Bevacizumab Safe, Effective in Reducing Corneal Neovascularization, a Symptom of NK

Bevacizumab Safe, Effective in Reducing Corneal Neovascularization, a Symptom of NK

Bevacizumab injection into the eye is safe and effective in reducing the abnormal formation of blood vessels in the cornea, a study suggests.

This condition, called corneal neovascularization, is a symptom of neurotrophic keratitis (NK) and can hinder the success of corneal transplants.

The study, “Intrastromal bevacizumab in the management of corneal neovascularization: a retrospective review,” was published in the journal Graefe’s Archive for Clinical and Experimental Ophthalmology.

NK is a rare degenerative eye disease that affects the cornea, the transparent protective outer layer of the eye that works like a window to control and focus the entry of light into the eye. In order to be a clear membrane for vision, the cornea has the special capacity to function without the presence of blood vessels.

NK is characterized by a reduction or loss of sensation in the cornea, spontaneous breakdown of the corneal epithelium (the outermost layer of the cornea), as well as impaired healing. Long-lasting or chronic NK also may lead to corneal neovascularization, abnormal growth of the corneal epithelium, and corneal scarring.

Many things can cause NK, however, two of the most common causes are infections by the herpes simplex virus or the herpes zoster virus, as well as laser eye surgeries.

Corneal transplants are commonly used, including in more severe cases of NK, to improve a person’s vision and lessen pain. However, more than half of patients with significant corneal neovascularization reject the new transplanted cornea, making the condition a risk factor for corneal transplant rejection.

Bevacizumab, sold under the brand name Avastin by Genentech, is an approved treatment for a number of cancers; it works by suppressing the growth of blood vessels. It does so by blocking the vascular endothelial growth factor (VEGF) protein, which promotes the formation of new blood vessels.

Several studies have shown that the injection of bevacizumab directly into the cornea (as an “off-label” use) results in partial-to-complete reduction of corneal neovascularization, with few complications. However, there is limited follow-up data on these patients.

Now, clinicians at the department of Ophthalmology & Visual Neurosciences at University of Minnesota Medical School set out to evaluate the long-term safety and effectiveness of bevacizumab treatment (injected directly into the cornea) in patients with chronic corneal neovascularization and classified as high-risk for corneal transplant.

They retrospectively analyzed the data of 14 eyes of 14 patients (eight women and six men) from 2011 to 2018. Patients were treated and followed at the University of Minnesota Medical Center.

Patients’ mean age was 62 (range 32-80 years) and they were followed-up for a median of three years, ranging from nine to 56 months. Nine of them (64.2%) had NK due to herpes zoster or herpes simplex infections. Other causes of corneal neovascularization included corneal inflammation caused by a fungus, a parasite or the use of contact lens, as well as chemical injury, and corneal transplant.

All but one patient showed invasion of blood vessels in the corneal regions mainly responsible for focused vision: seven of them (50%) in the central region and six of them (42.8%) in the paracentral region, adjacent to the central region.

Bevacizumab (0.05–0.15 mL of 2.5 mg/0.1 mL) was injected every four to eight weeks, with patients receiving, on average, one to three injections before partial or total corneal transplants.

Complete response to bevacizumab treatment was defined as a greater than 90% reduction in corneal blood vessels, moderate response as 25–90% reduction, and minimal response as minimal to no change or worsened corneal neovascularization.

Results showed that more than half of the patients (64.3%) had considerable improvements in visual acuity, while one patient showed no improvement. Five patients achieved complete responses (35.7%), six patients (42.9%) showed a moderate response, and three (21.4%) had minimal response.

Two of the complete responders presented a total elimination of blood vessels in the cornea, avoiding the need for a transplant. Eight patients (57%) with moderate to complete responses underwent total (six patients) or partial (two patients) corneal transplant. At the last follow-up, there were no signs of reappearance of corneal neovascularization or transplant rejection in the group of patients who received transplants.

Only three patients reported adverse side effects (one each), which were mild in nature and resolved naturally without additional treatment.

“The injection procedure itself causes minimal discomfort to patients and appears to be associated with minimal systemic risk,” the researchers wrote.

These findings are consistent with previous data and highlight that bevacizumab treatment “produces durable regression of [corneal neovascularization] and allows for persistent graft [transplant] survival in hosts with high pre-operative graft rejection risk due to neovascularization,” the researchers wrote.

More studies are required to investigate the effectiveness of other methods of administering bevacizumab, and for other anti-VEGF compounds, in reducing corneal neovascularization, in particular in patients with more resistant conditions.

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