© 2017 by Ophthalmic Communications Society. Inc. Purpose: To investigate the microscopic structure of outer retinal tubulation (ORT) and optical properties of cone photoreceptors in vivo, we studied ORT appearance by multimodal imaging, including spectral domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy. Methods: Four eyes of four subjects with advanced age-related macular degeneration underwent color fundus photography, infrared reflectance imaging, SD-OCT, and adaptive optics scanning laser ophthalmoscopy with a high-resolution research instrument. Outer retinal tubulation was identified in closely spaced (11 μm) SD-OCT volume scans. Results: Outer retinal tubulation in cross-sectional and en face SD-OCT was a hyporeflective area representing a lumen surrounded by a hyperreflective border consisting of cone photoreceptor mitochondria and external limiting membrane, per previous histology. In contrast, ORT by adaptive optics scanning laser ophthalmoscopy was a hyporeflective structure of the same shape as in en face SD-OCT but lacking visualizable cone photoreceptors. Conclusion: Lack of ORT cone reflectivity by adaptive optics scanning laser ophthalmoscopy indicates that cones have lost their normal directionality and waveguiding property due to loss of outer segments and subsequent retinal remodeling. Reflective ORT cones by SD-OCT, in contrast, may depend partly on mitochondria as light scatterers within inner segments of these degenerating cells, a phenomenon enhanced by coherent imaging. Multimodal imaging of ORT provides insight into cone degeneration and reflectivity sources in optical coherence tomography.