Purpose: The purpose of this study was to assess macular perfusion with fundus fluorescein angiography at the 4-month time point in a prospective randomized, single-center 2-year trial comparing intravitreal bevacizumab and laser therapy in patients with diabetic macular edema. Methods: All enrolled patients had standard Early Treatment of Diabetic Retinopathy Study 7-field fundus photographs and fundus fluorescein angiography at baseline and subsequently at 4-month intervals. Patients were excluded from the study if either the greatest linear dimension of the foveal avascular zone (FAZ) was >1,000 mu m in diameter or there was severe perifoveal capillary loss (Early Treatment of Diabetic Retinopathy Study criteria) on fundus fluorescein angiography. The fundus fluorescein angiograms of the bevacizumab (n = 42) and laser (n = 38) groups were graded for greatest linear dimension of the FAZ, area of the FAZ, and perifoveal capillary loss by the Moorfields Reading Centre in a masked fashion. Results: At baseline, the mean greatest linear dimension of the FAZ in the laser group was 685 +/- 262 mu m and in the bevacizumab group was 737 +/- 262 mu m. There was no significant difference at the 4-month time point (P = 0.40) with the mean greatest linear dimension of the FAZ in the laser group recorded as 678 +/- 221 mu m and in the bevacizumab group was 678 +/- 231 mu m. At baseline, the median area of the FAZ in the laser group was 0.36 mm(2) (interquartile range, 0.21-0.46) and in the bevacizumab group was 0.33 mm(2) (interquartile range, 0.27-0.49). There was no significant difference at the 4-month time point (P = 0.30) with the median area of the FAZ in the laser group recorded as 0.35 mm(2) (interquartile range, 0.20-0.52) and in the bevacizumab group was 0.34 mm(2) (interquartile range, 0.23-0.47). Similarly, there was no difference between the two treatment groups (P = 0.64) when a comparison was made of the number of grades of change in perifoveal capillary loss observed in each patient. To date, no patients have been withdrawn from the study because of worsening macular ischemia. Conclusion: At 4 months, there was no evidence of worsening macular ischemia in either group. RETINA 30:781-786, 2010