© 2016 Elsevier Inc. Purpose To test whether increased light transmission (hypertransmission) through subretinal drusenoid deposits (SDD) into the choroid in age-related macular degeneration (AMD) represented retinal pigment epithelium (RPE) degeneration. Design Cross-sectional study. Methods Nineteen eyes of 12 patients with early- to intermediate-stage AMD and 18 eyes of 12 normal subjects were evaluated with color fundus photography, optical coherence tomography (OCT), and high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) at baseline and 24 months later. SDD were classified using an OCT-based 3-stage grading system. Hypertransmission beneath SDD into the choroid was examined in OCT. SDD microstructure was assessed with AOSLO. To characterize the hypertransmission-associated chorioretinal degeneration, choroidal thickness and photoreceptor length were measured in OCT at 1 mm and 2 mm superior, inferior, temporal, and nasal to the foveal center. Results OCT disclosed hypertransmission beneath stage 3 SDD in 8 eyes. These lesions showed a distinctive regressing structure in AOSLO, compared with stage 3 lesions without hypertransmission. The phenomenon persisted at follow-up, and new hypertransmission developed as SDD advanced. In eyes with hypertransmission, choroids were thinner than those of normal eyes at all sites (by 44%–56%, P ≤ 0028) and those of eyes with SDD but without hypertransmission at superior and temporal sites (by 31%–46%, P ≤ 039). Photoreceptors were significantly shorter than those in normal eyes (by 6%–26%, P ≤ 0379). Conclusions Hypertransmission into the choroid, accompanied with SDD regression and thinning of choroid and photoreceptor layers, indicates RPE degeneration associated with advanced stages in the SDD life cycle.