BACKGROUND: Pegaptanib, an anti-vascular endothelial growth factor therapy, w as evaluated in the treatment of neovascular age-related macular degeneration. METHODS: We conducted two concurrent, prospective, randomized, double-blind, mu lticenter, dose-ranging, controlled clinical trials using broad entry criteria. Intravitreous injection into one eye per patient of pegaptanib (at a dose of 0. 3 mg, 1.0 mg, or 3.0 mg) or sham injections were administered every 6 weeks over a period of 48 weeks. The primary end point was the proportion of patients who had lost fewer than 15 letters of visual acuity at 54 weeks. RESULTS: In the com bined analysis of the primary end point (for a total of 1186 patients), efficacy was demonstrated, without a dose-response relationship, for all three doses of pegaptanib (P< 0.001 for the comparison of 0.3 mg with sham injection;P < 0.001 for the comparison of 1.0 mg with sham injection; and P=0.03 for the comparison of 3.0 mg with sham injection). In the group given pegaptanib at 0.3 mg, 70 per cent of patients lost fewer than 15 letters of visual acuity, as compared with 5 5 percent among the controls (P < 0.001). The risk of severe loss of visual acui ty (loss of 30 letters or more)-was reduced from 22 percent in the sham-inject ion group to 10 percent in the group receiving 0.3 mg of pegaptanib (P < 0.001). More patients receiving pegaptanib (0.3 mg), as compared with sham injection, m aintained their visual acuity or gained acuity (33 percent vs. 23 percent; P=0.0 03). As early as six weeks after beginning therapy with the study drug, and at a ll subsequent points, the mean visual acuity among patients receiving 0.3 mg of pegaptanib was better than in those receiving sham injections (P < 0.002). Among the adverse events that occurred, endophthalmitis (in 1.3 percent of patients), traumatic injury to the lens (in 0.7 percent), and retinal detachment (in 0.6 p ercent) were the most serious and required vigilance. These events were associat ed with a severe loss of visual acuity in 0.1 percent of patients. CONCLUSIONS: Pegaptanib appears to be an effective therapy for neovascular age-related macul ar degeneration. Its long-term safety is not known. METHODS: We conducted two concurrent, prospective, randomized, double-blind, mu lticenter, dose-ranging, controlled Clinical trials using broad entry criteria. Intravitreous injection into one eye per patient of pegaptanib (at a dose of 0.3 mg, 1.0 mg, or 3.0 mg) or sham injections were administered every 6 weeks over a period of 48 weeks. The primary end point was the proportion of patients who had lost fewer than 15 letters of visual acuity at 54 weeks. RESULTS: In the com bined analysis of the primary end point (for a total of 1186 patients) efficacy was demonstrated, without a dose- P & lt; 0.001 for the comparison of 1.0 mg with sham injection; and P = 0.03 for the comparison of 3.0 mg with sham injection; In the gro up given pegaptanib at 0.3 mg, 70 per cent of patients lost fewer than 15 letters of visual acuity, as compared with 5 5 percent among the controls (P <0.001). The risk of severe loss of visual acui ty (loss of 30 letters or more) -was reduced from 22 percent in the sham-inject ion group to 10 percent in the group receiving 0.3 mg of pegaptanib (P <0.001). More patients receiving pegaptanib (0.3 mg), as compared with sham injection, m inintained their visual acuity or gained acuity (33 percent vs. 23 percent; P = 0.0 03). As early as six weeks after beginning therapy with the study drug, and at a ll subsequent points, the mean visual acuity among patients receiving 0.3 mg of Among the adverse events that occurred, endophthalmitis (in 1.3 percent of patients), traumatic injury to the lens (in 0.7 percent), and retinal detachment (in 0.6 p ercent ) the the serious and required vigilance. These events were associat ed with a severe loss of visual acuity in 0.1 percent of patients. CONCLUSIONS: Pegaptanib appears to be an effective therapy for neovascular age-related macul ar degeneration. Its long-term safety is not known.