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

Area of Science:

• Ophthalmology
• Retinal Imaging
• Age-Related Macular Degeneration (AMD)

Background:

• Cuticular drusen are a hallmark of age-related macular degeneration (AMD).
• Understanding the microstructural changes associated with cuticular drusen is crucial for AMD research.

Purpose of the Study:

• To characterize microscopic alterations of photoreceptors and retinal pigment epithelium (RPE) surrounding cuticular drusen in AMD.
• To utilize multimodal imaging, including high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO), for detailed analysis.

Main Methods:

• Eyes with early to intermediate AMD and cuticular drusen underwent comprehensive imaging: color fundus photography, infrared reflectance, fundus autofluorescence, optical coherence tomography (OCT), and AOSLO.
• Cuticular drusen were classified into three OCT-defined phenotypes.
• Cone photoreceptor reflectivity was assessed using AOSLO, with longitudinal imaging in a subset of eyes.

Main Results:

• A total of 3177 cuticular drusen were classified into 3 types based on OCT.
• AOSLO demonstrated phenotype-dependent cone reflectivity alterations corresponding to the drusen types.
• Longitudinal imaging revealed that reduced outer retinal reflectivity on AOSLO preceded the OCT detection of new cuticular drusen.

Conclusions:

• Multimodal imaging at cellular resolution shows progressive, phenotype-specific disruption of the photoreceptor-RPE complex in AMD with cuticular drusen.
• Early reflectivity changes detected by AOSLO precede OCT-visible lesions, highlighting its sensitivity for identifying early outer retinal alterations.
• This study advances the understanding of cuticular drusen biogenesis and early AMD pathogenesis.