Pegaptanib shows promise as adjunct to progressive diabetic retinopathy treatment

August 1, 2008

Pegaptanib sodium (Macugen, [OSI] Eyetech/Pfizer) used as an adjunct to laser therapy has a significant impact in the treatment of patients with progressive diabetic retinopathy, offering much hope for the prognosis of patients who have this disorder.

Key Points

Fort Lauderdale, FL-Intravitreal injection of pegaptanib sodium (Macugen, [OSI] Eyetech/Pfizer) used as an adjunct in the treatment of proliferative diabetic retinopathy (PDR) refractory to laser can significantly help improve the prognosis of the condition, according to the results of a recent study reported at the annual meeting of the Association for Research in Vision and Ophthalmology.

The current gold standard treatment for PDR is pan-retinal photocoagulation (PRP) with either an argon or diode laser, said Victor H. Gonzalez, MD, an ophthalmologist at Valley Retina Institute, McAllen, TX. The idea is to destroy the vascular tissue in the proliferative areas of the retina. The indiscriminate destruction of retinal tissue comes at a price, however, he added.

"The side effects of this PRP treatment are a reduction in the visual field-because you are destroying some peripheral retina, a decrease in night vision, as well as idiopathic loss of central vision," said Dr. Gonzalez. "We believe that, in some people, the edema in combination with some inflammation may actually cause this idiopathic loss of vision."

"The problem with that is that if the eye is full of blood, then you cannot provide the treatment you need, which is still considered to be laser therapy," Dr. Gonzalez said. "Therefore, the goal is to try to 'laser' these patients before they start having significant bleeding."

The laser works by destroying the ischemic retina, which then decreases the production of vascular endothelial growth factor (VEGF) 165, according to Dr. Gonzalez. Patients who have laser treatment in the periphery of the retina, however, still have active neovascularization with intermittent bleeding into the eye. Obviously, from a functional standpoint, this situation is a nuisance for these patients.

Pegaptanib was one of the first anti-VEGF inhibitors to be approved by the FDA for the treatment of wet age-related macular degeneration. The drug is selective for VEGF 165, which primarily is associated with pathological neovascularization and works by inducing a regression of the abnormal blood vessels without the surgeon having to perform a laser procedure or a more invasive vitrectomy.

13 eyes studied

Dr. Gonzalez and colleagues conducted a study in 13 eyes of 13 patients with PDR. Each eye received an intravitreal injection of 0.3 mg pegaptanib just before argon laser therapy. Nine of the 13 patients (69.2%) demonstrated visual improvement from baseline, and all of the patients showed regression of neovascularization as well as a reduction of existing vitreous hemorrhage during the 6-month follow- up. Optical coherence tomography imaging revealed a decrease in mean retinal thickness in the foveal and parafoveal zones. No significant ocular or systemic adverse events were observed in the study.

"We were very pleased to see how well patients responded to this treatment. Following the injection of pegaptanib, we could effectively induce the regression of neovascularization, and the bleeding cleared up very well, paving the way for pin-point laser treatments," Dr. Gonzalez said.

"The neovascularization is the source of bleeding in the vitreous, and pegaptanib addresses these bleedings and stops them. We were able to avoid performing vitrectomy surgery in the majority of those patients that had bleeding in the eye where we used this drug, which would be a normal sequelae without pegaptanib," he continued.

Dr. Gonzalez has planned a three-arm study with pegaptanib. One arm will receive standard laser treatment, the second arm will first receive pegaptanib (for regression of neovascularization) and then a targeted laser therapy in the area of ischemia, and the third arm will receive three injections of pegaptanib, spaced 6 weeks apart, which then will be followed up with booster injections four times a year.

Seventy-seven percent of patients with diabetes and PDR also have diabetic macular edema (DME), he said, adding that this medication in the presence of DME with proliferative disease can have a very positive result in reducing the DME, because the VEGF in these patients plays an important role in DME.

Steroids are another therapeutic approach for patients with PDR, according to Dr. Gonzalez, but a good regression of neovacularization has not been seen with this class of medication. Steroids work better for DME, he said.

"The thought now is that laser photocoagulation is still the standard of care, but there is no doubt that we have to try to reduce the amount of laser that we use on these patients due to the debilitating side affects from the laser," Dr. Gonzalez said. "You may have 20/20 vision, but if your visual acuity is less than 30°, that is a problem."

Pegaptanib has been shown to cause regression of the abnormal vessels and dry them up within 6 weeks, he said. Once the neovascularization is controlled, then a laser can be used to specifically target areas.

"If the data continue to demonstrate the improvement in these patients and we can obtain a sustained-release formulation of the drug, then there may be the potential to be able to introduce this drug into the eye once every 6 months or even once every year," Dr. Gonzalez said. "The clear goal is to have a slow, low-level, continued suppression of VEGF to prevent the neovascularization from developing."