September 2009

 

OPHTHALMOLOGY NEWS

 

Quelling new corneal blood vessel growth


by Maxine Lipner Senior EyeWorld Contributing Editor

   

Topical drops help to shrink blood vessel size

Short-term use of topical Avastin (bevacizumab, Genentech, South San Francisco, Calif.) can help to stem the tide of corneal neovascularization, according to Reza Dana, M.D., professor of ophthalmology, Harvard Medical School, Boston, and director of cornea service, Massachusetts Eye and Ear Infirmary, Boston. Study results published in the April 2009 issue of Archives of Ophthalmology show that with topical Avastin treatment, the caliper of the neovascular blood vessels was diminished by a mean of 50%.

Neovascularization is an all too common problem. “It affects several million people worldwide,” Dr. Dana said. “It is the leading cause of blindness worldwide after cataracts.”

Paucity of treatments

Since current treatment strategies are extremely limited, investigators here hoped that topical applications of Avastin might prove helpful. “There really are no good ways to control growth of blood vessels in the cornea or strategies to cause a regression once they have been established,” Dr. Dana said. “People have used all sorts of technologies including laser and various pharmacological approaches like the use of steroids to cause regression of blood vessels—these either didn’t work or they caused additional problems.”

For the study, investigators included only those patients with established blood vessels in the cornea which were not actively growing. “The reason we did this is because we wanted to have a very high bar for demonstrating efficacy,” Dr. Dana said. “If you look at the patients who have active blood vessel growth it is certainly easier to suppress their growth.” Investigators also wanted to avoid incorporating improvement that would have occurred anyway during the normal course of the disease. “Sometimes with active conditions, even with a natural history of the disease, these things plateau off anyway,” Dr. Dana said. “We wanted to have people with established blood vessels so that if we saw a regression in the degree of angiogenesis in the cornea, we would know that it was because of the treatment that we were giving them, not because of the natural history.”

Measuring blood vessel growth

During the study, patients were asked to use a 1% topical drop of Avastin over the course of three weeks. From the outset this was applied as little as two times a day to as much as four times a day. Investigators then measured blood vessel growth or regression. “We looked at overall extent of the blood vessels, what we call the neovascular area, and we looked at the caliper of the blood vessels,” Dr. Dana said. “We also looked at the invasion area—that percentage of the cornea that is actually invaded with blood vessels.”

Results showed that with Avastin treatment, it was the size of the neovascular blood vessels that was affected most. “We noticed that our biggest and most immediate response was in the caliper of the blood vessels,” Dr. Dana said. “With the surface area we saw about a 50% diminishment, and in some cases this was close to 100%.” Unfortunately, similar improvement was not seen in the extent of the incursion of the neovascularization. “When we looked at the leading blood vessels we didn’t see a very big change in them regressing or going backward, but we saw a significant diminishment in their caliper and overall surface area.”

Investigators were a little surprised at how effective the topical treatment appeared to be. “We did not expect to see as much efficacy with the topical delivery because Avastin is a fairly large molecule and we didn’t expect to get much bioactivity,” Dr. Dana said. “However, we have done other studies looking at the absorption of Avastin, and although the molecule is so big, we did see that a lot of it gets into the cornea in these inflamed eyes.”

Dr. Dana feels very confident about the data, which has also been corroborated by ongoing work. “We have ongoing studies that we have been doing in collaboration with our colleagues in the army looking at use of these same strategies for many combat-related injuries and we have seen continued efficacy,” Dr. Dana said.

He urges other practitioners to consider use of Avastin for their patients with corneal neovascularization. However, he stresses that Avastin must be used judiciously. “We caution against prolonged use of anti-VEGFs [vascular endothelial growth factor] because it can have some deleterious effects if used for a long period—certainly more than one month,” Dr. Dana said. “But we feel that if you use this for three weeks at the regimen that we have recommended, it is a safe approach given the data that we have to date.”

Going forward, investigators hope to conduct further studies on this. “At this point we’re looking at actually broadening the indication to include patients with active blood vessels as well as those who are getting corneal transplants and who have other types of inflammatory disorders,” Dr. Dana said.

Editors’ note: Dr. Dana has no financial interests related to his comments.

Contact information

Dana: 617-573-4331, Reza_dana@meei.harvard.edu

Quelling new corneal blood vessel growth Quelling new corneal blood vessel growth
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