An interactive semi-automated procedure was developed to level the macular background reflectance for the purpose of morphometric analysis of drusen. In this study, 10 color fundus photographs of patients with age related macular degeneration (AMD) and drusen were used. After digitizing the photographs, the underlying background pattern in the green channel was leveled by a stepwise algorithm based on a geometric model of reflectance in the normal fovea and parafovea. Segmentation of drusen and measurements were made in the central and middle subfields (1000 /spl mu/m diameter circle and 3000 /spl mu/m diameter annulus). Two graders independently applied the digital method to the ten cases. The mean digital measurements were compared to stereo fundus gradings by an expert grader. The absolute mean differences between the digital and stereo gradings were 2.4 +/- 2.8% in the middle subfield and 2.6 +/- 3.1% in the central subfield. Two digital graders using the software achieved comparable drusen measurements to stereo gradings. This technique for macular image analysis has the potential of being adopted in large clinical trials.