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

September 12, 2019 updated by: Rabin Medical Center

The Effect of Subconjunctival Aflibercept on Regression 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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Petah Tikva, Israel
        • Rabin Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SC Aflibercept
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
Drug: Aflibercept
Eylea (aflibercept) Injection is a prescription medicine administered by injection into the eye.
Other Names:
  • Eylea

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Regression (change from baseline) of neovascularization clinically assessed by a corneal specialist
Time Frame: 3 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.
3 months (90 days), with repeat assessment at different follow up times at 7,14,30,60 and 90 days.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Corrected Visual Acuity (BCVA)
Time Frame: 3 months
BCVA will be assessed using a Snellen Chart at all follow-up meetings, and converted to logMAR for statistical analysis.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rabin Medical Center

Investigators

  • Principal Investigator: Irit Bahar, MD, Head of ophthalmology department

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2017

Primary Completion (Actual)

September 4, 2019

Study Completion (Actual)

September 10, 2019

Study Registration Dates

First Submitted

May 24, 2016

First Submitted That Met QC Criteria

June 10, 2016

First Posted (Estimate)

June 13, 2016

Study Record Updates

Last Update Posted (Actual)

September 16, 2019

Last Update Submitted That Met QC Criteria

September 12, 2019

Last Verified

May 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0134-16-RMC

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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