Cuticular Drusen Associated Photoreceptor and RPE Optical Property Perturbation Revealed by Adaptive Optics Scanning Laser Ophthalmoscopy

Purpose: To characterize microscopic alteration of photoreceptors and RPE surrounding cuticular drusen in age-related macular degeneration (AMD) using multimodal imaging, including high resolution adaptive optics scanning laser ophthalmoscopy (AOSLO). Methods: Eyes with early to intermediate AMD and predominantly cuticular drusen underwent color fundus photography, infrared reflectance, fundus autofluorescence, optical coherence tomography (OCT), and AOSLO. Cuticular drusen were identified using multimodal imaging and classified into three OCT-defined phenotypes. Cone photoreceptor reflectivity was assessed on AOSLO. A subset of eyes underwent longitudinal AOSLO and OCT imaging. Result: Nineteen eyes from 12 subjects aged 70.3 ± 5.8 years were studied. Six eyes had longitudinal follow-up imaging. A total of 3177 cuticular drusen were evaluated and classified into 3 types based on cross sectional OCT imaging. AOSLO revealed corresponding phenotype-dependent cone reflectivity alterations associated with the 3 types of cuticular drusen. Type 1: Maintained cone reflectivity overlying the drusen on a hyporeflective background. Type 2: Cone reflectivity loss overlying the cuticular drusen. Type 3: Cones are predominantly not visible over the cuticular drusen. Lesion diameters were 52.62 ± 9.38 μm (Type 1), 71.88 ± 12.39 μm (Type 2), and 124.72 ± 20.94 μm (Type 3). All lesions were accompanied by hypertransmission in the choroid on OCT. Longitudinal imaging showed that localized outer retinal reflectivity reduction on AOSLO preceded the detection of new cuticular drusen on OCT. Conclusions: Cellular-resolution multimodal imaging demonstrates progressive, phenotype-specific disruption of the photoreceptor-RPE complex associated with cuticular drusen in AMD. Early AOSLO-detected reflectivity changes preceding OCT-visible lesions highlight the sensitivity of adaptive optics imaging for identifying early outer retinal alterations and for advancing understanding of the biogenesis of cuticular drusen.