Another potential indication emerges for anti-VEGF therapy

Patients treated with pegaptanib sodium (Macugen, OSI/Eyetech Pharmaceuticals/Pfizer) were more likely to experience improvements such as regression of neovascularization, less severity of venous beading, and fewer intraretinal microvascular abnormalities than patients who received sham injections, said Dr. Altaweel, associate professor, Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison.

The study of the effects of pegaptanib on the severity of diabetic retinopathy was a prospectively defined secondary endpoint of a trial evaluating pegaptanib therapy for diabetic macular edema (DME). Subjects in the phase II multicenter, randomized, controlled study received a sham injection or pegaptanib (0.3, 1, or 3 mg) at study entry, week 6, and week 12. Additional injections were given as needed over an additional 18 weeks, with a maximum of six injections of the drug or sham therapy.

"We found some interesting changes," Dr. Altaweel said.

The effects of pegaptanib interested the investigators because anti-VEGF therapy accomplishes two things in patients with age-related macular degeneration (AMD): it decreases leakage from blood vessels and it can stop the growth of vessels or induce regression, Dr. Altaweel said.

"These actions are also important in diabetic retinopathy. The normal course in severe diabetic retinopathy is progression toward the growth of new vessels also," he added.

Laser therapy side effects

Panretinal laser is the standard therapy for patients who develop retinal neovascularization from diabetes, but laser therapy can worsen macular edema, damage eye tissue, affect peripheral vision, or potentially cause harmful burns when treatment is closer to the center.

"What is interesting about pegaptanib is that if you can use a treatment that potentially stabilizes or improves the diabetic retinopathy, then maybe you can avoid using as much laser treatment," Dr. Altaweel said.

Treatment with pegaptanib also could be helpful in cases where the disease has demonstrated resistance to laser therapy or where adjunctive therapy seems advisable, he continued.

Analysis of the effects of pegaptanib showed that improvement of one step or more along the ETDRS diabetic retinopathy severity scale had occurred at 36 weeks in 38% of patients who had received the 0.3-mg dose. Improvement occurred in 51% of the 1-mg dose group, 33% of the 3-mg dose group, and 16% of the sham treatment group. In the fellow eye, only 22% of patients had improvement by one step or more.

The results are statistically significant for the 0.3- and 1-mg doses and approach significance for the 3-mg dose, and are significant for subjects treated with pegaptanib as a whole when compared with sham.

Combined results for 107 patients who received pegaptanib showed that vision had improved by one step or more on the severity scale in 41.1% (n = 44/107) of the group by 36 weeks compared with baseline. In the sham group, 16.7% of patients (5/30) showed that degree of improvement.

Looking at the results in terms of patients whose diabetic retinopathy had worsened at week 36 compared with baseline, the data showed that 13% of the 0.3-mg group had worsening severity; in the fellow eyes of these patients, diabetic retinopathy became more severe in 35%.

"Within the same person, the other eye that wasn't getting pegaptanib was more likely to get worse over time," Dr. Altaweel said. "But with the pegaptanib treatment, it is a much lower proportion that worsened and a much higher proportion that improved."