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To evaluate macular thickness measured by optical coherence tomography (OCT) during pegaptanib therapy for neovascular age-related macular degeneration (AMD).For this prospective, nonrandomized, observational case series, 41 eyes from 41 patients with neovascular AMD received intravitreous pegaptanib (1 mg) injections repeated every 6 weeks. The primary outcome measure was central foveal thickness measured by OCT. Secondary outcomes were fluorescein angiographic leakage and visual acuity.Mean thickness of the central area on OCT decreased from 340 ± 24 μm to 299 ± 14 μm after 12 weeks of pegaptanib injections. This represents a reduction in thickening of 32%. Fluorescein angiograms with definite leakage decreased from 100% to 81%, and mean visual acuity decreased from 20/116 to 20/120.Intravitreal injections of pegaptanib at 6-week intervals result in a moderate reduction of central foveal thickness in eyes with subfoveal neovascular AMD. This presents a modest effect relative to that reported with other anti–angiogenic agents.