Age-related maculopathy (ARM) has become the major cause of blindness in the Western World. Currently its pathogenesis and primary site of functional damage is not fully understood but ischemia is believed to play a major role. Early detection and precise monitoring of progression of ARM are main goals of current research due to lack of sufficient treatment options, especially in the dry, atrophic form of this disease. We applied the multifocal electroretinogram (mfERG) that can detect any local functional deficit objectively in the central retina. We recorded two paradigms in early ARM patients, the fast flicker and the slow flash paradigm which both represent fast adaptation processes of the proximal retina but under differing photopic conditions and stimulation rates. By subtracting the waveform responses we extracted a late component in the difference waveform that was significantly reduced in the early ARM group compared to a healthy control group (p < or = 0.05). We propose that this multifocal nonlinear analysis permits the detection of adaptative deficits and provides topographic mapping of retinal dysfunction in early ARM. The difference waveform component we extracted with this novel approach might indicate early functional loss in ARM caused by ischemia in postreceptoral layers such as bipolar cells and inner plexiform regions.