PURPOSE: To investigate the value of multimodal confocal scanning laser ophthalmoscopy (cSLO) for phenotyping fundus lesions in patients with pseudoxanthoma elasticum (PXE) and to correlate these findings with morphologic alterations detected by spectral domain optical coherence tomography (SD-OCT). METHODS: Imaging was performed with a combined SD-OCT-cSLO system (Spectralis HRA-OCT; Heidelberg Engineering, Heidelberg, Germany). OCT scans were placed at locations of interest on near-infrared (NIR) reflectance, fundus autofluorescence (FAF), and fluorescein angiography (FA) images. The instrument allowed for exact topographic correlation of findings on OCT and cSLO images. RESULTS: NIR reflectance imaging showed the highest sensitivity to detect angioid streaks and peau d'orange compared to FAF or FA. On OCT scans, angioid streaks reliably showed breaks in Bruch's membrane. Peau d'orange was associated with alternating reflectivity within Bruch's membrane. Characteristic mid-peripheral chorioretinal atrophies showed hyporeflective spaces involving the outer neurosensory retina. In eyes with pattern dystrophy like alterations, subneurosensory accumulation of material was observed within areas of increased FAF. CONCLUSIONS: SD-OCT in combination with cSLO imaging using NIR light locates the primary pathologic formations of angioid streaks and peau d'orange in Bruch's membrane. NIR reflectance imaging may be superior for detecting PXE-related fundus lesions at the level of Bruch's membrane, because the blue laser light that is used in FAF and FA is markedly absorbed by the pigment epithelium and therefore may only detect alterations if this cell layer is also affected. The findings indicate that multimodal cSLO and SD-OCT imaging of the outer retina allows for screening of PXE related retinal alterations.