visit, a thorough eye examination will be performed (including: Best Corrected Visual
 Acuity (BCVA), slit lamp examination of anterior segment including fluorescein staining of
 cornea for the assessment of epithelial integrity, intraocular pressure (IOP) measurements
 with Goldman tonometry, and a specular microscopy examination). Follow-up examinations will
 occur on days 7, 14, 30, 60, 90 following injection. Each follow-up meeting will include
 documentation of BCVA, IOP, a slit lamp exam and specular microscopy exam. Investigators will
 also perform anterior segment color photography before injection and at the last visit to
 document regression of neovascularization.

 If no improvement or partial improvement is noted on the 30th day follow-up, the cornea
 specialist will consider a repeat subconjunctival aflibercept injection.
Inclusion Criteria:

 In this study, included will be patients with corneal neovascularization secondary to
 various pathologies, including: Pterygium, Corneal chemical burn, S/P corneal
 transplantation, Herpetic keratitis, atopic keratoconjunctivitis, Chronic retinal
 detachment, Uveitis, panus secondary to blepharitis, S/P corneal foreign body.

 Exclusion Criteria:

 1. Patients with a history of retinal vein/artery occlusion or diabetes, currently
 treated with anti-VEGF or with a history of such treatment 3 months prior to
 enrollment.

 2. Prior treatment for corneal neovascularization with the injection of Avastin/Lucentis.

 3. Patients under 18

 4. Pregnant women

 5. Contra indications for Eylea treatment, including intraocular or periocular
 infection/inflammation.