Regression of proliferative diabetic retinopathy drmatic

Fort Lauderdale, FL-Intravitreal injection of pegaptanib sodium (Macugen, OSI/Eyetech Pharmaceuticals/Pfizer) was well tolerated and effective in reducing the progression of proliferative diabetic retinopathy (PDR) in all 10 eyes of 10 patients in a small experimental study. Regression of neovascularization was seen as early as the first follow-up examination 3 weeks after the initial injection, said Victor H. Gonzalez, MD, who is in private practice with the Valley Retina Institute in McAllen, TX.

Dr. Gonzalez, speaking on behalf of the Macugen for Proliferative Diabetic Retinopathy Study Group, reported preliminary results indicating that vision has stabilized or improved in all patients and none have needed laser photocoagulation. Neovascularization in the disc and elsewhere regressed, and there was a decrease in central corneal thickness within the first month following treatment, without adverse effects.

"The remarkable thing is that in all 10 patients, 3 weeks after we injected pegaptanib sodium, there was more than 95% regression of the blood vessels," Dr. Gonzalez said. "The real 'wow' effect for us was to see how rapid the response was."

The study protocol calls for an intravitreal injection of 0.3 mg pegaptanib sodium every 6 weeks for 30 weeks. All patients had PDR and were eligible for laser treatment according to ETDRS guidelines. After the injection at baseline, patients were seen at 3 weeks. If at that time at least 50% of the neovascularization had not improved, they received laser therapy.

If the neovascularization had regressed by at least 50%, patients were monitored and re-checked every 6 weeks for the duration of the study while continuing to receive the injections.

Clinical endpoints are reduction in the progression of PDR, defined as regression of neovascularization of the disc and neovascularization elsewhere as assessed by fluorescein angiography; change in best-corrected visual acuity score from baseline; and change in retinal thickness measured at the center point by optical coherence tomography.

"These patients will be followed until week 36 to see if we can continue to improve the retinopathy and to see whether we'll be able to take them off the drug yet avoid recurrence," Dr. Gonzalez said.

He and his colleagues at the Valley Retina Institute embarked on this study after learning that in a large trial of pegaptanib sodium for diabetic macular edema several patients who had proliferative disease had benefited from this therapy.

They decided to conduct an independent study, knowing that pegaptanib sodium blocks production of vascular endothelial growth factor (VEGF) and inhibits the growth of new, abnormal blood vessels, and that elevated levels of VEGF are present in the vitreous of patients with active PDR.

If intravitreal injections of pegaptanib sodium reduce VEGF, they may in turn result in regression of retinal neovascularization and reduce the severity of any coexisting diabetic macular edema, Dr. Gonzalez said.

Ultimately, this therapeutic intervention should reduce the progression of PDR and prevent severe vision loss.

"The nice thing about this trial is it gives us hope for the future," he added. "If we can catch these patients early, potentially with the use of this medication, we may be able to decrease the amount of laser treatment we have to give them and as a corollary be able to preserve more of the visual field."

Complete results from the 36 weeks of the study of pegaptanib sodium in PDR will be released this fall.