Significant results show macular edema reduction

November 15, 2007

An international, phase II, randomized, double-blind, sham-controlled study evaluated pegaptanib sodium (Macugen, OSI Eyetech/Pfizer) for the treatment of macular edema secondary to central retinal vein occlusion. Results after 30 weeks showed significant benefits of treatment for improving vision and reducing edema.

Key Points

Boston-A phase II study evaluating pegaptanib sodium (Macugen, OSI Eyetech/Pfizer) for the treatment of macular edema secondary to nonischemic central retinal vein occlusion (CRVO) has yielded positive results in showing that the treatment was associated with significant anatomic and functional improvements compared with sham injection, reported Thomas A. Ciulla, MD, here at the Retina Society annual meeting.

"Based on these outcomes, anti-vascular endothelial growth factor [VEGF] therapy appears to have a promising role in the treatment of CRVO," said Dr. Ciulla, who was one of the study investigators and is a vitreoretinal specialist in private practice at the Midwest Eye Institute, Indianapolis.

The international, multicenter, double-blind study randomly assigned 98 patients 1:1:1 to treatment with pegaptanib 0.3 mg, pegaptanib 0.5 mg, or sham injection at week 0 and every 6 weeks through week 24. Patients returned for follow-up at week 30 for the primary efficacy analysis. Thereafter, patients were eligible for repeat injection if they showed a 15-letter loss in visual acuity (VA). Panretinal photocoagulation was allowed anytime during the study to treat any neovascularization according to the Central Vein Occlusion Study protocol.

Patients were eligible for enrollment if the CRVO had occurred within the past 6 months and they had a best-corrected VA in the study eye between 65 and 20 ETDRS letters (Snellen equivalent ~20/50 to 20/400). In addition, optical coherence tomography (OCT) had to demonstrate presence of macular edema documented by central retinal thickness of at least 250 μm at both a screening visit and the randomization visit. Patients were excluded if they had brisk afferent pupil defect or ocular neovascularization. The three treatment groups were well-balanced in their demographic features, baseline mean VA (~48 letters), and mean center point thickness (range, 642 to 687 μm).

At week 30, significant proportions of patients in the pegaptanib 0.3 mg, pegaptanib 1.0 mg, and sham groups gained 15 letters or more from baseline VA: 36%, 39%, and 28%, respectively.

"The improvement in the controls illustrates the variable natural history of this disease and the importance of randomized, controlled clinical trials, although there was a trend favoring the pegaptanib groups in the statistical analysis," Dr. Ciulla said.

The analysis of mean change in VA from baseline to week 30 showed that patients treated with pegaptanib 0.3 mg or 1.0 mg had gained letters by the time they returned for their second injection, whereas a loss was observed in the sham injection group. At week 30, patients treated with pegaptanib 0.3 mg and 1.0 mg gained an average of 7.1 and 9.9 letters from baseline, respectively, whereas patients in the sham injection group lost an average of 3.2 letters. The 13.1-letter difference between the pegaptanib 1.0 mg group and the controls was statistically significant.

Losing VA

Significant differences also favored both the pegaptanib 0.3 mg and 0.5 mg groups versus the controls in analyses of the proportions of patients losing 15 or more letters of VA at week 30 (9% and 6% versus 31%, respectively) and the proportion with VA of 35 letters (~20/200) or better (88% and 91% versus 63%, respectively).

Results from OCT imaging showed a progressive reduction in edema in all groups. At week 30, however, a significantly greater mean decrease in center point thickness occurred in patients treated with pegaptanib 0.3 mg and 1.0 mg compared with the sham-treated patients (–243 μm and –179 μm versus –148 μm, respectively).

"Interestingly, the effect of pegaptanib sodium occurred very rapidly," Dr. Ciulla said. "By 1 week after injection, mean center point thickness had already decreased by more than 250 μm in the lower-dose group and by about 200 μm in eyes treated with the 1.0-mg dose. In addition, about two-thirds of eyes in the lower-dose group and almost half of the eyes in the higher-dose group had a decrease of 200 μm or more, while there was essentially no change in the controls. Similar results were seen in an analysis of mean change in central subfield thickness, and collectively this is compelling evidence of the efficacy of pegaptanib sodium."

Edema recurs