Prospective Study to Determine the Effect of Subconjunctival Bevacizumab (AVASTIN) in Corneal Neovascularization

Corneal Neovascularization Clinical Trial

Official title:

Prospective Study to Determine the Effect of Subconjunctival Bevacizumab (AVASTIN) in Corneal Neovascularization

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00555594
• Other study ID #: Cornea2
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: November 7, 2007
• Last updated: November 7, 2007
• Start date: September 2006
• Est. completion date: October 2007

Study information

• Verified date: November 2007
• Source: Asociación para Evitar la Ceguera en México
• Contact: n/a
• Is FDA regulated: No
• Health authority: Mexico: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

To determine the effect of subconjunctival Bevacizumab in corneal neovascularization

Description:

Corneal transplantation is the most commonly performed transplant surgery in the world today. Immunologic rejection is the leading cause of graft failure, with about 25% of graft recipients experiencing at least one episode of rejection. Of these episodes, about 20% are irreversible. The rate of corneal graft rejection in high-risk eyes, such as corneal neovascularization, has been reported to be 50% to 70%. Vascularized corneas have a much higher rate of graft rejection than avascular corneas. Whereas the normal cornea is devoid of blood and lymphatic vessels, both can invade the cornea secondary to a variety of corneal diseases and after surgery. This not only reduces visual acuity, but also renders such a cornea high-risk, if subsequent corneal transplantation is performed.Anti-angiogenesis, the pharmacologic inhibition of new blood vessel growth and formation, is a new treatment strategy under active and vigorous investigation. Multiple growth factors have been shown to contribute to the molecular events involved in the regulation of blood vessel growth Similarly, it is assumed that angiogenic growth factors such as vascular endothelial growth factor (VEGF), considered a major pro-angiogenic factor, could play a role in the pathogenesis of neovascularization.

Several approaches can be taken to neutralize VEGF. Bevacizumab (Avastin) is a full-length humanized murine monoclonal antibody against the VEGF molecule.It binds to and inhibits the biologic activity of human VEGF preventing the interaction of this molecule to its receptors on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial cell proliferation and new vessel formation.

There is evidence that triamcinolone acetonide (TA) inhibits vasogenic edema and inflammation, decreases vascular leakage, reduces the secretion of VEGF by pigment epithelial cells during oxidative stress and, down-regulates the expression of the VEGF gene in vascular smooth muscle cells Furthermore, TA decreases the paracellular permeability of cultured epithelial cells and down-regulates the inflammatory expression of endothelial adhesion molecules.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Presence of vessels in minimum one quadrant

2. vessels that penetrate more than 0.5 mm of the limb, in any depth

3. who had signed the informed consent

4. those that could attend to frequent ophthalmologic revisions after treatment and could wait for 6 months before the surgical procedure.

Exclusion Criteria:

1. Patients with urgent need of a penetrating keratoplasty, pregnancy or lactancy

2. Patient that may need an additional procedure to penetrating keratoplasty.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Corneal Neovascularization
• Neovascularization, Pathologic

Intervention

Drug:
• Bevacizumab (Avastin)
One dose of 0.1cc of subconjunctival Bevacizumab was applied

Locations

Country	Name	City	State
Mexico	Asociación Para Evitar la Ceguera en México, IAP, Hospital "Dr. Luis Sánchez Bulnes"	Mexico City

Sponsors (3)

Lead Sponsor	Collaborator
Asociación para Evitar la Ceguera en México	National Council of Science and Technology, Mexico, Universidad Nacional Autonoma de Mexico

Country where clinical trial is conducted

Mexico, 

References & Publications (10)

Ciardella AP, Donsoff IM, Guyer DR, Adamis A, Yannuzzi LA. Antiangiogenesis agents. Ophthalmol Clin North Am. 2002 Dec;15(4):453-8. Review. — View Citation

Cursiefen C, Seitz B, Dana MR, Streilein JW. [Angiogenesis and lymphangiogenesis in the cornea. Pathogenesis, clinical implications and treatment options]. Ophthalmologe. 2003 Apr;100(4):292-9. German. — View Citation

Foulks GN, Sanfilippo F. Beneficial effects of histocompatibility in high-risk corneal transplantation. Am J Ophthalmol. 1982 Nov;94(5):622-9. — View Citation

Foulks GN, Sanfilippo FP, Locascio JA 3rd, MacQueen JM, Dawson DV. Histocompatibility testing for keratoplasty in high-risk patients. Ophthalmology. 1983 Mar;90(3):239-44. — View Citation

Gan L, Fagerholm P, Palmblad J. Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in the regulation of corneal neovascularization and wound healing. Acta Ophthalmol Scand. 2004 Oct;82(5):557-63. — View Citation

Kuwano M, Fukushi J, Okamoto M, Nishie A, Goto H, Ishibashi T, Ono M. Angiogenesis factors. Intern Med. 2001 Jul;40(7):565-72. Review. — View Citation

Kvanta A, Sarman S, Fagerholm P, Seregard S, Steen B. Expression of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in inflammation-associated corneal neovascularization. Exp Eye Res. 2000 Apr;70(4):419-28. — View Citation

Manzano RP, Peyman GA, Khan P, Carvounis PE, Kivilcim M, Ren M, Lake JC, Chévez-Barrios P. Inhibition of experimental corneal neovascularisation by bevacizumab (Avastin). Br J Ophthalmol. 2007 Jun;91(6):804-7. Epub 2006 Dec 19. — View Citation

Norrby K. In vivo models of angiogenesis. J Cell Mol Med. 2006 Jul-Sep;10(3):588-612. Review. — View Citation

Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, Ferrara N. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997 Oct 15;57(20):4593-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anterior segment slit-lamp photographs and fluorescein angiograms Compared for any sign of diminished vascularization		three weeks after treatment