Vasculopathies: Data support intravitreal bevacizumab

November 1, 2009

Data continue to support intravitreal bevacizumab injection for treatment of radiation maculopathy and radiation optic neuropathy.

New York-Data accumulating during lengthening follow-up continue to support intravitreal bevacizumab (Avastin, Genentech) injection for treatment of radiation maculopathy and radiation optic neuropathy (RON), said Paul T. Finger, MD, at the 2009 Retina Congress.

Dr. Finger has published several papers on his early experience with this use of the anti-vascular endothelial growth factor (VEGF), agent. At the congress, he provided an update from an interventional, consecutive case series composed of 16 eyes with RON and 31 eyes with radiation maculopathy. Treatment has been performed with approval from the institutional review board of the New York Eye Cancer Center, where Dr. Finger is director.

Duration of intravitreal bevacizumab treatment extends to about 40 months in both patient cohorts.

There have been no systemic adverse events associated with bevacizumab injection and no cases of endophthalmitis, retinal detachment, or vitreous hemorrhage, he said.

"These are uncontrolled series of patients with radiation maculopathy and optic neuropathy, but based on published data regarding vision loss developing with untreated disease, intravitreal injection of bevacizumab appears to be a game-changer, altering the course of these complications of tumor treatment by helping to preserve vision," he said. "However, careful monitoring of patients at risk is important because it appears that early intervention when patients first become symptomatic offers them the best chance for maintaining vision."

Early experience

Dr. Finger became interested in intravitreal bevacizumab treatment for radiation maculopathy and RON about 4 years ago based on his experience with anti-VEGF treatment for patients with choroidal neovascularization secondary to age-related macular degeneration.

Observing that anti-VEGF treatment effectively decreased vascular leakage and recognizing that early vision loss associated with radiation maculopathy and optic neuropathy is an acute transudative process relating to incompetence of and leakage from normal vessels, shunt vessels, and neovascularization, Dr. Finger reasoned that intravitreal bevacizumab might be helpful for restoring or maintaining vision. His early experience showed benefits for resolving the edema, reducing the size of hemorrhages and exudates, and inducing regression of neovascularization.

However, the question remained as to what would be the long-term efficacy, he said.

So far, there appears to be no evidence of tachyphylaxis. However, capillary dropout develops as a later component of the pathophysiology of radiation retinopathy. Although Dr. Finger is doubtful that intravitreal bevacizumab will directly prevent the long-term sequelae, he believes it may be helping to mitigate their onset.

"It appears that in the absence of edema, capillary dropout is occurring later and progressing less quickly. Nevertheless, late vascular closure and resultant vision loss will likely occur over time," Dr. Finger said.

Analysis of the patient data indicates the response to bevacizumab depends on both the magnitude of the radiation dose and timing of bevacizumab initiation.

Patients who were treated with a higher dose (e.g., those with larger tumors) are less likely to benefit and visual prognosis is better if the bevacizumab is initiated sooner after patients become symptomatic versus later.

"Once patients have lost vision from radiation-induced vasculopathy, they are less likely to get it back. That is not to say that there is no benefit for starting treatment as intravitreal bevacizumab can still help to stabilize vision. However, the likelihood for restoring vision is decreased," Dr. Finger said.

Considering the potential risks of intravitreal injection, Dr. Finger said he advocates initiating treatment only after patients develop symptoms, either metamorphopsia or decreased vision subjectively measured by standardized visual acuity. He suggested patients may be given an Amsler grid for at-home monitoring, noting that monocular vision loss in the eye exposed to radiation may go unnoticed by binocular patients who favor the better eye.

Although in early patients Dr. Finger said he tried tapering the intravitreal treatment, his impressions have been that maintaining a routine injection schedule is preferable because it offers the best chance for suppressing edema, which, if allowed to recur, can result in permanent vision loss. A few sample cases highlight some of the impressive results that have been achieved, including a patient who developed radiation maculopathy after treatment for a subfoveal choroidal melanoma and has 20/20 BCVA at 41 months after starting intravitreal bevacizumab injection.

"The course of this patient and others with posterior tumors has been particularly remarkable," Dr. Finger said.