Early Photoreceptor Disruption in Emerging Subretinal Drusenoid Deposits Detected by Adaptive Optics Imaging

PurposeSubretinal drusenoid deposits (SDDs) are a distinct entity in age-related macular degeneration (AMD) and associated with photoreceptor impairment during progression. Their early impact on photoreceptors remains incompletely understood. This study examined photoreceptor reflectivity during the phase when SDDs were not clinically detectable on optical coherence tomography (OCT) using adaptive optics scanning laser ophthalmoscopy (AOSLO). DesignLongitudinal observational study. ParticipantsPatients with intermediate AMD. MethodsSix eyes of four patients with intermediate AMD and predominantly SDDs underwent multimodal imaging 3-4 times over 3.5 years. Individual SDDs were graded using an OCT-based 3-stage system at each time point. Cross-sectional retinal structure and photoreceptor reflectivity at the location where the new SDDs developed during follow-up were evaluated using OCT and AOSLO. Main Outcome MeasuresPhotoreceptor reflectivity change prior to and during SDD development. ResultsForty-eight retinal locations where new dot-type SDDs developed during follow-up were identified. AOSLO revealed reduced photoreceptor reflectivity in these regions before OCT demonstrated clinically evident deposits (stage [≥] 1) between the ellipsoid zone and the retinal pigment epithelium at the corresponding sites. The mean time to development of stage 1, stage 2, and stage 3 SDDs was 11.78 {+/-} 5.01, 17.40 {+/-} 6.08, and 18.72 {+/-} 4.08 months, respectively. ConclusionsHigh-resolution adaptive optics confocal imaging enables detection of photoreceptor optical property alterations at a stage when SDDs are not yet evident on OCT. This finding underscores the exceptional sensitivity of photoreceptors to minimal structural or functional perturbations during SDD formation and defines an early window for potential intervention.