Purpose To evaluate melanin-related near-infrared fundus autofluorescence (NIA, excitation 787 nm, emission > 800 nm), lipofuscin-related fundus autofluorescence (FAF, excitation 488 nm, emission >500 nm), optical coherence tomography (OCT), and multifocal electroretinography (mfERG) in patients with chloroquine (CQ) retinopathy. Methods Two patients with progressed CQ retinopathy underwent clinical examination, ISCEV mfERG evaluation, and FAF and NIA imaging using a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2) with either a 30° or wide-angle field-of-view. OCT3 imaging was performed in one of these patients. Results In the foveola, FAF and NIA were relatively normal. Parafoveal loss of retinal pigment epithelium (RPE) was indicated by absent FAF and NIA. An area of reduced FAF and NIA surrounded the parafoveal region of RPE loss. In the adjacent area, FAF was increased and increased NIA marked the peripheral border of increased FAF. Wide-field imaging revealed increased FAF in association with retinal vessels. Retinal thickness was markedly reduced in the OCT predominantly in the parafoveal region. Visual field loss and mfERG amplitude reduction corresponded to areas with increased or reduced FAF and NIA. Conclusion Patterns of FAF and NIA indicate different stages of pathophysiologic processes involving lipofuscin and melanin in the RPE. Combined retinal imaging and functional testing provides further insights in the pathogenesis and development of retinal degenerative disease. An association of CQ retinopathy with retinal vessels architecture is hypothesized.