High-Resolution and Multimodal Structural Phenotyping of Intermediate and Advanced Non-Neovascular Age-Related...

To characterize structural phenotypes in intermediate and advanced non-neovascular age-related macular degeneration (AMD) using flood-illumination adaptive optics (FIAO) and to explore their relationship with established multimodal imaging biomarkers, including OCT-based atrophy classifications.

Prospective, cross-sectional observational study.

A total of 208 eyes from 117 patients (mean age 74 years; 63% female) with intermediate AMD (iAMD) or geographic atrophy (GA) were enrolled. Eligible participants had visual acuity ≥20/63, refractive error between -6 and +2 diopters, and sufficient media clarity for high-quality imaging.

Participants underwent multimodal imaging, including color fundus photography, spectral-domain OCT, infrared reflectance, fundus autofluorescence, and FIAO. Structural phenotypes (drusen, subretinal drusenoid deposits, pigmentary changes, and GA margins) were assessed qualitatively across modalities. Flood-illumination adaptive optics features were compared with OCT-based atrophy classifications (incomplete and complete retinal pigment epithelium and outer retinal atrophy [iRORA and cRORA]) using descriptive analyses and cross-tabulation.

Prevalence and multimodal characteristics of AMD structural phenotypes, and their correspondence with FIAO features.

Drusen and pigmentary abnormalities were detected in the majority of eyes across modalities, with variability in prevalence depending on imaging technique. Flood-illumination adaptive optics identified drusen in 70% of eyes revealing a consistent reflectivity pattern of hyperreflective borders and hyporeflective centers. Hyporeflective clumps corresponding to pigmentary changes were always observed on FIAO, frequently localizing to areas of atrophy or transition zones. Distinct FIAO-defined GA border phenotypes were observed, including well-demarcated and indistinct margins. In descriptive cross-tabulation, well-demarcated FIAO borders were more frequently associated with OCT-defined cRORA, whereas indistinct or hyporeflective margins were with iRORA.

Flood-illumination adaptive optics provides high-resolution visualization of structural features in iAMD and GA, revealing distinct patterns of drusen, pigmentary changes, and atrophic margins. While certain FIAO features show qualitative correspondence with OCT-defined atrophy stages, these relationships remain descriptive. Further quantitative and longitudinal studies are needed to determine their clinical relevance and role in disease characterization.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.