MedPath

Subconjunctival Aflibercept (EYLEA®) for the Treatment of Corneal Neovascularization

Phase 1
Terminated
Conditions
Corneal Neovascularization
Interventions
Registration Number
NCT02797704
Lead Sponsor
Rabin Medical Center
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
6
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
SC AfliberceptAfliberceptThe 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
Primary Outcome Measures
NameTimeMethod
Regression (change from baseline) of neovascularization clinically assessed by a corneal specialist3 months (90 days), with repeat assessment at different follow up times at 7,14,30,60 and 90 days.

Regression of corneal neovascularization as the change from baseline will be assessed at all follow-up times on days 7,14,30,60,90 following injection by the corneal specialist, both by a clinical slit lamp exam to evaluate the area of neovascularization from the entire corneal area (which will be determined clinically by the ophthalmologist), and by performing anterior segment color photography before injection and at the last visit for comparison and documentation purposes.

Secondary Outcome Measures
NameTimeMethod
Best Corrected Visual Acuity (BCVA)3 months

BCVA will be assessed using a Snellen Chart at all follow-up meetings, and converted to logMAR for statistical analysis.

Trial Locations

Locations (1)

Rabin Medical Center

🇮🇱

Petah Tikva, Israel

© Copyright 2025. All Rights Reserved by MedPath